tbuckley/cabot-search huggingface dataset:
Hyperhomocyst(e)inemia and Endothelial Dysfunction in IDDM
Authors: Marion A Hofmann, Brigitte Kohl, Martina S Zumbach, Valentin Borcea, Angelika Bierhaus, Mechthild Henkels, Jean Amiral, Ann Marie Schmidt, Walter Fiehn, Reinhard Ziegler, Peter Wahl, Peter P Nawroth
Journal: Diabetes Care (1998)

OBJECTIVE Considering that elevated blood levels of homocyst(e)ine represent a known independent risk factor for macrovascular disease, we assessed the link between hyperhomocyst(e)inemia and diabetic microvascular complications. RESEARCH DESIGN AND METHODS Homocyst(e)ine and thrombomodulin plasma levels, a marker of endothelial cell damage, were measured before and 3 h after oral methionine loading in 75 patients with stable, well-controlled IDDM and 40 healthy control subjects matched for sex and age. Exclusion criteria were hyperlipidemia, hypertension, smoking, or positive family history for cardiovascular disease. RESULTS IDDM patients had higher pre- and postload homocyst(e)ine plasma levels than did healthy control subjects (12.0 vs. 7.7 umol/1 and 27.6 vs. 16.0 umol/1; P &amp;lt; 0.001). Of 75 IDDM patients, 26 had homocyst(e)ine plasma levels above the normal range (defined as mean ± 2 SD of values obtained in the control group). The IDDM patients with hyperhomocyst(e)inemia had higher thrombomodulin plasma levels (62.2 vs. 38.2 ng/ml; P &amp;lt; 0.001), higher albumin excretion rates (485 vs. 115 mg/1; P &amp;lt; 0.005), and a higher prevalence of late diabetic complications (nephropathy 76 vs. 33%; retinopathy 69 vs. 51%; neuropathy, 57 vs. 41%; macroangiopathy 57 vs. 33%) compared with IDDM patients with normal plasma homocyst(e)ine. In vitro experiments with human umbilical vein cells show an increased release of thrombomodulin into the culture supernatant only when endothelial cells were pretreated with advanced glycation end product (AGE)-albumin before L-homocystine was added. A synergistic action of homocyst(e)ine and AGEs might contribute to vascular complications of patients with diabetes. CONCLUSIONS Hyperhomocyst(e)inemia is common in nephropathic diabetic patients and may contribute to the enhanced morbidity and mortality from cardiovascular diseases characteristically observed in IDDM patients with diabetic nephropathy.
Women in Psychiatry: Past and Present Areas of Concern
Authors: NANCY A. ROESKE
Journal: American Journal of Psychiatry (1973)

The APA Task Force on Women was created to study the special issues and problems of women, especially in relation to the practice of psychiatry, and the special concerns of women psychiatrists. In this paper, the author details the specific areas the task force is examining, summarizes the findings of some of the few reports in the literature, and outlines the projects the task force has undertaken.
Myeloablative chemotherapy for recurrent aggressive oligodendroglioma
Authors: Gregory Cairncross, Lode Swinnen, Robert Bayer, Steven Rosenfeld, Donna Salzman, Nina Paleologos, Lynn Kaminer, Peter Forsyth, Douglas Stewart, Kendra Peterson, Wendy Hu, David Macdonald, David Ramsay, Anne Smith
Journal: Neuro-Oncology (2000)

The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving aggressively at recurrence were eligible for this study. Only complete responders or major partial responders (75% reduction in tumor size) to induction chemotherapy—either intensive-dose procarbazine, lomustine, and vincristine or cisplatin plus etoposide—could receive high-dose thiotepa (300 mg/m2/day for 3 days) followed by hematopoietic reconstitution using either bone marrow or peripheral blood stem cells. Thirty-eight patients began induction chemotherapy and 20 (10 men, 10 women; median age 46 years; median Karnofsky score 80) received high-dose thiotepa. For the high-dose group, the median event-free, progression-free, and overall survival times from recurrence were 17, 20, and 49 months, respectively. Tumor control in excess of 2 years was observed in 6 patients (30%). Four patients (20%) are alive and tumor free 27 to 77 months (median, 42 months) from the start of induction therapy; however, fatal treatment-related toxicities also occurred in 4 patients (20%). Three patients died as a result of a progressive encephalopathy which, in 2 instances, was accompanied by a wasting syndrome; 1 patient died as a consequence of an intracerebral (intratumoral) hemorrhage. Fatal toxicities occurred in patients with pretreatment Karnofsky scores of 60 or 70. High-dose thiotepa to consolidate response was a disappointing treatment strategy for patients with recurrent aggressive oligodendroglial neoplasms, although several patients had durable responses. Moreover, as prescribed, high-dose thiotepa had significant toxic effects in previously irradiated patients, especially those with poorer performance status.
Characterization of Serum Resistance of Neisseria gonorrhoeae that Disseminate
Authors: Peter A. Rice, Dennis L. Kasper
Journal: Journal of Clinical Investigation (1982)

Neisseria gonorrhoeae isolated from patients with disseminated infection (DGI) often resist complement (C')-dependent killing by normal human serum (NHS) and less commonly by convalescent DGI serum. 7 of 10 NHS specimens completely inhibited killing of serum-resistant (ser(r)) gonococci by convalescent or immune DGI serum. Immunoglobulin G (IgG) purified from NHS was shown to be the blocking agent. In addition, IgM (plus C') purified from NHS was shown to be fivefold more effective (wt/wt) in killing serum-sensitive (ser(s)) gonococci than equivalent amounts of IgM tested in the presence of IgG (whole serum). Although inhibition of NHS killing of ser(s) gonococci required a 640% excess of IgG, only a 40% excess was required to block immune serum killing of ser(r) gonococci. F(ab')(2) prepared from IgG also blocked killing of ser(r) gonococci by immune serum indicating antigenic specificity of blocking IgG.IgG immunoconcentrated against outer membrane protein (OMP) derived from ser(r) gonococci showed 40-fold increased blocking activity over normal IgG (wt/wt) and lacked antibody activity directed against gonococcal lipopolysaccharide by ELISA. Using direct immunoabsorption of IgG with purified gonococcal OMP; ser(r)-OMP was found sixfold more effective than ser(s)-OMP in neutralizing the blocking of immune serum killing of ser(r) gonococci, and 10-fold more effective in systems that used excess blocking IgG, NHS, and ser(s) gonococci. Blocking IgG preabsorbed with whole ser(r) gonococci lost 75% of its ability to block immune serum killing compared with no loss in this system using a similar absorption with ser(s) gonococci. IgG purified from NHS contained fivefold higher titers of antibody against ser(r)-OMP than ser(s)-OMP by ELISA.
Sensitivity to First-Line Chemotherapy for Metastatic Breast Cancer in <i>BRCA1</i> and <i>BRCA2</i> Mutation Carriers
Authors: Mieke Kriege, Caroline Seynaeve, Hanne Meijers-Heijboer, J. Margriet Collee, Marian B.E. Menke-Pluymers, Carina C.M. Bartels, Madeleine M.A. Tilanus-Linthorst, Jannet Blom, Elisabeth Huijskens, Agnes Jager, Ans van den Ouweland, Bert van Geel, Maartje J. Hooning, Cecile T.M. Brekelmans, Jan G.M. Klijn
Journal: Journal of Clinical Oncology (2009)

Preclinical as well as a few small retrospective, neoadjuvant studies suggest that breast cancer (cells) without functional BRCA1 or BRCA2 protein have an increased sensitivity to some chemotherapeutic agents causing double-strand DNA breaks. In this study we assessed the sensitivity to standard first-line chemotherapy of metastatic BRCA1/2-associated breast cancer, compared with sporadic breast cancer patients.From the Family Cancer Clinic database, we selected 93 BRCA1- and 28 BRCA2-associated breast cancer patients treated with chemotherapy for metastatic disease before January 1, 2007. Objective response (OR), progression-free survival (PFS), and overall survival (OS) after start of first-line chemotherapy were compared with those of sporadic patients, matched for year of birth, age at diagnosis of primary breast cancer, and year of detection of metastatic disease.The chemotherapy regimens most frequently used were anthracycline-based (n = 147) and cyclophosphamide, methotrexate, and fluorouracil (CMF)/CMF like (n = 68). As compared to sporadic patients, BRCA2-associated patients had a significantly higher OR (89% v 50%; P = .001), a longer PFS (hazard ratio multivariate [HR(mult)] 0.64; P = .04) and a prolonged OS (HR(mult), 0.53; P = .005) after start of first-line chemotherapy for metastatic breast cancer. For BRCA1-associated patients, a nonsignificant trend for an increased OR (66% v 50%; P = .07), and a longer PFS (HR(mult), 0.79; P = .14) after first-line chemotherapy for metastatic breast cancer was observed, but not for OS.BRCA2-associated breast cancer is more sensitive to standard first-line chemotherapy for metastatic breast cancer in comparison with sporadic breast cancer, especially to anthracyclines. For BRCA1-associated breast cancer no statistically significant higher sensitivity was observed.
Polycystic Ovary Syndrome and Cardiovascular Disease: A Premature Association?
Authors: Richard S. Legro
Journal: Endocrine Reviews (2003)

Women with polycystic ovary syndrome (PCOS) are often assumed, a priori, to be at increased risk for cardiovascular disease (CVD), given the high prevalence of the metabolic syndrome X among them. There is, however, no single definition of PCOS, and for that reason a comparison of studies that have analyzed its association with CVD is compromised from the start. Long-term studies of well characterized women with PCOS are lacking, and the link to primary cardiovascular events such as stroke or myocardial infarction remains more speculative than substantive. Epidemiological studies that have focused on isolated signs and stigmata of PCOS, such as polycystic ovaries, hyperandrogenism, or chronic anovulation, have found mixed results. There are studies that suggest a slight increase in cardiovascular events in women with polycystic ovaries, with perhaps stronger evidence between an increased risk of cardiovascular events in women with menstrual irregularity. However, there is little evidence for an association between hyperandrogenism per se and cardiovascular events. Furthermore, there are less data to substantiate an increased risk of events in women with PCOS identified on the basis of a combination of signs and symptoms, such as hyperandrogenic chronic anovulation. The existing data suggest that PCOS may adversely affect or accelerate the development of an adverse cardiovascular risk profile, and even of subclinical signs of atherosclerosis, but it does not appear to lower the age of clinical presentation to a premenopausal age group. Future studies to identify the risk of cardiovascular events in women with PCOS will benefit from clear and extensive phenotyping of PCOS abnormalities at baseline, from a prospective design, from larger sample sizes, and from longer follow-up.
Peptides Mimicking the Unique ARTS-XIAP Binding Site Promote Apoptotic Cell Death in Cultured Cancer Cells
Authors: Natalia Edison, Tali-Haviv Reingewertz, Yossi Gottfried, Tali Lev, Dotan Zuri, Inbal Maniv, Marie-Jeanne Carp, Gil Shalev, Assaf Friedler, Sarit Larisch
Journal: Clinical Cancer Research (2012)

XIAP [X-linked inhibitor of apoptosis (IAP) protein] is the best characterized mammalian caspase inhibitor. XIAP is frequently overexpressed in a variety of human tumors, and genetic inactivation of XIAP in mice protects against lymphoma. Therefore, XIAP is an attractive target for anticancer therapy. IAP antagonists based on a conserved IAP-binding motif (IBM), often referred to as "Smac-mimetics," are currently being evaluated for cancer therapy in the clinic. ARTS (Sept4_i2) is a mitochondrial proapoptotic protein which promotes apoptosis by directly binding and inhibiting XIAP via a mechanism that is distinct from all other known IAP antagonists. Here, we investigated the ability of peptides derived from ARTS to antagonize XIAP and promote apoptosis in cancer cell lines.The ability of synthetic peptides, derived from the C-terminus of ARTS, to bind to XIAP, stimulate XIAP degradation, and induce apoptosis was examined. We compared the response of several cancer cell lines to different ARTS-derived peptides. Pull-down assays were used to examine binding to XIAP, and apoptosis was evaluated using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, caspase activation, and Western blot analyses of caspase substrates.The C-terminus of ARTS contains a unique sequence, termed ARTS-IBM (AIBM), which is important for binding to XIAP and cell killing. AIBM peptides can bind to XIAP-BIR3, penetrate cancer cells, reduce XIAP levels, and promote apoptosis.Short synthetic peptides derived from the C-terminus of ARTS are sufficient for binding to XIAP and can induce apoptosis in cancer cells. These results provide proof-of-concept for the feasibility of developing ARTS-based anticancer therapeutics.
Re: Is a Screening Interval of Every 4 Years for Prostate Cancer Acceptable?
Authors: Monique J. Roobol, Fritz H. Schröder
Journal: JNCI Journal of the National Cancer Institute (2008)

In an accompanying editorial, Crawford ( 1 ) critically reviewed our paper ( 2 ) “Interval cancers in prostate cancer screening: comparing 2- and 4-year screening intervals in the European Randomized Study of Screening for Prostate Cancer, Gothenburg and Rotterdam.” We would like to respond to some of his remarks. First, the analysis reported was not done with the intention to defend a 4-year screening interval. At the start of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, a 4-year screening interval was chosen based on the current available knowledge on lead time. The only center, and not several centers, as is mentioned in the editorial, that chose differently was the Swedish center in Gothenburg. However, as mentioned previously in the complete overview of the ERSPC in 2003 ( 3 ), the group was awaiting data that would confi rm the correctness of the screening interval of 4 years. The fi rst data that were published with respect to this choice were reassuring ( 4 , 5 ). Our comparative and longer term observations are confi rmatory and will be helpful in developing future screening strategies. Second, we acknowledge that the com
Intermittent pressure overload triggers hypertrophy-independent cardiac dysfunction and vascular rarefaction
Authors: C. Perrino
Journal: Journal of Clinical Investigation (2006)

For over a century, there has been intense debate as to the reason why some cardiac stresses are pathological and others are physiological. One long-standing theory is that physiological overloads such as exercise are intermittent, while pathological overloads such as hypertension are chronic. In this study, we hypothesized that the nature of the stress on the heart, rather than its duration, is the key determinant of the maladaptive phenotype. To test this, we applied intermittent pressure overload on the hearts of mice and tested the roles of duration and nature of the stress on the development of cardiac failure. Despite a mild hypertrophic response, preserved systolic function, and a favorable fetal gene expression profile, hearts exposed to intermittent pressure overload displayed pathological features. Importantly, intermittent pressure overload caused diastolic dysfunction, altered β-adrenergic receptor (βAR) function, and vascular rarefaction before the development of cardiac hypertrophy, which were largely normalized by preventing the recruitment of PI3K by βAR kinase 1 to ligand-activated receptors. Thus stress-induced activation of pathogenic signaling pathways, not the duration of stress or the hypertrophic growth per se, is the molecular trigger of cardiac dysfunction.
Onychomycosis of the toenails caused by Chaetomium globosum
Authors: Matthew J. Stiller, Stanley Rosenthal, Richard C. Summerbell, Jean Pollack, Amy Chan
Journal: Journal of the American Academy of Dermatology (1992)

Onychomycoses caused by nondermatophytes are not uncommon.In a recent 3-year survey Summerbell et al.' found that nondermatophytic filamentous fungi cause 3.3% of nail infections.The most common organisms were Scopulariopsis brevicaulis, Hendersonula toruloidea (now renamed Scytalidium dimidiatum), Aspergillus sydowii, and Candida albicans.I We report a case of toenail infection caused by a species of the genus Chaetomium in an
Increased Surgeon Experience With Rheumatoid Arthritis Reduces the Risk of Complications Following Total Joint Arthroplasty
Authors: Bheeshma Ravi, Ruth Croxford, Peter C. Austin, Simon Hollands, J. Michael Paterson, Earl Bogoch, Hans Kreder, Gillian A. Hawker
Journal: Arthritis & Rheumatology (2013)

To determine the relationship between surgeon experience with, and complications following, total joint arthroplasty (TJA) in patients with rheumatoid arthritis (RA).Using administrative data, we assembled a cohort of patients with RA who had undergone at least 1 elective primary hip or knee replacement procedure between 2002 and 2009. Cox proportional hazards, censored on death and accounting for clustering of patients within surgeons, were used to determine the relationship between overall and "RA-specific" surgeon TJA volume and the occurrence of a composite "complication" outcome (revision, infection, dislocation, or periprosthetic fracture within 2 years of the initial TJA), controlling for potential confounders (patient age, sex, comorbidity, and disease severity).We identified 4,762 patients with RA who were eligible for TJAs (1,515 total hip arthroplasties and 3,247 total knee arthroplasties). Among these patients, 152 (3.2%) experienced a surgical complication within 2 years of the procedure. After controlling for patient and hospital factors, greater surgeon TJA volume in patients with RA (RA TJA), but not overall TJA volume (all TJA), was associated with a reduced risk of complications (for surgeon RA TJA volume per 10 cases, adjusted hazard ratio [HR] 0.81, 95% confidence interval [95% CI] 0.71-0.93, P = 0.002; for surgeon all TJA volume, adjusted HR 0.98, 95% CI 0.97-1.00, P = 0.09).In a cohort of patients with RA who underwent hip or knee TJA, increased surgeon experience performing TJA in patients with RA, irrespective of their overall TJA experience and hospital factors, was associated with a decreased risk of surgical complications. These findings have potential implications for surgeon training and the referral practices of rheumatologists.
Evaluation of androgens in the scalp hair and plasma of patients with male-pattern baldness before and after finasteride administration
Authors: H.K. Ryu, K.M. Kim, E.A. Yoo, W.Y. Sim, B.C. Chung
Journal: British Journal of Dermatology (2006)

Background Finasteride, a competitive inhibitor of the enzyme 5α‐reductase II, is widely used as a medical treatment for patients with male‐pattern baldness (MPB), which is affected by the distribution of androgenic steroids. It is also notable that the androgenic effect in MPB is different for each region of the head. Objectives To study the effect of the drug finasteride, we quantified androgenic steroids in the vertex and occipital scalp hair and in the plasma of patients with MPB. Methods The patients with MPB, aged 23–52 years, were treated with finasteride 1 mg daily for 5 months. The hair and plasma samples were hydrolysed, extracted with n‐pentane, and derivatized with MSTFA : NH4I : DTE (1000 : 4 : 5, v/w/w). We analysed the concentrations of dihydrotestosterone (DHT) and testosterone (T) in the hair and plasma using gas chromatography–mass spectrometry (GC‐MS). Results In the hair, the ratio of DHT/T was decreased in the vertex scalp hair after the individual received finasteride (P < 0·005). However, we found no significant difference in the ratio of DHT/T in the occipital scalp hair before and after individuals received finasteride. Like the results in the vertex scalp hair, the ratio of DHT/T in the plasma was remarkably decreased after finasteride administration (P < 0·001). Conclusions This study supports the effect of finasteride in patients with MPB by examining the decreased level of DHT/T in scalp hair and in plasma. Thus, in view of the androgenic effect in the different hair regions, the vertex scalp hair plays a more important role for patients with MPB treated with finasteride than does the occipital hair.
Development and validation of the Adolescent Asthma Quality of Life Questionnaire (AAQOL)
Authors: C. Rutishauser, S.M. Sawyer, L. Bond, C. Coffey, G. Bowes
Journal: European Respiratory Journal (2001)

Current asthma-specific quality of life questionnaires have major conceptual and methodological deficiencies for use in adolescents. The aim of this study was to develop and validate the “Adolescent Asthma Quality of Life Questionnaire (AAQOL)”, specifically developed for adolescents with asthma. One-hundred and eleven adolescents with frequent-episodic or persistent asthma aged 12–17 yrs were recruited from three tertiary paediatric asthma clinics. The standardized multi-step method consisted of: 1) item selection including semistructured interviews (n=14); 2) item reduction and validation (n=66); and 3) assessment of reproducibility (n=31). Item reduction was performed applying the clinical impact method. The 32 item AAQOL covers six domains: symptoms, medication, physical activities, emotion, social interaction and positive effects. There was high internal consistency for the six domains (α=0.70–0.90) and for the total score (α=0.93). Test-retest reliability was high for all domain scores (r=0.76–0.85) and the total score (r=0.90), indicating high reproducibility of the AAQOL. There was high correlation with the paediatric Asthma Quality of Life Questionnaire (ρ=0.81) which focuses primarily on symptoms and emotional well-being. There was weak to moderate correlation with clinical parameters of asthma severity (ρ=0.25–0.65). The 32-item Adolescent Asthma Quality of Life Questionnaire is a valid, developmentally age-appropriate and dimensionally comprehensive asthma-specific quality of life measure for use in adolescents.
CTLA-4 directly inhibits osteoclast formation
Authors: R Axmann, S Herman, M Zaiss, S Franz, K Polzer, J Zwerina, M Herrmann, J Smolen, G Schett
Journal: Annals of the Rheumatic Diseases (2008)

CTLA-4 is a regulator of co-stimulation and inhibits the activation of T cells through interfering with the interaction of CD80/86 on antigen-presenting cells with CD28 on T cells. CTLA-4 binds to the surface of antigen-presenting cells, such as dendritic cells and monocytes through CD80/86. Monocytes can differentiate in osteoclasts, the primary bone resorbing cells. Herein, we investigated whether the binding of CTLA-4 affects the differentiation of monocytes into osteoclasts in vitro and vivo. We show that CTLA-4 dose-dependently inhibits RANKL- as well as tumour necrosis factor (TNF)-mediated osteoclastogenesis in vitro without the presence of T cells. Furthermore, CTLA-4 was effective in inhibiting TNF-induced osteoclast formation in a non-T cell dependent TNF-induced model of arthritis as well as the formation of inflammatory bone erosion in vivo. These data suggest that CTLA-4 is an anti-osteoclastogenic molecule that directly binds osteoclast precursor cells and inhibits their differentiation. These findings are an attractive explanation for the anti-erosive effect of abatacept, a CTLA-4 immunoglobulin fusion protein used for the treatment of rheumatoid arthritis.