tbuckley/cabot-search huggingface dataset:
Increased Tyrosine Nitration of the Brain in Chronic Renal Insufficiency
Authors: Gangmin Deng, Nosratola D. Vaziri, Bahman Jabbari, Zhemin Ni, Xiao-Xin Yan
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Interaction of reactive oxygen species with nitric oxide promotes nitric oxide inactivation and generation of cytotoxic reactive nitrogen species that attack DNA, lipids, and proteins. Nitration of free tyrosine and tyrosine residues of proteins results in production of nitrotyrosine, which can lead to excitotoxicity and frequently is found in the brain of patients and animals with various degenerative, ischemic, toxic, and other neurologic disorders. According to earlier studies, reactive oxygen species activity is increased and neuronal NO synthase expression in the brain is elevated in animals with chronic renal failure (CRF). It was hypothesized, therefore, that tyrosine nitration must be increased in the uremic brain. This hypothesis was tested, through determination of nitrotyrosine abundance (by Western blot analysis), as well as distribution (by immunohistology), in the cerebrum of rats with CRF 6 wk after 5/6 nephrectomy. The results were compared with those of sham-operated controls and antioxidant (lazaroid)-treated and captopril-treated rats with CRF. Western blot analysis revealed a significant increase in nitrotyrosine abundance in the cerebral cortex of rats with CRF. This was accompanied by an intense nitrotyrosine staining of the neuronal processes, including proximal segments of dendrites, axons, and axon terminals of the cortical neurons. Both antioxidant therapy and captopril administration alleviated oxidative stress (as evidenced by normalization of plasma lipid peroxidation product malondialdehyde) and significantly reduced nitrotyrosine abundance in the cerebral cortex of the treated CRF group. In conclusion, CRF resulted in oxidative stress and increased tyrosine nitration in the cerebral cortex. Antioxidant therapy and angiotensin-converting enzyme inhibition alleviated the CRF-induced oxidative stress and mitigated tyrosine nitration in the rats with CRF.
First consider the overall process of care
Authors: J C Petrie
Journal: BMJ (1994)

The description of Bochner et al's method deserves critical scrutiny as the subject of drug rationing raises important issues. The argument to ration drugs is based on the wish to obtain the greatest benefit for most patients for each dollar spent on drugs. This premise requires rigorous examination before local drug rationing is applied. Have the authors ensured that they have obtained full value for the money that they spend on drugs and on care services before implementing their rationing policy for drugs? In some health services, for each pounds sterling 100 spent on drugs as little as 15% of value may be obtained.

The price of individual drug entities is only one factor - and a minor factor - in the overall costs of the process of care. Should health professionals not act as advocates to ensure that essential drugs …
Abstract 17796: Pulmonary Artery Hypertension Improves Rapidly In Patients With Severe Aortic Stenosis Who Underwent Transcatheter Aortic Valve Replacement
Authors: Claudiu Stoicescu, Mariuca Vasa-Nicotera, Derek Chin, Dragos Vinereanu, Jan Kovac
Journal: Circulation (2010)

Background: Patients who associate severe aortic stenosis (AS) and severe pulmonary arterial hypertension (PAH) have a bad prognosis. There are poor data on the effect of transcatheter aortic valve...
A randomized trial of open lung biopsy versus empiric antimicrobial therapy in cancer patients with diffuse pulmonary infiltrates.
Authors: M J Browne, D Potter, J Gress, D Cotton, J Hiemenz, M Thaler, J Hathorn, S Brower, V Gill, E Glatstein
Journal: Journal of Clinical Oncology (1990)

Twenty-four cancer patients with diffuse interstitial pneumonitis (DIP) were randomized to undergo an open lung biopsy (OLB) within 8 hours of presentation (12 patients) or to receive empiric antimicrobial therapy (ET) with trimethoprim-sulfamethoxazole (TMP-SMX) erythromycin for a minimum of 4 days (12 patients). Patients whose condition deteriorated underwent an OLB on day 4. Eight of 12 patients (67%) having OLB survived versus 10 of 12 (83%) receiving ET (P = .64). Morbidity occurred in nine of 12 (75%) having OLB versus eight of 12 (67%) receiving ET (P = 1.0). Concurrently, there were 14 additional cancer patients with DIP who were not randomized (nine refused, three had a coagulopathy contraindicating surgery, two were excluded by primary care physicians) and who were comparable demographically to the randomized group. Two received OLB and 12 ET. Combining the randomized and nonrandomized groups, eight of 14 (57%) having an initial OLB survived versus 18 of 24 (75%) of ET-treated patients (P2 = .19). Results of the OLB were seven Pneumocystis carinii pneumonia (PCP), five nonspecific pneumonitis (NSP), one cytomegalovirus, and one lymphoma. Results of OLB led to discontinuation of antibiotics in three patients. Of the 24 ET patients, eight failed to improve by day 4 and had an OLB. Results were two NSP, two PCP, two cancer, one blastomycosis, and one Candida pneumonia. Complications were seen in 10 of 14 (72%) initial OLB patients versus 14 of 24 (58%) patients on the ET arm (P = .65). When the complication rate between patients receiving only empiric antibiotics was compared with all patients having an OLB (initially or on day 4), the difference was greater in patients undergoing OLB (37% v 72%, respectively) (P2 = .14). ET with TMP-SMX plus erythromycin and broad spectrum antibiotics in granulocytopenic patients appeared to be as successful and potentially less toxic than an OLB in this study. Although the number of patients in this study was small, these data suggest that a trial of empiric antibiotic management may be reasonable in cancer patients presenting with DIP, especially if they are nonneutropenic.
A Shorter Halving Time for BCR-ABL transcript Reduction Is a Novel Predictor of Molecular Response Achievement in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia (CML-CP) Patients Treated with Dasatinib: Results of D-First Study
Authors: Maki Hagihara, Noriyoshi Iriyama, Chikashi Yoshida, Shin Fujisawa, Hisashi Wakita, Shigeru Chiba, Naoki Takezako, Kimihiro Kawakami, Shinichiro Okamoto, Koiti Inokuchi, Kazuma Ohyashiki, Takashi Kumagai, Jun Taguchi, Shingo Yano, Tadahiko Igarashi, Yasuji Kouzai, Junichi Sakamoto, Satoshi Morita, Hisashi Sakamaki
Journal: Blood (2014)
Flow Cytometric Screening for Selective Toxicity to Multidrug-Resistant Cells&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: O S Frankfurt
Journal: JNCI Journal of the National Cancer Institute (1987)

Mixed cultures originally containing doxorubicin [(DOX) NCS-123127]-sensitive leukemia P388 (P388/S) cells and DOX-resistant leukemia P388 (P388/R) cells were treated with drugs for 1 hour or with radiation, grown until the cell numbers had increased 250 times (8 cell doublings), and incubated with 2 µg daunorubicin (NCS-82151)/ml for 1 hour. The fluorescence of intracellular anthracycline measured on a flow cytometer was used as a marker to distinguish P388/S and P388/R cells. The proportions of low-fluorescent P388/R cells and high-fluorescent P388/S cells were determined from fluorescence histograms. Selective toxicity for multidrug-resistant P388/R cells was indicated by the decreased proportion of these cells in the mixed cultures. In untreated cultures grown from suspensions containing equal proportions of P388/R and P388/S cells, the mean proportion of P388/R cells after 4 days' growth was 34.4%. DOX eliminated P388/S cells from mixed cultures. Nitrogen mustard [(HN2) NCS-762] and x-rays were selectively toxic to P388/R cells. The selectivity of HN2 and x-rays was observed in a narrow dose range by the absence of selective inhibition at low doses, the decreased proportion of P388/R cells at moderate doses, and the killing of all cells in mixed cultures at high doses. Combination treatment of mixed cultures with DOX plus x-rays, or HN2 plus x-rays, produced complete inhibition of growth. Mixed cultures recovered after treatment with DOX plus HN2 contained only P388/R cells. Results obtained by colony-formation assay showed the same patterns of relative sensitivity for P388/R and P388/S cells as the data obtained by flow cytometry (FCM) selectivity assay. FCM analysis of mixed cultures detected selective toxicity for P388/R cells after treatments, characterized by approximately 1 log higher cell killing of P388/R cells than of P388/S cells. It was concluded that FCM analysis of mixed cultures provided a sensitive and reliable assay for fast screening of drugs for selective toxicity to multidrug-resistant cells.
Childhood Malignancies in Central India
Authors: Shobha Grover, M.D., U. D. Hardas, M.Sc., M.D.
Journal: JNCI Journal of the National Cancer Institute (1972)

From 1966–71, diagnoses of 220 cancers were made in children under 15 years of age in central India. There was a high frequency of Hodgkin's disease, chronic leukemia, retinoblastoma, and oropharyngeal carcinoma and a low frequency of neuroblastoma. The high frequency of retinoblastoma could be attributed partially to greater ease of diagnosis of this visible malignancy. The relatively high frequency of oropharyngeal carcinoma apparently represents the childhood counterpart of a well-known adult predisposition to this form of cancer in India. Analysis of data from the other part of the Indian subcontinent shows considerable variation in the frequency of childhood cancer according to cell type.—J Natl Cancer Inst 49: 953–958, 1972
Adult acute lymphoblastic leukemia: results of the Iowa HOP-L protocol.
Authors: J E Radford, C P Burns, M P Jones, R D Gingrich, J D Kemp, R W Edwards, D B McFadden, F R Dick, B C Wen
Journal: Journal of Clinical Oncology (1989)

Fifty-nine consecutive previously untreated adult patients with acute lymphoblastic leukemia (ALL) were entered onto a prospective single-arm trial of doxorubicin, vincristine, prednisone, and asparaginase (HOP-L) induction therapy followed by CNS prophylaxis and 3 years of maintenance therapy. Consolidation therapy was not administered. The study population included a large number of older (greater than 50 years) patients. Seventy-five percent of patients achieved complete remission. With a median follow-up of 6 years, the median duration of complete remission is greater than 4 years, with 53% of patients expected to remain in remission at both 3 and 5 years. Overall, median survival duration is 27.9 months, with 45% and 35% of all patients expected to survive 3 and 5 years, respectively. Multivariate analysis identified patients with T-cell disease and mediastinal masses (P less than .001) and those with low values of lactic dehydrogenase (LDH) (P = .057) as being at greatest risk of relapse. Therapy was well tolerated by patients under age 35, but older patients suffered appreciable mortality. We conclude that this treatment program is effective therapy for adult ALL, yielding a large proportion of durable remissions despite the exclusion of consolidation therapy.
Novel role of a tyrosine kinase inhibitor by reversion of immune suppression in renal cell carcinoma.
Authors: B. Seliger, A. Mueller, Corinna Giersberg, Diana Handke
Journal: Journal of Clinical Oncology (2010)

e15122 Background: Immune suppression occurs at a high frequency in renal cell carcinoma (RCC) and might contribute to tumor progression and its reversal might be important for the success of T cell-based immunotherapies. It has recently be shown that sunitinib, a receptor tyrosine kinase inhibitor, could reverse the myeloid-derived suppressor cell (MDSC)-mediated immune suppression and prevent tumor-specific T cell anergy as well as the development of regulatory T cells (Treg). Methods: Monolayer and sphaeroid cultures of RCC cells were treated with various concentrations and for different length of time with sunitinib and the expression of HLA class I pathway components and of members of the B7-H family was determined by RT-PCR and flow cytometry. Results: We here show that sunitinib treatment not only reduce the frequency of MDSC and Treg, but also resulted in an enhanced expression of various components of the HLA class I antigen processing machinery (APM), such as e.g. the peptide transporter TAP, tapasin and the HLA class I molecules, and costimulatory molecules in RCC cells, whereas coinhibitory molecules were downregulated under these treatment modalities. This effect was even more pronounced in sphaeroid RCC cultures, which were even more sensitive to the growth inhibitory activity of sunitinib than monolayer cultures. Conclusions: These data suggest that sunitinib is a potential drug to reverse immune suppression not only at the level of immune cells, but also at the level of tumor cells thereby inducing their immunogenicity. No significant financial relationships to disclose.
X-Irradiation-Induced Mitotic Abnormalities in Mouse Liver Regenerating after Carbon Tetrachloride Injury. II. Partial-Body Irradiation&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: Mary Day Albert
Journal: JNCI Journal of the National Cancer Institute (1958)

X-Irradiation-Induced Mitotic Abnormalities in Mouse Liver Regenerating after Carbon Tetrachloride Injury. II. Partial-Body Irradiation Get access Mary Day Albert Mary Day Albert Department of Biology, Brown University, Providence, Rhode Island Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 20, Issue 2, February 1958, Pages 321–328, https://doi.org/10.1093/jnci/20.2.321 Published: 01 February 1958 Article history Received: 24 June 1957 Published: 01 February 1958
Cancer Mortality Among American Indians, 1950–67
Authors: Edward T. Creagan, M.D., Joseph F. Fraumeni, Jr., M.D.
Journal: JNCI Journal of the National Cancer Institute (1972)

During 1950–67, 5,897 deaths among American Indians were attributed to cancer. Gallbladder cancer was the only site for which mortality among Indian males and females was significantly higher than that among both white and black males and females in the United States. Well-documented among Indians are the unusually high rates for a variety of gallbladder diseases: neoplastic, calculous, and inflammatory. Indian females had a significant excess in mortality from cancers of the thyroid, and the nose and paranasal sinuses. However, Indian mortality from all neoplasms combined was significantly lower than expected, especially among males. Deficits in Indian mortality were statistically significant for many cancer sites, particularly large intestine, rectum, lung, prostate, breast, ovary, bladder, and brain, and for Hodgkin's disease. The favorable cancer mortality reported for Indians may be related to their high frequency of diabetes, since other population groups have exhibited a negative correlation between these disorders. The unusual patterns of cancer mortality among Indians suggest advantages in the use of this population for etiologic studies of cancer.—J Natl Cancer Inst 49: 959–967, 1972.
Studies on a Murine Erythroblastosis Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W. H. Kirsten, L. A. Mayer, R. L. Wollmann, M. I. Pierce
Journal: JNCI Journal of the National Cancer Institute (1967)

A murine erythroblastosis virus was recovered during serial cell-free passages of thymic lymphomas from old C3Hf/Gs mice. The virus induced proliferation of red cell precursors, particularly basophilic erythoblasts, in the spleen, bone marrow, and liver of newborn or suckling C3Hf/Gs or DBA/cJ mice. The basophilic erythroblasts multiplied at the expense of the lymphoreticular and myeloid cells. An erythroleukemia was not observed. Erythroblastosis was accompanied by a severe anemia that was probably hemolytic. Virus inoculation into suckling C3Hf/Gs mice doubled the size of the spleen within 25 days; all mice died after a mean survival time of 72 days. Weanling C3Hf/Gs and DBA/cJ were less susceptible than newborn or suckling mice of these strains to viral erythroblastosis; newborn BALB/cJ, AKR, and Swiss mice were resistant. Infectious virus could be recovered from the plasma or liver of infected mice. The erythroblastosis virus was inactivated by heat (56 C for 30 minutes) or ethyl ether. The infectious virus particles from plasma pellets were 80–120 mμ; their density in potassium-citrate gradients was 1.16–1.18 g/cm3. Transmission of erythroblastosis virus from mice to newborn W/Fu rats caused thymic lymphomas after 8–16 months; cell-free passages of the rat thymic lymphomas yielded erythroblastosis after 24–28 days in all rats of the second passage. Erythroblastosis of W/Fu rats was morphologically similar to the disease in mice, except for the large number of normoblasts in the peripheral blood of rats. Cells from erythroblastotic spleens of mice or rats were not transplantable to syngeneic neonatal or adult hosts. The erythroblastosis therefore cannot be considered an autonomous neoplasm.—J Nat Cancer Inst 38: 117–139, 1967.
Dihydropirimidin dehydrogenase (DPD29) single nucleotide polymorphism but not ERCC1, XPD, cytidine deaminase (CD) or DPD543, predicts duration of response to cisplatin/5FU based chemotherapy in oropharyngeal carcinoma
Authors: J. J. Grau, R. Palmero, M. Monzo, L. Alos, A. Navarro, M. Garrido, J. L. Blanch
Journal: Journal of Clinical Oncology (2005)

5547 Background: Single nucleotide polymorphisms (SNPs) correlate with response to chemotherapy. ERCC1 and XPD are DNA repair genes which SNPs predict response to cisplatin in non-small cell lung cancer. CD and DPD are intermediate pathways enzymes in the metabolism of the pirimidine analogues. We evaluated the presence of SNPs of these genes in patients (pts) with oropharyngeal carcinoma and its relationship with chemotherapy response. Methods: We analysed paraffin-embedded biopsies from 24 consecutive pts with locally advanced oropharyngeal carcinoma who received chemoradiotherapy based on platinum (Pt) and 5-fluorouracil (5FU) for SNPs of genes ERCC1 (Lys259Thr), XPD (Lys751Gln), CD intron (in an intronic region T/C), CD (Lys27Gln), DPD543 (Ile543Val) and DPD29 (Arg29Cys). The status of alleles (wild type or at least 1 polymorphism) was correlated with response rate (RR), time to progression (TTP) and overall survival (OS). Results: All 24 pts received Pt (n=24) or 5FU plus Pt (n=19). Overall RR was 75% (16/24) with a median TTP of 12 months (95% CI 6–18m) and a median OS of 32 months (95% CI 14–50m). The status of SNPs was classified as not available/wild type/heterozygous SNP/homozygous SNP, which frequencies were 5/16/3/0 in ERCC1; 2/8/12/2 in XPD; 2/2/10/10 in CD; 2/21/0/1 in CD intron; 1/18/5/0 in DPD543; and 1/15/7/1 in DPD29 respectively. Response rate in DPD29 was 70% for wild type vs 40% for polymorphism (p= 0.656). Only significant differences were seen in TTP between pts with wild type vs polymorphic DPD29 (p=0.037). No difference in survival was observed. Conclusions: SNPs of DPD29 predict duration of response to chemotherapy containing Pt-5FU in pts with oropharyngeal carcinoma. No significant financial relationships to disclose.
Trends in Self-Poisoning: Admissions to a Central London Hospital, 1991–1994
Authors: Christopher J B Mcevedy
Journal: Journal of the Royal Society of Medicine (1997)

Self-poisoning is a common reason for admission to hospital; and, although most patients admitted do not have a psychiatric disorder, as a group they are at greatly increased risk of completed suicide. Admissions to a hospital in Central London over a four-year period were examined with special attention to patients admitted more than once. From 1991 to 1994 admissions for self-poisoning rose by 108%, with larger increases in the younger age groups of both sexes. 9% of patients were admitted more than once, the mean interval to repetition being three months. A third of the repeaters were readmitted within one month. The increase in admissions for self-poisoning, which has been noted elsewhere in the UK, is unlikely to be due wholly to changes in clinical practice. In view of the relation between parasuicide and suicide, further research and analysis is urgently needed.
Prospective assessment of rapid diagnostic tests for the detection of antibodies to hepatitis C virus, a tool for improving access to care
Authors: S. Chevaliez, L. Poiteau, I. Rosa, A. Soulier, F. Roudot-Thoraval, S. Laperche, C. Hézode, J.-M. Pawlotsky
Journal: Clinical Microbiology and Infection (2016)
Role of bismuth in improving<i>Helicobacter pylori</i>eradication with triple therapy
Authors: Maria Pina Dore, Hong Lu, David Y Graham
Journal: Gut (2016)

In most regions of the world, antimicrobial resistance has increased to the point where empirical standard triple therapy for <i>Helicobacter pylori</i> eradication is no longer recommended. The treatment outcome in a population is calculated as the sum of the treatment success in the subpopulation with susceptible infections plus treatment success in the subpopulation with resistant infections. The addition of bismuth (ie, 14-day triple therapy plus bismuth) can improve cure rates despite a high prevalence of antimicrobial resistance. The major bismuth effect is to add an additional 30%–40% to the success with resistant infections. The overall result is therefore dependent on the prevalence of resistance and the treatment success in the subpopulation with resistant infections (eg, with proton-pump inhibitor–amoxicillin dual therapy). Here, we explore the contribution of each component and the mechanisms of how bismuth might enhance the effectiveness of triple therapy. We also discuss the limitations of this approach and provide suggestions how triple therapy plus bismuth might be further improved.
Abstract 11401: Late Initiation of Chronic CaMKII Inhibition Causes Regression in Rat Model of Progressive Heart Failure: Insights into the Underlying Cellular Mechanism
Authors: Qun Shao, Heng-Jie Cheng, Michael F Callahan, Wei-Min Li, Che Ping Cheng
Journal: Circulation (2012)

Background. Excessive activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) is linked to cardiomyopathy and arrhythmias. In heart failure (HF), cardiac CaMKII is upregulated. CaMKII ha...
MCPIP1 Selectively Destabilizes Transcripts Associated with an Antiapoptotic Gene Expression Program in Breast Cancer Cells That Can Elicit Complete Tumor Regression
Authors: Wenbao Lu, Huan Ning, Ling Gu, Hui Peng, Qinghong Wang, Rong Hou, Mingui Fu, Daniel F. Hoft, Jianguo Liu
Journal: Cancer Research (2016)

The ability of cancer cells to evade apoptosis is dictated by a shift in the balance between proapoptotic and antiapoptotic gene expression programs. Monocyte chemotactic protein-induced protein 1 (MCPIP1) is a zinc-finger RNA binding protein with important roles in mediating inflammatory responses. Overexpression of MCPIP1 in different cancer cell types has been implicated in eliciting an antitumor response, but a direct role of MCPIP1 in apoptosis has not been established. In this study, we demonstrate that MCPIP1 functions as a potent tumor suppressor that induces apoptosis of breast tumor cells by selectively enhancing mRNA decay of antiapoptotic gene transcripts, including Bcl2L1, Bcl2A1, RelB, Birc3, and Bcl3. Mechanistically, MCPIP1 physically interacted with a stem-loop structure in the 3' untranslated region of these transcripts through its PIN domain, causing mRNA destabilization. Furthermore, we found that MCPIP1 expression was repressed in breast tumor cells, and overexpression of MCPIP1 induced apoptosis, whereas its depletion enhanced cancer cell proliferation. Moreover, MCPIP1 induction in vivo resulted in complete regression of established tumors and a significant reduction in metastatic disease. Notably, low MCPIP1 expression in tumor samples from breast cancer patients was strongly associated with poor survival over 13 years of follow-up. Collectively, our results highlight that MCPIP1 is a new tumor suppressor in breast cancer that induces cell death by tipping the balance in favor of proapoptotic gene expression.