tbuckley/cabot-search huggingface dataset:
Immunoblastic Leukemia and a Chromosome Marker
Authors: RONALD A. SACHER
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 September 1983Immunoblastic Leukemia and a Chromosome MarkerRONALD A. SACHER, B.SC., M.B., B.CH., D.T.M.&H., MATTHEW J. TEMPLE, PH.D., ADRIANNE P. KELLY, M.D.RONALD A. SACHER, B.SC., M.B., B.CH., D.T.M.&H.Search for more papers by this author, MATTHEW J. TEMPLE, PH.D.Search for more papers by this author, ADRIANNE P. KELLY, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-99-3-411_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Distinctive chromosomal abnormalities in several histologic subtypes of non-Hodgkin's lymphomas have recently been described (1). The authors report two patients with immunoblastic lymphoma who had an unusual t(8;14) chromosomal rearrangement, a finding usually seen in Burkitt's lymphoma, and a rare translocation involving the terminal region of chromosome 8 and the short arm of chromosome 2 at band 2p13. That portion of chromosome 2 codes for the kappa immunoglobulin light chain. It is speculated that when DNA at the breakpoint of donor chromosome 8 (or 18) becomes contiguous with genes involved in immunoglobulin synthesis, lymphomatous transformation may occur....References1. YUNISOKENKAPLANENSRUDHOWETHEOLOGIDES JMMKRA. Distinctive chromosomal abnormalities in histologic subtypes of non-Hodgkin's lymphoma. N Engl J Med. 1982;307:1231-6. CrossrefMedlineGoogle Scholar2. KLEIN G. The role of gene dosage and genetic transpositions in carcinogenesis. Nature. 1981;294:313-8. CrossrefMedlineGoogle Scholar3. MITELMANLEVAN FG. Clustering of aberrations to specific chromosomes in human neoplasms: IV. A survey of 1,871 cases. Hereditas. 1981;95:79-139. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Georgetown University Medical Center Washington, DC 20007 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1983Volume 99, Issue 3Page: 411-411KeywordsBurkitt lymphomaChromosomal translocationsChromosomesDNALymphocytic leukemiaLymphoma Issue Published: 1 September 1983 PDF DownloadLoading ...
Oxidative Stress–Mediated Cardiac Cell Death Is a Major Determinant of Ventricular Dysfunction and Failure in Dog Dilated Cardiomyopathy
Authors: Daniela Cesselli, Igor Jakoniuk, Laura Barlucchi, Antonio P. Beltrami, Thomas H. Hintze, Bernardo Nadal-Ginard, Jan Kajstura, Annarosa Leri, Piero Anversa
Journal: Circulation Research (2001)

Cell death has been questioned as a mechanism of ventricular failure. In this report, we tested the hypothesis that apoptotic death of myocytes, endothelial cells, and fibroblasts is implicated in the development of the dilated myopathy induced by ventricular pacing. Accumulation of reactive oxygen products such as nitrotyrosine, potentiation of the oxidative stress response by p66 shc expression, formation of p53 fragments, release of cytochrome c , and caspase activation were examined to establish whether these events were coupled with apoptotic cell death in the paced dog heart. Myocyte, endothelial cell, and fibroblast apoptosis was detected before indices of severe impairment of cardiac function became apparent. Cell death increased with the duration of pacing, and myocyte death exceeded endothelial cell and fibroblast death throughout. Nitrotyrosine formation and p66 shc levels progressively increased with pacing and were associated with cell apoptosis. Similarly, p50 (ΔN) fragments augmented paralleling the degree of cell death in the failing heart. Moreover, cytochrome c release and activation of caspase-9 and -3 increased from 1 to 4 weeks of pacing. In conclusion, cardiac cell death precedes ventricular decompensation and correlates with the time-dependent deterioration of function in this model. Oxidative stress may be critical for activation of apoptosis in the overloaded heart.
Elevated TNFR1 and Serotonin in Bone Metastasis Are Correlated with Poor Survival following Bone Metastasis Diagnosis for Both Carcinoma and Sarcoma Primary Tumors
Authors: Antonella Chiechi, Chiara Novello, Giovanna Magagnoli, Emanuel F. Petricoin, Jianghong Deng, Maria S. Benassi, Piero Picci, Iosif Vaisman, Virginia Espina, Lance A. Liotta
Journal: Clinical Cancer Research (2013)

There is an urgent need for therapies that will reduce the mortality of patients with bone metastasis. In this study, we profiled the protein signal pathway networks of the human bone metastasis microenvironment. The goal was to identify sets of interacting proteins that correlate with survival time following the first diagnosis of bone metastasis.Using Reverse Phase Protein Microarray technology, we measured the expression of 88 end points in the bone microenvironment of 159 bone metastasis tissue samples derived from patients with primary carcinomas and sarcomas.Metastases originating from different primary tumors showed similar levels of cell signaling across tissue types for the majority of proteins analyzed, suggesting that the bone microenvironment strongly influences the metastatic tumor signaling profiles. In a training set (72 samples), TNF receptor 1, alone (P = 0.0013) or combined with serotonin (P = 0.0004), TNFα (P = 0.0214), and RANK (P = 0.0226), was associated with poor survival, regardless of the primary tumor of origin. Results were confirmed by (i) analysis of an independent validation set (71 samples) and (ii) independent bioinformatic analysis using a support vector machine learning model. Spearman rho analysis revealed a highly significant number of interactions intersecting with ERα S118, serotonin, TNFα, RANKL, and matrix metalloproteinase in the bone metastasis signaling network, regardless of the primary tumor. The interaction network pattern was significantly different in the short versus long survivors.TNF receptor 1 and neuroendocrine-regulated protein signal pathways seem to play an important role in bone metastasis and may constitute a novel drug-targetable mechanism of seed-soil cross talk in bone metastasis.
Psychology in the Curriculum
Authors: D. N. Hardcastle
Journal: BMJ (1933)

SIR,-The death of Sir Robert Jones of Liverpool has taken from us one of the most distinguished of English surgeons, the creator of modern orthopaedic surgery, and the founder of the British School of Orthopaedics.Many of his colleagues, patients, and friends feel that a last tribute should be paid to his memory in recognition of his services to the cause of surgery and to multitudes of patients, and to recall his service to the Army during
Differential regulation of glutathione S-transferases in cultured hepatocytes
Authors: Mark Abramovitz, Seishi Ishigaki, Irving Listowsky
Journal: Hepatology (1989)

Specific cDNA probes were used to determine steady-state mRNA levels for the multiple glutathione S-trans-ferases in primary hepatocyte cultures. In the first 24 hr of culture, gene transcripts for the Ya family decreased sharply, Yb3 disappeared completely, but changes in levels of mRNA for Yb1 and Yb2 were smaller. These results suggest that the isoenzymes are regulated independently. Yp mRNA, which is present at greatly elevated levels in hyperplastic nodules and hepatocel-lular carcinomas but not in normal adult livers, was hardly detectable in freshly isolated hepatocytes, but Yp transcripts rapidly accumulated in the first 24 hr in culture and continued to increase for 72 hr. Decreased levels in Ya and Yc and increases in Yp were detected by immunoblotting methods, indicating that translation products changed together with mRNA levels in the cultured cells. The appearance of Yp transcripts in hepatocytes was effectively blocked by addition of dexa-methasone to the culture medium. Elevations of Yp levels are characteristic of the cell culture system and factors regulating Yp transcription in nodules and carcinomas may also be operative in cultured hepatocytes.
Clinical outcome of progressive stenting in patients with anastomotic strictures after orthotopic liver transplantation
Authors: J. Poley, M. Lekkerkerker, H. Metselaar, E. Kuipers, M. Bruno
Journal: Endoscopy (2013)

<b>Background and study aims:</b> Anastomotic strictures are an important cause of morbidity after orthotopic liver transplantation (OLT). Endoscopic treatment is the primary treatment modality for biliary complications after OLT. The outcome and complications of a progressive stenting protocol are largely unknown. <b>Patients and methods:</b> A longitudinal cohort study of OLTs was conducted. Only patients with late strictures were included. Treatment success was defined as cholangiographic stricture resolution and liver enzymes returning to normal with follow-up of at least 12 months. <b>Results:</b> Between May 2000 and June 2009, 375 OLTs were performed. A duct-to-duct anastomosis was created in 304 cases (81 %). In 63 patients (21 %; 95 % confidence interval [CI] 16.5 % – 25.6 %) an anastomotic stricture developed and progressive stenting was started in 35. During treatment two patients died of a non-treatment-related cause and two patients underwent a second OLT during stent therapy. Therefore 31 patients were available for analysis (male : female 21:10; median age 61 years, range 28 – 75 years). Progressive stenting required a median number of 5 endoscopic retrograde cholangiopancreatography (ERCP) procedures (range 4 – 11). A median maximum of 4 stents (range 2 – 8) were inserted. A total of 21 patients (67.7 %; 95 %CI 50.1 % – 81.4 %) developed a treatment-related complication. In 33 out of a total of 155 ERCPs (21.3 %) a complication occurred: cholangitis (n = 12), transient cholestasis (n = 11), post-ERCP pancreatitis (n = 7), and treatment-related pain (n = 3). The median follow-up time after stent removal was 28 months (range 12 – 92). Treatment was successful in 25 patients (80.6 %; 95 %CI 63.7 % – 90.8 %). <b>Conclusion:</b> Progressive stenting for anastomotic strictures after OLT is demanding and burdensome, necessitating a median of 5 ERCP procedures with complications occurring in one out of five procedures. Its success rate however is high (81 %), avoiding surgery in the large majority of patients.
Dissociation between mitogenicity and immunogenicity of TNP- lipopolysaccharide, a T-independent antigen
Authors: DM Jacobs, DC Morrison
Journal: The Journal of Experimental Medicine (1975)

Two models have been proposed to explain triggering of B cells by so-called T-independent antigen. Feldmann and Basten (1) proposed that the interaction of multiple repeating determinants on polymeric antigens with specific Ig receptors on the B-cell surface is sufficient to provide the signals for division of these cells and differentiation to antibody-forming cells. In contrast, coutinho et al. (2, and see review, 3) have claimed that there is only one signal, a mitogenic signal, receptors acting merely as passive focusing devices to localize the antigen on specific cells where it delivers a mitogenic signal resulting in differentiation to an antibody-producing cell. This model rests primarily on the demonstration that at high concentration all T-independent antigens they have tested are mitogenic for B cells (4-6). Compatible with this hypothesis are the observations that hydrolysis of lipopolysaccharide (LPS) to remove the ester- linked fatty acids of the mitogenic lipid A component abrogates its mitogenic (7,8) activity as well as its ability, when substituted with the TNP hapten, to induce a T-independent anti- TNP response (9). However, alkali treatment of LPS, although not changing its antigenic component (8), may also modify the molecule physically or chemically which could account for loss of immunogenic properties (10). We therefore investigated other reagents which interact with LPS in a more chemically defined manner in an effort to clarify the relationship between the mitogenic and immunogenic properties of this molecule. Polymyxin B (PB) is one of a family of cyclic peptide antibiotics which are bactericidal for most gram-negative bacteria. It prevents the lethal endotoxic activity of LPS (11, 12) and changes the physical structure of LPS (13). We report here that low doses of PB added to cultures of mouse spleen cells inhibit the mitogenic activity of TNP-LPS, a T- independent antigen, and native LPS, but do not suppress the immune response to TNP-LPS. PB interacts with TNP-LPS and LPS causing a physical change in the molecule. In addition, polymyxin-treated LPS is no longer mitogenic. These results suggest a dissociation between the mitogenic and immunogenic properties of TNP-LPS.
Reproductive and hormonal factors and ovarian cancer
Authors: F. Chiaffarino, C. Pelucchi, F. Parazzini, E. Negri, S. Franceschi, R. Talamini, E. Conti, M. Montella, C. La Vecchia
Journal: Annals of Oncology (2001)

Menstrual, reproductive and hormonal factors have been related to ovarian cancer risk, but further quantification of their role in various populations is required.Patients and methods: Cases were 1031 women, below age 79, with incident, histologically confirmed epithelial ovarian cancer, and controls 2411 women, admitted between 1992 and 1999 to a network of hospitals in 4 Italian areas for acute, nonneoplastic, diseases.Odds ratios (OR) were obtained using multiple logistic regression.^/tesw/^Multiparity was associated with a significant reduction in risk of ovarian cancer (OR = 0.6 for 3, and 0.5 for ^4 births).No consistent association was observed with time since first or last birth, nor with spontaneous or induced abortions.Late age at menarche (OR = 0.8), and early menopause (OR = 0.6) were inversely related to risk, as did long-term oral contraceptive use (OR = 0.5, for >5 years).Hormone replacement therapy in menopause was associated with a nonsignificantly elevated risk (OR = 1.4).The pattern of risk was similar for women with and for those without family history of breast or ovarian cancer.Conclusions: This uniquely large study confirms and further quantities the relation between hormonal and reproductive factors and ovarian cancer.The pattern of risk observed cannot be totally explained by a role of ovulation in ovarian carcinogenesis.
Acute adverse reactions attributed to allopurinol in hospitalised patients.
Authors: G T McInnes, D H Lawson, H Jick
Journal: Annals of the Rheumatic Diseases (1981)

Of 29 524 hospitalised medical patients monitored in a drug surveillance programme 1835 (6.2%) received the xanthine oxidase inhibitor allopurinol. After the exclusion of skin reactions adverse effects were attributed to this drug in 33 (1.8%) patients, the most frequent being haematological abnormalities (11 patients, 0.6%) and diarrhoea and drug fever (5 each, 0.3%). Adverse effects were dose-related. Reactions were unrelated to age, weight, reason for therapy, admission blood urea, or albumin concentrations. Acute exacerbation of gout was troublesome in 3 patients (1 in 600 exposed).
Gemcitabine Plus Vinorelbine Compared With Cisplatin Plus Vinorelbine or Cisplatin Plus Gemcitabine for Advanced Non–Small-Cell Lung Cancer: A Phase III Trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group
Authors: Cesare Gridelli, Ciro Gallo, Frances A. Shepherd, Alfonso Illiano, Francovito Piantedosi, Sergio Federico Robbiati, Luigi Manzione, Santi Barbera, Luciano Frontini, Enzo Veltri, Brian Findlay, Silvio Cigolari, Robert Myers, Giovanni P. Ianniello, Vittorio Gebbia, Giampietro Gasparini, Sergio Fava, Vera Hirsh, Andrea Bezjak, Lesley Seymour, Francesco Perrone
Journal: Journal of Clinical Oncology (2003)

Platinum-containing chemotherapy regimens are the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), although toxicity is common and may significantly affect the patient's quality of life (QoL). This trial aimed to assess whether a combination of gemcitabine and vinorelbine had benefits in terms of QoL, without influencing negatively on survival, compared with cisplatin-containing regimens.Patients with stage IIIB (effusion and supraclavicular nodes) or IV documented NSCLC who were younger than 70 years of age were randomly assigned gemcitabine plus vinorelbine (GemVin) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin (cisplatin-based). European Organization for Research and Treatment of Cancer scales were used for QoL analysis.Five hundred one patients were randomly assigned to treatment. The median age was 62 years. There were no significant differences in global QoL scores between the two arms after 2 months of treatment. However, worsening scores for appetite, vomiting, and alopecia were significantly more common in the cisplatin-based arm. Median survival was 38 v 32 weeks and median progression-free survival was 23 v 17 weeks in the cisplatin-based versus GemVin arms, respectively. For the GemVin arm the hazard ratio for death was 1.15 (90% confidence interval [CI], 0.96 to 1.37) and the hazard ratio for progression was 1.29 (90% CI, 1.10 to 1.52). Grade 3 or 4 myelosuppression, vomiting, alopecia, and ototoxicity were significantly more frequent with cisplatin-based treatment.Global QoL is not improved with GemVin, although advantages in some components of QoL were apparent. GemVin is less toxic than standard cisplatin-based chemotherapy. There is a nonsignificant slight survival advantage with cisplatin-based chemotherapy. GemVin could be offered to advanced NSCLC patients who express concern about toxicity.
Government inaction over social injustice is failing children, says Marmot
Authors: Matthew Limb
Journal: BMJ (2015)

Social injustice is “killing 200 000 people in the UK every year” with an average loss of eight years of healthy life, a leading expert on health inequalities has said.

Michael Marmot said that the government, doctors, and other health professionals should do much more to improve healthy life expectancy for all, focusing not just on the poorest people but also on the rich and “people in the middle.” He said that austerity driven economic policies and enforced public health cuts were bad ideas and that the country was “failing children across the whole social gradient.”

Marmot is director of the University College London Institute of Health Equity and in 2010 led the Marmot review of health inequalities, Fair Society, Healthy Lives , for the UK government.

He spoke in London to launch his …
Absence of CD89, Polymeric Immunoglobulin Receptor, and Asialoglycoprotein Receptor on Human Mesangial Cells
Authors: JOSEPH C. K. LEUNG, ANITA W. L. TSANG, DANIEL T. M. CHAN, KAR NENG LAI
Journal: Journal of the American Society of Nephrology (2000)

IgA nephropathy (IgAN) is characterized by raised serum IgA and predominant mesangial IgA deposits of polymeric nature. The expression of IgA receptor molecules in white blood cells and glomerular mesangial cells has recently attracted much attention in relation to the uptake of IgA by these cells. This study investigates the expression of IgA Fc receptor (Fc alphaR1 or CD89), asialoglycoprotein receptor (ASGPR), and polymeric Ig receptor (pIgR) in cultured glomerular mesangial cells. Using a sensitive nested reverse transcription-PCR, mRNA encoding for Fc alphaR1, pIgR, or the H2 chain of ASGPR was not demonstrated on human mesangial cells. U937, HepG2, and HT29 cell lines, used as positive controls, strongly expressed the Fc alphaR1, ASGPR, and pIgR mRNA, respectively, under similar experimental conditions. Flow cytometry also demonstrated the presence of surface proteins for Fc alphaR1, ASGPR, and pIgR on the respective control cell lines but not on human mesangial cells. Expression of Fc alphaR1 mRNA on cultured U937 cells was upregulated by tumor necrosis factor-alpha. However, tumor necrosis factor-alpha, interleukin-1beta, or transforming growth factor-beta failed to induce the expression of Fc alphaR1 on human mesangial cells. Human serum IgA or secretory IgA bound to human mesangial cells, HepG2, or the U937 cell line in a dose-dependent manner. The binding of purified IgA to human mesangial cells was not blocked by preincubation with human IgG, IgM, orosomucoid, asialo-orosomucoid, anti-CD89 antibody (My43), or anti-secretory component antibody. The present study concluded that there was an absence of Fc alphaR1, ASGPR, or pIgR on human mesangial cells. These findings suggest that the predominant binding of human IgA to human mesangial cells is mediated by other mechanisms.
P157 Cancer Patients With Severe Community Acquired Pneumonia Have Poorer Outcomes Due To Increased Illness Severity And Septic Shock At Admission To Intensive Care
Authors: R. Jose, A. Mohammad, J. Goldring, R. Chambers, J. Brown, B. Agarwal
Journal: Thorax (2014)

<h3>Introduction</h3> Patients with community acquired pneumonia (CAP) and an underlying diagnosis of cancer have worse outcomes. However, the characteristics of cancer patients with severe CAP admitted to intensive care units are not well defined. <h3>Methods</h3> An observational study of patients admitted to a University hospital ICU with a primary diagnosis of CAP between January 2006 and October 2011. <h3>Results</h3> 96 patients met our inclusion criteria for a diagnosis of severe CAP. 19 (19.8%) had cancer at the time of admission to ICU (57.9% with haematological malignancy and 42.1% with solid organ cancer). There were no statistically significant differences in age, gender or co-morbidities between those with and those without cancer. Patients with cancer had significantly higher median [IQR] APACHE II (25 [20–19] vs 20 [16–24]; p = 0.009), SAPS (51 [42–62] vs 42 [34–53]; p = 0.039) and SOFA (12 [10–13] vs 9 [4–12]; p = 0.018) scores and a longer median [IQR] time interval between hospital and ICU admission (2 [1–5] vs 1 [0–3] days; p = 0.049). There were no statistically significant differences in the proportion of patients receiving mechanical ventilation or renal support and no differences in the duration of mechanical ventilation or duration of ICU or hospital stay. Patients with cancer included a significantly greater proportion of patients receiving vasopressors (89.5% vs 63.6%, p = 0.030) and a markedly increased ICU (68.4% vs 31.2%, p = 0.004) and hospital mortality (78.9% vs 33.8%, p = 0.001). There were no significant differences in leukocyte counts, CRP, clotting (PT, APTT and INR), renal function (urea and creatinine) or liver function (AST and ALT). There were no significant differences in heart rate, temperature, systolic blood pressure or oxygenation index. However, patients with cancer had significantly lower median diastolic blood pressure (40 mmHg vs 50 mmHg, p = 0.026). <h3>Conclusion</h3> Cancer patients with severe CAP continue to have an increased risk of death that appears to be related to increased illness severity at the time of ICU admission associated with septic shock. A delay in recognising the need for intensive care support in cancer patients with severe CAP may possibly explain the increased illness severity at the time of ICU admission.