tbuckley/cabot-search huggingface dataset:
Primary pulmonary cavitating carcinomas
Authors: M. R. Chaudhuri
Journal: Thorax (1973)

A primary lung cancer can produce a cavity in three ways. The first is `cavitary necrosis9 due to breakdown of the growth itself. The second is `stenotic abscess9 due to infection and breakdown of the lung parenchyma distal to bronchial obstruction caused by the growth. The third type is `spill-over abscess9. In the present series, necrosis and cavitation were observed in 100 cases out of a total of 632 primary bronchial carcinomas seen at the London Chest Hospital from July 1967 to June 1970. There were 91 males and nine females with an average age of 58·45 years. All except one smoked very heavily and had considerable symptoms. The size of the cavities ranged from 1 to 10 cm and their wall thickness from 0·5 to 3 cm. They were single in 92 cases and multiple (up to four) in eight. In 42 cases, the cancerous cavitation was central, in 38 intermediate, and in 20 peripheral. The segments most frequently affected were the apicoposterior segment of the left upper lobe and the superior segment of the left lower lobe. For descriptive purposes, these cavitating carcinomas were also divided into six broad groups on the basis of radiological and pathological correlations. Neoplastic cells in the sputum were found in 64 cases. Bronchoscopy revealed growth in 42 cases and biopsy was positive in 48. The main microscopic feature was vascular invasion of medium-sized muscular arteries and veins found in the vicinity of every cavitating bronchial carcinoma. Invasion along with tumour plugging of the vessels was observed in 75 cases and thrombosis alone in 55 cases. There were 82 squamous-cell carcinomas, 11 undifferentiated carcinomas of large polygonal-cell type, and seven adeno-alveolar cell carcinomas. The single most important and noteworthy feature in the present series was that oat-cell carcinoma hardly ever undergoes necrosis. Out of a total of 95 cases observed, only three showed necrosis, and this was minimal and characteristically devoid of cavitation. In oat-cell carcinoma vascular invasion and tumour plugging was not observed, though all showed rapid growth and most of them blocked the lobar bronchi completely. In the light of the present study, the main factors responsible for tumour necrosis were found to be gradual bronchial obstruction and associated vascular involvement, though in many cases an inherent propensity of the tumour played a major role.
Interaction of the Leucine-Rich Repeats of Polycystin-1 with Extracellular Matrix Proteins
Authors: Ashraf N. Malhas, Ramadan A. Abuknesha, Robert G. Price
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Polycystin-1, the product of the PKD1 gene, is a membrane-bound multidomain protein with a unique structure and a molecular weight of ≈460 kD. The purpose of this study is to investigate the binding of the cystein-flanked leucine-rich repeats (LRR) of polycystin-1 to extracellular matrix (ECM) components. These interactions may play a role in normal renal development as well as the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD). In vitro assays were used to assess the binding of a fusion protein containing the LRR of polycystin-1 and that of affinity purified polycystin-1 to a number of ECM components. The results showed that the LRR modulate the binding of polycystin-1 to collagen I, fibronectin, laminin, and cyst fluid–derived laminin fragments. The addition of the LRR fusion protein to cells in culture resulted in a significant dose-dependant reduction in the rate of proliferation. Cyst fluid–derived laminin fragments had a stimulatory effect on cell proliferation, which was reversed by the LRR fusion protein. These results suggest that the LRR of polycystin-1 act as mediators of the polycystin-1 interaction with the ECM. The observed suppression effect of the LRR on cell proliferation suggests a functional role of the LRR-mediated polycystin-1 involvement in cell-matrix and cell-cell interactions. These interactions may result in the enhanced cell proliferation that is a characteristic feature of ADPKD.
Evolution and Phylogenetic Utility of Alignment Gaps Within Intron Sequences of Three Nuclear Genes in Bumble Bees (Bombus)
Authors: Atsushi Kawakita, Teiji Sota, John S. Ascher, Masao Ito, Hiroyuki Tanaka, Makoto Kato
Journal: Molecular Biology and Evolution (2003)

To test whether gaps resulting from sequence alignment contain phylogenetic signal concordant with those of base substitutions, we analyzed the occurrence of indel mutations upon a well-resolved, substitution-based tree for three nuclear genes in bumble bees (Bombus, Apidae: Bombini). The regions analyzed were exon and intron sequences of long-wavelength rhodopsin (LW Rh), arginine kinase (ArgK), and elongation factor–1α (EF-1α) F2 copy genes. LW Rh intron had only a few uninformative gaps, ArgK intron had relatively long gaps that were easily aligned, and EF-1α intron had many short gaps, resulting in multiple optimal alignments. The unambiguously aligned gaps within ArgK intron sequences showed no homoplasy upon the substitution-based tree, and phylogenetic signals within ambiguously aligned regions of EF-1α intron were highly congruent with those of base substitutions. We further analyzed the contribution of gap characters to phylogenetic reconstruction by incorporating them in parsimony analysis. Inclusion of gap characters consistently improved support for nodes recovered by substitutions, and inclusion of ambiguously aligned regions of EF-1α intron resolved several additional nodes, most of which were apical on the phylogeny. We conclude that gaps are an exceptionally reliable source of phylogenetic information that can be used to corroborate and refine phylogenies hypothesized by base substitutions, at least at lower taxonomic levels. At present, full use of gaps in phylogenetic reconstruction is best achieved in parsimony analysis, pending development of well-justified and generally applicable methods for incorporating indels in explicitly model-based methods.
Residential pesticide use during pregnancy among a cohort of urban minority women.
Authors: Robin M Whyatt, David E Camann, Patrick L Kinney, Andria Reyes, Judy Ramirez, Jessica Dietrich, Diurka Diaz, Darrell Holmes, Frederica P Perera
Journal: Environmental Health Perspectives (2002)

Residential pesticide use is widespread in the United States. However, data are limited specific to use among minority populations. Nor are data available on the extent of pesticide exposure resulting from residential use during pregnancy. We have gathered questionnaire data on pesticide use in the home during pregnancy from 316 African-American and Dominican women residing in northern Manhattan and the South Bronx. Additionally, 72 women underwent personal air monitoring for 48 hr during their third trimester of pregnancy to determine exposure levels to 21 pesticides (19 insecticides and 2 fungicides). Of the women questioned, 266 of 314 (85%) reported that pest control measures were used in the home during pregnancy; 111 of 314 (35%) reported that their homes were sprayed by an exterminator, and of those, 45% said the spraying was done more than once per month. Most (>or= 90%) of the pesticide was used for cockroach control. Use of pest control measures increased significantly with the level of housing disrepair reported. Of the women monitored, all (100%) had detectable levels of three insecticides: the organophosphates diazinon (range, 2.0-6,010 ng/m3) and chlorpyrifos (range, 0.7-193 ng/m3) and the carbamate propoxur (range, 3.8-1,380 ng/m3), as well as the fungicide o-phenylphenol (range, 5.7-743 ng/m3). We also frequently detected the following four insecticides (47-83% of samples) but at lower concentrations: the pyrethroid trans-permethrin, piperonyl butoxide (an indicator of exposure to pyrethrins), and the organochlorines 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane and chlordane. Thirty percent of the women had detectable levels of all eight pesticides. Exposures were generally higher among African Americans than among Dominicans. We detected other pesticides in <or= 10% of samples. Results show widespread prenatal pesticide use among minority women in this cohort. Diazinon exposures for some women may have exceeded health-based levels, and our findings support recent federal action to phase out residential use of this insecticide.
Intracellular Calcium Dynamics and Acceleration of Sinus Rhythm by β-Adrenergic Stimulation
Authors: Boyoung Joung, Liang Tang, Mitsunori Maruyama, Seongwook Han, Zhenhui Chen, Marcelle Stucky, Larry R. Jones, Michael C. Fishbein, James N. Weiss, Peng-Sheng Chen, Shien-Fong Lin
Journal: Circulation (2009)

Recent evidence indicates that membrane voltage and Ca2+ clocks jointly regulate sinoatrial node (SAN) automaticity. Here we test the hypothesis that sinus rate acceleration by beta-adrenergic stimulation involves synergistic interactions between these clock mechanisms.We simultaneously mapped intracellular calcium (Ca(i)) and membrane potential in 25 isolated canine right atrium, using previously described criteria of the timing of late diastolic Ca(i) elevation (LDCAE) relative to the action potential upstroke to detect the Ca2+ clock. Before isoproterenol, the earliest pacemaking site occurred in the inferior SAN, and LDCAE was observed in only 4 of 25 preparations. Isoproterenol infusion (1 micromol/L) increased sinus rate and shifted pacemaking site to superior SAN, concomitant with the appearance of LDCAE preceding the action potential upstroke by 98+/-31 ms. Caffeine had similar effects, whereas sarcoplasmic reticulum Ca2+ depletion with ryanodine and thapsigargin prevented isoproterenol-induced LDCAE and blunted sinus rate acceleration. Ca(i) transient relaxation time during isoproterenol was shorter in superior SAN (124+/-34 ms) than inferior SAN (138+/-24 ms; P=0.01) or right atrium (164+/-33 ms; P=0.001) and was associated with a lower sarcoplasmic reticulum Ca2+ ATPase pump to phospholamban protein ratio in SAN than in right atrium. Hyperpolarization-activated pacemaker current (I(f)) blockade with ZD 7288 modestly blunted but did not prevent LDCAE or sinus rate acceleration by isoproterenol.Acceleration of the Ca2+ clock in the superior SAN plays an important role in sinus acceleration during beta-adrenergic stimulation, interacting synergistically with the voltage clock to increase sinus rate.
Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166/MEMD), a Novel Actor in Invasive Growth, Controls Matrix Metalloproteinase Activity
Authors: Pim C. Lunter, Jeroen W.J. van Kilsdonk, Hanneke van Beek, Ine M.H.A. Cornelissen, Mieke Bergers, Peter H.G.M. Willems, Goos N.P. van Muijen, Guido W.M. Swart
Journal: Cancer Research (2005)

Activated leukocyte cell adhesion molecule (ALCAM/CD166/MEMD) could function as a cell surface sensor for cell density, controlling the transition between local cell proliferation and tissue invasion in melanoma progression. We have tested the hypothesis that progressive cell clustering controls the proteolytic cascade for activation of gelatinase A/matrix metalloproteinase-2 (MMP-2), which involves formation of an intermediate ternary complex of membrane type 1 MMP (MT1-MMP/MMP-14), tissue inhibitor of metalloproteinase-2 (TIMP-2), and pro-MMP-2 at the cell surface. Surprisingly, truncation of ALCAM severely impaired MMP-2 activation in a nude mouse xenograft model, in which we previously observed diminished primary tumor growth and enhanced melanoma metastasis. Comparative studies of two-dimensional monolayer and three-dimensional collagen-gel cultures revealed that extensive cell-to-cell contacts, wild-type ALCAM, and cell-to-matrix interactions were all indispensable for efficient conversion of pro-MMP-2 to its active form in metastatic melanoma cells. Truncated, dominant-negative ALCAM diminished MMP-2 activation via reduced transcript levels and decreased processing of MT1-MMP. Failure of the proteolytic cascade after selective ALCAM depletion by RNA interference was mainly due to incomplete MT1-MMP processing, which was otherwise promoted by extensive cell-to-cell contacts. These data attribute a novel signaling role to ALCAM in regulation of proteolysis and support its previously postulated sensor function in invasive growth.
Effect of Aircraft-Cabin Altitude on Passenger Discomfort
Authors: J. Michael Muhm, Paul B. Rock, Dianne L. McMullin, Stephen P. Jones, I.L. Lu, Kyle D. Eilers, David R. Space, Aleksandra McMullen
Journal: New England Journal of Medicine (2007)

Acute mountain sickness occurs in some unacclimatized persons who travel to terrestrial altitudes at which barometric pressures are the same as those in commercial aircraft during flight. Whether the effects are similar in air travelers is unknown.We conducted a prospective, single-blind, controlled hypobaric-chamber study of adult volunteers to determine the effect of barometric pressures equivalent to terrestrial altitudes of 650, 4000, 6000, 7000, and 8000 ft (198, 1219, 1829, 2134, and 2438 m, respectively) above sea level on arterial oxygen saturation and the occurrence of acute mountain sickness and discomfort as measured by responses to the Environmental Symptoms Questionnaire IV during a 20-hour simulated flight.Among the 502 study participants, the mean oxygen saturation decreased with increasing altitude, with a maximum decrease of 4.4 percentage points (95% confidence interval, 3.9 to 4.9) at 8000 ft. Overall, acute mountain sickness occurred in 7.4% of the participants, but its frequency did not vary significantly among the altitudes studied. The frequency of reported discomfort increased with increasing altitude and decreasing oxygen saturation and was greater at 7000 to 8000 ft than at all the lower altitudes combined. Differences became apparent after 3 to 9 hours of exposure. Persons older than 60 years of age were less likely than younger persons and men were less likely than women to report discomfort. Four serious adverse events, 1 of which may have been related to the study exposures, and 15 adverse events, 9 of which were related to study exposures, were reported.Ascent from ground level to the conditions of 7000 to 8000 ft lowered oxygen saturation by approximately 4 percentage points. This level of hypoxemia was insufficient to affect the occurrence of acute mountain sickness but did contribute to the increased frequency of reports of discomfort in unacclimatized participants after 3 to 9 hours. (ClinicalTrials.gov number, NCT00326703 [ClinicalTrials.gov].).
The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease
Authors: Il-Kang Na, Sydney X. Lu, Nury L. Yim, Gabrielle L. Goldberg, Jennifer Tsai, Uttam Rao, Odette M. Smith, Christopher G. King, David Suh, Daniel Hirschhorn-Cymerman, Lia Palomba, Olaf Penack, Amanda M. Holland, Robert R. Jenq, Arnab Ghosh, Hien Tran, Taha Merghoub, Chen Liu, Gregory D. Sempowski, Melissa Ventevogel, Nicole Beauchemin, Marcel R.M. van den Brink
Journal: Journal of Clinical Investigation (2009)

Thymic graft-versus-host disease (tGVHD) can contribute to profound T cell deficiency and repertoire restriction after allogeneic BM transplantation (allo-BMT). However, the cellular mechanisms of tGVHD and interactions between donor alloreactive T cells and thymic tissues remain poorly defined. Using clinically relevant murine allo-BMT models, we show here that even minimal numbers of donor alloreactive T cells, which caused mild nonlethal systemic graft-versus-host disease, were sufficient to damage the thymus, delay T lineage reconstitution, and compromise donor peripheral T cell function. Furthermore, to mediate tGVHD, donor alloreactive T cells required trafficking molecules, including CCR9, L selectin, P selectin glycoprotein ligand-1, the integrin subunits alphaE and beta7, CCR2, and CXCR3, and costimulatory/inhibitory molecules, including Ox40 and carcinoembryonic antigen-associated cell adhesion molecule 1. We found that radiation in BMT conditioning regimens upregulated expression of the death receptors Fas and death receptor 5 (DR5) on thymic stromal cells (especially epithelium), while decreasing expression of the antiapoptotic regulator cellular caspase-8-like inhibitory protein. Donor alloreactive T cells used the cognate proteins FasL and TNF-related apoptosis-inducing ligand (TRAIL) (but not TNF or perforin) to mediate tGVHD, thereby damaging thymic stromal cells, cytoarchitecture, and function. Strategies that interfere with Fas/FasL and TRAIL/DR5 interactions may therefore represent a means to attenuate tGVHD and improve T cell reconstitution in allo-BMT recipients.
Accessing Genomic Medicine
Authors: Reed V. Tuckson, Lee Newcomer, Jeanne M. De Sa
Journal: JAMA (2013)

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
A CASE OF MULTIPLE GASTRIC ULCERS
Authors: A. W. Adams
Journal: BMJ (1933)

was enlarged -and thickened, and showed some cyst formation.A metal pin was in situ through the old fracture of the bone, which was not tender.The eighth left rib was thickened in its whole length.There was no deformity of the humerus, radius, ulna, scapula, sternum, clavicle, or other ribs.There was no gross abnormality of the heart and lungs.The blood pressure was 150/94.The blood count showed no anaemia andl no abnormal cells.The Wassermann reaction was negative on several occasions.The urine contained no abnormal constituent.On vaginal examination no abnor- mality could be discovered.The muscular power in the arms and legs was fairly good, and the limb reflexes were present and equal.The plantar reflexes were flexor.There was no loss of skin sensation.The pupils reacted sluggishly to light and on accommodation.The eye movements were full, and no nystagmus was present.The fields of vision showed temporal contraction for white, and in the right eye a marked contrac- tion for red.The optic disks were much cupped, and the right somewhat paler than the left.There were some unusual
HIGH-DOSE AMOXYCILLIN
Authors: R.W. Lacey, D.S. Tompkins, P.R. Godwin, M. Millar, S. Foulkes, F. Kenny, S.K. Devaraj, R.T. Calvert, R.K. Knight, R.A. Stockley, L. Smallman
Journal: The Lancet (1983)
Complete loss of murine Xin results in a mild cardiac phenotype with altered distribution of intercalated discs
Authors: Julia Otten, Peter F.M. van der Ven, Padmanabhan Vakeel, Stefan Eulitz, Gregor Kirfel, Oliver Brandau, Michael Boesl, Jan W. Schrickel, Markus Linhart, Katrin Hayeß, Francisco J. Naya, Hendrik Milting, Rainer Meyer, Dieter O. Fürst
Journal: Cardiovascular Research (2009)

Xin is a striated muscle-specific F-actin binding protein that has been implicated in cardiomyopathies. In cardiomyocytes, Xin is localized at intercalated discs (IDs). Mice lacking only two of the three Xin isoforms (XinAB−/− mice) develop severe cardiac hypertrophy. To further investigate the function of Xin variants in the mammalian heart, we generated XinABC−/− mice deficient in all Xin isoforms. XinABC−/− mice showed a very mild phenotype: heart weight, heart weight to tibia length ratios, and cardiac dimensions were not altered. Increased perivascular fibrosis was only observed in hearts of young XinABC−/− mice. Striking differences were revealed in isolated cardiomyocytes: XinABC−/− cells demonstrated a significantly increased number of non-terminally localized ID-like structures. Furthermore, resting sarcomere length was increased, sarcomere shortening, peak shortening at 0.5–1 Hz, and the duration of shortening were decreased, and shortening and relengthening velocities were accelerated at frequencies above 4 Hz in XinABC−/− cardiomyocytes. ECG showed a significantly shorter HV interval and a trend towards shorter QRS interval in XinABC−/− mice, suggesting a faster conduction velocity of the ventricular-specific conduction system. In human cardiac tissue, expression of XinC protein was detected solely in samples from patients with cardiac hypertrophy. Total Xin deficiency leads to topographical ID alterations, premature fibrosis and subtle changes in contractile behaviour; this is a milder cardiac phenotype than that observed in XinAB−/− mice, which still can express XinC. Together with the finding that XinC is detected solely in cardiomyopathic human tissues, this suggests that its expression is responsible for the stronger dominant phenotype in XinAB−/− mice. Furthermore, it indicates that XinC may be involved in the development of human cardiac hypertrophy.
Transcriptional regulatory network for sexual differentiation in fission yeast
Authors: Juan Mata, Anna Wilbrey, Jürg Bähler
Journal: Genome biology (2007)

Changes in gene expression are hallmarks of cellular differentiation. Sexual differentiation in fission yeast (Schizosaccharomyces pombe) provides a model system for gene expression programs accompanying and driving cellular specialization. The expression of hundreds of genes is modulated in successive waves during meiosis and sporulation in S. pombe, and several known transcription factors are critical for these processes. We used DNA microarrays to investigate meiotic gene regulation by examining transcriptomes after genetic perturbations (gene deletion and/or overexpression) of rep1, mei4, atf21 and atf31, which encode known transcription factors controlling sexual differentiation. This analysis reveals target genes at a genome-wide scale and uncovers combinatorial control by Atf21p and Atf31p. We also studied two transcription factors not previously implicated in sexual differentiation whose meiotic induction depended on Mei4p: Rsv2p induces stress-related genes during spore formation, while Rsv1p represses glucose-metabolism genes. Our data further reveal negative feedback interactions: both Rep1p and Mei4p not only activate specific gene expression waves (early and middle genes, respectively) but are also required for repression of genes induced in the previous waves (Ste11p-dependent and early genes, respectively). These data give insight into regulatory principles controlling the extensive gene expression program driving sexual differentiation and highlight sophisticated interactions and combinatorial control among transcription factors. Besides triggering simultaneous expression of gene waves, transcription factors also repress genes in the previous wave and induce other factors that in turn regulate a subsequent wave. These dependencies ensure an ordered and timely succession of transcriptional waves during cellular differentiation.
Mistakes avoided: On life and death certificates
Authors: D A. R Watson
Journal: BMJ (1997)

From my corner of the cramped outpatient consulting room I could see that the crowd in the waiting room was thinning out. The clinic had been particularly hectic. One colleague was doing a caesarean section. Another was on vacation in neighbouring Namibia. It was a blessing that the nurses could manage most of the minor cases.

I pressed on with the next case–a patient with Parkinson's disease who was nearly frozen because the country had run out of the …