tbuckley/cabot-search huggingface dataset:
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Authors: Luigi Di Biase, J. David Burkhardt, Prasant Mohanty, Sanghamitra Mohanty, Javier E. Sanchez, Chintan Trivedi, Mahmut Güneş, Yalçın Gökoğlan, Carola Gianni, Rodney P. Horton, Sakis Themistoclakis, G. Joseph Gallinghouse, Shane Bailey, Jason D. Zagrodzky, Richard H. Hongo, Salwa Beheiry, Pasquale Santangeli, Michela Casella, Antonio Dello Russo, Amin Al-Ahmad, Patrick Hranitzky, Dhanujaya R. Lakkireddy, Claudio Tondo, Andrea Natale
Journal: Journal of the American College of Cardiology (2017)
Profiling of signaling pathways in live tumor cells to assess drug mechanism of action: A method to predict drug efficacy in a patient.
Authors: Lance G. Laing, Ian A. MacNeil, Benjamin E. Rich, Edward Greeno
Journal: Journal of Clinical Oncology (2014)

e11583 Background: This work reports a dynamic real time analysis of live cells to detect drug attenuation of cell signaling related to the MOA of a targeted therapy. The assay employs an impedance biosensor to detect cellular changes in close proximity to a nanoelectrode caused by specific pathway perturbation. When applied to live patient diseased cells ex vivo, this approach holds great promise to determine a priori whether a targeted drug therapy will clinically benefit that patient. If the targeted therapy is not functional in the patient’s cells ex vivo, then it is not likely to function as intended in the patient. Methods: To demonstrate the utility of the assay, HER2+ and ER+/HER2- live breast cancer cell samples (both cell lines and primary cells from fresh tumor specimens) were tested with 6 targeted breast cancer therapies and specific pathway stimulating ligands corresponding to each drug target. Real time signaling impedance profiles were generated for each live cell sample under 3 different conditions: 1) buffer only (C); 2) addition of targeted therapy followed by ligand (CDF); and 3) cells exposed only to the pathway ligand (CF). In the first test series, 20 HER2+ breast cancer cell lines were exposed to lapatinib (an ErbB receptor disrupter). In another test series, 10 ER+/HER2- breast cancer cell lines were tested with 4 standard therapies, letrozole, tamoxifen, fulvestrant, and everolimus, with endocrine (ERa) or PI3K (mTOR) stimulation . This test series was repeated using 10 different ER+/HER2- breast cancer primary cell samples derived from fresh tumor specimens. Changes in cell signaling activity for the C, CDF, and CF samples were measured. Results: In each test series, the cell lines and primary cell samples demonstrated wide variation of signaling stimulation (delta low-high = 500%). Each drug also demonstrated a wide variation in ability to attenuate pathway signaling (ranging from <5% to >70%). These results were completely concordant with immuno-capture results evaluating pathway members. Conclusions: The results confirm the assay’s ability to detect broad sensitivity differences to pathway stimulation and drug attenuation thereof in individual cell samples.
Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis
Authors: Katrin Fischer, Henry H Ruiz, Kevin Jhun, Brian Finan, Douglas J Oberlin, Verena van der Heide, Anastasia V Kalinovich, Natasa Petrovic, Yochai Wolf, Christoffer Clemmensen, Andrew C Shin, Senad Divanovic, Frank Brombacher, Elke Glasmacher, Susanne Keipert, Martin Jastroch, Joachim Nagler, Karl-Werner Schramm, Dasa Medrikova, Gustav Collden, Stephen C Woods, Stephan Herzig, Dirk Homann, Steffen Jung, Jan Nedergaard, Barbara Cannon, Matthias H Tschöp, Timo D Müller, Christoph Buettner
Journal: Nature Medicine (2017)
TCTAP A-006 Early Experience and Favorable Clinical Outcomes of Everolimus-eluting Bioresorbable Scaffolds for Coronary Artery Disease in Korea; Excellent Procedural Outcome with Intravascular Imaging Support
Authors: Osung Kwon, Jung-Min Ahn, Do-Yoon Kang, Se Hun Kang, Pil Hyung Lee, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Seung-Jung Park, Cheol Whan Lee, Duk-Woo Park, Seong-Wook Park
Journal: Journal of the American College of Cardiology (2017)
Maturation of secreted HCV particles by incorporation of secreted ApoE protects from antibodies by enhancing infectivity
Authors: Dorothea Bankwitz, Mandy Doepke, Kathrin Hueging, Romy Weller, Janina Bruening, Patrick Behrendt, Ji-Young Lee, Florian W.R. Vondran, Michael P. Manns, Ralf Bartenschlager, Thomas Pietschmann
Journal: Journal of Hepatology (2017)

Hepatitis C virus (HCV) evades humoral immunity and establishes chronic infections. Virus particles circulate in complex with lipoproteins facilitating antibody escape. Apolipoprotein E (ApoE) is essential for intracellular HCV assembly and for HCV cell entry. We aimed to explore if ApoE released from non-infected cells interacts with and modulates secreted HCV particles.ApoE secreted from non-infected cells was incubated with HCV from primary human hepatocytes or Huh-7.5 cells. Co-immunoprecipitation, viral infectivity and neutralization experiments were conducted.Physiological levels of secreted ApoE (10-60µg/ml) enhanced the infectivity of HCV up to 8-fold across all genotypes, which indirectly decreased virus neutralization by antibodies targeting E1 or E2 up to 10-fold. Infection enhancement was observed for particles produced in primary human hepatocytes and Huh-7.5 cells. Selective depletion of ApoE ablated infection enhancement. Addition of HA-tagged ApoE to HCV particles permitted co-precipitation of HCV virions. Serum ApoE levels ranged between 10-60µg/ml, which is ca 100-fold higher than in Huh-7.5 conditioned cell culture fluids. Serum-derived HCV particles carried much higher amounts of ApoE than cell culture-derived HCV particles. Serum ApoE levels correlated with efficiency of co-precipitation of HCV upon exogenous addition of HA-ApoE. ApoE-dependent infection enhancement was independent of the hypervariable region 1 and SR-B1, but was dependent on heparan sulfate proteoglycans (HSPGs).Physiological quantities of secreted ApoE stimulate HCV infection and increase antibody escape, by incorporating into virus particles and enhancing particle interactions with cellular HSPGs. Thus, secreted particles undergo ApoE-dependent maturation to enhance infectivity and to facilitate evasion from neutralizing antibodies. Lay summary: This study shows that HCV particle infectivity is remodeled by secreted ApoE after particle release from cells. Fluctuation of the availability of ApoE likely influences HCV infectivity, antibody escape and transmission.
The Host Microbiome Regulates and Maintains Human Health: A Primer and Perspective for Non-Microbiologists
Authors: Sunil Thomas, Jacques Izard, Emily Walsh, Kristen Batich, Pakawat Chongsathidkiet, Gerard Clarke, David A. Sela, Alexander J. Muller, James M. Mullin, Korin Albert, John P. Gilligan, Katherine DiGuilio, Rima Dilbarova, Walker Alexander, George C. Prendergast
Journal: Cancer Research (2017)

Humans consider themselves discrete autonomous organisms, but recent research is rapidly strengthening the appreciation that associated microorganisms make essential contributions to human health and well being. Each person is inhabited and also surrounded by his/her own signature microbial cloud. A low diversity of microorganisms is associated with a plethora of diseases, including allergy, diabetes, obesity, arthritis, inflammatory bowel diseases, and even neuropsychiatric disorders. Thus, an interaction of microorganisms with the host immune system is required for a healthy body. Exposure to microorganisms from the moment we are born and appropriate microbiome assembly during childhood are essential for establishing an active immune system necessary to prevent disease later in life. Exposure to microorganisms educates the immune system, induces adaptive immunity, and initiates memory B and T cells that are essential to combat various pathogens. The correct microbial-based education of immune cells may be critical in preventing the development of autoimmune diseases and cancer. This review provides a broad overview of the importance of the host microbiome and accumulating knowledge of how it regulates and maintains a healthy human system.
Angiogenesis-targeting microbubbles combined with ultrasound-mediated gene therapy in brain tumors
Authors: En-Ling Chang, Chien-Yu Ting, Po-Hong Hsu, Yu-Chun Lin, En-Chi Liao, Chiung-Yin Huang, Yuan-Chih Chang, Hong-Lin Chan, Chi-Shiun Chiang, Hao-Li Liu, Kuo-Chen Wei, Ching-Hsiang Fan, Chih-Kuang Yeh
Journal: Journal of Controlled Release (2017)
Child psychopharmacology, effect sizes, and the big bang [14] (multiple letters)
Authors: Andrés Martin, Walter S. Gilliam, Jeffrey Q. Bostic, Joseph M. Rey, Rémy P. Barbe, Maju Mathews, Babatunde Adetunji, Joanne Mathews, Biju Basil, Vinu George, Manu Mathews, Kumar Budur, Shiny Abraham, Karen Dineen Wagner, Adelaide S. Robb, Robert L. Findling, Jianqing Jin
Journal: American Journal of Psychiatry (2005)
Epidemic Neuromyasthenia — Clinical Syndrome?
Authors: Donald A. Henderson, Alexis Shelokov
Journal: New England Journal of Medicine (1959)

Viral and Bacteriologic StudiesThe nature of these illnesses has suggested to most a viral etiology, but, despite intensive efforts to implicate such an agent, results have been meager. Cerebrospinal fluid, feces, throat washings, acute-phase serums and blood clots have been inoculated by a variety of routes into many different laboratory animals and various tissue-culture systems. Despite the frequent use of blind passages, attempts to infect the following animals have thus far proved futile: sucklingl,8,10,14,15,26,29–31,34 and adult mice8,14,26,29,31; guinea pigs with8 and without cortisone10,26,31; hamsters8,10,14,26; rabbits26,31; rats with and without cortisone15; ferrets8; and cynomologus . . .
TCTAP C-191 Healing of Coronary Dissection Following Directional Coronary Atherectomy
Authors: Hiroshi Kawahara, Mitsuyasu Terashima, Hideaki Kaneda, Maoto Habara, Kenya Nasu, Etsuo Tsuchikane, Yoshihisa Kinoshita, Tetsuo Matsubara, Takahiko Suzuki
Journal: Journal of the American College of Cardiology (2017)
Continuous blockade of CXCR4 results in dramatic mobilization and expansion of hematopoietic stem and progenitor cells
Authors: Darja Karpova, Julie K. Ritchey, Matthew S. Holt, Grazia Abou-Ezzi, Darlene Monlish, Lena Batoon, Susan Millard, Gabriele Spohn, Eliza Wiercinska, Ezhil Chendamarai, Wei Yang, Stephanie Christ, Leah Gehrs, Laura G. Schuettpelz, Klaus Dembowsky, Allison R. Pettit, Michael P. Rettig, Halvard Bonig, John F. DiPersio
Journal: Blood (2017)
TCTAP A-162 Late Recoil of Balloon-expandable Transcatheter Aortic Bioprosthesis: Insights from the OCEAN-TAVI Registry
Authors: Ryo Yanagisawa, Makoto Tanaka, Fumiaki Yashima, Yoshitake Yamada, Takahide Arai, Hideyuki Shimizu, Masahiro Jinzaki, Keiichi Fukuda, Yusuke Watanabe, Masanori Yamamoto, Ken Kozuma, Takahiko Suzuki, Kentaro Hayashida
Journal: Journal of the American College of Cardiology (2017)
Sjögren's Syndrome
Authors: R. MANTHORPE
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 October 1985Sjögren's SyndromeR. MANTHORPE, M.D., J. U. PRAUSE, M.D.R. MANTHORPE, M.D.Search for more papers by this author, J. U. PRAUSE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-103-4-640 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: A recent editorial (1) correctly points out that classification criteria are often vital to readers' judgments on the validity of conclusions in an article. Primary Sjögren's syndrome is the second commonest of the chronic inflammatory connective tissue diseases, but internationally accepted criteria for that disease are lacking. The confusion within the diagnosis of this disease varies. Even the terminology differs as authors refer to Sjögren's syndrome, sicca complex, dry syndrome, and so on. When the term dry-sicca-Sjögren is used, the confusion is obvious. Thus, we introduced the terms primary and secondary Sjögren's syndrome (2).Primary Sjögren's syndrome...References1. HUTH E. Criteria for classification of rheumatic diseases: a note to authors [Editorial]. Ann Intern Med. 1985;102:553. LinkGoogle Scholar2. MANTHORPEFROST-LARSENISAGERPRAUSE RKHJ. Sjøgren's syndrome: a review with emphasis on immunological features. Allergy. 1981;36:139-53. CrossrefMedlineGoogle Scholar3. FROST-LARSENISAGERMANTHORPEPRAUSE KHRJ. Sjøgren's syndrome. Ann Ophthalmol. 1980;12:836-46. Google Scholar4. MANTHORPEHAGEN PETERSENPRAUSE RSJ. Primary Sjøgren's syndrome treated with Efamol/Efavit: a double-blind cross-over investigation. Rheumatol Int. 1984;4:165-7. CrossrefMedlineGoogle Scholar5. PRAUSEFROST-LARSENHØJISAGERMANTHORPE JKLHR. Lacrimal and salivary secretion in Sjøgren's syndrome: the effect of systemic treatment with Bromhexine. Acta Ophthalmol. 1984;62:489-97. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Øjenpatologisk Institut Københavns Universitet DK-2100 Copenhagen Ø Denmark PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByKeratoconjunctivitis siccaAssessment of a patient‐completed questionnaire for keratoconjunctivitis siccaParaneoplastic Sjögren's syndrome 1 October 1985Volume 103, Issue 4Page: 640-641KeywordsConnective tissue diseases Issue Published: 1 October 1985 PDF DownloadLoading ...
Amino acid functionalized gadofullerene nanoparticles with superior antitumor activity via destruction of tumor vasculature in vivo
Authors: Yue Zhou, Ruijun Deng, Mingming Zhen, Jie Li, Mirong Guan, Wang Jia, Xue Li, Ying Zhang, Tong Yu, Toujun Zou, Zhigao Lu, Jun Guo, Lei Sun, Chunying Shu, Chunru Wang
Journal: Biomaterials (2017)
TCTAP A-062 Comparisons of Using Bioresorbable Vascular Scaffold Between Complex and Non-complex Cases: Real World Data from Single Center Experiences
Authors: Jen-Fang Cheng, Yi-Chih Wang, Cho-Kai Wu, Jen-Kuang Lee, Chia-Ti Tsai, Lian-Yu Lin, Ching-Chang Huang, Chih-Fan Yeh, Ying-Hsien Chen, Mao-Shin Lin, Yen-Hung Lin, Po-Yuan Chang, Paul Hsien-Li Kao, Chii-Ming Lee, Fu-Tien Chiang, Juey-Jen Hwang
Journal: Journal of the American College of Cardiology (2017)
Look. Listen. Receive.
Authors: John Brewer Eberly
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Impact on relapse free survival (RFS) of time to hormone therapy (HTx) after diagnosis (Dx) of low risk hormone receptor positive (HR+) early breast cancer (BC).
Authors: Wen Yee Chay, Caroline Speers, Lovedeep Gondara, Scott Tyldesley, Karen A. Gelmon, Caroline A. Lohrisch
Journal: Journal of Clinical Oncology (2015)

580 Background: Retrospective series show worse RFS for adjuvant chemotherapy (CTx) delay. We hypothesized the same effect for delays to HTx in low risk HR+ BC, for which CTx benefit is low. Methods: Histopathologic and demographic data were collected for all patients referred to the British Columbia Cancer Agency with a new dx of stage I or II, grade 1 or 2, HR+, HER2 negative BC from 01/2005 to 12/2009. Neoadjuvant-treated, prior or synchronous bilateral BC, no HTx prior to relapse, or > 53 weeks (w) to HTx start were excluded. RFS was calculated for three pre and postmenopausal cohorts (C), defined as 1) 0- < 20 w; 2) 20- < 34 w; 3) 34-53 w from dx to HTx, based on first prescription. Multivariable (M) analysis identified factors significant for RFS. Results: Median follow up for the 3737 cases was 6.4 years (y). 80% were stage I: 28% of C1 and 69% of C3 were stage II. 90% were strongly estrogen receptor (ER) positive. Median age was 64, 58, and 51y in C 1, 2, and 3. Most were menopausal (71%) and 23% had CTx (< 1%, 27%, and 76% of C 1, 2, 3). HTx was started < 20 w and > 34 w after dx in 57% and 15%, respectively. Five year RFS was 97.3%, 96.4%, and 95.5% for C1, 2, and 3 (p0.018). The table below shows univariate (U) and M results, M hazard ratios (Hz) and 95% confidence intervals. Conclusions: While unnecessary delays to HTx should be avoided, we did not detect a significant impact on RFS of up to 1 year delay in low stage and grade, population-based HR+ HER2 negative BCs. RFS was influenced by stage, PR level (all); grade and ER level (menopausal); and age at dx (premenopausal). If there is an impact on early RFS of HTx delay, it is likely subtle and only in premenopausal women. Our results do not exclude an impact on late RFS or in higher risk disease, or explore impact of longer delays. Menopausal Premenopausal p-value U M Hz U M Hz Time cohort 0.007 0.51 0.07 0.055 < 20 v 34+ w 0.90 (0.32, 2.54) pNS Stage I vs II < 0.0001 < 0.0001 0.24 (0.16,0.38) 0.005 0.001 0.32 (0.16,0.63) Progesterone receptor (PR) 0.003 0.0014 High vs zero 0.58 (0.35,0.99) p0.046 0.02 0.007 high vs zero 0.24 (0.10,0.58) p0.001 ER < 0.0001 0.016 high vs Low 0.21 (0.07,0.61) P0.004 0.88 Grade 1 vs 2 0.0003 0.0088 0.54 (0.34,0.86) 0.06 0.09 Age 0.77 0.04 0.022 0.94 (0.90,0.99)
Total hip arthroplasty for patients with Crowe type IV developmental dysplasia of the hip: Ten years results
Authors: Wei-Nan Zeng, Jun-Li Liu, Fu-You Wang, Xin Zhang, Hua-Quan Fan, Guang-Xing Chen, Lin Guo, Xiao-Jun Duan, Qiang Zhou, Liu Yang
Journal: International Journal of Surgery (2017)
TCTAP A-032 The Outcomes of Intense Anti-coagulation in Acute Coronary Syndrome Due to Thrombus-laden Vessel with Unsatisfactory Initial Thrombectomy
Authors: Michael Mao-Chen Liang, Ramkumar Sekar, Syed Saqib Imran, Teck-Kee Ang, Khang-Leng Leow, Brian Khoo
Journal: Journal of the American College of Cardiology (2017)
TCTAP A-104 Gender Difference in Coronary Artery Spasm in Korean Population
Authors: Ji Young Park, Byoung Geol Choi, Seung-Woon Rha, Se Yeon Choi, Jae Kyeong Byun, Cheol Ung Choi, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2017)
Role of phosphatase and tensin homolog in hypoxic pulmonary vasoconstriction
Authors: Adrienn Krauszman, Tak W. Mak, Katalin Szaszi, Wolfgang M. Kuebler
Journal: Cardiovascular Research (2017)

Hypoxic pulmonary vasoconstriction (HPV) redistributes blood flow from poorly ventilated to better aerated areas in the lung, thereby optimizing ventilation-perfusion ratio (V/Q). Pulmonary artery smooth muscle cell (PASMC) contraction in response to hypoxia is triggered by Ca2+ influx via transient receptor potential canonical 6 (TRPC6) cation channels that have translocated to caveolae in the plasma membrane. Since phosphatase and tensin homolog (PTEN) was suggested to regulate TRPC6 in endothelial cells, we aimed to define its role in the hypoxic response of PASMCs and as a putative mediator of HPV. In isolated perfused mouse lungs, smooth muscle specific PTEN deficiency attenuated pulmonary vasoconstriction in response to hypoxia but not to angiotensin II (Ang II). Analogously, siRNA-mediated knock down of PTEN in human PASMC inhibited the hypoxia-induced increase in cytosolic Ca2+ concentration ([Ca2+]i). Co-immunoprecipitation and proximity ligation assays revealed increased interaction of PTEN with TRPC6 in human PASMC and murine lungs in response to hypoxia. In hypoxic PASMC, both PTEN and TRPC6 translocated to caveolae, and this response was blocked by pharmacological inhibition of Rho-associated protein kinase (ROCK) which in parallel prevented PTEN-TRPC6 interaction, hypoxia-induced [Ca2+]i increase, and HPV in PASMC and murine lungs, respectively. Our data indicate a novel interplay between ROCK and [Ca2+]i signalling in HPV via PTEN, in that ROCK mediates interaction of PTEN and TRPC6 which then conjointly translocate to caveolae allowing for Ca2+ influx into and subsequent contraction of PASMC.
Simi Move: entry level mobile app to analyse walking and running gait
Authors: Boon Kiak Yeo, Dinesh Sirisena
Journal: British Journal of Sports Medicine (2017)

Sports medicine, gait analysis and sports biomechanics.

iOS 7.0 or later.

$9.99.

Simi Move is an entry level mobile app that offers a quick and easy way to analyse walking and running gait. The app requires the user to either upload or record a video via the inbuilt software, before analysing the video in slow motion or by individual still frames. Once the frame of interest has been identified, the app allows the user to employ its predefined protocols, such as sagittal and frontal plane analysis, where the anatomical landmarks are identified and prompted (figure 1). Joint angle points can then be positioned to allow angles to be measured. Each protocol allows the markers to be placed across multiple joints in a single frame, thereby enabling several angles to be measured simultaneously. This helps with quick and easy analyses. In addition, …
Premenstrual Dysphoric Disorder Symptoms Following Ovarian Suppression: Triggered by Change in Ovarian Steroid Levels But Not Continuous Stable Levels
Authors: Peter J. Schmidt, Pedro E. Martinez, Lynnette K. Nieman, Deloris E. Koziol, Karla D. Thompson, Linda Schenkel, Paul G. Wakim, David R. Rubinow
Journal: American Journal of Psychiatry (2017)

Objective: Premenstrual dysphoric disorder (PMDD) symptoms are eliminated by ovarian suppression and stimulated by administration of ovarian steroids, yet they appear with ovarian steroid levels indistinguishable from those in women without PMDD. Thus, symptoms could be precipitated either by an acute change in ovarian steroid levels or by stable levels above a critical threshold playing a permissive role in expression of an underlying infradian affective “pacemaker.” The authors attempted to determine which condition triggers PMDD symptoms. Method: The study included 22 women with PMDD, ages 30 to 50 years. Twelve women who experienced symptom remission after 2–3 months of GnRH agonist-induced ovarian suppression (leuprolide) then received 1 month of single-blind (participant only) placebo and then 3 months of continuous combined estradiol/progesterone. Primary outcome measures were the Rating for Premenstrual Tension observer and self-ratings completed every 2 weeks during clinic visits. Multivariate repeated-measure ANOVA for mixed models was employed. Results: Both self- and observer-rated scores on the Rating for Premenstrual Tension were significantly increased (more symptomatic) during the first month of combined estradiol/progesterone compared with the last month of leuprolide alone, the placebo month, and the second and third months of estradiol/progesterone. There were no significant differences in symptom severity between the last month of leuprolide alone, placebo month, or second and third months of estradiol/progesterone. Finally, the Rating for Premenstrual Tension scores in the second and third estradiol/progesterone months did not significantly differ. Conclusions: The findings demonstrate that the change in estradiol/progesterone levels from low to high, and not the steady-state level, was associated with onset of PMDD symptoms. Therapeutic efforts to modulate the change in steroid levels proximate to ovulation merit further study.