tbuckley/cabot-search huggingface dataset:
Cancer Immunotherapy Using Irradiated Tumor Cells Secreting Heat Shock Protein 70
Authors: Chih-Long Chang, Ya-Chea Tsai, Liangmei He, T.-C. Wu, Chien-Fu Hung
Journal: Cancer Research (2007)

Abstract Ovarian cancer is responsible for the highest mortality rate among patients with gynecologic malignancies. Therefore, there is an emerging need for innovative therapies for the control of advanced ovarian cancer. Immunotherapy has emerged as a potentially plausible approach for the control of ovarian cancer. In the current study, we have generated heat shock protein 70 (Hsp70)-secreting murine ovarian cancer cells that express luciferase (MOSEC/luc). Hsp70 has been shown to target and concentrate antigenic peptides in dendritic cells and is also able to activate dendritic cells. We characterized the antigen-specific immune response and the antitumor effect of the MOSEC/luc cells expressing Hsp70 using noninvasive luminescence images to measure the amount of ovarian tumors in the peritoneal cavity of mice. We found that mice challenged with MOSEC/luc cells expressing Hsp70 generate significant antigen-specific CD8+ T-cell immune responses. Furthermore, we also found that mice vaccinated with irradiated MOSEC/luc cells expressing Hsp70 generate significant therapeutic effect against MOSEC/luc cells. In addition, we have shown that CD8+, natural killer, and CD4+ cells are important for protective antitumor effect generated by irradiated tumor cell–based vaccines expressing Hsp70. Moreover, we also found that CD40 receptor is most important, followed by Toll-like receptor 4 receptor, for inhibiting in vivo tumor growth of the viable MOSEC/luc expressing Hsp70. Thus, the use of Hsp70-secreting ovarian tumor cells represents a potentially effective therapy for the control of lethal ovarian cancer. [Cancer Res 2007;67(20):10047–57]
The Small Organic Compound HA14-1 Prevents Bcl-2 Interaction with Bax to Sensitize Malignant Glioma Cells to Induction of Cell Death
Authors: Florence Manero, Fabien Gautier, Tristan Gallenne, Nicolas Cauquil, Danielle Grée, Pierre-François Cartron, Olivier Geneste, René Grée, François M. Vallette, Philippe Juin
Journal: Cancer Research (2006)

Abstract A functional imbalance between proapoptotic Bax and antiapoptotic Bcl-2 is likely to participate in the resistance of cancer cells to therapy. We show here that ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA14-1), a small organic compound recently proposed to function as an inhibitor of Bcl-2, increases the sensitivity of human glioblastoma cells to radiotherapy and chemotherapy. This sensitizing effect is lost if Bcl-2 expression, but not Bcl-xL expression, is knocked down or if cells only express a mutant of Bax that does not interact with Bcl-2. This points to a specific Bcl-2 inhibitory function of HA14-1 and implies that it selectively involves hindrance of Bcl-2 binding to Bax, which HA14-1 inhibits in cell-free assays and in cells in receipt of an apoptotic stimulation. Moreover, HA14-1, in combination with a cytotoxic treatment, slows down the growth of glioblastoma in vivo. Thus, the inhibition of Bcl-2 achieved by HA14-1 might improve treatment outcome. (Cancer Res 2006; 66(5): 2757-64)
Previously Unrecognized Diabetes Mellitus in Sexually Impotent Men
Authors: Stanley Deutsch
Journal: JAMA (1980)

Three-hour oral glucose tolerance tests (GTTs) were performed for 58 men with secondary impotence (SI), 63 with normal sexual function (NL), and 69 with premature ejaculation (PRE). All were apparently nondiabetic. Diagnoses of diabetes and impaired glucose tolerance were based on serum glucose levels during GTT as recently defined by the National Diabetes Data Group. Covariance analysis corrected for weight and age differences. Mean glucose levels in patients with SI were significantly higher at one and two hours after glucose ingestion than in the other groups. Seven patients with SI (12.1%) were found to have diabetes. The three groups did not differ notably in frequency of impaired glucose tolerance. Inorganic serum phosphate levels were lower for the SI group. The high frequency of diabetes in subjects with SI who have no diabetic symptoms (12.1%) suggests that localized neuropathy or penile ischemia may produce impotence in otherwise asymptomatic patients.
Competitive culture does not guarantee improved quality
Authors: Fahmy Hanna
Journal: Journal of the Royal Society of Medicine (2009)

I read with interest your editorial on the change in hospital culture.1 I share your concern about the impact of that on professionals, patients' experience and clinical outcomes.

Starting with the latter and most crucial issue, would a competitive environment result in better outcomes? Data from the literature remain inconclusive. However, there was evidence to suggest that in some sectors of a market culture, there may be insufficient incentive for quality improvement.2 More relevant to the UK was the recent mid-Staffordshire affair, with a Trust being pressurized to satisfy the stringent financial targets, at the expense of staffing levels with serious consequences.3

For most of the last decade, the rhetoric was for more freedom to frontline staff but realistically, the culture has been dominated by top-down approach, ‘Targets and Terror’4 as well as transactional interaction with professionals (e.g. the negotiated consultant and GP contracts). The collective negative impact of those on engaging frontline staff, especially doctors, was blamed for the failure of the ‘Big Bang’ health reforms to make a significant difference in the daily running of the NHS.5

Therefore, it was a breath of fresh air when Lord Darzi announced that there will be no more targets, but more ‘genuine’ frontline engagement.

As you indicated, the only way forward will be for strong clinical leadership especially, having enjoyed seven years of abundance, as we approach the seven years of famine!

The question is, where does Lord Darzi's resignation leave our hopes?
SPECIFIC MURINE B-CELL ACTIVATION BY SYNTHETIC SINGLE- AND DOUBLE-STRANDED POLYNUCLEOTIDES
Authors: Irwin Scher, Douglas M. Strong, Aftab Ahmed, Richard C. Knudsen, Kenneth W. Sell
Journal: The Journal of Experimental Medicine (1973)

The synthetic single- and double-stranded polynucleotides, poly I, poly C, and poly I.C, were shown to induce thymidine incorporation in six inbred strains of murine spleen cells. This stimulation was shown to be secondary to B-cell activation and not due to contamination of the polynucleotides with bacterial lipopolysaccharide (LPS). The ability of poly I.C to act as a B-cell mitogen, in addition to its behavior as a thymic-independent antigen, suggested that these two phenomena may be related. The similarity of the molecular structure of poly I.C to LPS, a material which also acts as a thymic-independent antigen and a B-cell mitogen, supports the hypothesis that the polyvalent nature of these materials accounts for their functional interaction with murine B cells.
Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report
Authors: Weston P. Miller, Steven M. Rothman, David Nascene, Teresa Kivisto, Todd E. DeFor, Richard S. Ziegler, Julie Eisengart, Kara Leiser, Gerald Raymond, Troy C. Lund, Jakub Tolar, Paul J. Orchard
Journal: Blood (2011)
How Doctors Choose Medications to Treat Type 2 Diabetes
Authors: Richard W. Grant, Deborah J. Wexler, Alice J. Watson, William T. Lester, Enrico Cagliero, Eric G. Campbell, David M. Nathan
Journal: Diabetes Care (2007)

Glycemic control remains suboptimal despite the wide range of available medications. More effective medication prescription might result in better control. However, the process by which physicians choose glucose-lowering medicines is poorly understood. We sought to study the means by which physicians choose medications for type 2 diabetic patients.We surveyed 886 physician members of either the Society of General Internal Medicine (academic generalists, response rate 30%) or the American Diabetes Association (specialists, response rate 23%) currently managing patients with type 2 diabetes. Respondents weighed the importance of 15 patient, physician, and nonclinical factors when deciding which medications to prescribe for type 2 diabetic subjects at each of three management stages (initiation, use of second-line oral agents, and insulin).Respondents reported using a median of five major considerations (interquartile range 4-6) at each stage. Frequently cited major considerations included overall assessment of the patient's health/comorbidity, A1C level, and patient's adherence behavior but not expert guidelines/hospital algorithms or patient age. For insulin initiation, academic generalists placed greater emphasis on patient adherence (76 vs. 60% of specialists, P < 0.001). These generalists also identified patient fear of injections (68%) and patient desire to prolong noninsulin therapy (68%) as major insulin barriers. Overall, qualitative factors (e.g., adherence, motivation, overall health assessment) were somewhat more highly considered than quantitative factors (e.g., A1C, age, weight) with mean aggregate scores of 7.3 vs. 6.9 on a scale of 0-10, P < 0.001.The physicians in our survey considered a wide range of qualitative and quantitative factors when making medication choices for hyperglycemia management. The apparent complexity of the medication choice process contrasts with current evidence-based treatment guidelines.
Metabolic Regulation of Immune Responses
Authors: Kirthana Ganeshan, Ajay Chawla
Journal: Annual Review of Immunology (2014)

The immune system defends against pathogens and maintains tissue homeostasis for the life of the organism. These diverse functions are bioenergetically expensive, requiring precise control of cellular metabolic pathways. Although initial observations in this area were made almost a century ago, studies over the past decade have elucidated the molecular basis for how extracellular signals control the uptake and catabolism of nutrients in quiescent and activated immune cells. Collectively, these studies have revealed that the metabolic pathways of oxidative metabolism, glycolysis, and glutaminolysis preferentially fuel the cell fate decisions and effector functions of immune cells. Here, we discuss these findings and provide a general framework for understanding how metabolism fuels and regulates the maturation of immune responses. A better understanding of the metabolic checkpoints that control these transitions might provide new insights for modulating immunity in infection, cancer, or inflammatory disorders.
The role of sperm morphology in assisted reproduction
Authors: T. Kruger
Journal: Human Reproduction Update (1999)

This article attempts to evaluate the value of sperm morphology in assisted reproduction by summarizing a recent structured literature review covering the topic. New developments in the field of sperm morphology with emphasis on computer evaluation of morphology and its latest clinical application are highlighted, as well as the correlation between sperm functional tests and sperm morphology. Based on the correlation between the sperm functional tests and sperm morphology, as well as the latter's proven value as a predictor in in-vitro fertilization, one can assume that sperm morphology reflects function, although based on definition it is not a sperm functional test per se. The evaluation of sperm morphology by strict criteria is a simple, cost-effective method and can be used to guide the clinician and scientist on a day-to-day basis to make sound clinical decisions.
Palliative percutaneous cryoablation in a patient with locally advanced invasive thymoma
Authors: Y. Yamauchi, Y. Izumi, K. Hashimoto, H. Yashiro, M. Inoue, S. Nakatsuka, M. Kawamura, H. Nomori
Journal: European Respiratory Journal (2012)

To the Editors:

Percutaneous cryoablation is considered to be a minimally invasive option for local treatment of cancer [1–3]. Its efficacy is now being documented in many organs, including the prostate, liver, kidney and lung. The goal of ablation procedures is typically complete local tumour control when surgical resection is not indicated, but ablation procedures, such as cryoablation, may also be applicable to the palliative care of cancer patients. Here, we present a case in which percutaneous cryoablation was considered to have contributed to symptom relief in a patient with unresectable, locally advanced, invasive thymoma of the mediastinum. To our knowledge, this is the first report of a needle ablation procedure performed for a mediastinal tumour.

A 29-yr-old female presented with intermittent cough that had existed for 2 yrs and had gradually worsened. An abnormal shadow on chest radiography was identified at another clinic and the patient was referred to our hospital (Division of General Thoracic Surgery, Dept of Surgery, School of Medicine, Keio University, Tokyo, Japan) in July 2004. At that time, she complained of frequent cough and dyspnoea. She could not lay flat on her back. Biopsy through parasternal mediastinotomy [4, 5] was performed, from which the pathological diagnosis was thymoma, type B3, according to the World Health Organization classification. The tumour was considered to be …
Effects of Exercise Training on Antitumor Efficacy of Doxorubicin in MDA-MB-231 Breast Cancer Xenografts
Authors: Lee W. Jones, Neil D. Eves, Kerry S. Courneya, Brian K. Chiu, Vickie E. Baracos, John Hanson, Lorelei Johnson, John R. Mackey
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Exercise is becoming readily accepted as a beneficial adjunct therapy to maintain or enhance quality of life in breast cancer patients undergoing adjuvant chemotherapy. An essential precursor to these studies is to investigate whether exercise modulates the antitumor efficacy of chemotherapeutic agents. Experimental Design: Athymic female mice were transplanted with MDA-MB-231 breast xenografts and randomly assigned to one of four groups (n = 21 per group): (a) control, (b) exercise-only, (c) doxorubicin-only, or (d) exercise + doxorubicin. Exercise groups performed progressive treadmill running up to 18 m/min at 0% grade for 45 minutes, 5 d/wk for 8 weeks. Results: Tumor growth delay was significantly longer in the doxorubicin-only and exercise + doxorubicin groups compared with the control (median 42 versus 25 days, P = 0.0082; 36 versus 25 days, P = 0.029, respectively) and exercise-only groups (median 42 versus 25 days, P = 0.029; 36 versus 25 days, P = 0.080, respectively). There was no significant difference between the doxorubicin-only and exercise + doxorubicin groups (median 42 versus 36 days, P = 0.33), suggesting that moderate intensity exercise does not significantly influence doxorubicin-induced tumor growth delay. Conclusion: These studies are essential to fully understand the safety and application of exercise as a supportive intervention in cancer control.
Caveats in treating thyroid disease: practical implications
Authors: G I Varughese, A A Tahrani, J Davis, R N Clayton, F W F Hanna
Journal: Journal of the Royal Society of Medicine (2006)

This case concerns a 47-year-old woman who was initially diagnosed as having primary hypothyroidism nearly four years prior to this incident; on treatment with levothyroxine sodium (LT4) 150 mg daily. Despite reasonable doses of LT4, and being fully compliant with her therapy, at no stage was her TSH less than 20 mU/L (Table 1). Malabsorption was ruled out and there were no clinical features to suggest this. When the patient was reviewed in the endocrine clinic, she was advised to take the tablets on an empty stomach (rather than with the white tea and breakfast that she had regularly been having immediately following her LT4 tablets). On subsequent follow-up four months later, the TFTs had improved on the same dose of LT4 and she had lost nearly 2 kg in weight despite the ‘Christmas Effect’, as she described it, and she felt well in herself. Subsequent TFTs continue to remain in the reference range with the altered timing of intake of LT4.
On Intrauterine Fractures: With an Illustrative Case
Authors: T. H. Barker
Journal: BMJ (1857)

substance of the lungs looked otherwise healthy.The bronchial glands contained large masses of crude tubercle.The glands in the gastro-hepatic omentum were similarly affected.The liver contained a copious deposit of miliary tubercle, as did the spleen.The other viscera seemed healthy.REMrARKs.Of all the varieties of strumous disease which directly threaten life, there is none more insidious than its deposition on the brain, unless, indeed, it be that in the suprarenal capsules.We have often seen its presence proved by post mortem exaamination in cases where it seemed impos- sible to determine from the symiptoms what the brain disease was, or, indeed, whether it were not merely functional disturb- ance owning some remote cause, and accompanied bv no organic lesion; still oftener we have seen its absence demonstrated where it had been pretty confidently predicted.Hence it may not be useless, as a matter bearing on diagnosis, to study the two cases (iII and iv) quoted above, even though the disease is beyond our present methods of treatment.In the first, so constant were the symptonms, and so distinct the functions which were interfered with, that Dr. Fuller was enabled, even without the evidence usually furnished by the presence of strumous disease in other organs, to indicate the nature and seat of the disease during life.The persistence of the same symptoms, and the evidence of pressure on one limited portion of the brain, denoted the presence of some solid deposit: the age of the patient, his appearance and constitution, with the history of the case, rendered it highly probable, at any rate, that this was of the nature of strumous tubercle.The well ORIGtINAL COMM1UNICATIONS.
Melanoma cells and normal melanocytes share antigens recognized by HLA-A2-restricted cytotoxic T cell clones from melanoma patients.
Authors: A Anichini, C Maccalli, R Mortarini, S Salvi, A Mazzocchi, P Squarcina, M Herlyn, G Parmiani
Journal: The Journal of Experimental Medicine (1993)

HLA-A2-restricted, CD3+, CD8+, alpha/beta+ cytotoxic T cell (CTL) clones were isolated from peripheral blood (PBL) or tumor infiltrating lymphocytes (TIL) of two HLA-A2+ melanoma patients (9742 and 5810), to evaluate the possible recognition of autologous melanoma and of allogeneic HLA-A2-matched normal melanocytes. These CTL clones lysed not only fresh and cultured autologous melanoma cells, but also allogeneic HLA-A2+, but not HLA-A2-, normal melanocytes. The lysis of autologous neoplastic cells and of melanocytes could be inhibited by an anti-HLA-A2 monoclonal antibody (mAb). Lysis of the normal melanocytes was not dependent on the presence of human or fetal calf serum in the culture medium. HLA-A2-restricted CTL clones recognized not only proliferating melanocytes cultured in complete melanocyte medium, but also melanocytes made quiescent by culture for up to 6 d in a basal medium devoid of exogenous factors such as phorbol ester (O-tetradecanoyl phorbol 13-acetate [TPA]), epidermal growth factor, insulin, and pituitary extracts. Analysis of specificity of four CTL clones (A75, A83, A94, and 119) from patient 9742, performed on a panel of 39 targets, indicated that the three HLA-A2-restricted CTL (A75, A83, and A94) lysed all but one of nine allogeneic melanomas expressing the HLA-A2 molecule with no reactivity on nine HLA-A2- allogeneic melanomas. Only a few instances of borderline reactivity were seen by the same effectors on 21 targets of nonmelanocyte lineage, including 12 carcinomas of different histology, four Epstein-Barr virus-transformed B cells (lymphoblastoid cell lines [LCL]), including the autologous LCL, four lines of normal fibroblasts, and normal kidney cells. Lack of reactivity on allogeneic targets of nonmelanocyte lineage occurred in spite of expression of HLA-A2 on 14 of these targets as determined by conventional tissue typing and cytofluorimetric analysis with four different anti-HLA-A2 mAb. These data indicate that tissue-related antigens can be expressed on normal and neoplastic cells of the melanocyte lineage and can be recognized in association with HLA-A2 by CTL clones from melanoma patients.
γδ T cell–induced hyaluronan production by epithelial cells regulates inflammation
Authors: Julie M. Jameson, Gabrielle Cauvi, Leslie L. Sharp, Deborah A. Witherden, Wendy L. Havran
Journal: The Journal of Experimental Medicine (2005)

Nonhealing wounds are a major complication of diseases such as diabetes and rheumatoid arthritis. For efficient tissue repair, inflammatory cells must infiltrate into the damaged tissue to orchestrate wound closure. Hyaluronan is involved in the inflammation associated with wound repair and binds the surface of leukocytes infiltrating damaged sites. Skin γδ T cells play specialized roles in keratinocyte proliferation during wound repair. Here, we show that γδ T cells are required for hyaluronan deposition in the extracellular matrix (ECM) and subsequent macrophage infiltration into wound sites. We describe a novel mechanism of control in which γδ T cell–derived keratinocyte growth factors induce epithelial cell production of hyaluronan. In turn, hyaluronan recruits macrophages to the site of damage. These results demonstrate a novel function for skin γδ T cells in inflammation and provide a new perspective on T cell regulation of ECM molecules.
Effect of Theophylline and Adrenergic Blocking Drugs on the Renin Response to Norepinephrine In Vitro
Authors: HECTOR L. NOLLY, IAN A. REID, WILLIAM F. GANONG
Journal: Circulation Research (1974)

The effects of norepinephrine, theophylline, and adrenergic blocking drugs on renin release from rat kidney slices were studied in vitro. l -Norepinephrine increased renin release into the incubation medium; this increase was accompanied by an increase in the renin content of the slices. Statistically significant increases in renin release were produced by 10 -5 M and 2 x 10 -5 M l -norepinephrine. d -Norepinephrine in the same doses was ineffective. Theophylline (10 -3 M ) had no effect by itself, but it potentiated the effect of l -norepinephrine on renin release. The response to l -norepinephrine was markedly suppressed by l -propranolol (10 -4 M ) but not by d -propranolol (10 -4 M ). The α-receptor blocking agents phentolamine (10 -4 M ) and phenoxybenzamine (10 -4 M ) increased rather than decreased the effect of l -norepinephrine. These results are consistent with a direct intrarenal effect of norepinephrine on renin release; this effect appears to be mediated by a β-adrenergic mechanism.