tbuckley/cabot-search huggingface dataset:
Population Genomics in Bacteria: A Case Study of Staphylococcus aureus
Authors: S. Takuno, T. Kado, R. P. Sugino, L. Nakhleh, H. Innan
Journal: Molecular Biology and Evolution (2011)

We analyzed the genome-wide pattern of single nucleotide polymorphisms (SNPs) in a sample with 12 strains of Staphylococcus aureus. Population structure of S. aureus seems to be complex, and the 12 strains were divided into five groups, named A, B, C, D, and E. We conducted a detailed analysis of the topologies of gene genealogies across the genomes and observed a high rate and frequency of tree-shape switching, indicating extensive homologous recombination. Most of the detected recombination occurred in the ancestral population of A, B, and C, whereas there are a number of small regions that exhibit evidence for homologous recombination with a distinct related species. As such regions would contain a number of novel mutations, it is suggested that homologous recombination would play a crucial role to maintain genetic variation within species. In the A-B-C ancestral population, we found multiple lines of evidence that the coalescent pattern is very similar to what is expected in a panmictic population, suggesting that this population is suitable to apply the standard population genetic theories. Our analysis showed that homologous recombination caused a dramatic decay in linkage disequilibrium (LD) and there is almost no LD between SNPs with distance more than 10 kb. Coalescent simulations demonstrated that a high rate of homologous recombination—a relative rate of 0.6 to the mutation rate with an average tract length of about 10 kb—is required to produce patterns similar to those observed in the S. aureus genomes. Our results call for more research into the evolutionary role of homologous recombination in bacterial populations.
PANIC STATES AND THEIR TREATMENT
Authors: HENRY W. BROSIN
Journal: American Journal of Psychiatry (1943)

1. Panic states are defined and conditions favoring their occurrence presented. 2. The acute course and good recovery are noted in an unexpectedly large number. The forms of these psychoses ape all known types, and defy rigid classification. The practice of diagnosing them "psychosis, unclassified, as manifested by . . . ." as recommended by Colonel W. C. Porter of the School of Military Neuropsychiatry Lawson General Hospital, has been found useful. 3. Most of our patients with panic states had an obviously poor pre-induction social history. Estimation of the total personality has been found more valuable than the study of "traits" or family history. Most of our panic cases were recruited from the following groups: (I) the mentally deficient; (2) the emotionally immature; (3) psychopathic personalities; (4) tension depressions. 4. Means of preventing panic are presented in detail. The basic principle consists of helping the individual improve and maintain his personality, organization or integrity under stress by better "orientation" or morale. 5. Treatment measures of acute panic states are presented, with the belief that select cases may be reclaimed for duty.
Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease
Authors: Franco Locatelli, Vanderson Rocha, William Reed, Françoise Bernaudin, Mehmet Ertem, Stelios Grafakos, Benedicte Brichard, Xiaxin Li, Arnon Nagler, Giovanna Giorgiani, Paul R. Haut, Joel A. Brochstein, Diane J. Nugent, Julie Blatt, Paul Woodard, Joanne Kurtzberg, Charles M. Rubin, Roberto Miniero, Patrick Lutz, Thirumalairaj Raja, Irene Roberts, Andrew M. Will, Isaac Yaniv, Christiane Vermylen, Nunzia Tannoia, Federico Garnier, Irina Ionescu, Mark C. Walters, Bertram H. Lubin, Eliane Gluckman
Journal: Blood (2002)
Phase II study of vinorelbine and gemcitabine for inoperable stage IIIB-IV non-small-cell lung cancer
Authors: O.-P. Isokangas, A. Knuuttila, M. Halme, M. Mäntylä, I. Lindström, V. Nikkanen, M. Viren, H. Joensuu, K. Mattson
Journal: Annals of Oncology (1999)
AN ACUTE CASE OF EXFOLIATIVE DERMATITIS
Authors: W. T. FREEMAN
Journal: British Journal of Dermatology (1901)

Journal Article AN ACUTE CASE OF EXFOLIATIVE DERMATITIS Get access W. T. FREEMAN W. T. FREEMAN Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 13, Issue 11, 1 November 1901, Pages 430–433, https://doi.org/10.1111/j.1365-2133.1901.tb16349.x Published: 01 November 1901
Centrosome Hyperamplification Predicts Progression and Tumor Recurrence in Bladder Cancer
Authors: Yoshiaki Yamamoto, Hideyasu Matsuyama, Tomoko Furuya, Atsunori Oga, Satoru Yoshihiro, Masaru Okuda, Shigeto Kawauchi, Kohsuke Sasaki, Katsusuke Naito
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Recent studies have reported that centrosome hyperamplification (CH) is closely related to chromosomal instability in bladder cancer. In this study, we investigated whether CH could be used as a prognostic biomarker for patients with bladder cancer. Experimental Design: CH was evaluated by immunohistochemistry in 50 bladder cancers (≤pT1: 43; ≥pT2: 7). In addition, numerical aberrations of chromosomes 7, 9, and 17 and gain of 20q13, on which the Aurora-A gene is located, were evaluated by fluorescence in situ hybridization, and DNA ploidy was assessed. Preliminary experiments on eight bladder cancer cell lines found that six had over 5% of CH cells associated with a gain of 20q13 and overexpression of Aurora-A; therefore, CH-positive cases (CH+) were defined as those having over 5% of cells with ≥3 centrosomes per cell. Results: CH+, 20q13 gain, chromosomal instability, and DNA aneuploidy were detected in 30 (60%), 18 (36%), 22 (44%), and 19 (38%) patients, respectively. There were significant differences in tumor number, grade, recurrence, and progression between the CH+ and CH− groups. The later had significantly higher recurrence-free and progression-free survivals than the former (P = 0.0028 and P = 0.0070, respectively, log-rank test). Multivariate analysis revealed that CH+ was the strongest predictor for tumor recurrence in nonmuscle invasive (pTa and pT1) bladder cancer (hazard ratio, 1.882; 95% confidence interval, 1.161–3.325; P = 0.0094). Conclusions: Detection of CH may provide crucial prognostic information about tumor recurrence in bladder cancer.
Long-term clinical outcome of somatostatin analogues for treatment of progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinoma
Authors: F. Panzuto, M. Di Fonzo, E. Iannicelli, R. Sciuto, C.L. Maini, G. Capurso, M. Milione, M.S. Cattaruzza, M. Falconi, V. David, V. Ziparo, P. Pederzoli, C. Bordi, G. lle De Fave
Journal: Annals of Oncology (2005)
Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin
Authors: Cevayir Coban, Ken J. Ishii, Taro Kawai, Hiroaki Hemmi, Shintaro Sato, Satoshi Uematsu, Masahiro Yamamoto, Osamu Takeuchi, Sawako Itagaki, Nirbhay Kumar, Toshihiro Horii, Shizuo Akira
Journal: The Journal of Experimental Medicine (2005)

Malaria parasites within red blood cells digest host hemoglobin into a hydrophobic heme polymer, known as hemozoin (HZ), which is subsequently released into the blood stream and then captured by and concentrated in the reticulo-endothelial system. Accumulating evidence suggests that HZ is immunologically active, but the molecular mechanism(s) through which HZ modulates the innate immune system has not been elucidated. This work demonstrates that HZ purified from Plasmodium falciparum is a novel non-DNA ligand for Toll-like receptor (TLR)9. HZ activated innate immune responses in vivo and in vitro, resulting in the production of cytokines, chemokines, and up-regulation of costimulatory molecules. Such responses were severely impaired in TLR9-/- and myeloid differentiation factor 88 (MyD88)-/-, but not in TLR2, TLR4, TLR7, or Toll/interleukin 1 receptor domain-containing adaptor-inducing interferon beta-/- mice. Synthetic HZ, which is free of the other contaminants, also activated innate immune responses in vivo in a TLR9-dependent manner. Chloroquine (CQ), an antimalarial drug, abrogated HZ-induced cytokine production. These data suggest that TLR9-mediated, MyD88-dependent, and CQ-sensitive innate immune activation by HZ may play an important role in malaria parasite-host interactions.
Novel Oncolytic Adenovirus Selectively Targets Tumor-Associated Polo-Like Kinase 1 and Tumor Cell Viability
Authors: Jianfeng Zhou, Qinglei Gao, Gang Chen, Xiaoyuan Huang, Yunping Lu, Kanyan Li, Daxing Xie, Liang Zhuang, Jingniu Deng, Ding Ma
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Polo-like kinase 1 (plk1) is a serine/threonine protein kinase essential for multiple mitotic processes. Previous observations have validated plk1 as a promising therapeutic target. Despite being conceptually attractive, the potency and specificity of current plk1-based therapies remain limited. We sought to develop a novel plk1-targeting strategy by constructing an oncolytic adenovirus to selectively silence plk1 in tumor cells. Experimental Design: Two artificial features were engineered into one wild-type adenovirus type 5 (wt-Adv5) genome to generate a new oncolytic adenovirus (M1). First, M1 contains a 27-bp deletion in E1A region, which confers potent, oncolytic efficacy. Second, M1 is armed with a fragment of antisense plk1 cDNA that substitutes the E3 region encoding 6.7K and gp19K. In this design, tumor-selective replication of M1 would activate the native adenovirus E3 promoters to express the antisense plk1 cDNA preferentially in tumor cells and silence tumor-associated plk1 protein. Results: By virtue of combining oncolysis with plk1 targeting, M1 exhibited potent antitumoral efficacy in vitro and in vivo. Systemic administration of M1 plus cisplatin induced complete tumor regression in 80% of orthotopic hepatic carcinoma model mice that were otherwise resistant to cisplatin and disseminated metastases. Conclusions: Coupling plk1 targeting with oncolysis had shown superior antitumor efficacy. Present findings would benefit the development of novel oncolytic adenoviruses generally applicable to a wide range of molecule-based therapeutics.
Hypermethylated APC DNA in Plasma and Prognosis of Patients With Esophageal Adenocarcinoma
Authors: K. Kawakami
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: The adenomatous polyposis coli (APC) locus on chromosome 5q21–22 shows frequent loss of heterozygosity (LOH) in esophageal carcinomas. However, the prevalence of truncating mutations in the APC gene in esophageal carcinomas is low. Because hypermethylation of promoter regions is known to affect several other tumor suppressor genes, we investigated whether the APC promoter region is hypermethylated in esophageal cancer patients and whether this abnormality could serve as a prognostic plasma biomarker. Methods: We assayed DNA from tumor tissue and matched plasma from esophageal cancer patients for hypermethylation of the promoter region of the APC gene. We used the maximal chi-square statistic to identify a discriminatory cutoff value for hypermethylated APC DNA levels in plasma and used bootstrap-like simulations to determine the P value to test for the strength of this association. This cutoff value was used to generate Kaplan–Meier survival curves. All P values were based on two-sided tests. Results: Hypermethylation of the promoter region of the APC gene occurred in abnormal esophageal tissue in 48 (92%) of 52 patients with esophageal adenocarcinoma, in 16 (50%) of 32 patients with esophageal squamous cell carcinoma, and in 17 (39.5%) of 43 patients with Barrett's metaplasia but not in matching normal esophageal tissues. Hypermethylated APC DNA was observed in the plasma of 13 (25%) of 52 adenocarcinoma patients and in two (6.3%) of 32 squamous carcinoma patients. High plasma levels of methylated APC DNA were statistically significantly associated with reduced patient survival (P = .016). Conclusion: The APC promoter region was hypermethylated in tumors of the majority of patients with primary esophageal adenocarcinomas. Levels of hypermethylated APC gene DNA in the plasma may be a useful biomarker of biologically aggressive disease in esophageal adenocarcinoma patients and should be evaluated as a potential biomarker in additional tumor types.
Mini symposium: non-surgical sperm recovery: Part II. Treatment of retrograde ejaculation and anejaculation
Authors: A Kamischke
Journal: Human Reproduction Update (1999)

The various options for the treatment of retrograde ejaculation (RE) and anejaculation (AE) are discussed systematically in this review. A total of 88 studies dealing with patients with RE emphasize medical treatment for reversal of RE and retrieval of spermatozoa from urine. In 136 studies concerning patients with AE, the main emphasis is on medical treatment, electroejaculation (EE) and electrovibration stimulation (EVS) for the reversal of AE. Sperm quality in patients with RE and AE is often impaired. However, with the help of assisted reproduction techniques (ART) available today, both ejaculation disorders can be considered as treatable diseases. The major problem when analysing the studies was the uneven methodological quality of the original articles and the difficulties presented by different drugs and dosages, equipment and techniques, along with different criteria for success. In conclusion, controlled clinical trials comparing different treatment options appear urgently warranted.
Aetiological diagnosis of acute respiratory failure in critical care oncology
Authors: Anne-Pascale Meert, Jean-Paul Sculier
Journal: European Respiratory Journal (2013)

Acute complications are frequent in cancer patients and their adequate management, including in critical care units, may be crucial [1]. The prognosis of such complications in terms of intensive care unit (ICU) and hospital mortality is mainly determined by the acute physiological perturbations they induce, as reflected by gravity scores in critically ill cancer patients [2, 3], but also by the degree of life-supporting therapy that is required, such as mechanical ventilation [3, 4, 5] or extra renal epuration [6]. This has been confirmed by many other studies summarised in a systematic review of the literature [7]. After recovery from the acute complication, the further prognosis is determined by the characteristics of the underlying cancer and no longer related to the perturbations induced by the complication [1].

The most frequent cause of ICU admission in cancer patients is acute respiratory failure (ARF). It can be due to a direct manifestation of the malignant disease (for example by airway obstruction or pleural effusion), treatment toxicity (for example by radiation or drug pneumonitis) or indirect complications, such as infections …
Development of Gastric Carcinoma from Intestinal Metaplasia in Cdx2-transgenic Mice
Authors: Hiroyuki Mutoh, Shinji Sakurai, Kiichi Satoh, Kiichi Tamada, Hiroto Kita, Hiroyuki Osawa, Takeshi Tomiyama, Yukihiro Sato, Hironori Yamamoto, Norio Isoda, Toru Yoshida, Kenichi Ido, Kentaro Sugano
Journal: Cancer Research (2004)

Abstract In the progression of chronic gastritis, gastric mucosal cells deviate from the normal pathway of gastric differentiation to an intestinal phenotype. Many epidemiologic studies have found an association between the formation of intestinal metaplasia and the development of gastric carcinoma. However, there is no direct evidence that shows intestinal metaplasia is a precursor lesion of gastric carcinoma, to date. We periodically examined the intestinal metaplastic mucosa of Cdx2-transgenic mice we have previously generated. Gastric polyps developed from intestinal metaplastic mucosa in all stomachs of Cdx2-transgenic mice examined. These gastric polyps consisted of intestinal-type adenocarcinoma that invaded the submucosa and muscularis propria and occasionally spread into the subserosa. p53 and APC gene mutations were recognized in the adenocarcinomas. The participation of APC and p53 gene mutations in gastric carcinogenesis from the intestinal metaplasia was verified by the Cdx2-transgenic mice, carrying ApcMin mutation or p53 deficiency, that developed gastric polyps much earlier than Cdx2 alone. We successfully showed that long-term intestinal metaplasia induces invasive gastric carcinoma. These results indicate that intestinal metaplasia itself plays a significant role in the genesis and progression of gastric carcinoma.
Signaling Pathways Regulating Interleukin-13–stimulated Chemokine Release from Airway Smooth Muscle
Authors: Qi Peng, Takeshi Matsuda, Stuart J. Hirst
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Interleukin (IL)-13 receptor activation on airway smooth muscle cells induces eotaxin release and activates multiple signaling pathways including mitogen-activated protein kinases, and signal transducer and activator of transcription 6 (STAT6). To examine a requirement for STAT6 in mediating IL-13-stimulated eotaxin release we used antisense oligodeoxynucleotides (ODNs) to downregulate endogenous STAT6 protein. STAT6 antisense ODNs were taken up by about 85% of cells. Selective downregulation of STAT6 protein occurred with antisense ODNs, but not with sense or scrambled ODNs. Eotaxin release induced by IL-13 or IL-4 (10 ng/ml) was reduced by 81 +/- 4 and 75 +/- 7%, respectively, in cells transfected with antisense ODNs (p < 0.001), but not with a sense ODN or a scrambled ODN. Eotaxin release induced by IL-1beta was unaffected by STAT6 antisense ODN (p > 0.05). Finally, IL-13- or IL-4-dependent eotaxin release was abolished when inhibitors of both p42/p44 ERK (U0126, 10 microM) and p38 (SB202190, 10 microM) mitogen-activated protein kinase pathways were combined in STAT6 antisense ODN-transfected cells. In contrast, about 25% of the response remained when each inhibitor was examined alone in STAT6 antisense ODN-treated cells. These data support roles for both STAT6- and mitogen-activated protein kinase-dependent pathways in mediating eotaxin release from airway smooth muscle by IL-13 or IL-4.
Moscatilin Induces Apoptosis in Human Colorectal Cancer Cells: A Crucial Role of c-Jun NH2-Terminal Protein Kinase Activation Caused by Tubulin Depolymerization and DNA Damage
Authors: Tzu-Hsuan Chen, Shiow-Lin Pan, Jih-Hwa Guh, Cho-Hwa Liao, Der-Yi Huang, Chien-Chih Chen, Che-Ming Teng
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To study the effect of moscatilin (purified from the stem of orchid Dendrobrium loddigesii) on the proliferation of human colorectal cancer HCT-116 cells in vitro and in vivo. Experimental Design: The growth inhibition of moscatilin was screened on several human cancer cell lines. The effect of moscatilin on tubulin was detected in vitro. Following moscatilin treatment on HCT-116 cells, c-Jun NH2-terminal protein kinase (JNK) and caspase activation was studied by Western blot analysis, and DNA damage was done by Comet assay. Specific JNK inhibitor SP600125 was cotreated to reverse moscatilin-induced apoptosis. Tumor growth inhibition of moscatilin was done on HCT-116 xenograft models. Results: Moscatilin induced a time-dependent arrest of the cell cycle at G2-M, with an increase of cells at sub-G1. Moscatilin inhibited tubulin polymerization, suggesting that it might bind to tubulins. Moscatilin also induced the phosphorylation of JNK1/2. SP600125 significantly inhibited the activation of caspase-9 and caspase-3 and the subsequent moscatilin-induced apoptosis. The data suggest that JNK activation may contribute to moscatilin-mediated apoptosis signaling. A parallel experiment showed that SP600125 significantly inhibits Taxol- and vincristine-induced HCT-116 cell apoptosis. This suggests that the JNK activation may be a common mechanism for tubulin-binding agents. Moreover, moscatilin induces DNA damage, phosphorylation of H2AX and p53, and up-regulation of p21. Our HCT-116 xenograft models show the in vivo efficacy of moscatilin. Conclusions: In summary, our results suggest that moscatilin induces apoptosis of colorectal HCT-116 cells via tubulin depolymerization and DNA damage stress and that this leads to the activation of JNK and mitochondria-involved intrinsic apoptosis pathway.
<i>Chlamydia</i>species as a cause of community-acquired pneumonia in Canada
Authors: T.J. Marrie, R.W. Peeling, T. Reid, E. De Carolis
Journal: European Respiratory Journal (2003)

<i>Chlamydia pneumoniae </i>has been implicated as a cause of community-acquired pneumonia (CAP) in several studies. However, there has been no comprehensive study of the role of <i>Chlamydia</i> species (<i>C. pneumoniae</i>, <i>C. psittaci</i> (avian and feline strains) and <i>C. pecorum</i>) as a cause of CAP. The aim of the present study was to determine the role of <i>C. pneumoniae</i>, <i>C. psittaci</i> and <i>C. pecorum</i> as causes of CAP. A prospective cohort observational study of CAP was conducted at 15 teaching centres in eight Canadian provinces between January 1996–October 1997. Acute (n=539) and convalescent (n=272) serum samples were obtained for determination of antibody titres to <i>C. pneumoniae</i>, <i>C. psittaci</i>, <i>C. pecorum</i>, <i>C. trachomatis</i>, <i>Mycoplasma pneumoniae</i>, <i>Legionella pneumophila</i> serogroups I–VI, <i>Streptococcus pneumoniae</i> and various respiratory viruses. Twelve of 539 (2.2%) patients had acute <i>C. pneumoniae</i> pneumonia and an additional 32 (5.9%) had possible acute infection. <i>C. pneumoniae</i> was the sole pathogen in 16 of 42 (38.1%) of these patients. The most common copathogens were <i>S. pneumoniae</i>, respiratory syncytial virus and influenza virus type A. <i>C. pneumoniae</i> pneumonia patients were older and more likely to show congestive heart failure compared to bacteraemic <i>S. pneumoniae</i> patients. The latter had a lower mean diastolic blood pressure, a higher white blood cell count and a lower arterial carbon dioxide tension. Two patients had antibody titres suggestive of recent infection with the feline strain of <i>C. psittaci</i>. Although numerically <i>Chlamydia pneumoniae</i> is an important cause of community-acquired pneumonia, no distinctive clinical features associated with this pathogen were detected in the present study. Feline <i>Chlamydia psittaci </i>may cause a few cases of community-acquired pneumonia. Avian <i>Chlamydia psittaci</i> should be considered only if there is a compatible epidemiological history.
A Quantitative System for Studying Metastasis Using Transparent Zebrafish
Authors: Silja Heilmann, Kajan Ratnakumar, Erin M. Langdon, Emily R. Kansler, Isabella S. Kim, Nathaniel R. Campbell, Elizabeth B. Perry, Amy J. McMahon, Charles K. Kaufman, Ellen van Rooijen, William Lee, Christine A. Iacobuzio-Donahue, Richard O. Hynes, Leonard I. Zon, Joao B. Xavier, Richard M. White
Journal: Cancer Research (2015)

Metastasis is the defining feature of advanced malignancy, yet remains challenging to study in laboratory environments. Here, we describe a high-throughput zebrafish system for comprehensive, in vivo assessment of metastatic biology. First, we generated several stable cell lines from melanomas of transgenic mitfa-BRAF(V600E);p53(-/-) fish. We then transplanted the melanoma cells into the transparent casper strain to enable highly quantitative measurement of the metastatic process at single-cell resolution. Using computational image analysis of the resulting metastases, we generated a metastasis score, μ, that can be applied to quantitative comparison of metastatic capacity between experimental conditions. Furthermore, image analysis also provided estimates of the frequency of metastasis-initiating cells (∼1/120,000 cells). Finally, we determined that the degree of pigmentation is a key feature defining cells with metastatic capability. The small size and rapid generation of progeny combined with superior imaging tools make zebrafish ideal for unbiased high-throughput investigations of cell-intrinsic or microenvironmental modifiers of metastasis. The approaches described here are readily applicable to other tumor types and thus serve to complement studies also employing murine and human cell culture systems.