tbuckley/cabot-search huggingface dataset:
Capturing the Ebb and Flow of Psychiatric Symptoms With Dynamical Systems Models
Authors: Candice L. Odgers, Edward P. Mulvey, Jennifer L. Skeem, William Gardner, Charles W. Lidz, Carol Schubert
Journal: American Journal of Psychiatry (2009)

Psychiatric symptoms play a crucial role in psychology and psychiatry. However, little is known about how dimensions of symptoms--other than symptom level--relate to psychiatric outcomes. Until recently, methods for measuring dynamic aspects of symptoms have not been available to clinicians or researchers. The authors sought to test whether systematic patterns of change in psychiatric symptoms can be recovered across weekly assessments of individuals at high risk for violence. A secondary objective was to explore whether dynamic features of symptoms (specifically, oscillation speed and dysregulation) are concurrently associated with violence, an important indicator of functional impairment for these individuals.Participants (N=132) were drawn from a sample of patients evaluated at the emergency room of an urban psychiatric hospital. Patients actuarially classified as being at high risk for violence were eligible for participation in the study. Participants and collateral informants were interviewed weekly for 26 weeks following an acute psychiatric evaluation. Psychiatric symptoms were assessed using the Brief Symptom Inventory. Measures of symptom fluctuation and regulation were derived using dynamical systems models. Involvement in violence was assessed using self, informant, and official reports.Individuals' symptom dynamics were recovered by a linear oscillator model that described how quickly symptoms oscillated and whether symptoms were amplifying or moving back toward equilibrium across time. Patterns of rapid symptom fluctuation and symptom amplification were concurrently associated with violence.Psychiatric researchers and clinicians have long been interested in adopting more dynamic approaches to understanding symptom change. This study is the first to demonstrate that systematic fluctuations in symptom patterns may be captured by dynamic models. Moreover, the concurrent association between symptom dynamics and violence suggests avenues for future research to test how features of symptom fluctuation could affect behavior.
Hypoxia Drives Breast Tumor Malignancy through a TET–TNFα–p38–MAPK Signaling Axis
Authors: Min-Zu Wu, Su-Feng Chen, Shin Nieh, Christopher Benner, Luo-Ping Ger, Chia-Ing Jan, Li Ma, Chien-Hung Chen, Tomoaki Hishida, Hong-Tai Chang, Yaoh-Shiang Lin, Nuria Montserrat, Pedro Gascon, Ignacio Sancho-Martinez, Juan Carlos Izpisua Belmonte
Journal: Cancer Research (2015)

Abstract Hypoxia is a hallmark of solid tumors that drives malignant progression by altering epigenetic controls. In breast tumors, aberrant DNA methylation is a prevalent epigenetic feature associated with increased risk of metastasis and poor prognosis. However, the mechanism by which hypoxia alters DNA methylation or other epigenetic controls that promote breast malignancy remains poorly understood. We discovered that hypoxia deregulates TET1 and TET3, the enzymes that catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), thereby leading to breast tumor–initiating cell (BTIC) properties. TET1/3 and 5hmC levels were closely associated with tumor hypoxia, tumor malignancy, and poor prognosis in breast cancer patients. Mechanistic investigations showed that hypoxia leads to genome-wide changes in DNA hydroxymethylation associated with upregulation of TNFα expression and activation of its downstream p38–MAPK effector pathway. Coordinate functions of TET1 and TET3 were also required to activate TNFα–p38–MAPK signaling as a response to hypoxia. Our results reveal how signal transduction through the TET–TNFα–p38–MAPK signaling axis is required for the acquisition of BTIC characteristics and tumorigenicity in vitro and in vivo, with potential implications for how to eradicate BTIC as a therapeutic strategy. Cancer Res; 75(18); 3912–24. ©2015 AACR.
Possibilities and Limitations of Endoscopic Resection for Early Gastric Cancer
Authors: M. Noda, T. Kodama, M. Atsumi, M. Nakajima, N. Sawai, K. Kashima, M. Pignatelli
Journal: Endoscopy (1997)

To date, the accepted criteria for endoscopic resection of early gastric cancer have been: a) elevated-type mucosal cancer less than 2 cm in size, and b) depressed-type mucosal cancer without ulceration less than 1 cm in size. In this study, we attempted to expand these indications.Sixty patients with early gastric cancer who did not meet the above criteria underwent endoscopic treatment, and were divided into four groups: those with elevated tumours larger than 2 cm with submucosal invasion (group 1 a); those without submucosal invasion (group 1 b); those with depressed tumours larger than 1 cm (group 2); and those with ulcerated tumours (group 3). The patients were treated with endoscopic resection using a two-channel scope, followed by additional laser irradiation or heater-probe coagulation (combination therapy) if residual cells were found. Follow-up was by endoscopy and biopsy for more than two years.Endoscopic treatment was effective in 87% of the patients (52 of 60), half of whom required combination therapy. In submucosal cancers, endoscopic treatment was effective in 76% of patients (13 of 17). However, tumours with deep invasion into the submucosa could not be cured. Mucosal cancers larger than 20 mm could be completely resected in 44% of patients (eight of 18) using endoscopic resection, but all five patients with tumours larger than 30 mm had incomplete resections.These results indicate that complete resection using endoscopic resection alone is possible in early gastric cancers measuring up to 30 mm in diameter. Tumours larger than 30 mm, and those with deep submucosal invasion, cannot be curatively treated by the current endoscopic modalities.
Breast and Ovarian Cancer
Authors: Richard Wooster, Barbara L. Weber
Journal: New England Journal of Medicine (2003)

espite years of intensive study and substantial progress in understanding susceptibility to breast and ovarian cancer, these diseases remain important causes of death in women.However, several recent critical advances -sequencing of the human genome and the development of high-throughput techniques for identifying DNA-sequence variants, changes in copy numbers, and global expression profiles -have dramatically accelerated the pace of research aimed at preventing and curing these diseases.We review some of the important discoveries in the genetics of breast and ovarian cancer, ongoing studies to isolate additional susceptibility genes, and early work on molecular profiling involving microarrays.In the United States, 10 to 20 percent of patients with breast cancer and patients with ovarian cancer have a first-or second-degree relative with one of these diseases. 1Two major genes associated with susceptibility to breast and ovarian cancer -breast cancer susceptibility gene 1 ( BRCA1 ) and breast cancer susceptibility gene 2 ( BRCA2 ) -have been identified to date. 2,3Mutations in either of these genes confer a lifetime risk of breast cancer of between 60 and 85 percent and a lifetime risk of ovarian cancer of between 15 and 40 percent. 4,5However, mutations in these genes account for only 2 to 3 percent of all breast cancers, 6,7 and susceptibility alleles in other genes, such as TP53, PTEN, and STK11/LKB1, are even less common causes of breast and ovarian cancer (Fig. 1).The prediction that there are common DNA-sequence variants that confer a small but appreciable enhanced risk of cancer has been validated with the recent discovery of the 1100delC mutation in the cell-cycle-checkpoint kinase gene ( CHEK2 ). 9 This mutation was found in 1.1 percent of women without breast cancer, 1.4 percent of women with a personal but no family history of breast cancer, and 4.2 percent of index patients from 718 families in which two or more members had been given a diagnosis of breast cancer before the age of 60 years but in which there was no detectable BRCA1 or BRCA2 mutation.This mutation doubles the risk of breast cancer among women and increases the risk among men by a factor of 10.CHEK2, an important component of the cellular machinery that recognizes and repairs damaged DNA, is activated after phosphorylation by the checkpoint gene ATM and in turn activates BRCA1.The role of ATM mutations in the predisposition to the early onset of breast cancer remains controversial, but some missense mutations do appear to increase susceptibility to breast cancer in humans 10 and mice. 11There is convincing evidence that additional high-penetrance genes that increase susceptibility to breast cancer exist.In contrast, it has been suggested that, other than BRCA1 and BRCA2, high-penetrance genes that confer susceptibility to ovarian cancer do not exist. 12An ovarian-cancer-susceptibility locus on chromosome 3p22-25 has d susceptibility to breast and ovarian cancer
Defective postbinding lysis underlies the impaired natural killer activity in factor VIII-treated, human T lymphotropic virus type III seropositive hemophiliacs.
Authors: M Katzman, M M Lederman
Journal: Journal of Clinical Investigation (1986)

We investigated the diminished natural killer (NK) activity in human T lymphotropic virus type III (HTLV-III) seropositive hemophiliacs. Despite normal percentages of NK cells, lymphocytes from five hemophiliacs showed impaired NK activity against K-562 tumor cells in 4-h chromium release microcytotoxicity assays. For example, at an effector-to-target cell ratio of 10:1, cells from patients caused 21.7 +/- 2.5% lysis of tumor targets compared with 47.9 +/- 5.1% lysis by cells from controls (mean +/- SEM, P less than 0.005). Cells from patients were as cytotoxic in 18 h as were cells from controls in 4 h. Binding to tumor targets was not impaired since 11.0 +/- 1.5% of cells from patients and 11.1 +/- 1.3% of cells from controls bound to K-562 cells. Patients' binding cells, however, showed defective killing of attached tumor cells at all time points tested from 0 to 18 h. At 4 h, for example, patients' cells had lysed 10.9 +/- 2.1% of attached tumor cells compared with 26.3 +/- 3.3% lysis by controls' cells (P less than 0.005). The percentage of lymphocytes which were active NK cells (i.e., cells that bound and lysed a tumor cell) was always lower for patients than for controls (1.17 +/- 0.25% vs. 2.82 +/- 0.33%, P less than 0.005). Two methods for estimating recycling of effector cells against multiple target cells demonstrated that active NK cells from patients could recycle as well as those from controls (approximately 3-4 times in 4 h). Mixing experiments showed no evidence for cellular suppression of NK activity. The lytic function of NK cells from HTLV-III seropositive hemophiliacs is thus heterogeneous. This is characterized by a defect in post-binding lysis, with relative sparing of binding capability and recycling capacity.
Regulation of angiotensin II receptor AT1 subtypes in renal afferent arterioles during chronic changes in sodium diet.
Authors: X Ruan, C Wagner, C Chatziantoniou, A Kurtz, W J Arendshorst
Journal: Journal of Clinical Investigation (1997)

Studies determined the effects of chronic changes in sodium diet on the expression, regulation, and function of different angiotensin II (ANG II) receptor subtypes in renal resistance vessels. Rats were fed low- or high-sodium diets for 3 wk before study. Receptor function was assessed in vivo by measuring transient renal blood flow responses to bolus injections of ANG II (2 ng) into the renal artery. ANG II produced less pronounced renal vasoconstriction in rats fed a low- compared with high-sodium diet (16% vs. 56% decrease in renal blood flow, P < 0.001). After acute blockade of ANG II formation by iv enalaprilat injection in sodium-restricted animals, ANG II produced a 40% decrease in renal blood flow, a level between untreated dietary groups and less than high salt diet. Intrarenal administration of angiotensin II receptor type 1 (AT1) receptor antagonists losartan or EXP-3174 simultaneously with ANG II caused dose-dependent inhibition of ANG II responses. Based on maximum vasoconstriction normalized to 100% ANG II effect in each group, AT1 receptor antagonists produced the same degree of blockade in all groups, with an apparent maximum of 80-90%. In contrast, similar doses of the angiotensin II receptor type 2 (AT2) receptor ligand CGP-42112 had only a weak inhibitory effect. In vitro equilibrium-saturation 125I-ANG II binding studies on freshly isolated afferent arterioles indicated that ANG II receptor density was lower in the low- vs. high-sodium animals (157 vs. 298 fmol/mg, P < 0.04); affinity was similar (0.65 nM). Losartan and EXP-3174 displaced up to 80-90% of the ANG II binding; fractional displacement was similar in both diet groups. In contrast, the AT2 receptor analogues PD-123319 and CGP-42112 at concentrations < 10(-6) M had no effect on ANG II binding. RT-PCR assays revealed the expression of both angiotensin II receptor type 1A (AT(1A)) and angiotensin II receptor type 1B (AT(1B)) subtypes in freshly isolated afferent arterioles, while there was very little AT2 receptor expression. Total AT1 receptor mRNA expression was suppressed by low sodium intake to 66% of control levels, whereas it was increased to 132% of control by high-sodium diet, as indicated by ribonuclease protection assay. Receptor regulation was associated with parallel changes in AT(1A) and AT(1B) expression; the AT(1A)/AT(1B) ratio was stable at 3.7. We conclude that AT1 receptors are the predominant ANG II receptor type in renal resistance vessels of 7-wk-old rats. Chronic changes in sodium intake caused parallel regulation of expression and amount of receptor protein of the two AT1 receptor genes that modulate receptor function and altered reactivity of renal vessels to ANG II.
Flying Doctors of the Australian Outback
Authors: Jack H. Prince
Journal: New England Journal of Medicine (1955)

IT is difficult to imagine an efficient medical service functioning over the whole of a 3,000,000-square-mile country with a population of only 8,500,000 people (an estimated 2.9 persons per square mile in 1952). That is an area as large as the United States; most of the people live in 5 state-capital cities and a number of smaller towns confined almost wholly to the eastern end of the country. Some of the cities have standards of living and culture as high as those in the United States, but the center of Australia, perhaps four fifths of the country equaling all the . . .
THE EPIDERMAL-DERMAL JUNCTION OF NORMAL HUMAN SKIN AS SEEN IN FREEZE-ETCH PREPARATIONS
Authors: R. REED, P. J. ROTHWELL
Journal: British Journal of Dermatology (1970)

SUMMARY.— The epidermal–dermal junction has been examined by the replication of freeze‐fractured human skin. A basement zone about 150 nm. in depth has been observed which continuously separates epidermis from dermis. This relatively broad region has been interpreted as the hydrated form of the basement membrane. The convoluted nature of the epidermal–dermal junction and the plasmalemmae of the basal cells is more easily followed by this method of examination, which also brings out the complexity of these appositions. No hemidesmosomes have been observed in the contacts between the basal cells and basement membrane. Desmosomal contacts between basal cells differ in appearance from those seen in thin sections and possibly involve portions of the basement zone.
Aberrant septin 11 is associated with sporadic frontotemporal lobar degeneration
Authors: Yair M Gozal, Nicholas T Seyfried, Marla Gearing, Jonathan D Glass, Craig J Heilman, Joanne Wuu, Duc M Duong, Dongmei Cheng, Qiangwei Xia, Howard D Rees, Jason J Fritz, Deborah S Cooper, Junmin Peng, Allan I Levey, James J Lah
Journal: Molecular Neurodegeneration (2011)

Abstract Background Detergent-insoluble protein accumulation and aggregation in the brain is one of the pathological hallmarks of neurodegenerative diseases. Here, we describe the identification of septin 11 (SEPT11), an enriched component of detergent-resistant fractions in frontotemporal lobar degeneration with ubiquitin-immunoreactive inclusions (FTLD-U), using large-scale unbiased proteomics approaches. Results We developed and applied orthogonal quantitative proteomic strategies for the unbiased identification of disease-associated proteins in FTLD-U. Using these approaches, we proteomically profiled detergent-insoluble protein extracts prepared from frontal cortex of FTLD-U cases, unaffected controls, or neurologic controls (i.e. Alzheimer's disease; AD). Among the proteins altered specifically in FTLD-U, we identified TAR DNA binding protein-43 (TDP-43), a known component of ubiquitinated inclusions. Moreover, we identified additional proteins enriched in detergent-resistant fractions in FTLD-U, and characterized one of them, SEPT11, in detail. Using independent highly sensitive targeted proteomics approaches, we confirmed the enrichment of SEPT11 in FTLD-U extracts. We further showed that SEPT11 is proteolytically cleaved into N-terminal fragments and, in addition to its prominent glial localization in normal brain, accumulates in thread-like pathology in affected cortex of FTLD-U patients. Conclusions The proteomic discovery of insoluble SEPT11 accumulation in FTLD-U, along with novel pathological associations, highlights a role for this cytoskeleton-associated protein in the pathogenesis of this complex disorder.
A Labour government will raise public health profile Consultants will prepare report on casualty services BMA re-emphasises condemnation of torture CMO attends consultants' committee Labour's plan to replace GP fundholding Reserve forces will not get special treatment BMA counselling scheme will start in April BMA supports regional public health consultants Medical students prepare safety guidelines
Authors: L. Beecham
Journal: BMJ (1996)

# A Labour government will raise public health profile {#article-title-2}

A senior minister for public health and a dedicated public health unit in the Department of Health are two of the ways that the Labour party would raise the profile of the discipline if it wins the next election. The Labour shadow health secretary, Ms Harriet Harman, reinforced this commitment when she spoke at last week's meeting of the Committee for Public Health Medicine and Community Health. Public health, she said, was one of Britain's great achievements and she agreed that there should be further meetings to discuss the role of public health doctors under a Labour government. Ms Harman agreed that the minister would have to have clout and that each government department should consider the public health effects of its decisions, but she was not so sympathetic to the suggestion that he or she should not be in the health department but should have a role similar to the leader of the House of Commons.

### CHIEF MEDICAL OFFICER MUST BE INDEPENDENT

The chief medical officer had to have an independent voice and be a thorn in the side of government and the shadow minister agreed with Dr Noel Olsen that the dilution of the CMO's role was disastrous. She regretted the fact that public health doctors felt marginalised and demoralised and that this meant that some of the best doctors felt that public health medicine was not for them. She wanted to see a more aggressive role for public health doctors who should regard themselves as advocates.

On the question of freedom of speech Ms Harman told the CPHMCH that she wanted everyone in the health professions to be able to speak out about their professional concerns. She reported that when she visited hospitals now she was taken round by managers and it was difficult to find out the views of doctors and nurses. …
Minority Health in America: Findings and Policy Implications from The Commonwealth Fund Minority Health Survey
Authors: Ben Hur P. Mobo
Journal: Annals of Internal Medicine (2001)

Medical Writings: Book Notes19 June 2001Minority Health in America: Findings and Policy Implications from The Commonwealth Fund Minority Health SurveyBen Hur P. Mobo Jr., MD, MPHBen Hur P. Mobo Jr., MD, MPHYale School of Medicine, New Haven, Connecticut. (Mobo)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-134-12-200106190-00034 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Hogue CJ, Hargraves MA, Collins KS. 352 pages. Baltimore: Johns Hopkins Univ Pr; 2000. $22.50. ISBN 080186299X. Order phone 800-537-5487.Field of medicine: Epidemiology and public health.Format: Softcover book.Audience: Physicians, nurses, case managers, health educators, and public health officials and advocates.Purpose: To present an analysis of the 1994 Commonwealth Fund Minority Health Survey and offer recommendations about future directions for public health policy with regard to ethnic minority groups.Content: The book begins with an overview of The Commonwealth Fund Minority Health Survey. Four chapters evaluate the associations between ethnicity and various health care outcomes. Seven chapters ... Author, Article, and Disclosure InformationAffiliations: Yale School of Medicine, New Haven, Connecticut. (Mobo) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 June 2001Volume 134, Issue 12Page: 1158KeywordsEpidemiologyHealth careHealth care qualityHealth information technologyHealth surveysInformation storage and retrievalPrevention, policy, and public healthPublic policyRacial and ethnic issuesSoftware tools ePublished: 19 June 2001 Issue Published: 19 June 2001 CopyrightCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Folate and Aplasia of Bone Marrow
Authors: Bernard M. Babior
Journal: New England Journal of Medicine (1978)

IN this issue of the Journal, Branda et al. report on a family in whom an inherited aplastic anemia, possibly preleukemic, is associated with a defect in folate metabolism. This family raises some interesting and puzzling questions. Why cannot cells from these patients take up folate in a normal fashion? What effect does this abnormality in folate metabolism have on cell replication in affected patients? Is the primary abnormality one of hematopoiesis, with the defect in folate uptake a consequence of the lesion in replication, or is it the other way around?The folate abnormality is described as an . . .
Implantation of the Right Ventricular Lead of an Implantable Cardioverter-Defibrillator Complicated by Apical Myocardial Infarction
Authors: Nobuhiro Nishiyama, Seiji Takatsuki, Takehiro Kimura, Yoshiyasu Aizawa, Kotaro Fukumoto, Yoko Hagiwara, Kojiro Tanimoto, Keiichi Fukuda
Journal: Circulation (2012)
Erythropoietic Protoporphyria
Authors: Edward S. Peterka
Journal: JAMA (1965)

For many years attempts have been made to associate polymorphic light eruptions, such as urticaria solaris, eczema solare, and purpura solaris with abnormalities of porphyrin metabolism. Hydroa aestivale or vesiculobullous photocutaneous lesions occur in congenital erythropoietic porphyria (Morbus Gunther) and with cutaneous forms of hepatic porphyria, in all of which the urinary uroporphyrin is invariably increased and characteristic, while in the polymorphous eruptions just alluded to, the urinary porphyrin is normal. In 1953, Kosenow and Treibs 1 reported the case of a 12-year-old male with atypical hydroa aestivale without excessive urinary porphyrin but with elevated erythrocyte protoporphyrin (EP) and fecal protoporphyrin (FP). Although this probably represents the first recorded example of what has come to be designated as erythropoietic protoporphyria, 2 interpretation is somewhat complicated by the presence in the patient's serum of a porphyrin metal complex, the absorption spectrum of which corresponded with that of uroporphyrin or coproporphyrin rather