tbuckley/cabot-search huggingface dataset:
A three-dimensional virtual environment for modeling mechanical cardiopulmonary interactions
Authors: Jonathan M. Kaye, Frank P. Primiano, Dimitris N. Metaxas
Journal: Medical Image Analysis (1998)

We have developed a real-time computer system for modeling mechanical physiological behavior in an interactive, 3-D virtual environment. Such an environment can be used to facilitate exploration of cardiopulmonary physiology, particularly in situations that are difficult to reproduce clinically. We integrate 3-D deformable body dynamics with new, formal models of (scalar) cardiorespiratory physiology, associating the scalar physiological variables and parameters with the corresponding 3-D anatomy. Our framework enables us to drive a high-dimensional system (the 3-D anatomical models) from one with fewer parameters (the scalar physiological models) because of the nature of the domain and our intended application. Our approach is amenable to modeling patient-specific circumstances in two ways. First, using CT scan data, we apply semi-automatic methods for extracting and reconstructing the anatomy to use in our simulations. Second, our scalar physiological models are defined in terms of clinically measurable, patient-specific parameters. This paper describes our approach, problems we have encountered and a sample of results showing normal breathing and acute effects of pneumothoraces.
Bronchial Artery Revascularization Affects Graft Recovery after Lung Transplantation
Authors: KAI NOWAK, MARKUS KAMLER, MATTHIAS BOCK, JOHANN MOTSCH, SIEGFRIED HAGL, HEINZ JAKOB, MARTHA-MARIA GEBHARD
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Restitution of bronchial artery circulation might alter ischemia- reperfusion injury and improve organ function after lung transplantation. Weight-matched dogs underwent a left lung allotransplantation either with bronchial artery revascularization (BAR; n = 6) or as conventional lung transplantation (LTX; n = 6), to evaluate effects of BAR on lung cell function over a period of 5 h postischemically. Lactate dehydrogenase (LDH) and marker enzymes for pneumocytes type I (carboxypeptidase M [CPM], pneumocytes type II (alkaline phosphatase [AP]), and pulmonary endothelium (angiotensin-converting-enzyme [ACE]) were determined from bronchoalveolar lavage fluid. Donor lungs were preserved with Euro-Collins solution. Total ischemic time was kept at 6 h. CPM and LDH activities were significantly higher in both groups at 2 h and 4 h of reperfusion compared with control dogs (p < 0.01). AP and ACE activities in lavage after 2 h of reperfusion were significantly elevated in animals that underwent LTX (AP: 60 +/- 28 IU/L; ACE: 1.39 +/- 1.13 IU/L) compared with animals with BAR (AP: 33 +/- 29 IU/L; ACE: 0.35 +/- 0.6 IU/L; p < 0.05) and with control animals (AP: 13.58 +/- 11.0 IU/L; ACE: 0.06 +/- 0.14 IU/L; p < 0.01). According to these results, BAR protects pulmonary endothelium and type II pneumocytes in the early phase after lung transplantation and might have consequences for lung tissue in the long term.
Augmented EPR effect by photo-triggered tumor vascular treatment improved therapeutic efficacy of liposomal paclitaxel in mice bearing tumors with low permeable vasculature
Authors: Tomoya Araki, Ken-ichi Ogawara, Haruka Suzuki, Rie Kawai, Taka-ichi Watanabe, Tsutomu Ono, Kazutaka Higaki
Journal: Journal of Controlled Release (2014)
Chinese Herbal Extract Glycyrrhiza uralensis (Gu), in the Absence or Presence of IL-1b, Decreases Nitrite Production and Proliferation of Human Type II Alveolar Epithelial Cells (A549)
Authors: A.R. Narayan, Y.C. Huang, Y.H. Zhang, X.M. Li, M. Frieri
Journal: Journal of Allergy and Clinical Immunology (2006)
AID overwhelms Polβ in class-switching B cells
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2007)

The machinery that repairs spontaneous DNA mutations fails when the mutations are purposely induced by an enzyme in activated B cells. Wu and Stavnezer (page 1677) now find that the enzyme wins because it induces too much damage for repair proteins to keep up with.






Figure 1

DNA Polβ-deficient B cells switch more frequently when AID targets are sparse (IgG2a).




The spontaneous mutation of cytosine bases to uracils is corrected by a process that removes the wrong bases, cuts the DNA at the empty spots, and reinserts the correct bases. This normally efficient process fails in B cells that are switching from producing IgM to making other classes of antibodies. In these cells, cytosines are converted to uracils by the enzyme activation-induced deaminase (AID). The mutated DNA is cut normally, but the ends then recombine to produce new types of antibodies. Recombination thus occurs at the expense of repair.

The repair failure is blamed on DNA polymerase β (Polβ), whose job is to add back the correct nucleotides. Scientists have proposed that B cells undergoing class switching have too little Polβ or that the damaged DNA sites are not accessible to the enzyme.

But Wu and Stavnezer now show that Polβ is probably as productive in B cells as it is in other cell types. Polymerase levels were normal, and the enzyme found its way to damaged sites. Activated B cells lacking the polymerase had even more mutations—and more recombination events—than usual.

The team needed a new explanation. They hypothesized that recombination happens because AID creates too many damaged sites for Polβ to repair. The absence of Polβ caused a noticeable increase in recombination only in antibody genes with relatively few AID target sequences. Recombination events were abundant, however, in genes with lots of AID targets whether or not Polβ was present. Thus Polβ repairs AID-induced lesions, but can only fix so many.

Activated B cells need their repair machinery to protect themselves from unwanted mutations during antibody gene rearrangement. The authors speculate that, to switch antibody types, B cells thus have had to dilute the efficiency of the repair process by gaining more AID targets in antibody genes.
Rethrombosis after reperfusion with streptokinase: importance of geometry of residual lesions.
Authors: D G Harrison, D W Ferguson, S M Collins, D J Skorton, E E Ericksen, J M Kioschos, M L Marcus, C W White
Journal: Circulation (1984)

We tested the hypothesis that lesion rethrombosis after streptokinase reperfusion is related to luminal size of the residual stenosis. Two independent techniques of analyzing coronary angiograms, quantitative coronary angiography and computer-based videodensitometry, were used to estimate the size of the residual lumen immediately after discontinuation of streptokinase. These techniques were selected because they provide independent estimates of cross-sectional area of a lesion with high degrees of reproducibility and minimal observer variability. Twenty-four patients who had undergone successful reperfusion with streptokinase were studied. Seven patients had lesion rethrombosis documented either on a repeat angiogram, at autopsy, or, in one case, by the fact that the patient had an acute transmural infarction resulting in death. Vessel patency was documented by repeat coronary angiography 8 to 14 days after initial streptokinase reperfusion in the other 17 patients. As assessed by quantitative coronary angiography, seven of 13 patients (54%) with minimal luminal cross-sectional areas of less than 0.4 mm2 had rethrombosis. None of the 11 patients with lumens greater than 0.4 mm2 had rethrombosis. In the 17 patients with vessels that remained patent the size of the residual lesion at repeat catheterization was compared with its size immediately after reperfusion with streptokinase. Over the intervening 8 to 14 day interval, an average percentage increase in minimal cross-sectional area of 116 +/- 34% was observed. In seven patients minimal luminal cross-sectional area more than doubled. Integrated optical density, an index of the severity of coronary stenosis derived from computer-based videodensitometry, was also useful in identifying a subgroup of patients at high risk for rethrombosis of lesion.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetyicholine and Electrolyte Metabolism in the Various Chambers of the Frog and Turtle Heart
Authors: PAUL MAZEL, WILLIAM C. HOLLAND
Journal: Circulation Research (1958)

Evidence has accumulated suggesting acetylcholine may he involved in initiation of the heart heat. Acetylcholine and electrolyte metabolism in the various chambers of the heart have been studied. The area of highest intrinsic rhythm (sinus) contained greater amounts of acetylcholine equivalents, true cholinesterase, choline acetylase and sodium; all of these decreasing in amount in areas of lower intrinsie rhythm. It is concluded that intrinsic rhythm may he directly correlated with overall acetylcholine metabolism and sodium content and inversely related to overall energy metabolism and potassium concentration.
A genome-wide association study identifies three new risk loci for Kawasaki disease
Authors: Yoshihiro Onouchi, Kouichi Ozaki, Jane C Burns, Chisato Shimizu, Masaru Terai, Hiromichi Hamada, Takafumi Honda, Hiroyuki Suzuki, Tomohiro Suenaga, Takashi Takeuchi, Norishige Yoshikawa, Yoichi Suzuki, Kumi Yasukawa, Ryota Ebata, Kouji Higashi, Tsutomu Saji, Yasushi Kemmotsu, Shinichi Takatsuki, Kazunobu Ouchi, Fumio Kishi, Tetsushi Yoshikawa, Toshiro Nagai, Kunihiro Hamamoto, Yoshitake Sato, Akihito Honda, Hironobu Kobayashi, Junichi Sato, Shoichi Shibuta, Masakazu Miyawaki, Ko Oishi, Hironobu Yamaga, Noriyuki Aoyagi, Seiji Iwahashi, Ritsuko Miyashita, Yuji Murata, Kumiko Sasago, Atsushi Takahashi, Naoyuki Kamatani, Michiaki Kubo, Tatsuhiko Tsunoda, Akira Hata, Yusuke Nakamura, Toshihiro Tanaka
Journal: Nature Genetics (2012)
Nonallele-specific Silencing of Mutant and Wild-type Huntingtin Demonstrates Therapeutic Efficacy in Huntington's Disease Mice
Authors: Ryan L Boudreau, Jodi L McBride, Inês Martins, Shihao Shen, Yi Xing, Barrie J Carter, Beverly L Davidson
Journal: Molecular Therapy (2009)

Huntington's disease (HD) is a fatal neurodegenerative disease caused by mutant huntingtin (htt) protein, and there are currently no effective treatments. Recently, we and others demonstrated that silencing mutant htt via RNA interference (RNAi) provides therapeutic benefit in HD mice. We have since found that silencing wild-type htt in adult mouse striatum is tolerated for at least 4 months. However, given the role of htt in various cellular processes, it remains unknown whether nonallele-specific silencing of both wild-type and mutant htt is a viable therapeutic strategy for HD. Here, we tested whether cosilencing wild-type and mutant htt provides therapeutic benefit and is tolerable in HD mice. After treatment, HD mice showed significant reductions in wild-type and mutant htt, and demonstrated improved motor coordination and survival. We performed transcriptional profiling to evaluate the effects of reducing wild-type htt in adult mouse striatum. We identified gene expression changes that are concordant with previously described roles for htt in various cellular processes. Also, several abnormally expressed transcripts associated with early-stage HD were differentially expressed in our studies, but intriguingly, those involved in neuronal function changed in opposing directions. Together, these encouraging and surprising findings support further testing of nonallele-specific RNAi therapeutics for HD. Huntington's disease (HD) is a fatal neurodegenerative disease caused by mutant huntingtin (htt) protein, and there are currently no effective treatments. Recently, we and others demonstrated that silencing mutant htt via RNA interference (RNAi) provides therapeutic benefit in HD mice. We have since found that silencing wild-type htt in adult mouse striatum is tolerated for at least 4 months. However, given the role of htt in various cellular processes, it remains unknown whether nonallele-specific silencing of both wild-type and mutant htt is a viable therapeutic strategy for HD. Here, we tested whether cosilencing wild-type and mutant htt provides therapeutic benefit and is tolerable in HD mice. After treatment, HD mice showed significant reductions in wild-type and mutant htt, and demonstrated improved motor coordination and survival. We performed transcriptional profiling to evaluate the effects of reducing wild-type htt in adult mouse striatum. We identified gene expression changes that are concordant with previously described roles for htt in various cellular processes. Also, several abnormally expressed transcripts associated with early-stage HD were differentially expressed in our studies, but intriguingly, those involved in neuronal function changed in opposing directions. Together, these encouraging and surprising findings support further testing of nonallele-specific RNAi therapeutics for HD.
Abstract 1367: An epigenetic screen unmasks metallothioneins as putative contributors to renal cell carcinogenesis
Authors: Hans Krause, Imad Al-Kamal, Odiljon Ikromov, Kurt Miller, Carsten Kempkensteffen
Journal: Cancer Research (2014)

Abstract Transcriptional silencing, as a result of aberrant promoter hypermethylation, is a common mechanism through which genes in cancer cells become inactive. Functional epigenetic screens using demethylating agents to re-express transcriptional silenced genes may identify such inactivated genes for further evaluation. We aimed to identify renal cell carcinoma (RCC) genes so far not known to be inactive due to promoter hypermethylation. The RCC cell line A-498 was treated with the DNA methyltransferase inhibitor zebularine under low cytotoxicity conditions. Expression changes of the transcriptome of treated and untreated cells were compared using RNA expression microarrays (Affymetrix Human Genome U133A v. 2.0). Eight candidate genes (criteria: upregulation more than 3-fold, presence of CpP islands in the promoter region, in silico predicted downregulation in tumors) were evaluated by Q-PCR in 49 paired normal and RCC tissues of patients (39 ccRCC, 7 pRCC, and 3 cRCC), who underwent radical nephrectectomy in our clinic between 2009 and 2010. Members of the metallothionein group were remarkably downregulated in tumor tissues. Metallothionein 1G (MT1G) was downregulated in 48 of 49 tumor tissues (p&amp;lt;0.0001), MT1H was downregulated in 42 out of 43 tumor tissues (p&amp;lt;0,0001), and MT2A expression was decreased in 73% (34/49) of all cases. The remaining 5 candidates (EFNB2, RRAD, TGM2, ITGA2, and MBD4) were found either upregulated in the majority of RCCs or without reasonable expression differences between normal und tumor tissues. To prove the consistency of our epigenetic screening approach we compared expression data of 308 upregulated transcripts (≥ 1.5-fold) to similar screens performed by other groups that revealed a high number of shared candidates. Although a possible contribution of metallothioneins to renal cell carcinogenesis is not fully understood, our discovery of an almost exclusively downregulation of selected MT genes in RCC tissues emphasizes a plausible link between deregulated metabolism and tumor development. In the context of an ever-increasing demand for suitable markers for clinical decision-making and a better understanding of renal cell carcinogenesis, selected members of the MT group may serve as appropriate candidates for these tasks. Citation Format: Hans Krause, Imad Al-Kamal, Odiljon Ikromov, Kurt Miller, Carsten Kempkensteffen. An epigenetic screen unmasks metallothioneins as putative contributors to renal cell carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1367. doi:10.1158/1538-7445.AM2014-1367
Cognitive Decline in Adulthood: An 11.5-Year Follow-Up of the Baltimore Epidemiologic Catchment Area Study
Authors: Constantine G. Lyketsos, Li-Shiun Chen, James C. Anthony
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The epidemiology of cognitive decline over 11.5 years was investigated in a large community-residing population, with a special emphasis on the relationship between education and cognitive decline. METHOD: The study was an 11.5-year follow-up of a probability sample of the adult household residents of east Baltimore. From the Baltimore cohort of the Epidemiologic Catchment Area study, 1,488 participants completed the Mini-Mental State during three study waves in 1981, 1982, and 1993–1996. For each study participant, the difference in scores on the Mini-Mental State between waves 2 and 3 was calculated. RESULTS: Over a median interval of 11.5 years, the study participants' scores on the Mini-Mental State declined a mean of 1.41 points, and the scores of 68% of the participants declined by at least 1 Mini-Mental State point. With and without adjustment for age, greater declines were associated with having 8 years or less of formal education and with being African American. CONCLUSIONS: Over a long time period, cognitive decline occurred in all age groups. Having more than 8 years of formal education was associated with less decline. However, beyond 9 years, additional education was not associated with a further reduction in cognitive decline. This suggests that a minimal amount of education during early critical periods might confer protection against cognitive decline later in life.
THE DANGERS OF INTRATHECAL MEDICATION
Authors: GEORGE WILSON
Journal: JAMA (1949)

The intrathecal space is so frequently chosen for the administration of serums, drugs, antibiotics and anesthetic agents that it is sometimes forgotten that numerous serious and tragic sequelae have been reported following the use of this route. It therefore seems advisable to reemphasize the dangers which may ensue and critically to reevaluate the rationale of this mode of drug administration. The injection of any foreign substance into the subarachnoid space produces an aseptic meningeal reaction characterized principally by pleocytosis and increased protein content.<sup>1</sup>This reaction may occur following a purely diagnostic spinal puncture, a later tap revealing pleocytosis. Reynolds and Wilson<sup>2</sup>reported 3 cases in which headache, nuchal stiffness, stupor, delirium and fever appeared from six to twelve hours after lumbar puncture. Repeated taps revealed sterile cloudy fluid with cell counts ranging from 2,900 to 17,670. The introduction of each new therapeutic agent into the intrathecal space has
Small Invasive Colonic Cancer Occurring in a Hyperplastic Polyp
Authors: T. Kudo, T. Matsumoto, M. Esaki, S. Yada, M. Hirahashi, K. Kayashima, T. Yao, M. Iida
Journal: Endoscopy (2004)

We report a case of advanced colon cancer which was supposed to have arisen from a hyperplastic polyp in a 68-year-old man. Colonoscopy revealed a depressed reddish area with a surrounding elevated lesion that was of a faded color compared with the normal mucosa. After the mucosal surface had been sprayed with crystal violet dye, magnifying colonoscopy showed an amorphous area in the central depression and the surrounding, slightly elevated lesion had an asteroid pattern. The depressed area was therefore considered to be a colonic cancer surrounded by a hyperplastic polyp. Endoscopic ultrasonography showed that the lesion was infiltrating further than the deep submucosal layer and it was therefore decided to treat the patient by laparoscopically assisted right hemicolectomy. The depressed lesion was found to be a well-differentiated adenocarcinoma invading the muscularis propria (diagnosed as IIc + IIa-like advanced adenocarcinoma). The surrounding flat elevated lesion was found to be hyperplastic mucosa. No adenomatous lesions were found. There have been few reported cases in which a preoperative diagnosis of carcinoma in a hyperplastic polyp has been made, but the possibility of carcinogenesis from hyperplastic polyps has come under consideration recently. This case was considered to be important because it raises the possibility that nonpolypoid cancer can develop from a hyperplastic polyp.
Admission Plasma Glucose
Authors: Dlear Zindrou, Kenneth M. Taylor, Jens Peder Bagger
Journal: Diabetes Care (2001)

OBJECTIVE—To investigate the relationship between admission plasma glucose and 30-day mortality after primary isolated coronary artery bypass grafting (CABG) in nondiabetic patients. RESEARCH DESIGN AND METHODS—All nondiabetic patients with admission plasma glucose measurement undergoing primary isolated CABG from 1993 to 1997 were included in this study. RESULTS—In 878 consecutive patients (155 women), overall mortality was 3.4% (95% CI 2.3–4.8). The mortality rate in women (n = 11; 7.1%, 3.6–12.3) was higher than in men (n = 19; 2.6%, 1.6–4.1) (P = 0.01). There was a positive correlation between plasma glucose and 30-day mortality among women only (P = 0.0001). There was a higher mortality rate in the upper two glucose quartiles (11.7%, 5.5–21.0) compared with the lower two quartiles (2.6%, 3.0–8.9) in the female patients (P = 0.03); a plasma glucose of 6.0 mmol/l separated high- and low-mortality groups. Furthermore, women in the upper two glucose quartiles had a fourfold higher mortality rate than men in the similar quartiles (P = 0.002). Among men, there was no difference in mortality rate across glucose quartiles. In a multivariate analysis, admission plasma glucose, history of thyroid disease, left ventricular ejection fraction &amp;lt;0.35, operation bypass time, and perioperative myocardial infarction were independently associated with mortality. CONCLUSIONS—Women with admission plasma glucose ≤6.0 mmol/l and men across the whole range of glucose values had similar mortality rates after CABG. The surplus female mortality was found only in subjects with plasma glucose &amp;gt;6 mmol/l. Further studies are needed to appraise the possible influence of glucose status on outcome from CABG in nondiabetic subjects.
Synovium: what's new?
Authors: J. Edwards
Journal: BMJ (1995)

Better understanding of how it is affected by disease

Until recently, the understanding of normal synovium was based solely on microanatomical studies and ideas about function based on classic observations on synovial fluid—but few experiments. We can now discuss the biology of the tissue in terms of the ontogeny of cells, morphogenesis, cell metabolism, the expression of cell surface ligands, matrix composition, and vascular and fluid physiology.1 A recurring theme is the interaction between cells and their matrix through adhesion systems that seem to modulate both cell behaviour and fluid flux. Having begun to understand how the tissue works, we can now construct models of how it becomes diseased.

Synovium carries a specialised surface layer of intimal cells,2 which …