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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jtcvs.2010.03.009 Byline: David Gomez-de-Antonio (a), Mercedes Zurita (b), Martin Santos (c), Isabel Salas (d), Jesus Vaquero (b)(c), Andres Varela (a) Abbreviations: BMSC, bone marrow stromal cell; BrdU, 5-bromo-2'-deoxyuridine; GFP, green fluorescent protein; PBS, phosphate-buffered saline Abstract: Bronchial stump dehiscence is still the most feared complication for the thoracic surgeon, with mortality rates ranging from 25% to 75%. This study reports the histologic effect of adult stem cells in the healing process of the bronchial stump after lung resection. Author Affiliation: (a) Thoracic Surgery Department, Thoracic Surgery, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain (b) Neuroscience Laboratory, Thoracic Surgery, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain (c) Surgical Research Department, Thoracic Surgery, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain (d) Pathology Department, Thoracic Surgery, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain Article History: Received 11 January 2010; Revised 23 February 2010; Accepted 12 March 2010 Article Note: (footnote) Disclosures: None.

The development of new vaccines has progressed from an empirical approach to more sophisticated vaccine design. This has been enabled by advances in our understanding of the immune system and by improvements in immunological tools, particularly the use of new adjuvant combinations. It is now possible to combine an antigen with a specific adjuvant system to design effective vaccines that provide an immune response tailored for each vaccine. The clinical application of the antigen-adjuvant system concept has shown benefits for diseases like pandemic influenza and human papillomavirus (HPV) cervical cancer. Observed benefits include higher and sustained immune response (humoral and cell mediated) and immune memory, cross-type immunity, and antigen-sparing, along with a favorable safety profile. The advantages of using an adjuvant system in the preventive field also have generated interest in the context of therapeutic vaccines, particularly in cancer immunotherapy. Strong signals of clinical activity of MAGE-A3 antigen-specific cancer immunotherapeutics (ASCI), demonstrated in proof-of-concept studies in melanoma and non-small cell lung cancer (NSCLC), have prompted the start of two large pivotal Phase 3 trials. The tailored antigen-adjuvant system combination approach is thus opening new possibilities for designing effective vaccines against unmet medical needs., The future of vaccine development is based on the ability to address remaining unmet medical needs linked to challenging pathogens or challenging populations. There are no vaccines available yet to [...]

ABSTRACT In cell line development, the integration of transgenes into the chromosomal DNA of the host cell is a crucial step. Targeted introduction has many advantages over classical random integration [...]

ABSTRACT Cation exchange capture chromatography is the basis of the well-established non-affinity purification processes for many human monoclonal antibodies (HuMAbs). In all these processes, a concentration and diafiltration tangential flow [...]

ABSTRACT The following article describes the development of a purification platform for monoclonal antibodies (MAbs) at Pfizer's Global Biologics division, including how the individual unit operations have been affected by [...]

Abstract There is accelerating interest in the use of nonspecific immunostimulants or adjuvants as a means of enhancing or inducing nonspecific immunity. A further requirement for the development of successful [...]

ABSTRACT Vaccines stimulate the body's immune system to prevent or control specific diseases. Vaccines against major human infectious diseases such as pertussis, diphtheria, tetanus, and tuberculosis were developed in the [...]

ABSTRACT Perinephric abscesses often present with flank pain and signs of sepsis, and are known to discharge to the skin. We report a case of a young patient presenting with [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjsurg.2006.02.007 Byline: A. Melck (a), S. Bugis (a), C. Baliski (a), R. Irvine (a), D.W. Anderson (a), G. Wilkins (b), H. Zhang (c), S.M. Wiseman (a) Keywords: Biopsy; Carcinoma; Hurthle cell; Needle; Neoplasm; Thyroid Abstract: The objective of this study was to evaluate the cancer risk of patient clinicopathologic characteristics to determine the optimal approach for the surgical management of individuals with Hurthle cell neoplasm (HN) diagnosed by cytology. Author Affiliation: (a) Department of Surgery, St. Paul's Hospital, University of British Columbia, C303-1081 Burrard St., V6Z 1Y6 Vancouver, British Columbia, Canada (b) Department of Medicine, St. Paul's Hospital, University of British Columbia, 548-1081 Burrard St., V6Z 1Y6 Vancouver, British Columbia, Canada (c) Knowledge Cycle Office, St. Paul's Hospital, Rm. 338 Comox Building, 1081 Burrard St., V6Z 1Y6 Vancouver, British Columbia, Canada Article History: Received 19 November 2005; Revised 17 January 2006

ABSTRACT Spinal epidural abscess is an uncommon condition. Predisposing factors include spinal surgery, recent trauma, immunosuppression, a distal site of infection and intravenous drug use; however, these are not always [...]

Byline: Hajime Otani, Hideyasu Ohmiya, Reiji Hattori, Hirofumi Fujii, Hideki Ninomiya, Masakuni Kido, Hideki Kawaguchi, Motohiko Osako, Hiroji Imamura, Tetsuo Ohta, Shoji Ohkuma Abstract: Objective: Vacuolar H.sup.+-adenosine triphosphatase plays a pivotal role in pH regulation and molecular transport across the vacuolar membranes and is involved in cell proliferation and transformation. In the present study, possible involvement of vacuolar H.sup.+-adenosine triphosphatase in neointimal formation was investigated in an organ culture model of human saphenous vein. Methods and results: Cultured saphenous vein segments developed neointimal formation and marked thickening of the media within 14 days. Neointimal formation and medial thickening were completely inhibited by 10 nmol/L bafilomycin A.sub.1, a selective inhibitor of vacuolar H.sup.+-adenosine triphosphatase, although structurally related macrolide antibiotics FK-506 and erythromycin were without an effect. The neointimal cells were positive for [alpha]-smooth muscle actin and vimentin but negative for desmin, indicative of myofibroblasts. The emergence of myofibroblasts was inhibited, and endothelial cells were preserved in the saphenous vein segments treated with bafilomycin A.sub.1. Uptake of bromodeoxyuridine, a proliferation marker, by myofibroblasts was abrogated in the saphenous vein segments treated with 10 nmol/L bafilomycin A.sub.1. Detection of apoptotic cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling concomitant with identification of desmin-expressing smooth muscle cells demonstrated that neointimal myofibroblasts, but not medial smooth muscle cells, that expressed desmin underwent apoptosis by treatment with bafilomycin A.sub.1. Conclusions: These results suggest that vacuolar H.sup.+-adenosine triphosphatase may be involved in myofibroblast growth that contributes to neointimal formation and medial thickening in cultured human saphenous vein. Increased sensitivity of myofibroblasts, but not endothelial cells, and differentiated smooth muscle cells to bafilomycin A.sub.1 may have potential therapeutic implications in the treatment for vein graft disease. (J Thorac Cardiovasc Surg 2000;119:998-1007) Author Affiliation: From the Department of Thoracic and Cardiovascular Surgery,.sup.a Kansai Medical University, Department of Surgery (II),.sup.b School of Medicine, Kanazawa University, and the Laboratory of Biochemistry,.sup.c Department of Molecular and Cell Biology, Faculty of Pharmaceutical Science, Kanazawa University, Kanazawa, Japan Article History: Received 27 July 1999; Revised 7 October 1999; Revised 16 December 1999; Accepted 16 December 1999 Article Note: (footnote) [star] Address for reprints: Hajime Otani, MD, Department of Thoracic and Cardiovascular Surgery, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570, Japan (E-mail: otanih@takii.kmu.ac.jp ).

Byline: Morihito Okada, Hiroyuki Yamagishi, Shinsuke Satake, Hidehito Matsuoka, Yoshifumi Miyamoto, Masahiro Yoshimura, Noriaki Tsubota Abstract: Objective: The purpose of this study was to compare the outcomes after sleeve lobectomy and pneumonectomy for patients with non-small cell lung cancer distributed according to their nodal involvement status. Methods: Of 1172 patients in whom primary non-small cell lung carcinoma, including mediastinal lymph nodes, was completely excised, 151 patients underwent sleeve lobectomy and 60 underwent pneumonectomy. For bias reduction in comparison with a nonrandomized control group, we paired 60 patients undergoing sleeve lobectomy with 60 patients undergoing pneumonectomy by using the nearest available matching method. Results: The 30-day postoperative mortality was 2% (1/60) in the pneumonectomy group and 0% in the sleeve lobectomy group. Postoperative complications occurred in 13% of patients in the sleeve lobectomy group and in 22% of those in the pneumonectomy group. Local recurrences occurred in 8% of patients in the sleeve lobectomy group and in 10% of those in the pneumonectomy group. The overall 5- and 10-year survivals for the sleeve lobectomy group were 48% and 36%, respectively, whereas those for the pneumonectomy group were 28% and 19%, respectively (P = .005). Multivariable analysis showed that the operative procedure, T factor, and N factor were significant independent prognostic factors and revealed that survival after sleeve lobectomy was significantly longer than that after pneumonectomy (P = .03). Conclusions: These data suggest that sleeve lobectomy should be performed instead of pneumonectomy in patients with non-small cell lung cancer regardless of their nodal status whenever complete resection can be achieved because this is a lung-saving procedure with lower postoperative risks and is as curative as pneumonectomy. (J Thorac Cardiovasc Surg 2000;119:814-9) Author Affiliation: Department of Thoracic Surgery, Hyogo Medical Center for Adults, Akashi City, Hyogo, and the Department of Thoracic Surgery, National Hyogo Central Hospital, Sanda City, Hyogo, Japan Article History: Received 22 June 1999; Revised 31 August 1999; Revised 1 November 1999; Accepted 23 November 1999 Article Note: (footnote) [star] Address for reprints: Noriaki Tsubota, MD, Department of Thoracic Surgery, Hyogo Medical Center for Adults, Kitaohji-cho 13-70, Akashi City 673, Hyogo, Japan (E-mail: n-tsubo@sanynet.ne.jp ).

Byline: S.E. Shackney, C.A. Smith, A. Pollice, M. Levitt, J.A. Magovern, R.J. Wiechmann, J. Silverman, L. Sweeney, R.J. Landreneau Abstract: Introduction: The sequence of genetic evolutionary abnormalities that have occurred in a given lung cancer tumor before tumor sampling can be inferred from patterns of intracellular co-occurrence of these abnormalities in tumor cell subpopulations at the time of sampling. The same evolutionary sequences that are present within each lung cancer were evident in intertumor comparisons. Methods: Correlated cell by cell measurements of cell DNA content, p53, Her-2/neu, and ras proteins were obtained by multiparameter flow cytometry on 46 surgically resected stage I-III primary non-small cell lung cancers. Early evolutionary changes were identified by the fact that they could appear alone in individual cells. Later appearing abnormalities were identified by the fact that they were accompanied by early abnormalities in the same cells. Patients were followed prospectively. Evolutionary patterns observed in individual tumors were correlated with subsequent clinical outcome of patients undergoing surgical resection. Results: Three common patterns were identified: (I) a diploid DNA pathway consisting of the sequence p53 overexpression [right arrow] Her-2/neu overexpression [right arrow] ras overexpression, (II) an aneuploid DNA pathway with the same p53 [right arrow] Her-2/neu [right arrow] ras sequence, and (III) a pathway in which none of the intracellular protein measurements made here were abnormal. Fourteen tumors recurred after 11.5 months' median study time. Nine of 12 recurrences in pathways I and II occurred in patients whose tumors were far advanced along these molecular genetic pathways. Conclusions: Multiparameter cell-based genetic evolutionary studies may be a promising approach for identifying patients with stage I-III non-small cell lung cancer at high risk for recurrence. (J Thorac Cardiovasc Surg 1999;118:259-69) Article History: Received 15 July 1998; Revised 12 October 1998; Revised 9 February 1999; Accepted 30 March 1999 Article Note: (footnote) [star] From the Laboratory of Cancer Cell Biology and Genetics, Department of Human Oncology (C.A.S., A.A.P., L.S., S.E.S.) and Human Genetics (S.E.S), Department of Human Oncology (M.L.), Department of Surgery (R.J.L., J.M., R.J.W.), and Department of Laboratory Medicine (J.S.), Allegheny University of the Health Sciences, Pittsburgh, Pa., [star][star] Read at the Twenty-fourth Annual Meeting of The Western Thoracic Surgical Association, Whistler, British Columbia, June 24-27, 1998., a Address for reprints: Allegheny University of the Health Sciences, Allegheny General Hospital, 320 East North Ave, Pittsburgh, PA 15212., aa 0022-5223/99 $8.00 + 0 12/6/98918

Byline: Hiroshige Mikamo, Kyoko Kawazoe, Yasumasa Sato, Atsushi Imai, Teruhiko Tamaya Keywords: Arachidonic acid; Fusobacterium nucleatum , phospholipase A.sub.2 , preterm labor Abstract: Objective: The studies presented in this report were undertaken to evaluate whether Fusobacterium nucleatum , a common anaerobic isolate in intrauterine infection, stimulates arachidonic acid metabolism, a rate-limiting step for prostaglandin synthesis, in the human uterine endometrium. Study Design: Effects of F nucleatum on arachidonic acid liberation from human uterine endometrial cells and of F nucleatum extract on lysophosphatidylcholine production in human uterine endometrial cells were investigated. Results: When human uterine endometrial cells labeled with tritiated arachidonic acid to an isotopically steady state were exposed to an extract of F nucleatum , arachidonic acid liberation was stimulated, accompanied by lysophospholipid formation. Similar stimulatory effects on phospholipid degradation were also observed in the experiment with bacterially conditioned media. Conclusions: These results suggest that F nucleatum stimulates endometrial phospholipid metabolism, related to activity of phospholipase A.sub.2 , which might induce the onset of labor associated with intraamniotic infection. (Am J Obstet Gynecol 1998;179:1579-82.) Author Affiliation: Department of Obstetrics and Gynecology, School of Medicine, Gifu University. Gifu, Japan Article History: Received 11 November 1997; Revised 29 May 1998; Accepted 29 May 1998 Article Note: (footnote) [star] Reprint requests: Hiroshige Mikamo, MD, PhD, Department of Obstetrics and Gynecology, School of Medicine, Gifu University, 40, Tsukasa-machi, Gifu-city, Gifu 500-8705, Japan., [star][star] 0002-9378/98 $5.00 + 0 6/1/92097

Byline: Junya Katoh, Kouji Tsuchiya, Hiroshi Osawa, Wataru Sato, Gouki Matsumura, Yoshinao Iida, Shoji Suzuki, Shigeru Hosaka, Shinpei Yoshii, Yusuke Tada Abstract: Objective: Depressive effects of cardiopulmonary bypass on cell-mediated immune responses may lead to postoperative infectious complications. We previously reported that cimetidine reduced postbypass depression of the cytotoxic activity of natural killer cells. This study evaluated cimetidine as an agent to preserve cellular immunity after cardiac operations. Methods: In a prospective randomized study, 20 patients were divided into two groups of equal size. Cimetidine-group patients received 400 mg of cimetidine intravenously before bypass and a 33 mg/hr intravenous infusion of cimetidine after the operation, continuing until the fifth postoperative day. Control-group patients received conventional perioperative therapy. Lymphocyte subsets, natural killer cell activity, percentage of CD56.sup.+CD16.sup.+ (percentage of natural killer cells), and percentage of CD11b.sup.+CD8.sup.+ (percentage of suppressor T lymphocytes) were measured perioperatively. Results: Although temporary postoperative reductions in percentages of CD3.sup.+, CD4.sup.+, and CD56.sup.+CD16.sup.+ cells were observed in both groups, CD8.sup.+ percentages on postoperative day 1 and CD11b.sup.+CD8.sup.+ percentages on postoperative days 1 and 3 in the cimetidine group were significantly lower compared with those in the control group (p = 0.01, p = 0.004, and p = 0.02, respectively). Temporary postoperative reduction of natural killer cell activity was also observed in both groups, but the natural killer cell activity on postoperative day 1 in the cimetidine group (17.1%) was significantly higher (p = 0.02) than that in the control group (8.20%). Conclusions: Cimetidine counteracts depressive effects of cardiopulmonary bypass on cell-mediated immunity and may possibly reduce postoperative susceptibility to infection. (J Thorac Cardiovasc Surg 1998;116:312-8) Article History: Received 3 June 1997; Revised 15 September 1997; Revised 25 February 1998; Accepted 5 March 1998 Article Note: (footnote) [star] From the Second Department of Surgery, Yamanashi Medical University,a and the Department of Cardiovascular Surgery,b Yamanashi Central Hospital, Yamanashi, Japan., [star][star] Address for reprints: Junya Katoh, MD, Second Department of Surgery, Yamanashi Medical University, 1110 Shimokato, Tamaho-cho, Nakakoma-gun, Yamanashi, 409-3821 Japan., a 12/1/90191

Byline: Suraiya Rasheed, Zhiliang Li, Dong Xu, Andrea Kovacs Keywords: Cervicovaginal secretions; blood; human immunodeficiency virus; CD4.sup.+ cell; antiviral drugs Abstract: OBJECTIVE: The purpose of this study was to establish virologic or molecular criteria for evaluating the rate of transmission of human immunodeficiency virus type 1 and for defining the role of virus burden in the development of gynecologic diseases in human immunodeficiency virus - infected women. STUDY DESIGN: Paired samples of blood and cervicovaginal secretions from 63 human immunodeficiency virus - seropositive women were evaluated for cell-free and cell-associated virus load by several methods, including quantitative cultures and reverse transcription polymerase chain reaction. RESULTS: All women showed evidence of virus infection in both blood and cervicovaginal secretions by a combination of in vitro culture and molecular detection methods. The CD4.sup.+ cell counts in these women ranged from 500/[mu]l. Blood plasma of 26% women (12/46) did not show detectable levels of human immunodeficiency virus ribonucleic acid by reverse transcription polymerase chain reaction ( Author Affiliation: Los Angeles, California Article History: Received 29 August 1995; Revised 22 November 1995; Accepted 18 December 1995 Article Note: (footnote) [star] From the Laboratory of Viral Oncology and AIDS Research, Department of Pathology, University of Southern California, School of Medicine., [star][star] Supported in part by National Institute of Allergy and Infectious Diseases, National Institutes of Health, AIDS Clinical Trial Unit grants No. AI127673-C1, AI127673-C3, and AI07383 Training Grant and by the University of Southern California Rasheed Research Fund., a Reprint requests: Suraiya Rasheed, PhD, Laboratory of Viral Oncology and AIDS Research, University of Southern California, School of Medicine, Department of Pathology, 1840 N. Soto St., Room 103, Los Angeles, CA 90032-3626., aa 0002-9378/96 $5.00 + 0 6/1/71432

Byline: Jeffrey K. Pollard, Murray D. Mitchell Keywords: Prostaglandins; myometrium; cytokines; intrauterine infection Abstract: OBJECTIVE: Our purpose was to evaluate the effects of known stimulants of prostaglandin production on cultured myometrial cells from women in labor with and without intrauterine infection. STUDY DESIGN: Myometrial segments were obtained from 16 patients between 33 and 40 weeks' gestation who had been in labor for [greater than or equal to]8 hours at cesarean delivery; 8 patients had clinical chorioamnionitis and 8 did not. Myometrial cells were isolated and grown in culture. Incubations were conducted with interleukin-1[beta], tumor necrosis factor-[alpha], or epidermal growth factor. Prostaglandin E.sub.2, prostaglandin F.sub.2[alpha], and 6-keto-prostaglandin F.sub.1[alpha] (the stable metabolite of prostacyclin) were measured by radioimmunoassay, and cellular protein was determined. RESULTS: Cultured myometrial cells from patients with and without prior intrauterine infection produced prostaglandins in response to interleukin-1[beta], tumor necrosis factor-[alpha], and epidermal growth factor at a significantly increased rate (p < 0.05 vs controls at and above 10 ng/ml of interleukin-1[beta], tumor necrosis factor-[alpha], and epidermal growth factor). The major prostaglandin produced in response to each stimulant was 6-keto-prostaglandin F.sub.1[alpha]; however, this response was attenuated in cells from patients with intrauterine infection. CONCLUSIONS: Cultured human myometrial cells from patients with and without prior intrauterine infection respond to known stimulants of prostaglandin production. Prior intrauterine infection has no effect on baseline prostaglandin production, but the amount of prostacyclin produced as a response to cellular stimulants is decreased with prior intrauterine infection. This effect may have a role in regulating myometrial function in intrauterine infection. (AM J OBSTET GYNECOL 1996;174:682-6.) Author Affiliation: Salt Lake City, Utah Article History: Received 10 November 1994; Revised 11 April 1995; Accepted 16 June 1995 Article Note: (footnote) [star] From the Department of Obstetrics and Gynecology, University of Utah., [star][star] Reprint requests: Jeffrey K. Pollard, MD, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Vermont, Burlington, VT 05401., a 0002-9378/96 $5.00 + 0 6/1/67237

Byline: Christian H. Wakefield, P. Declan Carey, Sharmila Foulds, John R.T. Monson, Pierre J. Guillou Abstract: The fact that the incidence and mortality from postsurgical sepsis have remained unchanged over the past 15 years raises the possibility that some patients possess an idiosyncratic predisposition to the development of a postoperative sepsis response. Genetic polymorphisms of the neutrophil receptor for immunoglobulin G, CD16, are known, and their inheritance is associated with functional differences in neutrophil phagocytosis. The present studies were designed to provide preliminary data on the effects of surgery on the level of expression of CD16 and its metabolism preparatory to detailed examination of the relationship of these polymorphisms to sepsis responses. Author Affiliation: From the Academic Surgical Unit, Imperial College of Science, Technology and Medicine, St. Mary's Hospital Medical School, London, United Kingdom Article History: Received 11 February 1994; Accepted 8 September 1994

A new study, 'Persistent expression of the full genome of hepatitis C virus in B cells induces spontaneous development of B-cell lymphomas in vivo,' is now available. According to recent [...]

Fresh data on candida infection are presented in the report 'Epithelial cell-derived S100 calcium-binding proteins as key mediators in the hallmark acute neutrophil response during Candida vaginitis.' According to recent [...]

A new study, 'Cytomegalovirus microRNAs facilitate persistent virus infection in salivary glands,' is now available. 'Micro (mi)RNAs are small non-coding RNAs that regulate the expression of their targets' messenger RNAs [...]

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