tbuckley/cabot-search huggingface dataset:
Depressive symptoms and suicidal behavior in adolescents
Authors: D R Robbins, N E Alessi
Journal: American Journal of Psychiatry (1985)

Depressive symptoms and suicidal behavior in 64 adolescent psychiatric patients were assessed by a structured interview and the Schedule for Affective Disorders and Schizophrenia. The medical seriousness of suicidal behavior was associated with conscious intent to die and with the number of previous nonlethal suicide attempts. Suicidal behavior was associated with depressed mood, negative self-evaluation, anhedonia, insomnia, poor concentration, indecisiveness, lack of reactivity of mood, psychomotor disturbance, and alcohol and drug abuse. The results suggest that adolescents can be reliable reporters of their suicide potential and that clinicians need to be sensitive to symptoms of major depressive disorder in assessing potentially suicidal adolescents.
Mutagenic Impurities in 1,3-Dichloropropene Preparations
Authors: R E Talcott, J King
Journal: JNCI Journal of the National Cancer Institute (1984)

A widely used pesticide, 1,3-dichloropropene [(DCP) CAS: 542-75-6], has been reported to be mutagenic to Salmonella typhimurium TA100, but large variations in specific mutagenic activity have been observed among different preparations. The purposes of this investigation were to determine the probable cause of the interpreparational variation and to provide new information on the nature of the mutagenic activity. Four preparations were assayed for mutagenic activity before and after silicic acid chromatography. None of the preparations retained mutagenic activity after chromatography, but each contained direct-acting mutagenic polar impurities. The specific mutagenic activities of the unpurified DCP samples appeared to be determined by the mutagenic activities of their polar impurities. A mixture of mutagenic polar impurities could be regenerated by refluxing a purified DCP preparation for 6 hours. The fraction of polar impurities from one of the preparations was analyzed by gas chromatography-mass spectroscopy. Although its composition was too complex to characterize completely, two known mutagens, epichlorhydrin (CAS: 106-89-8; 1-chloro-2,3-epoxy-propane) and 1,3-dichloro-2-propanol (CAS: 96-23-1), were tentatively identified. In view of these results, future studies are required to establish whether DCP itself is a chemical carcinogen or whether its previously observed carcinogenicity resulted from the presence of mutagenic impurities.
HIV/TB in Belarus
Authors: Andrei Astrauko, Aliaksandr Skrahin, Alena Skrahina
Journal: European Respiratory Journal (2011)

Understanding the key role which HIV infection plays in deteriorating TB epidemic situation is crucial for implementing HIV/TB collaborating activities in the Belarusian health care system.  The following trends on TB and HIV incidence were reported during the last eight years (2002 – 2009) in Belarus: 10% decrease in TB incidence from 5 139 to 4 633 with the 17% increase in HIV incidence from 915 to 1072, and dramatic (7.5 fold) increase in TB/HIV co-infection incidence from 35 up to 265. The following trends in HIV mortality has been observed in these years: 24 cases in 2002 and 223 cases in 2009 (9.3 fold increase). In the reasons of death for HIV positive patients only 4 (16.7%) patients of all HIV patients died of TB in 2002 to compare with 123 (55.2%) of HIV patients died of TB in 2009. The following social structure of the patients with HIV/TB co-infection has been reported: intravenous drug users (63.4%), heavy drinkers/alcohol addicts (26.8%), patients with history of imprisonment (40.9%), and unemployed (67.1%). Gomel region is the most TB/HIV affected Belarus region, where 61.1% of cases were concentrated of all registered TB/HIV in the country (01.01.2010).  In order to control TB/HIV co-infection spread specific measures based on close cooperation between TB and HIV programs has been implemented in Belarus including: TB prevention, early diagnosis and adequate treatment of TB in HIV positive people.
NCCTG phase I trial of temsirolimus (CCI-779) and temozolomide (TMZ) in combination with radiation therapy (RT) in newly diagnosed glioblastoma multiforme (GBM) patients
Authors: J. N. Sarkaria, E. Galanis, W. Wu, C. Giannini, K. A. Jaeckle, L. Doyle, J. Uhm, P. Brown, A. B. Dietz, J. Buckner
Journal: Journal of Clinical Oncology (2009)

2019 Background: The mammalian target of rapamycin (mTOR) functions within the PI3K/Akt signaling pathway as a critical modulator of cell survival. We previously demonstrated significant synergy of the mTOR inhibitor sirolimus with RT in glioma xenografts. Methods: The standard cohorts of 3 design was applied with dose escalation of weekly IV CCI-779 in combination with standard TMZ/RT. CCI-779 was given during both RT (60 Gy)/TMZ (75 mg/m2 daily) and adjuvant TMZ (200 mg/m2 daily x 5 every 28 days). Results: A total of 17 patients were enrolled. CCI-779 therapy during RT/TMZ was well tolerated at dose level 0 (25 mg CCI-779, n = 3) and dose level 1 (50 mg CCI-779, n = 6) with 1 of 9 patients experiencing a DLT (Gr 3 fatigue). Dose level 2 (75 mg CCI-779) exceeded the maximally tolerated dose with two of six patients with DLT (&lt;75% CCI-779 delivered; Gr 4 dyspnea). Despite reasonable tolerance during RT/TMZ, the overall regimen was associated with a high rate of infection associated with lymphopenia. After a patient died from PCP on cycle 2 of adjuvant TMZ/CCI-779, antibiotic prophylaxis was mandated. Two other patients died of gram-negative sepsis despite prophylaxis: one after their first dose of CCI-779 and one during cycle 4 of adjuvant therapy. In contrast to our 18% grade 5 infection rate, only 4% grade 3 (no grade 4/5) infections were observed in 26 other CTEP-sponsored clinical trials involving 1,006 patients treated with CCI-779. Results from translational studies evaluating the effects of treatment on immune function will be presented. Further infections were avoided on this trial after CCI-779 therapy was limited to RT/TMZ. Conclusions: Although CCI-779 in combination with RT/TMZ was well-tolerated, adjuvant therapy with TMZ/CCI-779 was associated with an increased risk of opportunistic infections. [Table: see text]
Keratins: Biomarkers and modulators of apoptotic and necrotic cell death in the liver
Authors: Nam‐On Ku, Pavel Strnad, Heike Bantel, M. Bishr Omary
Journal: Hepatology (2016)

Keratins, formerly known as cytokeratins, are the major epithelial-specific subgroup of intermediate filament proteins. Adult hepatocytes express keratin polypeptides 8 and 18 (K8/K18), whereas cholangiocytes express K8/K18 and keratins 7 and 19 (K7/K19). Keratins function primarily to protect hepatocytes from apoptosis and necrosis, which was revealed using several genetic mouse models. This cytoprotective function was further clarified by the identification of natural human keratin variants that are normally silent, but become pathogenic by predisposing their carriers to apoptosis during acute or chronic liver injury mediated by toxins, virus infection, or metabolic stress. During apoptosis, caspases cleave K18 and K19 at conserved aspartates (human K18/K19: (235) Val-Glu-Val-Asp(↓) ) and K18 at a unique aspartate (human K18: (394) Asp-Ala-Leu-Asp(↓) ), with the latter exposed epitope becoming recognized by the M30 antibody in blood and tissues. Additional K18-containing protein backbone epitopes are detected using the M6 and M5 (termed M65) antibodies. Intact K18 and its associated fragments, which are released into blood during apoptosis and necrosis in various diseases, have been analyzed by enzyme-linked immunosorbent assay using the M30/M65 antibodies or their signal ratios. Furthermore, M30/M65 levels have been used as diagnostic and prognostic biomarkers in acute and chronic liver diseases, including nonalcoholic steatohepatitis and acute liver failure. Other keratin biomarkers include K8/K18/K19-related tissue polypeptide antigen, K18-related tissue polypeptide-specific antigen, and K19-related CYFRA-21-1, which have been evaluated mostly in patients with epithelial tumors.Keratins and their fragments are released into blood during liver and other epithelial tissue injury. The epithelial specificity of K18/K19, epitope unmasking upon caspase digestion, keratin abundance, and relative keratin stability render them useful biomarkers for hepatocyte and cholangiocyte apoptosis and necrosis. However, the precise biochemical nature and release mechanism of circulating keratins remain unknown. (Hepatology 2016;64:966-976).
AQP5 variant associated with prognosis in patients with early breast cancer.
Authors: Ho Yong Park, Soo Jung Lee, Yee Soo Chae, Jong Gwang Kim, Byung Woog Kang, Yoo Jin Lee, Ji Yun Jeong, Ji-young Park
Journal: Journal of Clinical Oncology (2013)

e11505 Background: Our previous study showed the association of AQP5 expression with unfavorable prognosis in patients with early breast cancer (EBC). In addition, we analyzed the prognostic impact of polymorphisms of AQP5 gene in the chromosomal region 12q13 on breast cancer. Methods: The genomic DNA was extracted from paraffin-embedded tumor-free tissue from 609 early breast cancer (EBC) patients underwent curative surgery and then genotyped for 3 polymorphisms (rs3736309, rs1964676, and rs74091167) using the Sequenom Mass array system. Results: The median age of patients was 49 years (range 23-79). 106 (18.2%) patients underwent breast conserving surgery and adjuvant chemotherapy was given to 562 (92.3%) patients. Among enrolled subjects, 447 (73.3%) were hormone-responsive, 94 (15.3%) for HER2 overexpressed, and 98 (16.1%) for triple negative EBC. Among the 3 polymorphisms, AQP5 rs74091167 was significantly associated with disease-free survival (DFS) and distant disease-free survival (DDFS) in a dominant model (P &lt; 0.001 and P = 0.021, respectively). Moreover, multivariate survival analysis revealed that the GG genotype of AQP5 rs74091167 was significantly associated with better DFS (HR = 0.377; 95% CI 0.179-0.793; P = 0.010) when compared with the combine GC/CC genotype adjusted to clinicopathological variables. However, no difference in AQP5 rs74091167 polymorphism was observed based on patient and tumor characteristics. Conclusions: AQP5 rs74091167 variant can be considered as a prognostic marker in patients with EBC after curative operation. In the future, functional relevance of this variant needs to be clarified.
구연 : 간암 세포주에서 Cyclooxygenase-2 (COX-2) 억제 선택성에 따른 화학적 암예방 효과의 차이
Authors: 정재연, 황일란, 김도현, 송현주, 진주현, 이은희, 이기명, 유병무, 함기백, 김진홍, 조성원
Journal: Clinical and Molecular Hepatology (2003)

배경/목적: 간세포암에서 효과적인 화학예방제는 간세포암 고위험군에서 간암 발생을 줄일것으로 기대되나 현재까지 안전성과 효능이 입증된 약물은 없다. 장상피세포의 경우 cyclooxygenase-2 (COX-2)가 과발현되면 세포성장 및 증식에 유리해지고, 세포사멸에 저항성을 가진다. 임상 연구에서는 선택적 COX-2 억제제인 celecoxib이 대장 선종의 크기와 숫자를 줄임이 확인되었다. 최근 일부 간세포암에서 COX-2 발현이 증가하고, COX-2 발현이 종양의 분화도와 연관됨이 보고되었다. 선택적 COX-2 억제제는 간암세포주에서 세포사멸을 유도함이 보고되었으나, 세포사멸의 기전은 아직 밝혀지지 않았다. 본 연구는 간암세포주에서 COX-2 억제제의 선택성에 따른 세포사멸 효과를 살펴보고, 세포사멸과 관련된 단백의 분석을 통해 세포사멸의 기전을 알아보고자 하였다. 대상과 방법: 두 종류의 간암세포주(Huh-7, Hep3B)에서 COX-2 발현을 RT-PCR 및 western blot을 이용하여 측정하였고, 본 연구에는 비선택적(nonselective) COX-2 억제제인 sulindac, 우선선택적(preferred) COX-2 억제제인 nimesulide, 선택적 COX-2 억제제인 celecoxib이 사용되었다. COX의 대사 산물인 prostaglandin-E2 (PGE2)는 ELISA에 의해 측정하였다. 세포사멸은 Anexin-Propidium Iodide 염색후 Fluorescence Activated Cell Sorter (FACS) 분석, DNA fragmentation, 4`6-diamino-2-phenylindole (DAPI) 염색을 통해 확인하였다. 세포사멸 조절 단백인 Bcl-2, Bax 단백의 유전자 전사는 RNase protection assay(RPA)로 mRNA 발현을 측정하여 조사하였고, western blot을 이용하여 단백 합성을 조사하였다. 결과: 1) 실험에 사용한 COX-2 억제제 (sulindac, nimesulide, celecoxib) 모두에서 간암세포주의 세포사멸이 관찰되었으며, 세포사멸 효과는 약물의 용량과 처리 시간에 비례하였으나, PGE2의 농도 감소는 관찰되지 않았다. 2) 같은 IC50 농도로 유지되었을때 COX 선택성이 증가할수록 세포사멸 효과가 증대되어 celecoxib이 가장 효과적으로 세포사멸을 유도하였다. 3) 약물 처리후 COX-2 유전자 전사와 단백질 합성이 증가하였고, COX-2 발현과 세포사멸 사이에 상관관계는 없었다. 4) 세포사멸 과정은 Bcl-2 및 Bax 유전자 전사 및 단백 합성과는 무관하였다. 5) COX-2 선택성이 증가할수록 caspase 3와 caspase 9 및 poly(ADP-ribose) polymerase (PARP) 활성이 증가하였다. 결론: COX-2 억제제는 간암세포주에서 세포사멸을 유도하였고, 이는 prostaglandin E2와는 무관하였으며, 선택적 COX-2 억제제인 celecoxib의 세포사멸 효과가 가장 우수하였다. 이러한 세포사멸 효과는 COX-2 선택성에 따라 증가하였고, 이에 대한 기전 연구가 더 필요하리라 생각된다.
Abstract 10097: Clinical Use of Ambulatory Blood Pressure Monitoring in the Prediction of Prognosis in Stroke Patients
Authors: Jae Hyeong Park, Hyun-Seok Lee, Jun Hyung Kim, Jae-Hwan Lee, Jei Kim, Si Wan Choi, Jin-Ok Jeong, In-Whan Seong
Journal: Circulation (2013)

Background: Arterial blood pressure (BP) has a daily variation. Hypertensive patients with an excessive morning surge in BP and/or lack of nocturnal BP fall have been shown to have increased incide...
Lack of Population Diversity in Human Embryonic Stem-Cell Lines
Authors: Jack T Mosher, Trevor J Pemberton, Kristina Harter, Chaolong Wang, Erkan O Busbas, Petr Dvořák, Carlos Simón, Sean J Morrison, Noah A Rosenberg
Journal: New England Journal of Medicine (2009)

We determined the genetic ancestry of large collection of
stem-cell lines. We have found that widely distributed
stem-cell lines lack population diversity and that none of
these lines derive from populations with recent African
ancestry. Efforts to derive and disseminate new stem-cell lines
should now emphasize underrepresented pupulations, to allow
researchers to assess the extent to which the ancestry of
stem-cell lines influences diesease models, cellular therapies,
and drug screening with the use of stem cells.
Phase 1 and pharmacokinetic (PK) study of weekly KOS-862 (Epothilone D) combined with gemcitabine (GEM) in patients (Pts) with advanced solid tumors
Authors: J. L. Marshall, S. Ramalingam, J. J. Hwang, R. Ramanathan, S. Malik, M. Egorin, A. Hannah, G. F. Cropp, R. G. Johnson, C. Belani
Journal: Journal of Clinical Oncology (2005)

2041 KOS-862 (a mitotic spindle poison causing G2/M arrest) and GEM (a pyrimidine antimetabolite) are anti-cancer agents with different mechanisms of antitumor activity and potentially non-overlapping toxicities. In vitro treatment of 2 human lung cancer cell lines (MV522; SK-MES) with the two agents showed additive antitumor activity without sequence dependence. Methods: To define the MTD, toxicity profile and PK of KOS-862 and GEM when administered weekly for 3 out of every 4 weeks, pts received KOS-862 (50, 60 and 75 mg/m2) and GEM (750 mg/m2) in 3 cohorts. KOS-862 was given IV over 90 min. with appropriate prophylaxis for Cremophor; GEM was given IV over 30 min. PK studies were performed for KOS-862, seco-KOS-862 (metabolite) and GEM. Results: 14 pts (7 F; median age 58; median ECOG PS 1; median prior regimens 2, range 0–4) enrolled in 3 dose levels. The toxicities included mild-to-moderate fatigue, nausea/abdominal pain, diarrhea, vomiting, neurosensory deficits, fever and chills. At KOS-862 (75 mg/m2) and GEM (750 mg/m2), 2 pts (both cholangiocarcinoma) out of 4 pts experienced dose-limiting toxicity (DLT), consisting of severe dehydration, diarrhea and neutropenia. 1 of these had twice the expected Cmax for KOS-862. An intermediate KOS-862 dose level (60 mg/m2) produced no DLT in 6 pts, however the Day 15 dose could not be delivered in 2 of 6 pts due to thrombocytopenia. The study was therefore amended to a 3-week cycle (2 weeks on, 1 week off). No alteration in PK was seen for KOS-862 and its metabolite between weeks 1 & 2. KOS-862 (n=11): t½ 9.2 ± 3.7 h, Vss 117±57 L/m2 and CL 6.67 ± 4.0 L/h/m2; 60mg/m2 Cmax 1806 - 3991 ng/mL; AUCtot 9984 ± 3883 ng/mL*h. Tmax (metabolite) occurs 0.5 h after KOS-862. GEM PK (n=12): t½ 23 ± 7min (range 15 - 36), Vss 62.7 ± 32 L/m2, AUCtot (750 mg/m2) range 3.6 - 16.7 ug/mL*h. There was 1 PR (unknown primary cancer) and 2 pts had SD > 3 months, suggesting evidence of activity. Conclusions: This novel regimen of KOS-862 and GEM has evidence of activity. Accrual is continuing in order to define the optimal dose on the 3-week regimen. There is no PK interaction when both agents are given in combination. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Kosan Kosan Biosciences, Lilly Eli Lilly, Kosan Biosciences Lilly Oncology
Abstract 138: The Use of β-1.3/1.6-D-Glucan as Complementary Therapy for Cardiovascular Diseases
Authors: Peter Sugita
Journal: Circulation Research (2014)

Cardiovascular disease nowadays is still the one silent killer over the world.So far, current standard therapies for cardiovascular diseases do not reach expected results such as the improving heart function by rehabilitating the damaged cardiomyocytes For thousands of years Ganoderma lucidum extract has been used as herbal therapy for various types of diseases, including cardiovascular diseases. An International Publication No. WO 2005/084692 A2 with the title Effect of Glucan on Stem Cell Recruitment and Tissue Repair mentions that “ the orally administered glucan enhances proliferation, activation and differentiation of committed stem progenitor cells by functioning with the complement system by providing a second signal for CR3 activation .” Furthermore, it is also discussed that “ the committed stem cells are selected from the group consisting of committed stem cells from the liver, heart, muscle, kidney and neural tissue .” In 1995 we began a research on β-D-Glucan derived from the purified extract of East-Java Indonesian Ganoderma lucidum mycelia.At the end of 2009 we have the first clinical experience the use of our β-1.3/1.6-D-Glucan for cardiovascular diseases patient. A bypass surgery patient who was also a candidate for heart transplant experienced a good clinical result after 8 months use of our beta glucan with dose of 3 x 200 mg beta glucan a day. A significant improvement of Ejection Fraction (EF) was reached from 22% to 44%. Previously, when he only took standard drug therapy for cardiovascular disease after bypass surgery, the improvement of EF was not significant (from 13% as baseline to 22%).This result also applied to 4 other patients. We presumed that this specific Ganoderma lucidum β-D-Glucan has similar mechanism of actions as mentioned in the above publication and also in a journal Modulating Toll-like receptor mediated signaling by(1-3)-β-D-glucan rapidly induces cardioprotection . The conclusion is β-D-Glucan could serve as a complementary therapy in cardiovascular diseases but it still needs further investigations through in vitro / in vivo assays and clinical trials.
Discordance QuantiFERON-TB Gold in-tube and tuberculin skin test: Latent tuberculosis infection or immunological memory?
Authors: Michele Spinicci, Delia Goletti, Jessica Mencarini, Letizia Attala, Antonella Mantella, Nunzia Della Malva, Annalisa Cavallo, Alessandro Bartoloni, Filippo Bartalesi
Journal: European Respiratory Journal (2013)

Screening for latent tuberculosis infection (LTBI) in patients with immune-mediated inflammatory diseases (IMID) is mandatory before starting treatment with tumor necrosis factor-α antagonists. In a considerable number of cases, the adopted tests, i.e. QuantiFERON-TB Gold In-Tube (QFT), Tuberculin Skin Test (TST), Chest X-ray (CXr), provide discordant results, whose significance is doubtful.  In this study we evaluated the role of a II level protocol for the interpretation of discordant results obtained in the baseline LTBI screening.  We enrolled 45 IMID patients with discordant tests at LTBI screening from a total of 1490, screened in our dedicated outpatients service in Florence. All of them underwent a further QFT and T.SPOT-TB, whereas two-step TST was performed in patients with negative TST, 14-21 days later the first tests.  At baseline screening 11 patients scored TST+/QFT-, 7 TST-/QFT+, 27 TST-/QFT- with LTBI signs on the CXr.  At the II level screening, in the TST+/QFT- group 6/11 (55%) resulted T.SPOT-TB positive and no QFT conversion was observed. In the TST-/QFT+ group, the patients with QFT-response   In the studied population, T.SPOT-TB showed a better agreement with TST than QFT. QFT confirmed reliability and reproducibility issues for results around the cut-off value. The use of T.SPOT-TB more than the two step TST, seems useful to investigate discordant results and to point out immunological responses otherwise undetected.
Original article: Long-term effects on pulmonary function of mantle radiotherapy in patients with Hodgkin’s disease
Authors: A. Gustavsson, J. Eskilsson, T. Landberg, H. Larusdottir, G. Svahn-Tapper, T. White, P. Wollmer
Journal: Annals of Oncology (1992)

Twenty-five patients (21-45 years old) treated for Hodgkin's disease with mantle radiotherapy but no chemotherapy underwent chest radiography and pulmonary testing with spirometry, pulmonary mechanics and exercise test combined with arterial blood gas analysis, lung scintigraphy, assessment of pulmonary artery pressure with Doppler cardiography and vector ECG 10-20 years after treatment. The doses to mediastinum ranged from 35-43 (mean 40) Gy given in 26 fractions with the split-course technique. Radiographic signs of slight to moderate pulmonary fibrosis were seen in 18 patients. Minor restrictive ventilatory defects were found with decreased VC, TLC and lung compliance and increased maximal elastic recoil. Little evidence of airflow obstruction was found. Exercise capacity was decreased in three individuals but the mean value for the study group as a whole was normal. Arterial PO2 at maximum exercise was reduced but no patient had diminished hemoglobin saturation. Lung scintigraphy showed defects in 21 patients, mostly consisting of slight abnormalities at the lung periphery and apices. The perfusion seemed to be more affected than the ventilation, suggesting primary vascular lesions. Twelve patients showed signs of right ventricular hypertrophy in vector ECG and four of these had systolic pulmonary artery pressure greater than or equal to 30 mm Hg. The observed abnormalities were mostly of a minor degree and few clinically significant long-term effects of mantle radiotherapy on pulmonary function were observed.