tbuckley/cabot-search huggingface dataset:
Abstract 19: Myocyte Turnover in the Aging Human Heart
Authors: Barbara OgÓrek, Toru Hosoda, Carlos Rondon, Narasimman Gurusamy, Alessandro Gatti, Silvana Bardelli, Federico Quaini, Rossana Bussani, Furio Silvestri, Cesselli Daniela, Antonio P Beltrami, Federica del Monte, Marcello Rota, Konrad Urbanek, Bruce A Buchholz, Annarosa Leri, Carlo A Beltrami, Piero Anversa, Jan Kajstura
Journal: Circulation Research (2012)

The controversy on the growth reserve of the adult human heart has not been resolved and the extent of myocyte renewal reported by different groups varies significantly. Additionally, myocyte regeneration has been claimed to decrease with aging, although cell death is markedly enhanced in the old myocardium. Thus, the effects of age and gender on the magnitude of myocyte turnover were determined. Myocyte replication, senescence and apoptosis were measured in normal female and male human hearts collected from patients 19 to 104 years of age who died from causes other than cardiovascular diseases. Myocardial aging was characterized by a time-dependent increase in the generation of amplifying cardiomyocytes in women and men. Levels of Ki67 and phospho-H3 were comparable in the young female and male heart but differed later in life. As a function of age, the pool of amplifying myocytes was 2-fold higher in women than men, pointing to enhanced myocyte renewal in the female heart. The frequency of p16 INK4a -positive myocytes was higher in men than in women. From 19 to 104 years of age, the time-dependent increase in senescent myocytes was 0.68% per year in women and 0.89% per year in men; the 31% higher rate of accumulation of old myocytes in the aging male heart was significant. Myocyte apoptosis occurred only in p16 INK4a -positive cells and was consistently higher in men than in women at all age intervals. However, the increase in myocyte apoptosis with age did not differ with gender. Based on these parameters, we measured the average age of cardiomyocytes, their age distribution, turnover rate and time to acquire the senescent phenotype to define the biology of myocardial aging as a function of lifespan. In the female heart, myocyte turnover occurs at a rate of 10%, 15% and 40% per year at 20, 60 and 100 years of age, respectively. Corresponding values in the male heart are 7%, 12% and 32% per year, documenting that cardiomyogenesis involves a large and progressively increasing number of parenchymal cells with aging. In conclusion, the human heart is a highly dynamic organ in which progressive myocyte loss is at least in part counteracted by enhanced myocyte renewal. Myocyte regeneration in the physiologically aging heart takes place at previously unexpected levels in both women and men.
Binding of Released Bim to Mcl-1 is a Mechanism of Intrinsic Resistance to ABT-199 which can be Overcome by Combination with Daunorubicin or Cytarabine in AML Cells
Authors: Xiaojia Niu, Jianyun Zhao, Jun Ma, Chengzhi Xie, Holly Edwards, Guan Wang, J. Timothy Caldwell, Shengyan Xiang, Xiaohong Zhang, Roland Chu, Zhihong J. Wang, Hai Lin, Jeffrey W. Taub, Yubin Ge
Journal: Clinical Cancer Research (2016)

Abstract Purpose: To investigate the molecular mechanism underlying intrinsic resistance to ABT-199. Experimental Design: Western blots and real-time RT-PCR were used to determine levels of Mcl-1 after ABT-199 treatment alone or in combination with cytarabine or daunorubicin. Immunoprecipitation of Bim and Mcl-1 were used to determine the effect of ABT-199 treatment on their interactions with Bcl-2 family members. Lentiviral short hairpin RNA knockdown of Bim and CRISPR knockdown of Mcl-1 were used to confirm their role in resistance to ABT-199. JC-1 assays and flow cytometry were used to determine drug-induced apoptosis. Results: Immunoprecipitation of Bim from ABT-199–treated cell lines and a primary patient sample demonstrated decreased association with Bcl-2, but increased association with Mcl-1 without corresponding change in mitochondrial outer membrane potential. ABT-199 treatment resulted in increased levels of Mcl-1 protein, unchanged or decreased Mcl-1 transcript levels, and increased Mcl-1 protein half-life, suggesting that the association with Bim plays a role in stabilizing Mcl-1 protein. Combining conventional chemotherapeutic agent cytarabine or daunorubicin with ABT-199 resulted in increased DNA damage along with decreased Mcl-1 protein levels, compared with ABT-199 alone, and synergistic induction of cell death in both AML cell lines and primary patient samples obtained from AML patients at diagnosis. Conclusions: Our results demonstrate that sequestration of Bim by Mcl-1 is a mechanism of intrinsic ABT-199 resistance and supports the clinical development of ABT-199 in combination with cytarabine or daunorubicin for the treatment of AML. Clin Cancer Res; 22(17); 4440–51. ©2016 AACR.
A Preliminary Report Comparing Magnetic Resonance Coronary Angiography with Conventional Angiography
Authors: Warren J. Manning, Wei Li, Robert R. Edelman
Journal: New England Journal of Medicine (1993)

The ability to assess the patency of coronary arteries by noninvasive means would represent an important advance. We have developed a magnetic resonance imaging (MRI) coronary angiographic technique that permits the display of areas of abnormal coronary blood flow. We have compared this method with conventional contrast angiography for the identification of coronary-artery stenoses.MRI coronary angiography was performed with an electrocardiographically gated sequence in 39 subjects, 33 to 84 years of age, who were scheduled for elective cardiac catheterization with coronary angiography. Sequential overlapping transverse and oblique sections were acquired during periods of breath-holding and were displayed as cine loops for analysis. MRI and conventional angiographic data were compared in a blinded manner. The four major epicardial coronary arteries were classified by MRI coronary angiography as being normal (or having only minimal irregularities) or as having disease that was moderately severe to severe.The sensitivity and specificity of MRI coronary angiography, as compared with conventional angiography, for correctly identifying individual vessels with > or = 50 percent angiographic stenoses were 90 percent and 92 percent, respectively. The corresponding positive and negative predictive values were 0.85 and 0.95, respectively. The sensitivity and specificity of the technique were 100 percent and 100 percent, respectively, for the left main coronary artery, 87 percent and 92 percent for the left anterior descending coronary artery, 71 percent and 90 percent for the left circumflex coronary artery, and 100 percent and 78 percent for the right coronary artery.MRI coronary angiography provides a new approach to evaluating the patency of coronary arteries. These preliminary data suggest that this technique may provide a noninvasive means of evaluating patients with known or suspected coronary artery disease. At its current stage of development, this procedure may be most helpful for excluding clinically important stenoses in patients referred for diagnostic contrast angiography.
What is a best choice at the second-line chemotherapy for advanced or recurrent gastric cancer?
Authors: M. Yamamoto
Journal: Journal of Clinical Oncology (2010)

e14663 Background: The first-line chemotherapy for advanced/recurrent gastric cancer established by JCOG9912 and Spirit Trial in Japan (ASCO 2007, abstr 4513, 4514). The first-line chemotherapy for advanced/recurrent gastric cancer was cisplatin plus S-1. However, the treatments after first-line chemotherapies were unknown in Japan. Methods: We have examined findings with 82 cases for advanced/recurrent gastric cancer between 2005-2009 in our hospital. Forty-five of 82 cases, which had been treated at the second-line chemotherapies were examined, retrospectively. The patients had administrated S-1 alone, S-1 + cisplatin, S-1 + docetaxel, S-1 + paclitaxel (S-1 base), CPT alone, CPT + cisplatin (CPT base), weekly paclitaxel or triweekly docetaxel (taxane). Results: The overall survival with 82 cases was 15.9 months. Progression-free survival (PFS) was 7.8 months. The 45 cases, that had treated at the second-line chemotherapies, were divided among S-1 base (n = 9), CPT11 base (n = 17) or taxane (n = 19) group. The median survival times (MST) of S-1 base, CPT base or taxane group were 189, 208 or 260 days, respectively. The overall survivals with patients after second-line chemotherapies were not significant differ among three groups. Next, we examined whether age, sex, PS, advanced/recurrent, S-1 base, CPT base, taxane and cisplatin become independent prognostic factors for the survivals after second-line chemotherapies. In the multivariate analysis, PS (p < 0.001) and cisplatin (p < 0.05) were found to be significant and independently related to prognostic factors. Conclusions: The survival with patients after S-1 base treatment for advanced/recurrent gastric cancer is significantly related to PS and cisplatin. No significant financial relationships to disclose.
Genistein combined polysaccharide (GCP) is highly active in both human and canine lymphoma models
Authors: P. C. Mack, R. A. Burich, J. L. McCall, M. S. Kent, R. M. Hackman, J. M. Tuscano, R. W. deVere White
Journal: Journal of Clinical Oncology (2007)

14126 Background: The soy isoflavones genistein and daidzein have demonstrated anticancer activity in vitro in multiple tumor types including leukemia/lymphoma, with evidence for a role in chemoprevention. GCP (Amino Up Chemical Co.) is a fermentation product of soy extract and the mycelium of Basidiomycetes, a process which converts soy isoflavones to their aglycone form, greatly increasing intestinal absorption. In humans, GCP has negligible toxicity at potentially active concentrations. We hypothesized that GCP would have significant anticancer activity in hematologic malignancies. Methods: Three human lymphoma cell lines (Jurkat, Raji, and Ramos), a leukemia line (HL60), and four canine lymphoid cell lines (GL-1, CLGL-90, CL1, and CLL-1390) were treated with GCP at doses ranging from 25 to 200 μg/ml. Growth effects were assessed by trypan blue exclusion 5–7 days following a single treatment. Flow cytometry and Westerns were used to measure changes in cell cycling, protein expression and apoptosis. We are conducting a single-agent dose escalation clinical trial in chemo-naïve canines with lymphoma. Results: GCP had striking cytotoxic effects in both canine and human lymphoma cell lines. In all human lines, the 50% inhibitory concentrations (IC50s) were less than 25μg/ml. At 100μg/ml, a concentration achievable in patient plasma, virtually no viable cells remained. Three of four canine lines were sensitive with IC50s in the range of 15–50μg/ml. Substantial G2 cell cycle accumulation was observed, apparent within two hours and maintained for at least 48h. GCP treatment induced apoptosis, as shown by an increase in sub-G1 DNA content and cleavage of PARP and caspase 3. At higher doses, elevated Bcl-2 levels were observed, suggesting a potential mechanism of resistance. These results provided the rationale for a clinical trial in canine patients at UC Davis. One patient with aggressive diffuse large B-cell lymphoma treated at 93 mg/kg/day (dose level 2) had a confirmed partial response. Conclusions: GCP has potent anticancer activity in vitro against lymphoid cell lines, with almost complete cell kill at doses achievable in patient plasma with minimal toxicity. A phase I clinical trial in canine lymphoma will determine whether testing in human lymphoma patients is warranted. No significant financial relationships to disclose.
Clinical Value of the Forced Expiratory Time Measured during Auscultation
Authors: Gerald Rosenblatt, Myron Stein
Journal: New England Journal of Medicine (1962)

CERTAIN cases of obstructive lung disease demonstrate a wide discrepancy between interpretation of physical findings and appraisal by pulmonary-function studies. The inadequacies of the usual clinical examination of the chest are indicated by the study of Fletcher,1 which concluded that the diagnosis of obstructive pulmonary emphysema could not be made with any degree of certainty on the basis of physical examination alone, by the observation of abnormal pulmonary function in many asthmatic subjects when they are symptom free and without clinical signs2 and by the unreliability of routine x-ray examination of the chest.3 It is well known that expiration time . . .
Ethanol-Induced Hyperuricemia
Authors: Jason Faller, Irving H. Fox
Journal: New England Journal of Medicine (1982)

Consumption of alcoholic beverages is associated with hyperuricemia and gout. To determine the contributions to this process of increased production and decreased excretion of uric acid, we gave oral ethanol (1.8 g per kilogram of body weight every 24 hours) for eight days or intravenous ethanol (0.25 to 0.35 g per kilogram per hour) for two hours to six patients with gout. During the long-term oral study we observed the following: serum urate levels increased from 8.4±0.4 (mean ±S.E.) to 10.1 ±0.9 mg per deciliter; whole blood lactate reached a peak of 3.1 ±0.7 mM from a base line of 1.3±0.3 mM; and urinary oxypurines increased to 641 ±397 per cent of the base-line value. Urate clearance increased to 145±25 per cent of the base-line value. Daily uric acid turnover increased from 1010 mg per deciliter to 170±17 per cent of the base-line value. During short-term intravenous ethanol administration, serum urate levels, urate clearance, and urinary uric acid excretion were not substantially altered from the baseline period. Urinary oxypurine levels increased to 341 to 415 per cent of base-line values. Urinary radioactivity, originating from the adenine nucleotide pool labeled by [8–14C]adenine, increased to 127 to 149 per cent of baseline values. These data indicate that ethanol increases urate synthesis by enhancing the turnover of adenine nucleotides. (N Engl J Med. 1982; 307:1598–1602.)
A wandering path toward prevention for acute kidney injury
Authors: Simon J. Atkinson
Journal: Journal of Clinical Investigation (2016)

Acute kidney injury (AKI) is a common cause of hospital-related mortality; therefore, strategies to either prevent or treat this complication are of great interest. In this issue of the JCI, Inoue, Abe, and colleagues have uncovered a targetable neuroimmunomodulatory mechanism that protects mice from ischemia-reperfusion injury (IRI) and subsequent AKI. Specifically, the authors demonstrate that vagus nerve stimulation (VNS) activates the cholinergic antiinflammatory pathway (CAP), resulting in activation of antiinflammatory effects via α7 nicotinic acetylcholine receptor–expressing splenic macrophages. Together, the results of this study have potential clinical implications in the prevention of AKI in at-risk individuals.
A Review of Seven Years' Experience with Excision and Graft Replacement in 150 Ruptured and Unruptured Aneurysms of the Abdominal Aorta
Authors: Paul F. Gryska, C. Gene Wheeler, Robert R. Linton
Journal: New England Journal of Medicine (1961)

SUCCESSFUL excision of formidable vascular lesions, with replacement by a graft or prosthesis, has prompted surgeons to attack acute catastrophic vascular emergencies with increasing vigor during the past decade. In our experience of excision and grafting of 150 abdominal aneurysms we have treated 26 patients with frank rupture of their aneurysms, and it is our purpose to report these problems.We consider rupture the culmination of the life history of an aortic aneurysm, and a challenge to discover and excise these aortic lesions before rupture faces the medical profession. Often, these patients are otherwise quite healthy, productive senior citizens who . . .
Case 7-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, John W. Braasch, Carolyn C. Compton
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 32-year-old man was admitted to the hospital because of fever, diarrhea, and jaundice.He was well until one week earlier, when he experienced the onset of malaise, fever, night sweats, anorexia, diffuse aches, and pain in the right upper abdominal quadrant; two days later he became jaundiced. Four days before entry diarrhea developed, and the patient noticed that his stools were lighter than usual. Two days before admission he was seen at another facility with a complaint of pain along the right costal margin. An x-ray film of the chest was reported to show a questionable . . .
Pharmacokinetic analysis of two dose levels of rasburicase in adult patients with hematologic malignancies at high or potential risk for tumor lysis syndrome
Authors: A. Huen, D. DeAngelo, M. Fanale, S. Vadhan-Raj
Journal: Journal of Clinical Oncology (2008)

14545 Background: Tumor lysis syndrome (TLS) is an oncologic emergency characterized by hyperuricemia and electrolyte abnormalities which can result in renal failure and death. The new uricolytic agent rasburicase (RSB) is approved for treatment of TLS in pediatric patients in the United States, but studies in adults have been limited. Methods: Adult patients with aggressive lymphoma or leukemia, deemed at high or potential risk for TLS, were treated with RSB at 0.15 mg/kg or 0.20 mg/kg IV over 30 mins daily for 5 consecutive days. First dose of RSB was initiated at least 4 hours prior to start of antineoplastic treatment. Pharmacokinetic (PK) analysis was performed with efficacy and safety evaluation as secondary endpoints. Response was defined as maintaining uric acid (UA) levels ≤7.5mg/dL at 48 hours after first RSB dose. Results: No drug accumulation was observed in 25 patients (0.15mg/kg n=13; 0.20mg/kg n=12) following 5 doses of RSB (95% CI for the accumulation ratios of AUC0–24 and end-of-infusion concentration included 1.00). Half life was comparable for both groups (approx. 16–20 hours). In an intent-to-treat analysis, the overall response rate in both dose groups was 100%, with no difference between those at high or potential risk of TLS. At 4 hours post first dose, % change in UA was similar between the dose levels. Plasma UA AUC was comparable between the groups (151.38 mg*h/dL in the 0.15 mg/kg and 150.77 mg*h/dL in the 0.20 mg/kg group). Grades 1 or 2 hypersensitivity and skin reactions were the most common non-hematologic toxicity. There were no severe Grade 3 and 4 events related to RSB. Conclusions: In adult patients, PK parameters, safety and efficacy of RSB were similar between the 0.15mg/kg and 0.20mg/kg dose levels suggesting that both doses can be used effectively to treat patients at risk for TLS. No significant financial relationships to disclose.
Breast cancer tumor size in MRI versus surgical pathological specimen: A correlative study
Authors: A. K. Swayampakula, A. Schwartzman, A. Saad, C. Dillis, J. Schreiman, G. Hobbs, J. Abraham
Journal: Journal of Clinical Oncology (2008)

11550 Background: Although magnetic resonance imaging (MRI) is superior to conventional imaging techniques in breast cancer, its correlation with actual tumor size has not been shown to be impressive. The purpose of our study is to determine the correlation of MRI with pathological findings of breast cancer in patients treated in West Virginia University Hospitals. Methods: This is a retrospective study analyzing a database of 43 patients with breast cancer who had preoperative MRI. We estimated the correlation between the preoperative largest tumor diameter on MRI and diameter on pathological evaluation after surgery. The size of the surgical specimen is considered the gold standard for tumor measurement. A subset of 15 patients received neoadjuvant chemotherapy, while 28 patients did not. In all patients, MRI diameters were measured preoperatively. All MRI diameters were estimated by only two radiologists in our institution. Results: The mean age of our patient population was 47.4 years (range: 36–70). The median of the largest preoperative diameter as seen in the MRI was 20 mm, while the median of the diameter at surgery was 15 mm. The difference was significant (Wilcoxon Signed Rank Test, p= 0.0054). The correlation coefficient was 0.47 (P= 0.0016). Further analysis of the same population based on whether they received neoadjuvant chemotherapy or not showed no difference in the level of correlation. Conclusions: MRI of the breast tends to overestimate the tumor diameter seen in the pathological specimen of resected masses. However, an evident correlation exists between the MRI-estimated diameter and the actual tumor size. No significant financial relationships to disclose.
Carriage of meningococci in contacts of patients with meningococcal disease
Authors: A. Hayward, P. Dutton, R. Winterton, E. Wright, H. S. A. Yeang, R. Reintjes, M. A E C.-v. Spaendonck, A. Jenkins, Y. Tveten, B.-E. Kristiansen
Journal: BMJ (1999)

# “Kissing contacts” need to be defined {#article-title-2} EDITOR—In their study Kristiansen et al show high carriage rates of pathogenic strains of Neisseria menigitidis in household and kissing contacts of patients with invasive meningococcal disease.1 While it is easy to define a household contact it may be more difficult to define a kissing contact. There are many types of kiss, ranging from a “peck on the cheek” to much more! In some cultures kissing is as common as shaking hands. In such situations widespread chemoprophylaxis to “kissing contacts” may not be appropriate. It would be valuable to know whether Kristiansen et al placed any restrictions on who was defined as a kissing contact. 1. ↵1. Kristiansen BE, 2. Tveten Y, 3. Jenkins A . Which contacts of patients with meningococcal disease carry the pathogenic strain of Neisseria meningitidis? A population based study. BMJ 1998; 317: 621–625. (5 September.) [OpenUrl][1][Abstract/FREE Full Text][2] # Chemoprophylaxic strategy needs to be determined {#article-title-4} EDITOR—The study by Kristiansen et al addresses important questions about the use of chemoprophylaxis in contacts of patients with meningococcal disease.1 We believe, however, that the data presented do not fully support the conclusions. Kristiansen et al found high rates of meningococcal carriers among class 1contacts (12.4%) and advocated the use of chemoprophylaxis in this group, on the basis of their assumption that carrying the pathogenic strain increases the likelihood of contracting the disease. One concern is that this group accounts for only 18 of 42 contacts who … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DKristiansen%26rft.auinit1%253DB.-E.%26rft.volume%253D317%26rft.issue%253D7159%26rft.spage%253D621%26rft.epage%253D625%26rft.atitle%253DWhich%2Bcontacts%2Bof%2Bpatients%2Bwith%2Bmeningococcal%2Bdisease%2Bcarry%2Bthe%2Bpathogenic%2Bstrain%2Bof%2BNeisseria%2Bmeningitidis%253F%2BA%2Bpopulation%2Bbased%2Bstudy%26rft_id%253Dinfo%253Apmid%252F9727987%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=bmj&resid=317/7159/621&atom=%2Fbmj%2F318%2F7184%2F665.atom