tbuckley/cabot-search huggingface dataset:
Kuljit Gill (née Sidhu)
Journal: BMJ (2006)

​FormerFormer general practitioner Nuneaton (b 1935; q Jaipur Medical College, India, 1959; DA), d 9 May 2006.



Figure 1



Kuljit moved to the United Kingdom in 1961 with her husband, Rajindra. After various junior hospital jobs she worked as a registrar in anaesthetics at the General Hospital in Bishop Auckland, County Durham. She entered general practice in 1981, later becoming a senior partner in Nuneaton. She was in general practice for several years, her particular interests being paediatrics and the care of the elderly. Outside the practice Kuljit had many creative interests, including gardening, cooking, entertaining, and needlecraft. After retirement from medicine she achieved success as a designer under the name of Kuljit Sidhu. She leaves a husband and two children.
Phosphoinositide 3-kinase required for lipopolysaccharide-induced transepithelial neutrophil trafficking in the lung
Authors: J. Reutershan, M. S. Saprito, D. Wu, T. Ruckle, K. Ley
Journal: European Respiratory Journal (2009)

Phosphoinositide 3-kinase γ(<i>PI3Kγ</i>) is a critical mediator of directional cell movement. Here, we sought to characterise the role of <i>PI3Kγ</i> in mediating the different steps of polymorphonuclear leukocyte (PMN) trafficking in the lung. In a murine model of lipopolysaccharide (LPS)-induced lung injury, PMN migration into the different lung compartments was determined in <i>PI3Kγ</i> gene-deficient (<i>PI3Kγ<sup>-/-</sup></i>) and wild-type mice. Bone marrow chimeras were created to characterise the role of <i>PI3Kγ</i> on haematopoietic <i>versus</i> nonhaematopoietic cells. A small-molecule <i>PI3Kγ</i> inhibitor was tested <i>in vitro</i> and <i>in vivo</i>. PMN adhesion to the pulmonary endothelium and transendothelial migration into the lung interstitium was enhanced in <i>PI3Kγ<sup>-/-</sup></i> mice. However, transepithelial migration into the alveolar space was reduced in these mice. When irradiated <i>PI3Kγ<sup>-/-</sup></i> mice were reconstituted with bone marrow from wild-type mice, migratory activity into the alveolar space was restored partially. A small-molecule <i>PI3Kγ</i> inhibitor reduced chemokine-induced PMN migration <i>in vitro</i> when PMNs or epithelial cells, but not when endothelial cells, were treated. The inhibitor also reduced LPS-induced PMN migration <i>in vivo</i>. We conclude that <i>PI3Kγ</i> is required for transepithelial but not for transendothelial migration in LPS-induced lung injury. Inhibition of <i>PI3Kγ</i> activity may be effective at curbing excessive PMN infiltration in lung injury.
Obesity in the Elderly Diabetic Patient
Authors: Ioannis Kyrou, Constantine Tsigos
Journal: Diabetes Care (2009)

Obesity and type 2 diabetes constitute major public health issues in modern societies worldwide. Their prevalence on a global scale is alarming, and efforts to control their spread represent a priority of the public health agenda (1). Obesity is clearly driving a parallel epidemic of associated chronic diseases in all age-groups, including type 2 diabetes, hyperlipidemia, hypertension, atherosclerosis, obstructive sleep apnea, and liver dysfunction. Considerable attention is currently being focused on the consequences of obesity in vulnerable populations at both ends of the age spectrum, namely in youth and in the elderly.

Elderly people, defined as individuals >65 years of age, comprise a substantial and growing part of the population in developed countries. Current demographic data in Western societies report that 12–15% of the general population is over the age of 65 years, and this proportion is projected to reach 20–25% by the year 2030 (2). Moreover, in the last 2 decades, the rate of obesity has risen dramatically among older adults, independently of sex, race, and educational level (3). This obesity epidemic significantly affects the health status of the geriatric population, since excess body weight in the elderly also correlates strongly with chronic ill health, poor quality of life, functional decline, disability, and dependency (4).

Conversely, evidence suggests that obesity in the elderly is probably not associated with the same risks as in younger individuals, while in certain aspects, can even be protective (5). Furthermore, the prevalence of underweight is higher among older adults, who are also more vulnerable to unintentional weight loss either as a result of illness, or due to the aging process itself.

The objective of this article is to assess the benefits relative to risks of weight loss that may be attained in the geriatric population, with special reference to the elderly diabetic patient. …
IMMUNOPATHOGENESIS OF ACUTE CENTRAL NERVOUS SYSTEM DISEASE PRODUCED BY LYMPHOCYTIC CHORIOMENINGITIS VIRUS
Authors: Donald H. Gilden, Gerald A. Cole, Andrew A. Monjan, Neal Nathanson
Journal: The Journal of Experimental Medicine (1972)

A single dose of 150 mg/g of cyclophosphamide (CY), given 3 days after intracerebral (i.c.) inoculation of lymphocytic choriomeningitis (LCM) virus, protected over 90% of adult BALB/c mice against acutely fatal choriomeningitis. Surviving mice became persistently infected carriers, with high virus titers in blood and brain. Immunofluorescent examination of the brain showed that in CY-induced carriers infection was initially confined to the choroid plexus, ependyma, and leptomeninges, but over the next 30 days gradually spread to the neural parenchyma, most notably to the molecular layer of the cerebellum. By contrast, LCM virus-carrier mice produced by neonatal virus injection and examined as adults, showed a much less marked infection of choroid plexus and much more widespread infection of parenchyma, with a different distribution among brain nuclei, including heavy infection of the Purkinje cells of the cerebellum.
Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity
Authors: Francis Mussai, Sharon Egan, Stuart Hunter, Hannah Webber, Jonathan Fisher, Rachel Wheat, Carmel McConville, Yordan Sbirkov, Kate Wheeler, Gavin Bendle, Kevin Petrie, John Anderson, Louis Chesler, Carmela De Santo
Journal: Cancer Research (2015)

Neuroblastoma is the most common extracranial solid tumor of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not matched preclinical results. Here, we describe key mechanisms in which neuroblastoma inhibits the immune response. We show that murine and human neuroblastoma tumor cells suppress T-cell proliferation through increased arginase activity. Arginase II is the predominant isoform expressed and creates an arginine-deplete local and systemic microenvironment. Neuroblastoma arginase activity results in inhibition of myeloid cell activation and suppression of bone marrow CD34(+) progenitor proliferation. Finally, we demonstrate that the arginase activity of neuroblastoma impairs NY-ESO-1-specific T-cell receptor and GD2-specific chimeric antigen receptor-engineered T-cell proliferation and cytotoxicity. High arginase II expression correlates with poor survival for patients with neuroblastoma. The results support the hypothesis that neuroblastoma creates an arginase-dependent immunosuppressive microenvironment in both the tumor and blood that leads to impaired immunosurveillance and suboptimal efficacy of immunotherapeutic approaches.
Expression of the Deleted in Colorectal Cancer Gene Is Related to Prognosis in DNA Diploid and Low Proliferative Colorectal Adenocarcinoma
Authors: Xiao-Feng Sun, Sabine Rütten, Hong Zhang, Bo Nordenskjöld
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Whether or not the deleted in colorectal cancer (DCC) gene is implicated in metastases or in predicting prognosis in patients with colorectal cancer has not previously been substantiated. Our aims were to investigate DCC expression in primary colorectal cancers and in metastases to identify any prognostic significance. PATIENTS AND METHODS: DCC expression was examined immunohistochemically in 195 primary colorectal adenocarcinomas and in 23 paired primary tumors and lymph node metastases. DNA content and S-phase fraction were measured by flow cytometry. RESULTS: The absence of DCC expression was observed in 55 primary tumors (28%). DCC negativity was significantly related to poor prognosis in patients with DNA diploid tumors (P = .03) and those with a low S-phase fraction (&lt; 5%, P = .02) but not in patients with nondiploid tumors or those with a higher S-phase fraction. Furthermore, DCC expression retained its prognostic significance in the diploid subgroup after adjusting for sex, age, site, stage, growth pattern, and differentiation (P = .01). DCC expression was similar in primary tumors and their metastases. CONCLUSION: The absence of DCC predicted a poor outcome in the patients with diploid tumors and those tumors with a low S-phase fraction. Immunohistochemistry may be considered as a practical test to assess prognosis in this subgroup of patients.
Role of CYP2E1 in Diethylnitrosamine-Induced Hepatocarcinogenesis <i>In vivo</i>
Authors: Jin Seok Kang, Hideki Wanibuchi, Keiichirou Morimura, Frank J. Gonzalez, Shoji Fukushima
Journal: Cancer Research (2007)

Abstract CYP2E1 metabolizes many low–molecular weight toxins and carcinogens. Some in vitro experiments suggest that CYP2E1 may be involved in the metabolic activation of diethylnitrosamine. However, there has been no direct evidence demonstrating a role for CYP2E1 in diethylnitrosamine-mediated carcinogenesis in vivo. To clarify this, we carried out a diethylnitrosamine-induced hepatocarcinogenesis experiment using Cyp2e1-null mice. Male 14-day-old wild-type and Cyp2e1-null mice were treated with diethylnitrosamine (10 mg/kg of body weight) and killed at weeks 24 and 36 after diethylnitrosamine treatment for investigation of tumors and at 6, 24, and 48 h for examination of apoptosis and gene expression. Liver weights of Cyp2e1-null mice were significantly different at weeks 24 and 36 compared with wild-type mice (P &amp;lt; 0.01). Liver tumor incidences of Cyp2e1-null mice were significantly decreased at weeks 24 and 36 compared with wild-type mice (P &amp;lt; 0.01). Cyp2e1-null mice showed significant decrease in the multiplicities of hepatocellular adenoma at weeks 24 and 36 (P &amp;lt; 0.05 and P &amp;lt; 0.01, respectively), and of hepatocellular carcinoma at week 36 (P &amp;lt; 0.01) compared with wild-type mice. Apoptotic index and caspase-3 and/or Bax mRNA expression of Cyp2e1-null mice were significantly different at 6, 24, and 48 h after diethylnitrosamine treatment compared with wild-type mice (P &amp;lt; 0.05). We conclude that Cyp2e1-null mice show lower tumor incidence and multiplicity compared with wild-type mice in diethylnitrosamine-induced hepatocarcinogenesis. It is suggested that CYP2E1 completely participates in diethylnitrosamine-induced hepatocarcinogenesis, and high frequency of tumors in wild-type mice could be associated with the increased apoptosis. [Cancer Res 2007;67(23):11141–6]
Genome-Wide Analysis of Epigenetic Silencing Identifies <i>BEX1</i> and <i>BEX2</i> as Candidate Tumor Suppressor Genes in Malignant Glioma
Authors: Greg Foltz, Gi-Yung Ryu, Jae-Geun Yoon, Timothy Nelson, Jessica Fahey, Amanda Frakes, Hwahyung Lee, Lorie Field, Kaitlin Zander, Zita Sibenaller, Timothy C. Ryken, Rajeev Vibhakar, Leroy Hood, Anup Madan
Journal: Cancer Research (2006)

Abstract Promoter hypermethylation and histone deacetylation are common epigenetic mechanisms implicated in the transcriptional silencing of tumor suppressor genes in human cancer. We treated two immortalized glioma cell lines, T98 and U87, and 10 patient-derived primary glioma cell lines with trichostatin A (TSA), a histone deacetylase inhibitor, or 5-aza-2′-deoxycytidine (5-AzaC), a DNA methyltransferase inhibitor, to comprehensively identify the cohort of genes reactivated through the pharmacologic reversal of these distinct but related epigenetic processes. Whole-genome microarray analysis identified genes induced by TSA (653) or 5-AzaC treatment (170). We selected a subset of reactivated genes that were markedly induced (greater than two-fold) after treatment with either TSA or 5-AzaC in a majority of glioma cell lines but not in cultured normal astrocytes. We then characterized the degree of promoter methylation and transcriptional silencing of selected genes in histologically confirmed human tumor and nontumor brain specimens. We identified two novel brain expressed genes, BEX1 and BEX2, which were silenced in all tumor specimens and exhibited extensive promoter hypermethylation. Viral-mediated reexpression of either BEX1 or BEX2 led to increased sensitivity to chemotherapy-induced apoptosis and potent tumor suppressor effects in vitro and in a xenograft mouse model. Using an integrated approach, we have established a novel platform for the genome-wide screening of epigenetically silenced genes in malignant glioma. This experimental paradigm provides a powerful new method for the identification of epigenetically silenced genes with potential function as tumor suppressors, biomarkers for disease diagnosis and detection, and therapeutically reversible modulators of critical regulatory pathways important in glioma pathogenesis. (Cancer Res 2006; 66(13): 6665-74)
Comparative evaluation of homeopathy and allopathy within the Parisian hospital system, 1849–1851
Authors: Michael Dean
Journal: Journal of the Royal Society of Medicine (2010)

Jean-Paul Tessier (1811–62) was a former student of the physiologist Francois Magendie (1783–1855) and the surgeon Guillaume Dupuytren (1777–1835). He was still a rising star in the competitive Parisian hospital system in 1846 or 1847 when, on Magendie’s advice, he began his investigation of homeopathy. This was a brave move, as the powerful Academie de Medecine had debated and formally rejected homeopathy a few years earlier. Nevertheless, the new therapy had continued to spread throughout France. After three years of research, Tessier recounted the precise steps he had taken to understand and evaluate homeopathy before making it part of his hospital practice. He had begun by studying the general principles of the therapy in the works of Hahnemann and his disciples, before moving on to accounts of treatments for specific illnesses. Next came a six-month test to ascertain the safety and biological activity of the medicines. For this he chose patients with acute or chronic illnesses whom he judged unlikely to be harmed by the treatment. Convinced after a few days that the highly dilute homeopathic drugs were both harmless but medicinally active, he continued with the study for the six months originally planned. Only then was he confident enough to begin testing the ‘therapeutic value’ [original stress] of homeopathy. Tessier then reported the results of treatment from two prospective case series in pneumonia and cholera. He chose pneumonia for the first series because it was a well-known disease, which was considered to have a clear diagnosis and prognosis. Before his study, Tessier had applied the standard treatments of bleeding, vesicants and antimony tartrate, but abandoned each of these successively as he found patients responded better without them. To counter bias in reporting the effects of his own experimental treatments, Tessier arranged for two allopathic interns to make the observations and write the reports. Of 41 consecutive patients with a firm diagnosis of pneumonia treated with homeopathy, only three died. He observed that treatment of pneumonia exclusively with homeopathy appeared to be associated with similar results on the symptoms, progression and duration of the condition, regardless of the patient’s age, and he called for the method to be tested further. Tessier’s cholera results were more ambiguous, although comparison with the mortality in a parallel allopathic ward in the same hospital favoured homeopathy.
Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis
Authors: Dipak Kotecha, Jane Holmes, Henry Krum, Douglas G Altman, Luis Manzano, John G F Cleland, Gregory Y H Lip, Andrew J S Coats, Bert Andersson, Paulus Kirchhof, Thomas G von Lueder, Hans Wedel, Giuseppe Rosano, Marcelo C Shibata, Alan Rigby, Marcus D Flather
Journal: The Lancet (2014)
Serum tumour markers in lung cancer: history, biology and clinical applications
Authors: D Ferrigno, G Buccheri, A Biggi
Journal: European Respiratory Journal (1994)

The association of biological markers with cancer has been recognized for many decades. Current interest in markers for cancer arose in the mid 1960s, with the discoveries of alpha-fetoprotein and carcinoembryonic antigen. They were called oncofetal proteins, because of their presence in high concentrations during embryonic development, their virtual disappearance in the neonatal period, and their reappearance with cancers of specific cell types. Essentially, any molecular species may be produced in abnormal amounts or under abnormal circumstances by a tumour, and thereby become useful as a tumour marker. Several tumour markers have been studied in lung cancer. Unfortunately, none of these appear to be sufficiently sensitive and specific to be reliable for screening and diagnostic purposes. However, there is a body of evidence which proves that at least some of these substances may be useful in the evaluation of the course and prognosis of the disease. This review presents data concerning the most studied and interesting tumour markers in lung cancer.
An Embarrassment of Riches: Neoadjuvant Therapy of Rectal Cancer
Authors: Joel E. Tepper, Richard M. Goldberg
Journal: Journal of Clinical Oncology (2005)

Two decades ago, therapy for locally advanced rectal cancer included surgery followed by additional radiation therapy or fluorouracil (FU) chemotherapy. The principles of surgery for rectal cancer included the freeing of the rectum from the surrounding mesorectal tissues via blunt dissection with a low anterior, sphincter-sparing resection whenever possible. Sphincter preservation was rarely accomplishedfortumorswithinreachoftheexaminingfinger on rectal examination. With the exception of the introduction of mechanical stapling devices permitting low anterior resections for low-lying lesions, surgical techniques remained static for decades. Single-agent FU was delivered in a bolus technique, as it had been since the 1960s, and radiation therapy, although technically improved, was similar to that used in the 1950s. Adjuvant therapy was embracedbymanyinthe1980s;intheearly1990stheresultsof randomized trials led a National Cancer Institute Consensus Conference to endorse the use of postoperative radiation therapy and chemotherapy for patients with T3 or node-positive disease. In contrast, the last decade has brought enormous ad
Management of Metastatic Cervical Cancer: Review of the Literature
Authors: Harry J. Long
Journal: Journal of Clinical Oncology (2007)

This article reviews the English-language literature concerning chemotherapy for advanced, recurrent, or metastatic cervix carcinoma. Specifically, it reviews the available literature for active single agents, doublets, triplets, and multiple drug combination chemotherapy. Until recently, single-agent cisplatin was the drug of choice in metastatic cervix cancer. Various doublets, triplets, and quartlets have been reported to have higher objective response rates than single-agent cisplatin when compared in phase III clinical trials. Some have demonstrated improvements in progression-free survival, but only topotecan plus cisplatin has demonstrated an improvement in overall survival. This benefit is most apparent in patients who have a long disease-free interval from primary therapy and who have not received prior cisplatin as a radiosensitizer.
IMMUNOGLOBULIN MOLECULES ON THE SURFACE OF ACTIVATED T LYMPHOCYTES IN THE RAT
Authors: Irving Goldschneider, Ronald B. Cogen
Journal: The Journal of Experimental Medicine (1973)

Lewis strain rat lymphocytes were exposed in vitro to a variety of specific and nonspecific blastogenic stimuli. The surfaces of the transformed lymphocytes were examined by indirect immunofluorescence for the presence of T cell antigens and immunoglobulin molecules. More than 90% of lymphocytes that underwent blast transformation after exposure to foreign histocompatibility antigens (mixed lymphocyte reaction; in vitro allograft reaction), purified tuberculin, phytohemagglutinin (PHA), and concanavalin A (Con-A) had T cell antigenic markers on their surfaces. 70-92% of the antigen-stimulated blast cells also had readily detectable surface immunoglobulin molecules, whereas less than 3% of the PHA- and Con-A-activated cells were Ig(+). Pokeweed mitogen (PWM) appeared to activate both B and T cells, but the T cells did not have detectable surface immunoglobulin molecules. Nonactivated control cultures contained T(+)Ig(-) lymphocytes almost exclusively. The results suggest that thymus-dependent rat lymphocytes express increased amounts of detectable immunoglobulin on their surface in response to specific stimulation with antigen. It is postulated that the acquisition of immunological competence by activated T cells may be related to this expression of surface immunoglobulin.
Syncytin: the major regulator of trophoblast fusion? Recent developments and hypotheses on its action
Authors: A.J.G. Pötgens, S. Drewlo, M. Kokozidou, P. Kaufmann
Journal: Human Reproduction Update (2004)

Syncytin is a membrane protein derived from the envelope gene of an endogenous retrovirus of the HERV-W family. The gene appears to be almost exclusively expressed in placenta; the protein was found in particular in syncytiotrophoblast. After transfection into various cell types it has proven to be a very fusogenic protein, inducing the formation of syncytia. Therefore, the question rises as to whether syncytin is responsible for the fusion process of villous cytotrophoblast into syncytiotrophoblast in vivo. If so, how is this fusion process regulated if syncytin is found all over the syncytiotrophoblast? Can this process be regulated through local or temporal changes in syncytin expression, or is syncytin merely one factor in a cascade of events leading to fusion limited at some other level? This review will try to summarize the published data on the regulation of fusion in trophoblast models as well as on the localization and regulation of syncytin expression and of its presumed receptors. Assuming that syncytin is the key factor inducing trophoblast fusion, a number of models will be presented by which syncytin and/or its receptors might regulate this process. In some of the hypotheses proposed, local coexpression of syncytin and receptor, leading to blocking of one factor by the other, is of functional relevance.