tbuckley/cabot-search huggingface dataset:
In grandfather's room
Authors: A M Clarfield
Journal: BMJ (2001)

My maternal grandfather lived until the age of 111. He was lucid to the end, but a few years before he died, the family assigned me the task of talking to him about his problem with alcohol. My aunt, with whom he had lived for the last 20 years of his life, had been a healthfood fanatic for as long as I could remember. She was considered somewhat of a crank when I was a child, but as the 1960s approached and we all started joining her in eating bean sprouts, she gained respectability. Being a teetotaler, she was worried about my grandfather's desire to indulge, three to four times a day, in a drink of his favourite whisky, fretting that he was about to become an alcoholic any day. > ![Graphic][1]</img> "Never get excited, go for a walk" He could not understand her fears and would slip himself a few drinks above and beyond the watered-down ration she would dole out each evening before supper. I was a medical student at the time and not yet conscious of my future role as a geriatrician. However, because I represented the closest thing to medical authority, I was delegated by the extended family—my parents, two siblings, eight uncles and aunts, 11 cousins, various dogs, cats, and birds—to "speak to Zayde" … [1]: /embed/inline-graphic-1.gif
Histiocytic medullary reticulosis occurring with small cell lung carcinoma
Authors: H de Cremoux, I Monnet, J Fleury, C Chleq
Journal: European Respiratory Journal (1991)

Haematophagocytic activity is a salient feature of malignant histiocytic medullary reticulosis. This potency has also been observed as an aberrant property of non-histiocytic malignant cells or as a benign histiocytic process in response to infections or malignancies. We report the case of a patient who presented simultaneously with a limited stage small cell lung carcinoma and a fatal reactive form of histiocytosis. We conclude that such a haematophagocytic syndrome may occur in the setting of small cell lung carcinoma s previously described in other malignancies.
Induction of Cardiac Angptl4 by Dietary Fatty Acids Is Mediated by Peroxisome Proliferator-Activated Receptor β/δ and Protects Against Fatty Acid–Induced Oxidative Stress
Authors: Anastasia Georgiadi, Laeticia Lichtenstein, Tatjana Degenhardt, Mark V. Boekschoten, Marc van Bilsen, Beatrice Desvergne, Michael Müller, Sander Kersten
Journal: Circulation Research (2010)

Although dietary fatty acids are a major fuel for the heart, little is known about the direct effects of dietary fatty acids on gene regulation in the intact heart.To study the effect of dietary fatty acids on cardiac gene expression and explore the functional consequences.Oral administration of synthetic triglycerides composed of one single fatty acid altered cardiac expression of numerous genes, many of which are involved in the oxidative stress response. The gene most significantly and consistently upregulated by dietary fatty acids encoded Angiopoietin-like protein (Angptl)4, a circulating inhibitor of lipoprotein lipase expressed by cardiomyocytes. Induction of Angptl4 by the fatty acid linolenic acid was specifically abolished in peroxisome proliferator-activated receptor (PPAR)beta/delta(-/-) and not PPARalpha(-/-) mice and was blunted on siRNA-mediated PPARbeta/delta knockdown in cultured cardiomyocytes. Consistent with these data, linolenic acid stimulated binding of PPARbeta/delta but not PPARalpha to the Angptl4 gene. Upregulation of Angptl4 resulted in decreased cardiac uptake of plasma triglyceride-derived fatty acids and decreased fatty acid-induced oxidative stress and lipid peroxidation. In contrast, Angptl4 deletion led to enhanced oxidative stress in the heart, both after an acute oral fat load and after prolonged high fat feeding.Stimulation of cardiac Angptl4 gene expression by dietary fatty acids and via PPARbeta/delta is part of a feedback mechanism aimed at protecting the heart against lipid overload and consequently fatty acid-induced oxidative stress.
Podoplanin-Positive Fibroblasts Enhance Lung Adenocarcinoma Tumor Formation: Podoplanin in Fibroblast Functions for Tumor Progression
Authors: Ayuko Hoshino, Genichiro Ishii, Takashi Ito, Kazuhiko Aoyagi, Yoichi Ohtaki, Kanji Nagai, Hiroki Sasaki, Atsushi Ochiai
Journal: Cancer Research (2011)

During the metastatic process, cancer cells interact with vascular adventitial fibroblasts (VAF), which are the main components of the outermost connective tissue layer of blood vessels. This activity suggests the presence of a specific tumor microenvironment in the perivascular area. The s.c. coinjection of human lung adenocarcinoma cell lines (A549, PC-14, and CRL-5807) and human VAF (hVAF) resulted in a high rate of tumor formation, compared with the coinjection of these cell lines and human lung tissue-derived fibroblasts (hLF). A cDNA microarray analysis revealed a higher expression level of podoplanin in hVAFs than in hLFs (4.7-fold). Flow cytometry analysis also showed a higher expression level of podoplanin in hVAFs (43% ± 17.5%) than in hLFs (16% ± 10.3%). Sorted podoplanin-positive hVAFs displayed enhanced tumor formation, lymph node metastasis, and lung metastasis of A549 compared to sorted podoplanin-negative hVAFs. Knockdown of podoplanin in hVAFs decreased the augmenting effect of tumor formation and in vitro colony formation. The overexpression of podoplanin in hVAFs hastened the tumor formation of A549, compared with control hVAFs. Furthermore, the analysis of small-sized human lung adenocarcinoma (n = 112) revealed that patients with podoplanin-positive cancer-associated fibroblasts had a significantly higher rate of lymph node metastasis and a high risk of recurrence. These results indicate a promotive effect of hVAFs mediated by podoplanin on cancer progression and suggest that the perivascular environment may constitute a specific niche for tumor progression.
Axis I and II Psychiatric Disorders After Traumatic Brain Injury: A 30-Year Follow-Up Study
Authors: Salla Koponen, Tero Taiminen, Raija Portin, Leena Himanen, Heli Isoniemi, Hanna Heinonen, Susanna Hinkka, Olli Tenovuo
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Patients who had suffered traumatic brain injury were evaluated to determine the occurrence of psychiatric disorders during a 30-year follow-up. METHOD: Sixty patients were assessed on average 30 years after traumatic brain injury. DSM-IV axis I disorders were diagnosed on a clinical basis with the aid of the Schedules for Clinical Assessment in Neuropsychiatry (version 2.1), and axis II disorders were diagnosed with the Structured Clinical Interview for DSM-III-R Personality Disorders. Cognitive impairment was measured with a neuropsychological test battery and the Mini-Mental State Examination. RESULTS: Of the 60 patients, 29 (48.3%) had had an axis I disorder that began after traumatic brain injury, and 37 (61.7%) had had an axis I disorder during their lifetimes. The most common novel disorders after traumatic brain injury were major depression (26.7%), alcohol abuse or dependence (11.7%), panic disorder (8.3%), specific phobia (8.3%), and psychotic disorders (6.7%). Fourteen patients (23.3%) had at least one personality disorder. The most prevalent individual disorders were avoidant (15.0%), paranoid (8.3%), and schizoid (6.7%) personality disorders. Nine patients (15.0%) had DSM-III-R organic personality syndrome. CONCLUSIONS: The results suggest that traumatic brain injury may cause decades-lasting vulnerability to psychiatric illness in some individuals. Traumatic brain injury seems to make patients particularly susceptible to depressive episodes, delusional disorder, and personality disturbances. The high rate of psychiatric disorders found in this study emphasizes the importance of psychiatric follow-up after traumatic brain injury.
Noninvasive In Vivo High-Resolution Magnetic Resonance Imaging of Atherosclerotic Lesions in Genetically Engineered Mice
Authors: Zahi A. Fayad, John T. Fallon, Meir Shinnar, Suzanne Wehrli, Hayes M. Dansky, Michael Poon, Juan J. Badimon, Sherri A. Charlton, Edward A. Fisher, Jan L. Breslow, Valentin Fuster
Journal: Circulation (1998)

Background —The pathogenesis of atherosclerosis is currently being investigated in genetically engineered small animals. Methods to follow the time course of the developing pathology and/or the responses to therapy in vivo are limited. Methods and Results —To address this problem, we developed a noninvasive MR microscopy technique to study in vivo atherosclerotic lesions (without a priori knowledge of the lesion location or lesion type) in live apolipoprotein E–knockout (apoE-KO) mice. The spatial resolution was 0.0012 to 0.005 mm 3 . The lumen and wall of the abdominal aorta and iliac arteries were identified on all images in apoE-KO (n=8) and wild-type (n=5) mice on chow diet. Images obtained with MR were compared with corresponding cross-sectional histopathology (n=58). MR accurately determined wall area in comparison to histopathology (slope=1.0, r =0.86). In addition, atherosclerotic lesions were characterized in terms of lesion shape and type. Lesion type was graded by MR according to morphological appearance/severity and by histopathology according to the AHA classification. There was excellent agreement between MR and histopathology in grading of lesion shape and type (slope=0.97, r =0.91 for lesion shape; slope=0.64, r =0.90 for lesion type). Conclusions —The combination of high-resolution MR microscopy and genetically engineered animals is a powerful tool to investigate serially and noninvasively the progression and regression of atherosclerotic lesions in an intact animal model and should greatly enhance basic studies of atherosclerotic disease.
Cost of illness of atopic asthma and seasonal allergic rhinitis in Germany: 1‐yr retrospective study
Authors: B. Schramm, B. Ehlken, A. Smala, K. Quednau, K. Berger, D. Nowak
Journal: European Respiratory Journal (2003)

The purpose of this study was to evaluate the cost of illness of moderate-to-severe atopic asthma and/or seasonal allergic rhinitis (SAR) in Germany from the perspective of third-party payers (TPP) and patients. Five-hundred patients (276 children/adolescents) with moderate-to-severe asthma and/or SAR were included in this cross-sectional study. Information was collected using a specific patient questionnaire and the abstraction of patient records. Overall, annual costs per patient increased with the severity of atopic asthma and if it was associated with SAR. The average annual cost of SAR was 1,089 per child/adolescent and 1,543 per adult. Annual costs of severe asthma plus SAR increased to 7,928 per child/adolescent and to 9,287 per adult. For TPPs, the main cost drivers were medication, hospitalisation, and rehabilitation. The most significant costs for patients were household modifications. For children/adolescents, 60–78% of the expenditures were direct costs, while in adults, 58% of expenditures were indirect costs. It was also observed that patients with moderate and severe asthma used inhaled corticosteroids less frequently than recommended by treatment guidelines. In summary, the total cost for patients increases with the severity of atopic asthma and/or seasonal allergic rhinitis and indirect costs represent a large proportion of the total cost.
Birth weight and later life adherence to unhealthy lifestyles in predicting type 2 diabetes: prospective cohort study
Authors: Yanping Li, Sylvia H Ley, Deirdre K Tobias, Stephanie E Chiuve, Tyler J VanderWeele, Janet W Rich-Edwards, Gary C Curhan, Walter C Willett, JoAnn E Manson, Frank B Hu, Lu Qi
Journal: BMJ (2015)

<b>Objectives </b>To prospectively assess the joint association of birth weight and established lifestyle risk factors in adulthood with incident type 2 diabetes and to quantitatively decompose the attributing effects to birth weight only, to adulthood lifestyle only, and to their interaction. <b>Design</b> Prospective cohort study. <b>Setting</b> Health Professionals Follow-up Study (1986-2010), Nurses' Health Study (1980-2010), and Nurses' Health Study II (1991-2011). <b>Participants</b> 149 794 men and women without diabetes, cardiovascular disease, or cancer at baseline. <b>Main outcome measure</b> Incident cases of type 2 diabetes, identified through self report and validated by a supplementary questionnaire. Unhealthy lifestyle was defined on the basis of body mass index, smoking, physical activity, alcohol consumption, and the alternate healthy eating index. <b>Results</b> During 20-30 years of follow-up, 11 709 new cases of type 2 diabetes were documented. The multivariate adjusted relative risk of type 2 diabetes was 1.45 (95% confidence interval 1.32 to 1.59) per kg lower birth weight and 2.10 (1.71 to 2.58) per unhealthy lifestyle factor. The relative risk of type 2 diabetes associated with a combination of per kg lower birth weight and per unhealthy lifestyle factor was 2.86 (2.26 to 3.63), which was more than the addition of the risk associated with each individual factor, indicating a significant interaction on an additive scale (P for interaction&lt;0.001). The attributable proportions of joint effect were 22% (95% confidence interval 18.3% to 26.4%) to lower birth weight alone, 59% (57.1% to 61.5%) to unhealthy lifestyle alone, and 18% (13.9% to 21.3%) to their interaction. <b>Conclusion</b> Most cases of type 2 diabetes could be prevented by the adoption of a healthier lifestyle, but simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases.
Androgens and Bone
Authors: Dirk Vanderschueren, Liesbeth Vandenput, Steven Boonen, Marie K. Lindberg, Roger Bouillon, Claes Ohlsson
Journal: Endocrine Reviews (2004)

Loss of estrogens or androgens increases the rate of bone remodeling by removing restraining effects on osteoblastogenesis and osteoclastogenesis, and also causes a focal imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. Conversely, androgens, as well as estrogens, maintain cancellous bone mass and integrity, regardless of age or sex. Although androgens, via the androgen receptor (AR), and estrogens, via the estrogen receptors (ERs), can exert these effects, their relative contribution remains uncertain. Recent studies suggest that androgen action on cancellous bone depends on (local) aromatization of androgens into estrogens. However, at least in rodents, androgen action on cancellous bone can be directly mediated via AR activation, even in the absence of ERs. Androgens also increase cortical bone size via stimulation of both longitudinal and radial growth. First, androgens, like estrogens, have a biphasic effect on endochondral bone formation: at the start of puberty, sex steroids stimulate endochondral bone formation, whereas they induce epiphyseal closure at the end of puberty. Androgen action on the growth plate is, however, clearly mediated via aromatization in estrogens and interaction with ERα. Androgens increase radial growth, whereas estrogens decrease periosteal bone formation. This effect of androgens may be important because bone strength in males seems to be determined by relatively higher periosteal bone formation and, therefore, greater bone dimensions, relative to muscle mass at older age. Experiments in mice again suggest that both the AR and ERα pathways are involved in androgen action on radial bone growth. ERβ may mediate growth-limiting effects of estrogens in the female but does not seem to be involved in the regulation of bone size in males. In conclusion, androgens may protect men against osteoporosis via maintenance of cancellous bone mass and expansion of cortical bone. Such androgen action on bone is mediated by the AR and ERα.
Chlamydia trachomatis diversity viewed as a tissue-specific coevolutionary arms race
Authors: Alexandra Nunes, Paulo J Nogueira, Maria J Borrego, João P Gomes
Journal: Genome biology (2008)

Abstract Background The genomes of pathogens are thought to have evolved under selective pressure provided by the host in a coevolutionary arms race (the 'Red Queen's Hypothesis'). Traditionally, adaptation by pathogens is thought to rely not on whole chromosome dynamics but on gain/loss of specific genes, yielding differential abilities to infect distinct tissues. Thus, it is not known whether distinct host organs differently shape the genome of the same pathogen. We tested this hypothesis using Chlamydia trachomatis as model species, looking at 15 serovars that infect different organs: eyes, genitalia and lymph nodes. Results We analyzed over 51,000 base pairs from all serovars using various phylogenetic approaches and a non-phylogenetic indel-based algorithm to study the evolution of individual and concatenated loci. This survey comprised about 33% of all single nucleotide polymorphisms in C. trachomatis chromosomes. We present a model in which genome evolution indeed correlates with the cell type (epithelial versus lymph cells) and organ (eyes versus genitalia) that a serovar infects, illustrating an adaptation to physiologically distinct niches, and discarding genetic drift as the dominant evolutionary driving force. We show that radiation of serovars occurred primarily by accumulation of single nucleotide polymorphisms in intergenomic regions, housekeeping genes, and genes encoding hypothetical and cell envelope proteins. Furthermore, serovar evolution also correlates with ecological success, as the two most successful serovars showed a parallel evolution. Conclusion We identified a single nucleotide polymorphism-based tissue-specific arms race for strains in the same species, reflecting global chromosomal dynamics. Studying such tissue-specific arms race scenarios is crucial for understanding pathogen-host interactions during the course of infectious diseases, in order to dissect pathogen biology and develop preventive and therapeutic strategies.
miR-211 suppresses epithelial ovarian cancer proliferation and cell-cycle progression by targeting Cyclin D1 and CDK6
Authors: Bairong Xia, Shanshan Yang, Tianbo Liu, Ge Lou
Journal: Molecular Cancer (2015)

Epithelial ovarian cancer (EOC) is a significant cause of morbidity and mortality. MicroRNAs play important roles in cancer development and progression. The microRNA miR-211 is localized on intron 6 of the Trpm1 gene at 15q13-q14, a locus that is frequently lost in neoplasms. Its function and loss-of-function have been described in normal and cancer cells and tissues. miR-211 is known to be dysregulated in ovarian cancer: however, its function and the downstream effect of its loss-of-function in ovarian cancer have not been described before. We analyzed miR-211 expression in clinical samples of primary EOC tissues compared to normal epithelial ovarian tissues and in the EOC cell lines: OVCAR3, Caov3, OVCA429, SKOV3 and A2780 compared to human ovarian surface epithelial cells. We then investigated the effect of miR-211 on EOC cell proliferation and apoptosis by counting cell numbers, MTT, colony formation, cell cycle, and PI/Annexin V staining assays. A luciferase reporter system was developed to assess miR-211 regulation of the predicted targets. Expression level of discovered targets and correlation with miR-211 expression were analyzed in EOC tissues. Finally, OVCAR3 stably expressing miR-211 or control cells were injected subcutaneously into mice to determine in vivo effect of miR-211 on tumorigenesis. We found that the expression of miR-211 is downregulated in EOC tissues and cell lines compared to normal epithelial ovarian tissue and human ovarian surface epithelial cells, respectively. miR-211 was found to arrest cells in the G0/G1-phase, inhibit proliferation and induce apoptosis. Cyclin D1 and CDK6 were found to be direct targets of miR-211, and when overexpressed in miR-211-expressing EOC cells, could restore proliferative ability. Finally, in vitro investigation confirmed that miR-211 is a tumor suppressor that controls Cyclin D1 and CDK6 expression. Our results demonstrate that miR-211 is a tumor suppressor that controls expression of Cyclin D1 and CDK6, and that its downregulation results in overexpression of Cyclin D1 and CDK6 which increases proliferation ability of EOC cells to proliferate compared to normal cells.
Prolonged Inflammatory Response to Acute<i>Pseudomonas</i>Challenge in Interleukin-10 Knockout Mice
Authors: James F. Chmiel, Michael W. Konstan, Aicha Saadane, Jeanne E. Krenicky, H. Lester Kirchner, Melvin Berger
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Cystic fibrosis (CF) lung disease is characterized by a neutrophilic infiltrate that is excessive relative to the burden of infection. Decreased interleukin-10 in CF airways may impair proper termination of inflammation, leading to persistence of neutrophils after acute infections have been cleared. This could explain reports of lung inflammation in the absence of bacteria in infants with CF. We evaluated the kinetics of inflammation after transient Pseudomonas aeruginosa challenge in IL-10 knockout (KO) and wild-type (WT) mice. Both types of mice cleared the infection by Day 6 (p ⩾ 0.29). However, IL-10 KO mice had more neutrophils in bronchoalveolar lavage fluid than did WT mice on Days 4 (p < 0.0001), 6 (p < 0.0001), and 8 (p = 0.042). IL-10 KO mice had high concentrations of proinflammatory cytokines in BAL on Days 2 and 4, with some cytokines detectable on Days 6 and 8, whereas cytokines in BAL from WT mice were greatest on Day 2 and undetectable by Day 4. Moreover, IL-10 KO mice failed to regenerate I κ B α once degraded and subsequently had prolonged activation of NF- κ B. These data suggest that IL-10 deficiency contributes to prolonged inflammatory responses early in CF, when infection may be transient.
Mitochondria and Endothelial Function
Authors: Matthew A. Kluge, Jessica L. Fetterman, Joseph A. Vita
Journal: Circulation Research (2013)

In contrast to their role in cell types with higher energy demands, mitochondria in endothelial cells primarily function in signaling cellular responses to environmental cues. This article provides an overview of key aspects of mitochondrial biology in endothelial cells, including subcellular location, biogenesis, dynamics, autophagy, reactive oxygen species production and signaling, calcium homeostasis, regulated cell death, and heme biosynthesis. In each section, we introduce key concepts and then review studies showing the importance of that mechanism to endothelial control of vasomotor tone, angiogenesis, and/or inflammatory activation. We particularly highlight the small number of clinical and translational studies that have investigated each mechanism in human subjects. Finally, we review interventions that target different aspects of mitochondrial function and their effects on endothelial function. The ultimate goal of such research is the identification of new approaches for therapy. The reviewed studies make it clear that mitochondria are important in endothelial physiology and pathophysiology. A great deal of work will be needed, however, before mitochondria-directed therapies are available for the prevention and treatment of cardiovascular disease.
Simultaneous occurrence of pulmonary interstitial fibrosis and alveolar cell carcinoma in one family.
Authors: F Beaumont, H M Jansen, J D Elema, L P ten Kate, H J Sluiter
Journal: Thorax (1981)

The coexistence of interstitial pulmonary fibrosis and alveolar cell carcinoma is well known. The familial occurrence of a combination of these two entities, however, is very rare. We present a family of which five members had diffuse interstitial pulmonary fibrosis. Three of them had in addition alveolar cell carcinoma. In a sixth family member, evidence of alveolar cell carcinoma was present without proven interstitial fibrosis. An autosomal dominant trait is suggested as the mode of inheritance of both interstitial fibrosis and alveolar cell carcinoma in this family.