tbuckley/cabot-search huggingface dataset:
Influence of a single nucleotide polymorphism in the P1 promoter of the furin gene on transcription activity and hepatitis B virus infection
Authors: Rui Xiang Lei, Hong Shi, Xiao Mou Peng, Yin Hong Zhu, Jie Cheng, Gui Hua Chen
Journal: Hepatology (2009)

Abstract Hepatitis B e antigen (HBeAg) is a viral strategy of immune response evasion associated with hepatitis B virus (HBV) persistence. Spontaneous HBeAg seroconversion is usually accompanied by liver disease remission. Unfortunately, this goal is difficult to achieve and requires expensive and time-consuming treatment. Furin, a proprotein convertase, is involved in HBeAg maturation and is therefore a potential therapeutic target or indicator for predicting disease progression and antiviral response. Here we demonstrate that healthy Han Chinese from southern China (an endemic area of HBV infection) harbor a common single nucleotide polymorphism (SNP; −229 C/T) in a 1268-bp region of the P1 promoter of the furin gene [FES upstream region ( Fur )]. A luciferase reporter gene assay showed that transcription activity is about 3 times higher in allele T carriers than in allele C carriers of this SNP. Allele T includes a suboptimal transcription factor NF-E2 [i.e., nuclear factor (erythroid-derived 2)]–binding motif according to bioinformatics and studies using site-directed mutagenesis. We also observed that individuals carrying allele T were more likely to become persistently infected. When persistently infected patients were divided into subgroups according to recent guidelines and HBeAg-defective virus infection was taken into account, patients with allele T or genotype TT had a decreased likelihood of HBeAg seroconversion or an increased likelihood of progressing to HBeAg-negative chronic hepatitis B or liver cirrhosis if accompanied by HBeAg-defective virus infection. Conclusion: The common SNP in the P1 promoter of the Fur gene affects furin transcription activity and HBV infection outcome, possibly by increasing furin messenger RNA expression, and this suggests that furin is a potential therapeutic target and that this SNP is a potential predictor of disease progression or therapeutic response. (Hepatology 2009.)
The evaluation of chemical mutagenicity data in relation to population risk: the need for better methods of extrapolation.
Authors: L Friedman
Journal: Environmental Health Perspectives (1973)

In the fall of 1966 the Food and Drug Administration established an Advisory Com- mittee on Protocols for Safety Evaluation.The first problem to be reviewed was the requirement for reproduction studies in the safety evaluation of pesticides and food ad- ditives, and the adequacy of the current me- thods involved.Reproduction studies are de- signed to give information on: (1) effects on male and female fertility, (2) effects during gestation on the mother and the fetus, (3) effects appearing after parturition on the mother (for example, lactation) and the off- spring (for example, growth, development, sexual maturation), and (4) mutagenic ef- fects, particularly those which might not appear in the first generation.The report of panel dealing with this problem was written in November 1968 and published later (1).During the time the panel was considering the problem, a re- port prepared by the Genetic Study Section under the chairmanship of Dr. James F. Crow (2), became available to us (C.C. Cockerham, personal communication).The emphasis in this particular report of the Genetic Study Section was that there is reason to be concerned about chemicals as a mut- agenic risk equivalent to radiation, possibly even more serious.The concern, of course, is with the welfare of future generations as well as with the health of contemporary pop- ulations.It is useful to emphasize again that
Ga-68 DOTATOC PET/CT Changed the Therapeutic Course of a Patient With the Sudden Onset of Vision Problems
Authors: Jelle Van Riet, Dirk Rattat, Alfons Verbruggen, Luc Mortelmans, Felix M. Mottaghy
Journal: Clinical Nuclear Medicine (2008)

A 61-year-old man presented with the sudden onset of blurry vision of the right eye. Conventional ophthalmologic examination and magnetic resonance index were suspicious for a choroidal melanoma. Fludeoxyglucose positron emission tomography imaging showed no increased uptake, rendering the diagnosis of melanoma most unlikely. Because of the patient had a history of bronchial carcinoid tumor (pT2N0Mx) 3 years ago, further work-up included ophthalmologic echography (A-scan) showing a probable metastatic lesion. Evaluation of the chromogranin blood level and Ga-68 Positron emission tomography-computed tomography DOTATOC-PET/CT revealed high uptake in the ocular lesion and further tumor localization in the mediastinum, liver, and pancreas. The pattern was considered highly suspicious for metastases, and without further anatomopathological analysis, the patient was referred for external beam radiotherapy and additional radiopeptide receptor therapy with Lu-177-DOTATATE. This case illustrates the use of Ga-68 DOTATOC-PET/CT in a difficult clinical problem, where fludeoxyglucose-PET/CT did not provide a final diagnosis.
Abstract PD04-07: Monitoring Circulating Tumor Cells (CTC) and Circulating Endothelial Cells (CEC) during Neoadjuvant Combination of Trastuzumab and Bevacizumab with Chemotherapy in HER2 Overexpressing Inflammatory Breast Cancer (IBC): An Ancillary Study of BEVERLY 2 Multicenter Phase II Trial
Authors: J-Y Pierga, F-C Bidard, T Petit, T Delozier, J-M Ferrero, M Campone, J Gligorov, F Lerebours, H Roche, S Kraemer, C Mathiot, P. Viens
Journal: Cancer Research (2010)

Abstract Introduction: CTC detection in peripheral blood is an independent prognostic factor in early breast cancer but with a low detection rate of 10% to 23% of the patients (B. Rack, ASCO 2010, FC Bidard, Ann Oncol 2010). Changes in the HER2 status of CTC compared to the primary tumor have been reported (Riethdorf S CCR 2010). Predictive value of CEC for response to anti-angiogenic agents is debated. Material and methods: CTC and CEC were detected in 7.5 ml and 4 ml of blood respectively in IBC (T4d) patients enrolled in the phase II multicenter trial, BEVERLY 2. This study is evaluating the efficacy of bevacizumab (15mg/kg q3w given concurrently) in combination with sequential neoadjuvant chemotherapy of 4 cycles of FEC followed by 4 cycles of Docetaxel-Trastuzumab. Bevacizumab was stopped 4 weeks before and reintroduced 4 weeks (w) after mastectomy. All patients had non metastatic IBC and over expressed HER2 (3+ in IHC or FISH +). The CellSearch™ System, combining EpCAM immunomagnetic selection (IMS) followed by anti-cytokeratin (A45B/B3) and anti-HER2 fluorescently staining for CTC and CD146 IMS and CD105 staining for CEC, was used at baseline, before cycle 5, before and after surgery. Results: From Oct 2008 to Oct 2009, 52 patients were included in this study and 51 were evaluable for CTC. At baseline, 18 patients out of 51 had ≥ one detectable CTC (35.3%, 95%CI 22-48%, range 1 to 92). Pathological complete response rate according to local review was 33/47 (70%) or 15/22 (68%) for centrally reviewed cases. At baseline, CTC level was not correlated with CEC level, neither with other patients and tumor characteristics’ (age, nodal status, PeV) nor pCR (centrally reviewed in 24). All positive cases for CTC detection had HER2 positive CTC. Five pts out of 18 (28%) had both HER2+ and HER2 negative CTCs in their blood. A lower level of CEC (&amp;lt; 20/4ml) before C5 could be associated with a higher probability of pCR (Khi2 test, p=0.053). Conclusion: We observed a high CTC detection rate of 35% in this population of patients with HER2+ IBC and a dramatic drop in CTC level during treatment in concordance with the high efficiency of this combination of chemotherapy and targeted therapy. We observed heterogeneity in the HER2 status of CTC in some patients. CEC levels increased progressively during neoadjuvant treatment and decreased after its interruption. Longer follow-up will show if CTC and CEC variations are early predictive factors for this highly efficient combination in HER2+ IBC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-07.
Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers May Reduce Breast Cancer Recurrence.
Authors: Y. Chae, M. Valsecchi, A. Lucca, J. Kim, A. Desai
Journal: Cancer Research (2009)

Abstract There have been epidemiologic and biochemical findings alluding to the role of angiotensin converting enzyme inhibitors(ACEIs) and angiotensin receptor blockers(ARBs) in reducing the risk of developing cancer. To date, there exists no study that reported any relationship between their use and the risk of cancer recurrence. Thus, we investigated the associations between the use of ACEI/ARB and the risk of tumor recurrence among breast cancer patients without any evidence of disease.We reviewed the medical records of female patients diagnosed with stage II/III breast cancer in Albert Einstein Medical Center between 1999 and 2005 and later reached no evident disease (NED) stage after curative therapy. Follow up period was from 1999 to 2008 with mean and maximum being 4.4 years and 9.8 years, respectively. ACEI/ARB user was defined as patients taking the medication in NED stage for at least 6 months. Multivariate analyses were performed using logistic regression and Cox proportional hazard model.Of 707 cancer patients and of 335 cancer patients with hypertension, 164, representing 23.3% of total and 49.0% of those with hypertension were prescribed ACEI/ARB. ACEI/ARB use was associated with older age (P&amp;lt;0.001), postmenopausal status (P&amp;lt;0.001), and diabetes (P&amp;lt;0.01). Fourteen percent (23/164) of ACEI/ARB users developed cancer recurrence, while 23.3% (125/541) of nonusers developed a recurrence (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.33-0.97; P=0.01). Kaplan-Meier survival analysis revealed that ACEI/ARB use was related to disease-free survival benefit (log-rank test P&amp;lt;0.01). Five year disease-free survival for ACEI/ARB users was 0.85 compared with 0.76 for nonusers (P&amp;lt;0.01). Adjusting for statistically significant variables above, ACEI/ARB use was associated with reduced risk of developing recurrence not only in all breast cancer patients but also when they were compared to a subset of the nonusers who had hypertension (AHR, 0.41; 0.23-0.80; P&amp;lt;0.01). While ACEI/ARB use was not associated with reduced mortality in all breast cancer patients (AHR, 1.01; 95% CI: 0.61-1.65; P=0.36; log-rank test P=0.52), it was when compared to the subset of patients with hypertension (AHR, 0.43; 95% CI, 0.25-0.68; P&amp;lt;0.01; log-rank test P&amp;lt;0.01).The use of ACEI/ARB is related to reduced risk of developing recurrence in patients with breast cancer. This result provides clinical evidence, in accordance with existing biochemical and epidemiologic data, that antagonizing angiotensin system is inversely associated with tumor recurrence. However, prospective randomized trials are needed to validate this finding. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3121.
The Free Medical and Surgical Treatment of the Well-to-do in Michigan University.
Authors: Horace M. Starkey
Journal: JAMA (1898)

Chicago, March 24,1898. <h3>To the Editor:</h3> —I am very glad to see Dr. Vaughan's statement of the policy of the Board of Regents of Michigan University with regard to the admission of patients able to pay for treatment to the free clinics of their medical department. It would be well for the credit of the University of Michigan, whose faculty and teachings we all respect and admire, that this statement should be given the widest publicity not only among the profession at large, but also among the members of their teaching corps; because the ideas entertained by the writer of the editorial corrected by Dr. Vaughan, are very widely entertained. Last summer, your correspondent was discussing with one of the clinical instructors of the University, the clinical advantages to be found in Ann Arbor (we were<i>not</i>discussing the abuse of medical charity), and he spoke of the very large
Information about wanted persons and medical ethics
Authors: M. J G Thomas
Journal: BMJ (1979)

<h3>Abstract</h3> Transcription regulator on-off binding to DNA constitutes a mechanistic paradigm in gene regulation, in which the repressors/activators bind to operator sites tightly while the corresponding non-repressors/non-activators do not. Another paradigm regards regulator unbinding from DNA to be a unimolecular process whose kinetics is independent of regulator concentration. Using single-molecule single-cell measurements, we find that the behaviors of the zinc-responsive uptake regulator Zur challenges these paradigms. Apo-Zur, a non-repressor and presumed non-DNA binder, can bind to chromosome tightly in live <i>E. coli</i> cells, likely at non-consensus sequence sites. Moreover, the unbinding from DNA of its apo-non-repressor and holo-repressor forms both show a biphasic, repressed-followed-by-facilitated kinetics with increasing cellular protein concentrations. The facilitated unbinding likely occurs via a ternary complex formation mechanism; the repressed unbinding is <i>first-of-its-kind</i> and likely results from protein oligomerization on chromosome, in which an inter-protein salt-bridge plays a key role. This biphasic unbinding could provide functional advantages in Zur9s facile switching between repression and derepression.
Feeling the pressure.
Authors: P A Simkin
Journal: Annals of the Rheumatic Diseases (1995)

Feeling the pressureThe normal synovium occupies a tissue space confined by the joint capsule.This outer limit is sometimes clear, as in the volar plate of digital hinge joints, and sometimes imperceptible, as in the normal suprapatellar region where areolar synovial tissue appears to blend into the interstitial spaces of the thigh.The limit becomes obvious in chronic synovitis, however, when the capsule clearly confines the distribution of radiolabelled albumin and serves as a relatively non-compliant rind in the presence of pressur-
Evaluation of colestipol/niacin therapy with computer-derived coronary end point measures. A comparison of different measures of treatment effect.
Authors: D H Blankenhorn, R H Selzer, W J Mack, D W Crawford, J Pogoda, P L Lee, A M Shircore, S P Azen
Journal: Circulation (1992)

BACKGROUND The Cholesterol Lowering Atherosclerosis Study has demonstrated beneficial effect of colestipol/niacin on coronary atherosclerosis using a panel-determined global coronary change score. We now report treatment group comparisons using quantitative coronary angiographic (QCA) measures from all processable segments in 85 of 162 randomly selected baseline/2-year film pairs. METHODS AND RESULTS Treatment benefit was established for percent stenosis for either continuous or categorical analyses with regression established regardless of the per-patient scoring procedure. In addition, treatment benefit favoring regression was established in some cases for roughness and for percent involvement, a longitudinal estimate of the percent of coronary surface involved by raised lesions. Benefit on minimum diameter was directly related to whether the segment was proximal to a graft insertion and hemodynamically related to the bypass graft. QCA correlates of panel-determined progression were increases in percent stenosis and numbers of occluded lesions in native arteries and the number of progressing lesions in bypass grafts. CONCLUSIONS These results demonstrate that a variety of computer measures can be used as end points in coronary angiographic therapy trials, but change in percent stenosis correlates best with visual panel assessments and best reflects the treatment benefit; when treatment effect sizes are moderate to large, the required sample size of coronary angiographic trials can be reduced when QCA is used.
Bone-Marrow-Derived Macrophages Genetically Modified to Produce IL-10 Reduce Injury in Experimental Glomerulonephritis
Authors: Heather M. Wilson, Keith N. Stewart, Paul A.J. Brown, Ignacio Anegon, Salah Chettibi, Andrew J. Rees, David C. Kluth
Journal: Molecular Therapy (2002)

Macrophages are intimately involved in the development of immune-mediated inflammation, including glomerulonephritis. We have transduced primary cultures of macrophages to express IL-10 and tested the ability of these cells to control rat nephrotoxic nephritis (NTN), a model of human glomerulonephritis. Ad-IL-10-transduced bone-marrow-derived macrophages (BMDM) produced large amounts of IL-10 in culture, and their TNF-alpha production was decreased in response to interferon-gamma and LPS. Transduced macrophages were injected into the renal artery of rats, 6 h after the induction of NTN, where they localized efficiently to inflamed rat glomeruli. Delivery of IL-10-expressing macrophages to nephritic rats produced a marked reduction in albuminuria compared with unmodified NTN or injection of Ad-null-transduced BMDM. IL-10 treatment decreased the number of glomerular ED1- and ED3-positive cells, MHC class II expression, and the number of fibrinoid lesions. Interestingly, anti-inflammatory changes in the Ad-IL-10-injected kidney were mirrored by changes in the contralateral kidney. These results highlight that Ad-IL-10-transduced macrophages infiltrate inflamed glomeruli and reduce the severity of glomerular inflammation, emphasizing the value of local delivery of genetically modified macrophages in the manipulation of inflammatory disease.
Aortocoronary bypass surgery: a 7-year follow-up.
Authors: A Cameron, H G Kemp, S Shimomura, E Santilli, G E Green, J E Hutchinson, H A Mekhjian
Journal: Circulation (1979)

Follow-up of 748 consecutive patients who underwent aortocoronary artery bypass grafts was obtained for 5 to 94 months (average, 59 months). Operative mortality of 2.5% did not vary with number of vessels bypassed. There was a linear 3.5% annual recurrence rate of angina, and average annual late infarction rate of 1.4%. The cumulative survival rates did not differ for the number of grafts performed or for men and women, but did differ for left main coronary stenosis and impaired ejection fractions. The late cumulative survival rates for the entire group approached those of the general U.S. population.
MEPs try to mobilise public opinion against extension of euthanasia.
Authors: Rory Watson
Journal: BMJ (2001)

European politicians are being urged to oppose plans to extend the practice of euthanasia in the Netherlands and Belgium. The controversial issue is currently on the parliamentary agenda in both countries.

The Dutch Senate is due to decide on the bill, which already has the support of the parliament’s second chamber (the equivalent of the House of Commons). At stake are proposals to liberalise existing legislation, in particular to allow children …
CNTO 530 functions as a potent EPO mimetic via unique sustained effects on bone marrow proerythroblast pools
Authors: Pradeep Sathyanarayana, Estelle Houde, Deborah Marshall, Amy Volk, Dorie Makropoulos, Christine Emerson, Anamika Pradeep, Peter J. Bugelski, Don M. Wojchowski
Journal: Blood (2009)
Developmental aspects of xenobiotic transformation.
Authors: W Klinger, D Muller
Journal: Environmental Health Perspectives (1976)

In most laboratory animals monooxygenases are apparently absent or barely detectable in fetal organs until just before birth. In this contribution hepatic cytochrome P-450-dependent reactions in the rat are considered only. The results are interpreted on basis of the reaction scheme of Estabrook. To avoid methodological pitfalls the basic kinetics for all reactions investigated have been investigated with liver preparations from newborn and adult rats. The low monooxygenase activity of rat liver during the perinatal period can be observed even under optimal conditions for the in vitro enzyme assay. There are different developmental patterns for various reactions O-demethylation of codeine, phenazone-hydroxylation, first and second steps on N-demethylation of amidopyrine, N-demethylation of ethylmorphine. There are marked differences not only in Vmax but also in the postnatal development of Km and the inductibility by phenobarbital. Thus the existence of a different cytochrome P-450 is evident also by this approach. The low monooxygenase activity of rat liver during the perinatal period is not due to a lack of NADPH or NADH, to an age-dependent NADPH cytochrome P-450 reductase activity or to an age-dependent NADH-cytochrome P-450 reduction. Moreover this low activity is not due to an insufficient mitochondria-endoplasmic reticulum interaction. It is accompanied by low delta Amax after addition of a typical type I substrate (hexobarbital) and by a small amount of metyrapone-binding centers: it can be explained by a smaller percentage of active cytochrome P-450 in comparison to adult rat liver.
Tc-99m MDP Uptake in Ischemic Hepatopathy
Authors: JAMES H. TIMMONS, MICHAEL F. HARTSHORNE, ROBERT J. TELEPAK, ARTHUR B. BUCKNER
Journal: Clinical Nuclear Medicine (1988)

A 56-year-old woman had partial necrosis of her liver after a hypotensive episode due to duodenal bleeding. Renal and cardiac damage and mental status changes were also noted. Liver enzymes, normal one week previously, became sharply elevated (lactate dehydrogenase 45,000 u/l, normal: 80-225 u/l; aspartate aminotransferase 11,270 u/l, normal: 3-45 u/l; and alanine aminotransferase 3807 u/l, normal: 3-45 u/l). Injection of 740 MBq at 99m-Tc MDP, after the hypotensive episode, revealed sharp uptake within the ischemic liver. Fifteen days after admission, the patient had clinically recovered and normalized all laboratory values.
HOSPITALS AND GENERAL PRACTITIONERS
Authors: J. Batteson
Journal: BMJ (1906)

Hospitals and General Practitioners.It must, we fear, be admitted that hospitals do not invariably hold a secure position in the affec- tions of those engaged in general practice in their neighbourhood.Occasions for annoyance and irritation readily arise and even a few of these are sufficient to breed a general attitude of suspicion and mistrust.There are according to existing arrangements no ready opportunities for removing misunderstandings, and often, therefore, these remain, and with them hostility and bitter- ness.
Therapy of Atrioventricular Block
Authors: M. G. Criscitiello
Journal: New England Journal of Medicine (1968)

First-Degree BlockPROLONGATION of the PR interval beyond 0.20 second may occur in many disorders including acute myocardial infarction, aortic stenosis, severe aortic insufficiency, adrenal insufficiency, rheumatic fever and a number of systemic infectious diseases. An occasional normal person will have first-degree heart block in the absence of any apparent disease. Although an optimal role for atrial contraction may be provided by a normal PR interval, the delayed onset of ventricular contraction in first-degree block rarely produces significant changes in heart function. A prolonged PR interval will usually return to normal with atropine or sympathomimetic agents, but treatment of this . . .
Pulmonary hypertension associated with primary biliary cirrhosis in the absence of portal hypertension: a case report.
Authors: E M Yoshida, S R Erb, D N Ostrow, D R Ricci, C H Scudamore, G Fradet
Journal: Gut (1994)

Pulmonary hypertension is well described in association with portal hypertension of any cause including end stage primary biliary cirrhosis (PBC). The essential feature of this association is the presence of portosystemic shunting, including surgically created shunts. A patient with primary pulmonary hypertension and PBC without portal hypertension is reported. This suggests that primary pulmonary hypertension may be associated with PBC in the absence of portal hypertension. Decisions regarding appropriate organ transplantation may depend on whether pulmonary hypertension is primary or secondary to portal hypertension.