tbuckley/cabot-search huggingface dataset:
TMTP1, a Novel Tumor-Homing Peptide Specifically Targeting Metastasis
Authors: Wanhua Yang, Danfeng Luo, Shixuan Wang, Rui Wang, Rui Chen, Yan Liu, Tao Zhu, Xiangyi Ma, Ronghua Liu, Gang Xu, Li Meng, Yunping Lu, Jianfeng Zhou, Ding Ma
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Tumor metastasis continues to be the major obstacle to cancer therapy and the leading cause of cancer-related death. Methods used to detect metastasis, especially occult metastases, have received a great deal attention. In this study, a novel selective peptide was assessed for its specific binding to metastasis. Methods: The FliTrx bacterial peptide display system, an alternative to phage peptide display, was used to identify a 5-amino acid peptide termed TMTP1 (NVVRQ), which binds to the highly metastatic prostate cancer cell line PC-3M-1E8. The synthetic TMTP1 was tested in vitro for its binding specificity and affinity to highly metastatic cancer cells. The tumor targeting assays were done in vivo by i.v. injection of FITC-conjugated TMTP1 into tumor-bearing mice. Results: TMTP1 specifically bound to a series of highly metastatic tumor cells, including prostate cancer PC-3M-1E8, breast cancer MDA-MB-435S, lung cancer PG-BE1, and gastric cancer MKN-45sci, in vitro and in vivo but not to the poorly metastatic or nonmetastatic cell line, including prostate cancer PC-3M-2B4, breast cancer MCF-7, lung cancer PG-LH7, or murine fibroblast cell NIH/3T3. FITC-TMTP1 strongly and specifically targeted the metastasis foci in tumor-bearing mice 24 h after i.v. peptide injection. Moreover, the occult metastases were specifically detected by FITC-TMTP1. Conclusion: Our results suggest that TMTP1 is a potential strategy for the development of new diagnostic tracers or alternative anticancer agents for tumor metastasis.
A search for microtubular inclusions in endothelial cells in a variety of skin diseases
Authors: R. F. MACADAM, J. M. VETTERS, N. K. SAIKIA
Journal: British Journal of Dermatology (1975)

An electron microscopic study of a variety of skin diseases has demonstrated microtubular 'inclusions' in vascular endothelium in bullous pemphigoid for the first time. The 'inclusions' are similar to those originally reported in lupus erythematosus by Fresco (1968) and presently being detected in an increasing number and variety of pathological processes.
Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised, double blind, parallel group study
Authors: J. Berth-Jones
Journal: BMJ (2003)

To explore the efficacy and safety of fluticasone propionate, cream and ointment, applied twice weekly in addition to maintenance treatment with emollients, in reducing the risk of relapse of chronic recurrent atopic dermatitis.Randomised, double blind, parallel group study of 20 weeks' duration.Dermatology outpatient clinics (6 countries, 39 centres).Adult (aged 12-65) patients with moderate to severe atopic dermatitis who were experiencing a flare.Participants applied fluticasone propionate (0.05% cream or 0.005% ointment; once or twice daily) regularly for four weeks to stabilise their condition. The patients whose disease was brought under control then continued into a 16 week maintenance phase, applying emollient on a daily basis with a bath oil as needed and either the same formulation of fluticasone propionate or its placebo base (emollient alone) twice weekly to the areas that were usually affected.Time to relapse of atopic dermatitis during maintenance phase.376 patients entered the stabilisation phase, and 295 continued into the maintenance phase. After 16 weeks in the maintenance phase, the disease remained under control in 133 patients (87 using fluticasone propionate twice weekly, 46 using emollient alone), 135 (40 fluticasone propionate, 95 emollient) had experienced a relapse, and 27 had discontinued. Median time to relapse was six weeks for emollient alone compared with more than 16 weeks for additional fluticasone propionate. Patients who applied fluticasone propionate cream twice weekly were 5.8 times less likely (95% confidence interval 3.1 to 10.8, P < 0.001) and patients using fluticasone propionate ointment 1.9 times less likely (1.2 to 3.2, P=0.010) to have a relapse than patients applying emollient alone. The groups showed no differences in adverse events.After atopic dermatitis had been stabilised the addition of fluticasone propionate twice weekly to maintenance treatment with emollients significantly reduced the risk of relapse.
HLA Class II Alleles Specify Phenotypes of Ketosis-Prone Diabetes
Authors: Ramaswami Nalini, Lakshmi K. Gaur, Mario Maldonado, Christiane S. Hampe, Lucille Rodriguez, Gilberto Garza, Ake Lernmark, Ashok Balasubramanyam
Journal: Diabetes Care (2008)

OBJECTIVE—Ketosis-prone diabetes (KPD) comprises four subgroups based on the presence or absence of β-cell autoantibodies (A+ or A−) and β-cell functional reserve (β+ or β−). Genetic factors could contribute to their distinctive phenotypes. Our aim was to specify the role of HLA class II alleles associated with susceptibility or resistance to autoimmune type 1 diabetes in determining KPD phenotypes. RESEARCH DESIGN AND METHODS—A total of 185 adults presenting with diabetic ketoacidosis were followed longitudinally for a mean of 5.5 years, with measurements of autoantibodies, β-cell functional reserve, insulin sensitivity, and insulin requirement. Frequencies of susceptibility and resistance alleles at HLA DQA1, DQB1, and DRB1 loci were correlated with clinical and phenotypic features of KPD subgroups and compared with those of ethnic-specific population control subjects. RESULTS—Susceptibility alleles were more frequent (P &amp;lt; 0.0001) in the two A+ than the two A− KPD subgroups; in the latter, the frequency was no greater than in population control subjects (except for DQB1*0302). Susceptibility alleles differentiated the two clinically similar β− subgroups (more frequent in A+β− than A−β− KPD; P &amp;lt; 0.01). Resistance alleles were more frequent in the two β+ than the two β− KPD subgroups (P &amp;lt; 0.01). The frequencies of certain susceptibility (e.g., DQB1*02) and resistance (DQB1*0602) alleles were higher in African-American A−β+ KPD patients than in African-American control subjects. DQB1*0302 was more frequent in all KPD subgroups compared with control subjects. CONCLUSIONS—HLA class II alleles associated with susceptibility or resistance to autoimmune type 1 diabetes help specify the four subgroups of KPD. Inheritance of these alleles may influence long-term β-cell functional reserve.
Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study
Authors: F Nosten, M van Vugt, R Price, C Luxemburger, KL Thway, A Brockman, R McGready, F ter Kuile, S Looareesuwan, NJ White
Journal: The Lancet (2000)
ORGANIC COGNATES OF ACUTE PSYCHIATRIC ILLNESS
Authors: IVER F. SMALL, JOYCE G. SMALL, STANTON P. FJELD, MARY P. HAYDEN
Journal: American Journal of Psychiatry (1966)

One hundred selected (one of every 20) admissions to an acute psychiatric hospital were evaluated by means of independent psychiatric and neurologic, EEG and psychological examinations. Final diagnoses were established by means of longitudinal studies. It was determined that: 1) 60 percent of patients had no demonstrable organic brain disorder; 2) 20 percent had chronic brain disorders; 3) ten percent had acute brain disorders, mostly associated with alcoholism; 4) seven percent had functional mental illnesses in the presence of known central nervous system pathology and 5) three percent could not be classified as either with or without brain disorders. Mental status examinations on admission which revealed no evidence of organic dysfunction were associated with final diagnoses of functional mental illness with rare exceptions. Admission mental status examinations showing defects of memory and typical changes in affect were significantly more often associated with definable brain damage. Impaired intellectual functioning and defects of judgment and states of confusion were encountered in both organic and functional disorders, especially in acute schizophrenics. EEG abnormalities were present in 60 percent of patients with organic brain disorders. Normal EEGs in this group (40 percent) were associated with acute and chronic brain syndromes associated with alcoholism and acute brain disorders related to amphetamine intoxication. Forty percent of patients without known organic diagnoses also displayed EEG abnormalities. Psychological test findings agreed with the final diagnosis in two-thirds of cases, with a similar rate of agreement for organic and nonorganic disorders. Disagreement of psychological test results with the final diagnosis was prone to occur in acutely disturbed schizophrenics and alcoholics. These findings can provide some guidelines for clinical practice in similar settings. An admission mental status examination which reveals no typical indications of organic brain disorder is usually associated with a final diagnosis of "functional mental illness." A mental status examination, when done at the time of admission and which shows characteristic indications of organic impairment, is also predictive of a nonorganic final diagnosis if associated with a normal EEG, a negative psychological test result and a clinical history negative for alcoholism or other addiction. An admission mental status examination with organic findings in the absence of these conditions is generally associated with a final diagnosis of organic brain disorder.
Hypertrophic pulmonary osteoarthropathy in association with pulmonary metastases from extrathoracic tumours
Authors: M. H. Yacoub, G. Simon, J. Ohnsorge
Journal: Thorax (1967)

Three cases of pulmonary osteoarthropathy secondary to pulmonary metastases from extrathoracic tumours are described. Analysis of the reported cases shows that most of them were secondary to osteosarcoma, nasopharyngeal tumour, fibrosarcoma, and uterine tumour. Fibrous tumours and tumours with a predominantly fibrous stroma tend to be associated with osteoarthropathy more than others. This suggests that the fibrous stroma may be a factor in the stimulation of the reflex mechanism responsible for osteoarthropathy.
Blocking of in vitro and in vivo susceptibility to mouse hepatitis virus.
Authors: W Y Weiser, F B Bang
Journal: The Journal of Experimental Medicine (1977)

By pretreatment with concanavalin A (Con A) both in vivo and in vitro genetically susceptible mice and their cultured macrophages have been converted to animals and cells which are phenotypically resistant to mouse hepatitus virus (MHV). Con A at 1.0 mg/mouse decreased the mortality from 100% to less than 40% by inducing a prominent inflammatory response, increasing the number of macrophages in the virus inoculation site, and producing a population of macrophages not uniformly susceptible to the virus. In addition, mediators derived from Con A-treated spleen cells conferred resistance to normally susceptible syngeneic macrophages to 100 TCID50 of MHV.
Number of tuberculosis (TB) cases reported by primary care physicians (PCPs) in India: Results of a 1-day point prevalence study in 880 urban cities and towns in India
Authors: Komalkirti Apte, Monica Barne, Sapna Madas, Jaideep Gogtay, Sushmeeta Chhowwala, Nadar Maharajan, Sundeep Salvi
Journal: European Respiratory Journal (2013)

The burden of multi drug resistant (MDR) TB is increasing in India. Previous studies show that PCPs are poorly versed with standard TB chemotherapeutic regimens. This may be a major factor for the growing prevalence of MDR-TB (Udwadia, Plos One 2010). We aimed to study the prevalence of PCP reported prevalence of TB in India. Methods: 13,225 general practitioners (GPs), general physicians (GenPs) and paediatricians (Ps) from 880 urban cities and towns were randomly selected and invited to participate in a 1-day point prevalence study. All doctors completed a questionnaire based on the ICD-10 classification. They captured age, gender and diagnosis of all patients who visited them on the study day. Clean data was entered in Epi-Info software. Simple descriptive analysis was performed. Results: 7400 physicians (60.6% GPs, 20.8% GenPs, 18.8% Ps) consented and provided clean data of 204,912 patients. Among these, 3719 were reported to have TB. 55.5%, 30.7% and 13.8% of these were seen by GPs, GenPs and Ps respectively. 54% of the GPs were trained in alternative/ complementary forms of medicine (Alt. Med.) & 46% in modern medicine. 65.8% of TB cases were seen in private (pvt) clinics, 2.7% in pvt hospitals and 12.5% in government hospitals. 67.7% of reported TB cases were between the ages of 18-60 yrs. Conclusion: PCPs from pvt clinics see substantially large numbers of TB cases in India (estimated 700,000 TB cases/day). GPs (majority trained in Alt. Med.) see over 50% of these patients. These observations mandate development of appropriate health care strategies to restrict the increasing prevalence of MDR TB.
The frame/content theory of evolution of speech production
Authors: Peter F. MacNeilage
Journal: Behavioral and Brain Sciences (1998)

The species-specific organizational property of speech is a continual mouth open-close alternation, the two phases of which are subject to continual articulatory modulation. The cycle constitutes the syllable, and the open and closed phases are segments – vowels and consonants, respectively. The fact that segmental serial ordering errors in normal adults obey syllable structure constraints suggests that syllabic “frames” and segmental “content” elements are separately controlled in the speech production process. The frames may derive from cycles of mandibular oscillation present in humans from babbling onset, which are responsible for the open-close alternation. These communication- related frames perhaps first evolved when the ingestion-related cyclicities of mandibular oscillation (associated with mastication [chewing] sucking and licking) took on communicative significance as lipsmacks, tonguesmacks, and teeth chatters – displays that are prominent in many nonhuman primates. The new role of Broca's area and its surround in human vocal communication may have derived from its evolutionary history as the main cortical center for the control of ingestive processes. The frame and content components of speech may have subsequently evolved separate realizations within two general purpose primate motor control systems: (1) a motivation-related medial “intrinsic” system, including anterior cingulate cortex and the supplementary motor area, for self-generated behavior, formerly responsible for ancestral vocalization control and now also responsible for frames, and (2) a lateral “extrinsic” system, including Broca's area and surround, and Wernicke's area, specialized for response to external input (and therefore the emergent vocal learning capacity) and more responsible for content.
Prevention and Reduction of Obesity through Active Living (PROACTIVE): rationale, design and methods
Authors: R Ross, S N Blair, M Godwin, S Hotz, P T Katzmarzyk, M Lam, L Lévesque, S MacDonald
Journal: British Journal of Sports Medicine (2008)

The Prevention and Reduction of Obesity through Active Living (PROACTIVE) is a randomised controlled trial to evaluate the effectiveness of a behaviourally based physical activity and diet composition programme to prevent and reduce obesity and related comorbidities in a primary healthcare setting. 491 abdominally obese men and women 25-75 years of age who were patients of primary care physicians were randomly assigned to either a usual care group (N = 242) or a behavioural intervention group (N = 249). Those in usual care received general advice from the physician regarding the merits of physical activity and a healthy diet as a strategy for obesity reduction. Those in the behavioural intervention group received an individually designed counselling programme from a specially trained health educator, with respect to physical activity, diet and obesity reduction. The study was designed to provide 95% power in both men and women to detect a 2% (2 cm) difference in waist circumference and 80% power to identify a 15% reduction in the prevalence of the metabolic syndrome, the two primary outcomes. PROACTIVE is the first behavioural intervention study to assess the effects of physical activity and diet on abdominal obesity and associated metabolic risk factors in a primary healthcare setting, include a generalised sample of men and women and examine long-term (24 months) effects. PROACTIVE has the potential to provide the basis for changing clinical practice (primary care) with respect to the prevention and reduction of obesity and related health risks. The purpose of this report is to present and discuss the rationale, design and methods of PROACTIVE.
Long-term follow-up of patients treated with short-term high-dose chlorambucil for sight-threatening ocular inflammation1 1The authors have no financial interest in any of the drugs used in this study.
Authors: Debra A. Goldstein, Fernandino A. Fontanilla, Suruchi Kaul, Ozlem Sahin, Howard H. Tessler
Journal: Ophthalmology (2002)
Caveolin-1 is essential for protecting against binge drinking-induced liver damage through inhibiting reactive nitrogen species
Authors: Lei Gao, Yingchun Zhou, Weichao Zhong, Xiaohua Zhao, Chun Chen, Xingmiao Chen, Yong Gu, Jianping Chen, Zhiping Lv, Jiangang Shen
Journal: Hepatology (2014)

Caveolin-1 (Cav-1) is known to participate in many diseases, but its roles in alcoholic liver injury remain unknown. In the present study, we aimed to explore the roles of Cav-1 in protecting hepatocytes from ethanol-mediated nitrosative injury. We hypothesized that Cav-1 could attenuate ethanol-mediated nitrosative stress and liver damage through regulating epidermal growth factor receptor/signal transducer and activator of transcription 3/inducible nitric oxide synthase (EGFR/STAT3/iNOS)-signaling cascades. Ethanol-fed mice had time- and dose-dependent increases of Cav-1 in serum and liver with peak increase at 12 hours. Compared to wild-type mice, Cav-1 deficiency mice revealed higher expression of iNOS, higher levels of nitrate/nitrite and peroxynitrite, and had more serious liver damage, accompanied with higher levels of cleaved caspase-3 and apoptotic cell death in liver, and higher levels of alanine aminotransferase and aspartate aminotransferase in serum. Furthermore, the results revealed that the ethanol-mediated Cav-1 increase was in an extracellular signal-regulated kinase–dependent manner, and Cav-1 protected hepatocytes from ethanol-mediated apoptosis by inhibiting iNOS activity and regulating EGFR- and STAT3-signaling cascades. In agreement with these findings, clinical trials in human subjects revealed that serum Cav-1 level was time dependently elevated and peak concentration was observed 12 hours after binge drinking. Alcohol-induced liver lesions were negatively correlated with Cav-1 level, but positively correlated with nitrate/nitrite level, in serum of binge drinkers. Conclusions : Cav-1 could be a cellular defense protein against alcoholic hepatic injury through inhibiting reactive nitrogen species and regulating EGFR/STAT3/iNOS-signaling cascades. (Hepatology 2014;60:687–699)
Brain cancer mortality in the United States, 1986 to 1995: A geographic analysis
Authors: Zixing Fang, Martin Kulldorff, David I. Gregorio
Journal: Neuro-Oncology (2004)

The Atlas of Cancer Mortality in the United States, 1950-94 (Devesa et al.) published in 1999 by the National Institutes of Health suggests that there are elevated rates of brain and other nervous system cancer in the northwestern, north central, and southeastern parts of the country. Being descriptive in nature, the atlas does not evaluate whether observed patterns are simply due to random variation or if they are reflective of true geographical differences in disease risk or treatment practices. To formally test for geographical clustering of disease, we analyzed U.S. brain cancer mortality data from 1986 to 1995 with Tango's Excess Events test, the Cuzick-Edwards k-Nearest-Neighbors test, and the spatial scan statistic. All tests revealed statistically significant geographical clustering for both adult men and women. The spatial scan statistic indicated that the most likely cluster of high mortality was in parts of Arkansas, Mississippi, and Oklahoma (relative risk [RR] = 1.22, P < 0.0001) for women and in parts of Tennessee and Kentucky (RR = 1.15, P < 0.0001) for men. Several secondary clusters were detected, but there were no statistically significant clusters of a very localized nature and a high RR. For childhood brain cancer, there were no statistically significant geographical clusters. It is reassuring that no local brain cancer mortality "hot spots" with very high RRs were found. While the causes of the large geographical clusters with modest RRs are unclear, the geographical pattern of brain cancer mortality provides valuable information that can help in formulating etiological hypotheses and in targeting high-risk populations for further epidemiological and health services research.
Pomalidomide Is Active in the Treatment of Anemia Associated With Myelofibrosis
Authors: Ayalew Tefferi, Srdan Verstovsek, Giovanni Barosi, Francesco Passamonti, Gail J. Roboz, Heinz Gisslinger, Ronald L. Paquette, Francisco Cervantes, Candido E. Rivera, H. Joachim Deeg, Juergen Thiele, Hans M. Kvasnicka, James W. Vardiman, Yanming Zhang, B. Nebiyou Bekele, Ruben A. Mesa, Robert P. Gale, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2009)

Thalidomide and lenalidomide can alleviate anemia in myelofibrosis. However, their value is undermined by their respective potential to cause peripheral neuropathy and myelosuppression. We therefore evaluated the safety and therapeutic activity of another immunomodulatory drug, pomalidomide.In a phase II randomized, multicenter, double-blind, adaptive design study, four treatment arms were evaluated: pomalidomide (2 mg/d) plus placebo, pomalidomide (2 mg/d) plus prednisone, pomalidomide (0.5 mg/d) plus prednisone, and prednisone plus placebo. Pomalidomide was administered for up to 12 28-day treatment cycles. Prednisone (30 mg/d) was given in a tapering dose schedule during the first three cycles. Response was assessed by International Working Group criteria.Eighty-four patients with myelofibrosis-associated anemia were randomly assigned to the aforementioned treatment arms: 22, 19, 22, and 21, respectively. Response in anemia was documented in 20 patients, including 15 who became transfusion independent. Response rates in the four treatment arms were 23% (95% CI, 5% to 41%), 16% (95% CI, 0% to 33%), 36% (95% CI, 16% to 56%), and 19% (95% CI, 2% to 36%). The corresponding figures for patients receiving > or = 3 cycles of treatment (n = 62) were 38%, 23%, 40%, and 25%. Response to pomalidomide with or without prednisone was durable (range, 3.2 to 16.9+ months) and significantly better in the absence of leukocytosis (37% v 8%; P = .01); JAK2V617F or cytogenetic status did not affect response. Grade > or = 3 toxicities were infrequent and included (in each treatment arm) neutropenia (9%; 16%; 5%; 5%), thrombocytopenia (14%; 16%; 9%; 5%), and thrombosis (9%; 5%; 0%; 0%).Pomalidomide therapy at 0.5 or 2 mg/d with or without an abbreviated course of prednisone is well tolerated in patients with myelofibrosis and active in the treatment of anemia.