tbuckley/cabot-search huggingface dataset:
Phase II Study of Sorafenib in Patients With Metastatic or Recurrent Sarcomas
Authors: Robert G. Maki, David R. D'Adamo, Mary L. Keohan, Michael Saulle, Scott M. Schuetze, Samir D. Undevia, Michael B. Livingston, Matthew M. Cooney, Martee L. Hensley, Monica M. Mita, Chris H. Takimoto, Andrew S. Kraft, Anthony D. Elias, Bruce Brockstein, Nathalie E. Blachère, Mark A. Edgar, Lawrence H. Schwartz, Li-Xuan Qin, Cristina R. Antonescu, Gary K. Schwartz
Journal: Journal of Clinical Oncology (2009)

PURPOSE Since activity of sorafenib was observed in sarcoma patients in a phase I study, we performed a multicenter phase II study of daily oral sorafenib in patients with recurrent or metastatic sarcoma. PATIENTS AND METHODS We employed a multiarm study design, each representing a sarcoma subtype with its own Simon optimal two-stage design. In each arm, 12 patients who received 0 to 1 prior lines of therapy were treated (0 to 3 for angiosarcoma and malignant peripheral-nerve sheath tumor). If at least one Response Evaluation Criteria in Solid Tumors (RECIST) was observed, 25 further patients with that sarcoma subtype were accrued. Results Between October 2005 and November 2007, 145 patients were treated; 144 were eligible for toxicity and 122 for response. Median age was 55 years; female-male ratio was 1.8:1. The median number of cycles was 3. Five of 37 patients with angiosarcoma had a partial response (response rate, 14%). This was the only arm to meet the RECIST response rate primary end point. Median progression-free survival was 3.2 months; median overall survival was 14.3 months. Adverse events (typically dermatological) necessitated dose reduction for 61% of patients. Statistical modeling in this limited patient cohort indicated sorafenib toxicity was correlated inversely to patient height. There was no correlation between phosphorylated extracellular signal regulated kinase expression and response in six patients with angiosarcoma with paired pre- and post-therapy biopsies. CONCLUSION As a single agent, sorafenib has activity against angiosarcoma and minimal activity against other sarcomas. Further evaluation of sorafenib in these and possibly other sarcoma subtypes appears warranted, presumably in combination with cytotoxic or kinase-specific agents.
Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma
Authors: Paul G. Richardson, Robert L. Schlossman, Edie Weller, Teru Hideshima, Constantine Mitsiades, Faith Davies, Richard LeBlanc, Laurence P. Catley, Deborah Doss, Kathleen Kelly, Mary McKenney, Julie Mechlowicz, Andrea Freeman, Reggie Deocampo, Rebecca Rich, Joan J. Ryoo, Dharminder Chauhan, Kathe Balinski, Jerome Zeldis, Kenneth C. Anderson
Journal: Blood (2002)
Origin and diversification of hindwingless Damaster ground beetles within the Japanese islands as deduced from mitochondrial ND5 gene sequences (Coleoptera, Carabidae)
Authors: Z. H. Su, O. Tominaga, M. Okamoto, S. Osawa
Journal: Molecular Biology and Evolution (1998)

Genealogical trees have been constructed using mitochondrial ND5 gene sequences of 78 Damaster (s. str.) specimens from all over the Japanese Islands. Eight lineages (called races in this paper) have been recognized. The races are tightly linked to geography with sharp distribution boundaries between them. The races and their distribution ranges do not coincide with those of classical morphology. Based on the observed distribution of the mitochondrial DNA haplotypes and the geohistorical data, we propose a diversification scenario of Damaster.
Lung and chest wall mechanics in patients with acquired immunodeficiency syndrome and severe Pneumocystis carinii pneumonia
Authors: E D'Angelo, E Calderini, FM Robatto, P Puccio, J Milic-Emili
Journal: European Respiratory Journal (1997)

The aim of this study was to assess the mechanical characteristics of the respiratory system in patients with acquired immune deficiency syndrome (AIDS) and acute respiratory distress syndrome (ARDS) caused by Pneumocystis carinii pneumonia (PCP). In 12 mechanically ventilated patients, total respiratory system mechanics was assessed using the technique of rapid airway occlusion during constant flow inflation, and was partitioned into lung and chest wall components using the oesophageal balloon technique. We measured interrupter resistance (Rint), which mainly reflects airway resistance, additional resistance (deltaR) due to viscoelastic behaviour and time constant inequalities, and static elastance (Est). In addition, the static inflation volume-pressure (V-P) curve was assessed. In eight patients, computed tomography scans were performed within 2 days of the assessment of respiratory mechanics. Compared to values reported in the literature for normal subjects, Est and deltaR were markedly increased in AIDS patients with PCP, whilst Rint exhibited a relatively smaller increase. These changes, which involved only the lung and airways, were mainly due to the reduction of ventilated lung units, but additional factors were involved to cause independent modifications of lung stiffness, airway calibre, and viscoelastic properties. The changes in Rint, deltaR, and Est were similar to those observed in other studies on patients with ARDS of different aetiologies. At variance with common observations in the latter patients, none of the AIDS patients with PCP exhibited an inflection point on the static inflation V-P curve, suggesting little or no alveolar recruitment during lung inflation. This finding could be related to the distinctive histopathology of Pneumocystis carinii pneumonia. Indeed, computed tomography revealed homogeneous diffuse interstitial and alveolar infiltration rather than the dense, dependent opacities observed in other studies on acute respiratory distress syndrome of different aetiologies.
Problems of Black Psychiatric Residents in White Training Institutes
Authors: BILLY E. JONES, ORLANDO B. LIGHTFOOT, DON PALMER, RAYMOND G. WILKERSON, DONALD H. WILLIAMS
Journal: American Journal of Psychiatry (1970)

The authors, who recently completed residencies in three predominantly white psychoanalytically oriented training programs, believe that such programs are failing to produce psychiatrists—black or white—who are prepared to address themselves to the mental health needs of the black community. They offer a number of recommendations for correcting this situation.
Southern-blot analysis and simultaneousIn Situ detection of hepatitis B virus–associated DNA and antigens in patients with end-stage liver disease
Authors: Kwang Hyub Han, Blaine F. Hollinger, Christine A. Noonan, Harvey Solomon, Goran B. G. Klintmalm, Robert M. Genta, Boris Yoffe
Journal: Hepatology (1993)

To gain new insights into the pathogenesis of hepatitis B virus-induced chronic liver disease, we have used nonisotopic in situ detection methods for the simultaneous analysis of hepatitis B virus DNA and antigens at the single-cell level. Paraffin-embedded liver specimens from 23 cirrhotic patients (12 HBsAg positive and 11 HBsAg negative) who underwent liver transplantation were evaluated by in situ hybridization with a digoxigenin-labeled DNA probe and digoxigenin detection system and by immunohistochemistry with an enhanced biotin-streptavidin technique. DNAs extracted from liver and serum specimens were analyzed by Southern- and slot-blot hybridization, respectively. Using the in situ techniques, we detected hepatitis B virus-specific DNA and antigens in 11 of 12 HBsAg-positive patients and in none of the 11 HBsAg-negative individuals. Replicative intermediates of hepatitis B virus DNA were detected by Southern-blot analysis in the same 11 HBsAg-positive patients, 6 of whom had no serological markers of hepatitis B virus replication. Therefore a good correlation was found between the results obtained by the in situ and Southern-blot hybridization analyses of tissue specimens. However, a lack of correlation was found between serum- and tissue-associated markers of viral replication. In addition, the simultaneous in situ detection analyses revealed that some hepatocytes containing high levels of viral DNA were devoid of detectable HBcAg, suggesting a mechanism by which the virus may escape immunological surveillance.(ABSTRACT TRUNCATED AT 250 WORDS)
Evaluation of knee braces in Swedish ice hockey players.
Authors: Y Tegner, R Lorentzon
Journal: British Journal of Sports Medicine (1991)

In this retrospective investigation we have determined the rate and types of knee injuries among Swedish ice hockey players, and related these data to the use of knee braces. Thirty-seven of the originally selected 50 hockey teams (74%) of elite or first division calibre took part in the study, and 600 players answered a questionnaire. A total of 254 previous knee injuries sustained while playing hockey were reported by 243 players; tears of the medical collateral ligament (60%), meniscus (15%) or anterior cruciate ligament (12%) were the most commonly reported injuries. Prophylactic knee braces were worn by 138 (23%) of the players. Of these, 122 (88%) had earlier sustained a knee injury, and 16 had not. A total of 17 knee injuries had occurred while the players were wearing a brace. Six of these players had previously uninjured knees while 11 had repeat injury in a brace despite earlier successful rehabilitation or operation. The most common injury in braced knees was a tear of the medial collateral ligament. We conclude that the number of knee injuries is high among Swedish ice hockey players, and that the efficacy of functional knee braces to reduce knee injuries is questionable.
Cigarette Smoking Increases the Risk of Albuminuria Among Subjects With Type I Diabetes
Authors: H. Peter Chase
Journal: JAMA (1991)

The effect of cigarette smoking on diabetic renal and retinal complications was evaluated in 359 young subjects with insulin-dependent diabetes mellitus. The prevalence of increased albumin excretion rates was 2.8 times higher in smokers than nonsmokers. Mean glycohemoglobin levels and duration of diabetes were also significant factors in the development of diabetic nephropathy and retinopathy in a logistic regression model. Smoking remained a significant factor in the logistic regression model for albuminuria (but not retinopathy) when controlled for glycohemoglobin level, duration of diabetes, age, gender, and blood pressure. The progression of albuminuria and of retinopathy was also greater in smokers. Albuminuria improved significantly when subjects ceased smoking. It is concluded that cigarette smoking is an independent risk factor and is associated with the development and progression of early diabetic renal damage (albuminuria) and with the worsening of retinal disease in young subjects with diabetes.
THE ACTION OF THE SYMPATHETIC UPON THE EXCITATORY PROCESS IN THE MAMMALIAN HEART
Authors: E. Cowles Andrus, Louis E. Martin
Journal: The Journal of Experimental Medicine (1927)

Stimulation of the sympathetic nerve endings, after paralysis of the vagus, accelerates the transmission of the excitatory process in the dog's auricle. Following the functional exclusion of the vagus ergotamine slows the rate of the sinus rhythm, depresses A-V conduction, and delays the transmission of the excitatory process in the auricle. The relation of the sympathetic and parasympathetic nerves in the control of the cardiac rhythm is discussed.
Sex Affects Bone Morphogenetic Protein Type II Receptor Signaling in Pulmonary Artery Smooth Muscle Cells
Authors: Kirsty M. Mair, Xu Dong Yang, Lu Long, Kevin White, Emma Wallace, Marie-Ann Ewart, Craig K. Docherty, Nicholas W. Morrell, Margaret R. MacLean
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Major pulmonary arterial hypertension (PAH) registries report a greater incidence of PAH in women; mutations in the bone morphogenic protein type II receptor (BMPR-II) occur in approximately 80% of patients with heritable PAH (hPAH).Objectives: We addressed the hypothesis that women may be predisposed to PAH due to normally reduced basal BMPR-II signaling in human pulmonary artery smooth muscle cells (hPASMCs).Methods: We examined the BMPR-II signaling pathway in hPASMCs derived from men and women with no underlying cardiovascular disease (non-PAH hPASMCs). We also determined the development of pulmonary hypertension in male and female mice deficient in Smad1.Measurements and Main Results: Platelet-derived growth factor, estrogen, and serotonin induced proliferation only in non-PAH female hPASMCs. Female non-PAH hPASMCs exhibited reduced messenger RNA and protein expression of BMPR-II, the signaling intermediary Smad1, and the downstream genes, inhibitors of DNA binding proteins, Id1 and Id3. Induction of phospho-Smad1/5/8 and Id protein by BMP4 was also reduced in female hPASMCs. BMP4 induced proliferation in female, but not male, hPASMCs. However, small interfering RNA silencing of Smad1 invoked proliferative responses to BMP4 in male hPASMCs. In male hPASMCs, estrogen decreased messenger RNA and protein expression of Id genes. The estrogen metabolite 4-hydroxyestradiol decreased phospho-Smad1/5/8 and Id expression in female hPASMCs while increasing these in males commensurate with a decreased proliferative effect in male hPASMCs. Female Smad1+/− mice developed pulmonary hypertension (reversed by ovariectomy).Conclusions: We conclude that estrogen-driven suppression of BMPR-II signaling in non-PAH hPASMCs derived from women contributes to a pro-proliferative phenotype in hPASMCs that may predispose women to PAH.
Predominance of type 1 (Th1) cytokine production in the liver of patients with HCV-associated mixed cryoglobulinemia vasculitis
Authors: David Saadoun, Olivier Boyer, Hélène Trébeden-Nègre, Nicolas Limal, Véronique Bon-Durand, Marita Andreu, David Klatzmann, Jean Charles Piette, Patrice Cacoub
Journal: Journal of Hepatology (2004)
An International Ki67 Reproducibility Study
Authors: Mei-Yin C. Polley, Samuel C. Y. Leung, Lisa M. McShane, Dongxia Gao, Judith C. Hugh, Mauro G. Mastropasqua, Giuseppe Viale, Lila A. Zabaglo, Frédérique Penault-Llorca, John M.S. Bartlett, Allen M. Gown, W. Fraser Symmans, Tammy Piper, Erika Mehl, Rebecca A. Enos, Daniel F. Hayes, Mitch Dowsett, Torsten O. Nielsen
Journal: JNCI Journal of the National Cancer Institute (2013)

In breast cancer, immunohistochemical assessment of proliferation using the marker Ki67 has potential use in both research and clinical management. However, lack of consistency across laboratories has limited Ki67's value. A working group was assembled to devise a strategy to harmonize Ki67 analysis and increase scoring concordance. Toward that goal, we conducted a Ki67 reproducibility study. Eight laboratories received 100 breast cancer cases arranged into 1-mm core tissue microarrays—one set stained by the participating laboratory and one set stained by the central laboratory, both using antibody MIB-1. Each laboratory scored Ki67 as percentage of positively stained invasive tumor cells using its own method. Six laboratories repeated scoring of 50 locally stained cases on 3 different days. Sources of variation were analyzed using random effects models with log2-transformed measurements. Reproducibility was quantified by intraclass correlation coefficient (ICC), and the approximate two-sided 95% confidence intervals (CIs) for the true intraclass correlation coefficients in these experiments were provided. Intralaboratory reproducibility was high (ICC = 0.94; 95% CI = 0.93 to 0.97). Interlaboratory reproducibility was only moderate (central staining: ICC = 0.71, 95% CI = 0.47 to 0.78; local staining: ICC = 0.59, 95% CI = 0.37 to 0.68). Geometric mean of Ki67 values for each laboratory across the 100 cases ranged 7.1% to 23.9% with central staining and 6.1% to 30.1% with local staining. Factors contributing to interlaboratory discordance included tumor region selection, counting method, and subjective assessment of staining positivity. Formal counting methods gave more consistent results than visual estimation. Substantial variability in Ki67 scoring was observed among some of the world's most experienced laboratories. Ki67 values and cutoffs for clinical decision-making cannot be transferred between laboratories without standardizing scoring methodology because analytical validity is limited.
HIV infection and the kidney.
Authors: V D'Agati, G B Appel
Journal: Journal of the American Society of Nephrology (1997)

HIV-infected patients may present with a variety of patterns of renal involvement. Acute renal failure is common and most often a result of sepsis, hypotension, and nephrotoxic agents. It is potentially avoidable, and support through the period of renal failure may lead to resolution of the renal dysfunction. HIV-associated nephropathy is a unique pattern of sclerosing glomerulopathy that ranges in prevalence from 1 to 10% of the HIV-infected population in different geographic locales. This complication of HIV infection will likely present a growing challenge to the medical community as HIV infection continues to spread worldwide. Deciphering the pathogenetic mechanisms of this most rapidly progressive form of focal segmental sclerosis is not only clinically relevant, but will hopefully provide valuable insights into the mediation of the more common idiopathic form of the disease. The potential for improved renal survival of patients with HIV-associated nephropathy has become more realistic with the development and use of antiretroviral agents, as well as studies on the role of immunosuppression and ACE inhibition in this population. An awareness of other glomerular lesion and tubulointerstitial lesions has broadened our understanding of populations with renal disease who have been infected by HIV. Moreover, as prolonged survival of HIV-infected individuals is being achieved with modern antiviral therapy, the percentage of patients surviving with nephropathy will likely grow in coming years. Awareness of the growth of this population and those requiring short- and long-term hemodialysis and peritoneal dialysis will allow appropriate planning for ESRD in the HIV-infected population.
Thomas Cyril Noble
Authors: A. Craft
Journal: BMJ (2008)

“Dr Cyril Noble, a gentle pipe-puffing paediatrician” was how Thomas Cyril Noble was described in the local papers when he retired from the Newcastle General Hospital in 1982.

Cyril Noble was a caring and inspiring doctor, much loved by his patients, their parents and his professional colleagues.

A few years ago I was asked by a medical journal to answer a few questions about my own career. I was asked who had provided the greatest influence on my career as a doctor. I was able to say without hesitation that there were two doctors who had inspired me most. One was Tommie Studdert, a wonderful old-fashioned physician from Carlisle who really switched me on to clinical medicine as a final year student, and the other was Cyril, who showed me what being a good doctor was all about.

The basic facts of his medical career are straightforward. He qualified in Edinburgh in 1944, decided to specialise in paediatrics, and became a registrar at Newcastle General Hospital. He was appointed to a consultant post at Sunderland at the very early age of 29 at a time when the NHS had decreed that the starting age for consultants was to be 31. I remember him telling me how miffed he was to be given minus two increments to start with. He survived his time working with John Heycock and while there wrote …
Involvement of Ras Activation in Human Breast Cancer Cell Signaling, Invasion, and Anoikis
Authors: Lynn B. Eckert, Gretchen A. Repasky, Aylin S. Ülkü, Aidan McFall, Hong Zhou, Carolyn I. Sartor, Channing J. Der
Journal: Cancer Research (2004)

Abstract Although mutated forms of ras are not associated with the majority of breast cancers (&amp;lt;5%), there is considerable experimental evidence that hyperactive Ras can promote breast cancer growth and development. Therefore, we determined whether Ras and Ras-responsive signaling pathways were activated persistently in nine widely studied human breast cancer cell lines. Although only two of the lines harbor mutationally activated ras, we found that five of nine breast cancer cell lines showed elevated active Ras-GTP levels that may be due, in part, to HER2 activation. Unexpectedly, activation of two key Ras effector pathways, the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase and phosphatidylinositol 3′-kinase/AKT signaling pathways, was not always associated with Ras activation. Ras activation also did not correlate with invasion or the expression of proteins associated with tumor cell invasion (estrogen receptor α and cyclooxygenase 2). We then examined the role of Ras signaling in mediating resistance to matrix deprivation-induced apoptosis (anoikis). Surprisingly, we found that ERK and phosphatidylinositol 3′-kinase/AKT activation did not have significant roles in conferring anoikis resistance. Taken together, these observations show that Ras signaling exhibits significant cell context variations and that other effector pathways may be important for Ras-mediated oncogenesis, as well as for anoikis resistance, in breast cancer. Additionally, because ERK and AKT activation are not strictly associated with Ras activation, pharmacological inhibitors of these two signaling pathways may not be the best approach for inhibition of aberrant Ras function in breast cancer treatment.
Combined and Individual Mitochondrial HSP60 and HSP10 Expression in Cardiac Myocytes Protects Mitochondrial Function and Prevents Apoptotic Cell Deaths Induced by Simulated Ischemia-Reoxygenation
Authors: Kurt M. Lin, Brian Lin, Ian Y. Lian, Ruben Mestril, Immo E. Scheffler, Wolfgang H. Dillmann
Journal: Circulation (2001)

Background —The mitochondrial heat-shock proteins HSP60 and HSP10 form a mitochondrial chaperonin complex, and previous studies have shown that their increased expression exerts a protective effect against ischemic injury when cardiac myocytes are submitted to simulated ischemia. The more detailed mechanisms by which such a protective effect occurs are currently unclear. We wanted to determine whether HSP60 and HSP10 could exert a protection against simulated ischemia and reoxygenation (SI/RO)–induced apoptotic cell death and whether such protection results from decreased mitochondrial cytochrome c release and caspase-3 activation and from the preservation of ATP levels by preservation of the electron transport chain complexes. In addition, we explored whether increased expression of HSP60 or HSP10 by itself exerts a protective effect. Methods and Results —We overexpressed HSP60 and HSP10 together or separately in rat neonatal cardiac myocytes using an adenoviral vector and then subjected the myocytes to SI/RO. Cell death and apoptosis in myocytes were quantified by parameters such as enzyme release, DNA fragmentation, and caspase-3 activation. Overexpression of the combination of HSP60 and HSP10 and of HSP60 or HSP10 individually protected myocytes against apoptosis. This protection is accompanied by decreases in mitochondrial cytochrome c release and in caspase-3 activity and increases in ATP recovery and activities of complex III and IV in mitochondria after SI/RO. Conclusions —These results suggest that mitochondrial chaperonins HSP60 and HSP10 in combination or individually play an important role in maintaining mitochondrial integrity and capacity for ATP generation, which are the crucial factors in determining survival of cardiac myocytes undergoing ischemia/reperfusion injury.
Prospective study to assess fluid accumulation and tenosynovial changes in the aromatase inhibitor-induced musculoskeletal syndrome: 2-year follow-up data
Authors: A. Lintermans, A. Laenen, B. Van Calster, M. Van Hoydonck, S. Pans, J. Verhaeghe, R. Westhovens, N.L. Henry, H. Wildiers, R. Paridaens, A.S. Dieudonné, K. Leunen, L. Morales, K. Verschueren, D. Timmerman, L. De Smet, I. Vergote, M.R. Christiaens, P. Neven
Journal: Annals of Oncology (2012)