tbuckley/cabot-search huggingface dataset:
Relapsed Schizophrenics: Earlier Discharge from the Hospital After Cereal-Free, Milk-Free Diet
Authors: F. C. DOHAN, J. C. GRASBERGER
Journal: American Journal of Psychiatry (1973)

Routinely treated schizophrenics, who on admission were randomly assigned to a diet free of cereal grains and milk while on the locked ward, were discharged from the hospital about twice as rapidly as control patients assigned to a high-cereal diet. Wheat gluten secretly added to the cereal-free diet abolished this effect. These and previous findings suggest that cereal grains may be pathogenic for those hereditarily predisposed to schizophrenia just as they are for celiac disease, a disorder that may be genetically related.
The draft genome of a diploid cotton Gossypium raimondii
Authors: Kunbo Wang, Zhiwen Wang, Fuguang Li, Wuwei Ye, Junyi Wang, Guoli Song, Zhen Yue, Lin Cong, Haihong Shang, Shilin Zhu, Changsong Zou, Qin Li, Youlu Yuan, Cairui Lu, Hengling Wei, Caiyun Gou, Zequn Zheng, Ye Yin, Xueyan Zhang, Kun Liu, Bo Wang, Chi Song, Nan Shi, Russell J Kohel, Richard G Percy, John Z Yu, Yu-Xian Zhu, Jun Wang, Shuxun Yu
Journal: Nature Genetics (2012)

Yuxian Zhu and colleagues report the draft genome of a diploid cotton Gossypium raimondii. This species is a wild South American cotton, whose progenitor is thought to have been the contributor of the D subgenome of the allotetraploid commercial species Gossypium hirsutum and Gossypium barbadense, which account for ~95% of the worldwide cotton crop. We have sequenced and assembled a draft genome of G. raimondii, whose progenitor is the putative contributor of the D subgenome to the economically important fiber-producing cotton species Gossypium hirsutum and Gossypium barbadense. Over 73% of the assembled sequences were anchored on 13 G. raimondii chromosomes. The genome contains 40,976 protein-coding genes, with 92.2% of these further confirmed by transcriptome data. Evidence of the hexaploidization event shared by the eudicots as well as of a cotton-specific whole-genome duplication approximately 13–20 million years ago was observed. We identified 2,355 syntenic blocks in the G. raimondii genome, and we found that approximately 40% of the paralogous genes were present in more than 1 block, which suggests that this genome has undergone substantial chromosome rearrangement during its evolution. Cotton, and probably Theobroma cacao, are the only sequenced plant species that possess an authentic CDN1 gene family for gossypol biosynthesis, as revealed by phylogenetic analysis.
Evaluation of Epothilone B Analog in Advanced Soft Tissue Sarcoma: A Phase II Study of the Phase II Consortium
Authors: Scott Okuno, William J. Maples, Michelle R. Mahoney, Tom Fitch, James Stewart, Paula M. Fracasso, Michael Kraut, David S. Ettinger, Fitzroy Dawkins, Charles Erlichman
Journal: Journal of Clinical Oncology (2005)

Purpose Epothilones are a new class of nontaxane tubulin polymerization agents that have activity in taxane-resistant tumors. Epothilone B (BMS-247550) is a semisynthetic analog of the natural product epothilone B. This study was performed to determine the activity of BMS-247550 in patients with soft tissue sarcomas (STSs) who had not received prior chemotherapy for metastatic disease. Patients and Methods Patients with measurable, advanced, or metastatic STS with no prior chemotherapy for metastatic disease were treated with BMS-2457550 50 mg/m 2 intravenously during 1 hour every 21 days. All responses were confirmed 4 weeks later. Results Thirty-one patients (median age, 54 years; range, 19 to 78 years; 48% female) were entered onto the trial and were assessable for response. All but one patient had an Eastern Cooperative Oncology Group performance score of 0% or 1%, and 39% had received prior adjuvant chemotherapy. Mean follow-up was 22 months, with a confirmed response rate of 6% (95% CI, 0% to 17%). Median time to progression was 4.5 months (95% CI, 1.9 to 8.3 months), and 1 year progression-free survival was 17% (95% CI, 8% to 38%). Median survival was 16.4 months, with a 1-year survival of 61% (95% CI, 46% to 81%). Toxicity was mainly hematologic, with eight of 31 (26%) patients experiencing grade 3 to 4 leukopenia; 15 of 31 patients (48%) experienced grade 3 to 4 neutropenia. The grade 3 to 4 nonhematologic toxicities included neuropathies (26%), myalgia (13%), and fatigue (10%). Conclusion BMS-247550 has limited activity against STSs when given in this dose and schedule. The clinical toxicity is similar to that of taxanes.
Hypertension and Rarefaction during Treatment with Telatinib, a Small Molecule Angiogenesis Inhibitor
Authors: Neeltje Steeghs, Hans Gelderblom, Jos op 't Roodt, Olaf Christensen, Prabhu Rajagopalan, Marcel Hovens, Hein Putter, Ton J. Rabelink, Eelco de Koning
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Hypertension is a commonly reported side effect in antiangiogenic therapy. We investigated the hypothesis that telatinib, a small molecule angiogenesis inhibitor, impairs vascular function, induces rarefaction, and causes hypertension. Experimental Design: A side-study was done in a phase I trial of telatinib, a small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptors 2 and 3, platelet-derived growth factor receptor, and c-KIT in patients with advanced solid tumors. Measurements of blood pressure, flow-mediated dilation, nitroglycerin-mediated dilation, aortic pulse wave velocity, skin blood flux with laser Doppler flow, and capillary density with sidestream dark field imaging were done at baseline and after 5 weeks of treatment. Blood pressure and proteinuria were measured weekly. Results: Mean systolic and diastolic blood pressure values increased significantly at +6.6 mm Hg (P = 0.009) and +4.7 mm Hg (P = 0.016), respectively. Mean flow-mediated dilation and mean nitroglycerin-mediated dilation values significantly decreased by −2.1% (P = 0.003) and −5.1% (P = 0.001), respectively. After 5 weeks of treatment, mean pulse wave velocity significantly increased by 1.2 m/s (P = 0.001). A statistically significant reduction of mean skin blood flux of 532.8% arbitrary units was seen (P = 0.015). Capillary density statistically significantly decreased from 20.8 to 16.7 capillary loops (P = 0.015). Proteinuria developed or increased in six patients during telatinib treatment. Conclusion: The increase in blood pressure observed in the treatment with telatinib, an angiogenesis inhibitor, may be caused by functional or structural rarefaction.
Liver Transplantation in Man--I, Observations on Technique and Organization in Five Cases
Authors: R. Y. Calne, R. Williams
Journal: BMJ (1968)

In view of the extreme sensitivity of the human liver to ischaemic damage, the organization of clinical transplantation is of necessity complicated. From our preliminary experience of five human liver allografts we feel that active collaboration between hospitals is essential in order to practise human liver transplantation. It is unnecessary and undesirable to interfere in any way with potential liver donors. Nevertheless, the nature of the surgical technique requires that the liver is cooled within 15 minutes of death if satisfactory function is to result in the grafted organ.This report describes technical difficulties that were encountered which can limit successful liver transplantation. The first patient was in severe liver failure and had an accessory liver graft in the splenic fossa after splenectomy. This liver suffered irreversible ischaemic damage, which led to an uncontrollable haemorrhagic state with exsanguination that resulted in death the day after operation. The second patient, a 10-month-old infant with biliary atresia and liver failure, died from cardiac arrest shortly after the operation.The remaining three transplants developed good initial function. One patient survived 11 weeks, and one has returned to work.
US woman gives birth to daughter after transplant of ovarian tissue from her twin
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

An American woman has given birth to a baby after a successful transplant of ovarian tissue from her identical twin sister. Two previous ovarian transplants have been reported, one in Belgium and one in China.

Stephanie Yarber, aged 25, gave birth to a healthy daughter on 6 June, 15 months after receiving an ovarian transplant from her identical twin sister, Melanie Morgan.

The event was reported in an early release paper on the website of the New England Journal of Medicine on 7 June (http://www.nejm.org/,dx.doi.org/10.1056/NEJMoa043157). It was also reported in national and international news media and on the website of the doctor who did the procedure, Sherman Silber from the Infertility Center of St Louis at St Luke's Hospital in St Louis, Missouri (www.infertile.com).

The twin sisters are from the town of Muscle Shoals in Alabama. Ms Morgan has three naturally …
Magnetic Resonance Assessment of the Substrate for Inducible Ventricular Tachycardia in Nonischemic Cardiomyopathy
Authors: Saman Nazarian, David A. Bluemke, Albert C. Lardo, Menekhem M. Zviman, Stanley P. Watkins, Timm L. Dickfeld, Glenn R. Meininger, Ariel Roguin, Hugh Calkins, Gordon F. Tomaselli, Robert G. Weiss, Ronald D. Berger, João A.C. Lima, Henry R. Halperin
Journal: Circulation (2005)

Patients with left ventricular dysfunction have an elevated risk of sudden cardiac death. However, the substrate for ventricular arrhythmia in patients with nonischemic cardiomyopathy remains poorly understood. We hypothesized that the distribution of scar identified by MRI is predictive of inducible ventricular tachycardia.Short-axis cine steady-state free-precession and postcontrast inversion-recovery gradient-echo MRI sequences were obtained before electrophysiological study in 26 patients with nonischemic cardiomyopathy. Left ventricular ejection fraction was measured from end-diastolic and end-systolic cine images. The transmural extent of scar as a percentage of wall thickness (percent scar transmurality) in each of 12 radial sectors per slice was calculated in all myocardial slices. The percentages of sectors with 1% to 25%, 26% to 50%, 51% to 75%, and 76% to 100% scar transmurality were determined for each patient. Predominance of scar distribution involving 26% to 75% of wall thickness was significantly predictive of inducible ventricular tachycardia and remained independently predictive in the multivariable model after adjustment for left ventricular ejection fraction (odds ratio, 9.125; P=0.020).MR assessment of scar distribution can identify the substrate for inducible ventricular tachycardia and may identify high-risk patients with nonischemic cardiomyopathy currently missed by ejection fraction criteria.
Positive Cross-Talk between Estrogen Receptor and NF-κB in Breast Cancer
Authors: Jonna Frasor, Aisha Weaver, Madhumita Pradhan, Yang Dai, Lance D. Miller, Chin-Yo Lin, Adina Stanculescu
Journal: Cancer Research (2009)

Estrogen receptors (ER) and nuclear factor-kappaB (NF-kappaB) are known to play important roles in breast cancer, but these factors are generally thought to repress each other's activity. However, we have recently found that ER and NF-kappaB can also act together in a positive manner to synergistically increase gene transcription. To examine the extent of cross-talk between ER and NF-kappaB, a microarray study was conducted in which MCF-7 breast cancer cells were treated with 17beta-estradiol (E(2)), tumor necrosis factor alpha (TNFalpha), or both. Follow-up studies with an ER antagonist and NF-kappaB inhibitors show that cross-talk between E(2) and TNFalpha is mediated by these two factors. We find that although transrepression between ER and NF-kappaB does occur, positive cross-talk is more prominent with three gene-specific patterns of regulation: (a) TNFalpha enhances E(2) action on approximately 30% of E(2)-upregulated genes; (b) E(2) enhances TNFalpha activity on approximately 15% of TNFalpha-upregulated genes; and (c) E(2) + TNFalpha causes a more than additive upregulation of approximately 60 genes. Consistent with their prosurvival roles, ER and NF-kappaB and their target gene, BIRC3, are involved in protecting breast cancer cells against apoptosis. Furthermore, genes positively regulated by E(2) + TNFalpha are clinically relevant because they are enriched in luminal B breast tumors and their expression profiles can distinguish a cohort of patients with poor outcome following endocrine treatment. Taken together, our findings suggest that positive cross-talk between ER and NF-kappaB is more extensive than anticipated and that these factors may act together to promote survival of breast cancer cells and progression to a more aggressive phenotype.
Sleep disordered breathing in children with trisomy 21 and pulmonary hypertension
Authors: Jonathon Wong, Jaques Belik, Tilman Humpl, Janettte Reyes, Indra Narang
Journal: European Respiratory Journal (2012)

Introduction: Children with trisomy 21 (T21) have a significantly high prevalence of sleep disordered breathing (SDB), specifically obstructive sleep apnea (OSA). Children with T21 are also at risk for pulmonary arterial hypertension (PAH). It is unclear if PAH per se confers additional risk for OSA in this population.

Aim: To compare the prevalence of SDB in T21 children with PAH and without PAH and with controls.

Methods: This was a retrospective study where PSG data on all non-obese children at the Hospital for Sick Children, Toronto with T21 and/or PAH referred over a 5 year period, were reviewed and compared with PSG data in age-matched controls. The main outcome measure was the obstructive apnea-hypopnea index (OAHI).

Results: PSG of 33 children aged 0.2 – 8 years with a BMI < 25kg/m2 were reviewed and compared in 4 groups; 1) controls (n=8), 2) children with PAH (n=9), 3) children with T21 (n=10), and 4) children with both T21 and PAH (n=6). In children with both T21 and PAH, there was a significantly higher OAHI (p=0.01) and a trend for lower oxygen saturations and a higher tcCO2 when compared with the other groups (see figures below).

Conclusions: Children with both T21 and PAH are at increased risk of severe OSA. All children with T21 who are known to have PAH should undergo sleep surveillance with PSG. Future research may be directed towards understanding the interaction of T21 and PAH predisposing to OSA.

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Melanocyte-like cells in the heart and pulmonary veins contribute to atrial arrhythmia triggers
Authors: Mark D. Levin, Min Min Lu, Nataliya B. Petrenko, Brian J. Hawkins, Tara H. Gupta, Deborah Lang, Peter T. Buckley, Jeanine Jochems, Fang Liu, Christopher F. Spurney, Li J. Yuan, Jason T. Jacobson, Christopher B. Brown, Li Huang, Friedrich Beermann, Kenneth B. Margulies, Muniswamy Madesh, James H. Eberwine, Jonathan A. Epstein, Vickas V. Patel
Journal: Journal of Clinical Investigation (2009)

Atrial fibrillation is the most common clinical cardiac arrhythmia. It is often initiated by ectopic beats arising from the pulmonary veins and atrium, but the source and mechanism of these beats remains unclear. The melanin synthesis enzyme dopachrome tautomerase (DCT) is involved in intracellular calcium and reactive species regulation in melanocytes. Given that dysregulation of intracellular calcium and reactive species has been described in patients with atrial fibrillation, we investigated the role of DCT in this process. Here, we characterize a unique DCT-expressing cell population within murine and human hearts that populated the pulmonary veins, atria, and atrioventricular canal. Expression profiling demonstrated that this population expressed adrenergic and muscarinic receptors and displayed transcriptional profiles distinct from dermal melanocytes. Adult mice lacking DCT displayed normal cardiac development but an increased susceptibility to atrial arrhythmias. Cultured primary cardiac melanocyte-like cells were excitable, and those lacking DCT displayed prolonged repolarization with early afterdepolarizations. Furthermore, mice with mutations in the tyrosine kinase receptor Kit lacked cardiac melanocyte-like cells and did not develop atrial arrhythmias in the absence of DCT. These data suggest that dysfunction of melanocyte-like cells in the atrium and pulmonary veins may contribute to atrial arrhythmias.
Ontario Cancer Research Ethics Board: Lessons Learned From Developing a Multicenter Regional Institutional Review Board
Authors: Raphael Saginur, Susan F. Dent, Lisa Schwartz, Ronald Heslegrave, Sid Stacey, Janet Manzo
Journal: Journal of Clinical Oncology (2008)

We describe issues and outcomes in the development of a specialized, central institutional review board (IRB) for multicenter oncology protocols. Numerous authoritative bodies have called for a change to the ethics review system to better manage multicenter trials in terms of quality, timeliness, and efficiency. In 2003, the American Society of Clinical Oncology proposed a network of regional IRBs for cancer. Previous experience with central IRBs has been met with mixed success.We took a bottom-up approach to organizing a province-wide IRB, which was led by an IRB chair and a clinical investigator at one cancer center. Participation on the part of institutions was voluntary.Uptake in the first 2 years was modest and increased from 11 clinical trials in year 1 to 21 in year 2. In the third year, there was an apparent upsurge in the number of involved centers (14) and in the number of submitted clinical protocols (54).Sponsors and investigators are loath to risk development of a novel IRB until there is a clear demonstration of quality, efficiency, and timeliness of decision. Development of a regional, specialized IRB requires considerable efforts to develop and maintain the trust of sponsors, investigators, and institutions despite prior demands for more efficient and timely ethics review. Voluntary institutional participation, clear delineation of roles and responsibilities, and effective execution promote development of this trust.
Hepatitis B virus precore mutation and fulminant hepatitis in the United States. A polymerase chain reaction-based assay for the detection of specific mutation.
Authors: T J Liang, K Hasegawa, S J Munoz, C N Shapiro, B Yoffe, B J McMahon, C Feng, H Bei, M J Alter, J L Dienstag
Journal: Journal of Clinical Investigation (1994)

Hepatitis B virus (HBV) variants with precore mutation(s) resulting in the absence of HBeAg production have been associated with the occurrence of fulminant hepatitis in Japan, Israel, and southern Europe, where the prevalence of this HBV strain appears common. In areas such as United States, where HBV infection is not endemic, the role of this mutant virus in fulminant hepatitis is unknown. We developed an amplification refractory mutation detection system to detect specifically the presence of the G to A mutation at nucleotide position 1898, which is the most frequently observed mutation resulting in a precore stop codon. In addition, this method provided a quantitative measurement of the relative ratio of one strain to the other. Using this system, we tested HBV strains for the presence of the stop codon mutation in sera from 40 cases of fulminant hepatitis B occurring in the United States. Serum HBV DNAs from 28 patients were analyzed successfully. A mixture of wild-type and mutant strains in various ratios were observed in 15 patients, wild type exclusively in 11, and mutant exclusively in 2. Four of these patients had undergone liver transplantation for HBV-associated cirrhosis and developed fulminant HBV-associated hepatitis after transplantation. Pre- and posttransplant serum samples from one patient were analyzed: a mixture of wild-type and mutant HBV strains was detected in both samples. Our study demonstrated that both wild-type and mutant HBV strains are associated with fulminant hepatitis, and that in some patients in the United States, factors other than precore mutations contribute to the development of fulminant hepatitis.
G Protein Coupled Receptor Kinases as Therapeutic Targets in Cardiovascular Disease
Authors: Stephen L. Belmonte, Burns C. Blaxall
Journal: Circulation Research (2011)

G protein-coupled receptors (GPCRs) represent the largest family of membrane receptors and are responsible for regulating a wide variety of physiological processes. This is accomplished via ligand binding to GPCRs, activating associated heterotrimeric G proteins and intracellular signaling pathways. G protein-coupled receptor kinases (GRKs), in concert with β-arrestins, classically desensitize receptor signal transduction, thus preventing hyperactivation of GPCR second-messenger cascades. As changes in GRK expression have featured prominently in many cardiovascular pathologies, including heart failure, myocardial infarction, hypertension, and cardiac hypertrophy, GRKs have been intensively studied as potential diagnostic or therapeutic targets. Herein, we review our evolving understanding of the role of GRKs in cardiovascular pathophysiology.
Suprabasal expression of epidermal alpha2beta1 and alpha3beta1 integrins in skin treated with topical retinoic acid
Authors: None HAkkinen, None Westermarck, None Johansson, None Aho, None Peltonen, None Heino, None KAHAri
Journal: British Journal of Dermatology (1998)

Journal Article Suprabasal expression of epidermal α2β1 and α3β1 integrins in skin treated with topical retinoic acid Get access L. HÄkkinen, L. HÄkkinen Periodontology,MediCity Research Laboratory, University of Turku, Finland Search for other works by this author on: Oxford Academic Google Scholar J. Westermarck, J. Westermarck MediCity Research Laboratory, University of Turku, FinlandMedical Biochemistry, Search for other works by this author on: Oxford Academic Google Scholar N. Johansson, N. Johansson MediCity Research Laboratory, University of Turku, FinlandMedical Biochemistry, Search for other works by this author on: Oxford Academic Google Scholar H. Aho, H. Aho Pathology, Search for other works by this author on: Oxford Academic Google Scholar J. Peltonen, J. Peltonen Medical Biochemistry, Search for other works by this author on: Oxford Academic Google Scholar J. Heino, J. Heino MediCity Research Laboratory, University of Turku, FinlandMedical Biochemistry, Search for other works by this author on: Oxford Academic Google Scholar V-M. KÄHÄri V-M. KÄHÄri MediCity Research Laboratory, University of Turku, FinlandMedical Biochemistry,Department of Dermatology, Turku University Central Hospital, Turku, Finland, Departments of Correspondence: Veli‐MattiKähäri Department of Dermatology, Turku University Central Hospital, Kiinanmyllynkatu 4–8, FIN‐20520 Turku, Finland. E‐mail: velkah@utu.fi Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 138, Issue 1, 1 January 1998, Pages 29–36, https://doi.org/10.1046/j.1365-2133.1998.02023.x Published: 01 January 1998