In vitro immunization of patient T cells with autologous bone marrow antigen presenting cells pulsed with tumor lysates.

PubMed

Coulon, V; Ravaud, A; Gaston, R; Delaunay, M; Pariente, J L; Verdier, D; Scrivante, V; Gualde, N

2000-12-01

Presentation of cell-associated antigen to T cells is a critical event in the initiation of an anti-tumor immune response but it appears to often be deficient or limiting. Here we report an experimental system for stimulation of human T lymphocytes using autologous antigen presenting cells (APCs) and autologous tumor cells. Two types of APCs were prepared from human bone marrow: MC and DC. MC were produced by using GM-CSF and SCF. DC were obtained with the same cytokines plus IL-4. DC and MC were generated in parallel from the same patients and their phenotypes and capacities to prime T lymphocytes were analyzed and compared. MC were CD14+, CD1a-, CD33+ and HLA-DR+. Two populations of DC were defined: immature DC were uniformly CD1a-; mature DC expressed CD1a, CD80, CD86, HLA-DR, CD54 and CD58 but lacked surface CD14. Stimulation of autologous T lymphocytes was studied by measuring their proliferation and cytotoxic function. In more than 80% of our experiments the proliferation of autologous T lymphocytes cocultured with APC pulsed or not with tumor cell lysates was higher than that of T cells cultured alone. DC were more effective than MC in stimulating proliferation of lymphocytes. The capacity of a patient's autologous bone marrow-derived APC to stimulate T cells when exposed to autologous tumor cell lysates suggest that such antigen-exposed APC may be useful in specific anti-tumor immunotherapy protocols. Copyright 2000 Wiley-Liss, Inc.

Localization of antigen-specific lymphocytes following lymph node challenge.

PubMed Central

Liu, H; Splitter, G A

1986-01-01

The effect of subcutaneous injections of Brucella abortus strain 19 antigen on the specific localization of autologous lymphocytes in the regional nodes of calves was analysed by fluorescent labelling and flow cytometry. Both in vitro and in vivo FITC labelling of lymphocytes indicated the preferential migration of lymphocytes from a previously challenged lymph node to a recently challenged lymph node. However, lymphocytes from a lymph node challenged with B. abortus failed to localize preferentially in a lymph node challenged with a control antigen, Listeria monocytogenes. Lymph node cells, enriched for T lymphocytes and isolated from primary stimulated or secondary challenged B. abortus lymph nodes, could proliferate when cultured with autologous antigen-pulsed macrophages. The kinetics of [3H]thymidine incorporation in lymphocytes from secondarily challenged lymph nodes occurred earlier and to a greater extent when compared with lymphocytes from primary challenged lymph nodes. Our data show that the accumulation of B. abortus-specific lymphocytes in secondarily challenged lymph nodes is increased by the presence of the specific antigen. Images Figure 4 PMID:2426183

Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer.

PubMed

Bernhard, Helga; Neudorfer, Julia; Gebhard, Kerstin; Conrad, Heinke; Hermann, Christine; Nährig, Jörg; Fend, Falko; Weber, Wolfgang; Busch, Dirk H; Peschel, Christian

2008-02-01

The human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated antigen by immunotherapeutical approaches based on HER2-directed monoclonal antibodies and cancer vaccines. We describe the adoptive transfer of autologous HER2-specific T-lymphocyte clones to a patient with metastatic HER2-overexpressing breast cancer. The HLA/multimer-based monitoring of the transferred T lymphocytes revealed that the T cells rapidly disappeared from the peripheral blood. The imaging studies indicated that the T cells accumulated in the bone marrow (BM) and migrated to the liver, but were unable to penetrate into the solid metastases. The disseminated tumor cells in the BM disappeared after the completion of adoptive T-cell therapy. This study suggests the therapeutic potential for HER2-specific T cells for eliminating disseminated HER2-positive tumor cells and proposes the combination of T cell-based therapies with strategies targeting the tumor stroma to improve T-cell infiltration into solid tumors.

A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease

PubMed Central

Bagnara, Davide; Kaufman, Matthew S.; Calissano, Carlo; Marsilio, Sonia; Patten, Piers E. M.; Simone, Rita; Chum, Philip; Yan, Xiao-Jie; Allen, Steven L.; Kolitz, Jonathan E.; Baskar, Sivasubramanian; Rader, Christoph; Mellstedt, Hakan; Rabbani, Hodjattallah; Lee, Annette; Gregersen, Peter K.; Rai, Kanti R.

2011-01-01

Chronic lymphocytic leukemia (CLL) is an incurable adult disease of unknown etiology. Understanding the biology of CLL cells, particularly cell maturation and growth in vivo, has been impeded by lack of a reproducible adoptive transfer model. We report a simple, reproducible system in which primary CLL cells proliferate in nonobese diabetes/severe combined immunodeficiency/γcnull mice under the influence of activated CLL-derived T lymphocytes. By cotransferring autologous T lymphocytes, activated in vivo by alloantigens, the survival and growth of primary CFSE-labeled CLL cells in vivo is achieved and quantified. Using this approach, we have identified key roles for CD4+ T cells in CLL expansion, a direct link between CD38 expression by leukemic B cells and their activation, and support for CLL cells preferentially proliferating in secondary lymphoid tissues. The model should simplify analyzing kinetics of CLL cells in vivo, deciphering involvement of nonleukemic elements and nongenetic factors promoting CLL cell growth, identifying and characterizing potential leukemic stem cells, and permitting preclinical studies of novel therapeutics. Because autologous activated T lymphocytes are 2-edged swords, generating unwanted graph-versus-host and possibly autologous antitumor reactions, the model may also facilitate analyses of T-cell populations involved in immune surveillance relevant to hematopoietic transplantation and tumor cytoxicity. PMID:21385850

Evidence for the separate human T-lymphocyte subpopulations that collaborate with autologous monocyte/macrophages in the elaboration of colony-stimulating activity and those that suppress this collaboration.

PubMed

Verma, D S; Johnston, D A; McCredie, K B

1983-11-01

We investigated the interaction of monocyte/macrophages and autologous T lymphocytes in the methanol extraction residue (MER) of BCG-induced production of granulocyte-macrophage colony-stimulating activity (CSA). Coincubation of monocyte/macrophages and T lymphocytes at a 1:3 ratio produces an optimum collaboration; a change to a 1:9 ratio diminished this collaboration. Coincubation of monocyte/macrophages and T lymphocytes primed with lithium carbonate (2 meq/liter) for 40 hr synergistically increased CSA elaboration and prevented the decline in CSA noted for the 1:9 monocyte/macrophage: T lymphocyte ratio. In contrast, concanavalin-A-primed T lymphocytes did not enhance CSA elaboration at any monocyte/macrophage:T lymphocyte ratio except, occasionally, at 1:9. However, this was overcome if the T lymphocytes were primed with both concanavalin-A and lithium carbonate before their coincubation with monocyte/macrophages. Further cell-mixing experiments revealed that concanavalin-A-primed T lymphocytes contained a subpopulation that suppressed monocyte/macrophage and T-lymphocyte collaboration. Activation of suppressor T lymphocytes could be effectively prevented by lithium carbonate and, in a dose-dependent manner, by irradiation. Also, suppressor T lymphocytes not only diminished the elaboration of colony-stimulating factor(s), but also elaborated an inhibitor of granulocyte-macrophage colony-forming cells. We further demonstrated that the respective hemopoietic helper and suppressor T-lymphocyte activities could be enriched with OKT8- (or OKT4+) and OKT8+ subpopulations.

Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2017-10-24

CD19-Positive Neoplastic Cells Present; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Acute Lymphoblastic Leukemia; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

The production of granulocyte-monocyte colony-stimulating activity by isolated human T lymphocyte subpopulations.

PubMed

Hesketh, P J; Sullivan, R; Valeri, C R; McCarroll, L A

1984-05-01

Isolated human T lymphocyte subpopulations were obtained by fluorescence-activated cell sorting using the murine monoclonal antibodies, OKT4 and OKT8. The capabilities of the isolated lymphocytes to produce granulocyte-monocyte colony-stimulating activity (CSA) in response to mitogen challenge were assessed by in vitro assays employing light density nonadherent bone marrow cells. Essentially, no CSA production was noted by any isolated T lymphocyte population [OKT4 positive (+) or OKT8 positive (+)] cultured alone or following the addition of 10(4) autologous monocytes/ml. When phytohemagglutinin (PHA) alone was added, OKT4+ lymphocytes elaborated small amounts of CSA. With the addition of concanavalin A (Con-A) alone, both OKT4+ and OKT8+ cells were able to produce modest amounts of CSA. Significantly enhanced CSA production was observed when either OKT4+ or OKT8+ lymphocytes were coincubated with autologous monocytes in the presence of mitogen. We conclude that highly purified T lymphocyte subpopulations, free of monocytes as assessed by nonspecific esterase staining, can elaborate small amounts of CSA in response to PHA or Con-A challenge. A synergistic augmentation of CSA production was noted with coincubation of sorted lymphocytes and autologous monocytes in the presence of mitogen. Finally, our results suggest that the ability of T lymphocytes to make CSA is not exclusively limited to either the OKT4+ or OKT8+ defined subsets.

Immunization of Cattle by Infection with Cowdria ruminantium Elicits T Lymphocytes That Recognize Autologous, Infected Endothelial Cells and Monocytes†

PubMed Central

Mwangi, Duncan M.; Mahan, Suman M.; Nyanjui, John K.; Taracha, Evans L. N.; McKeever, Declan J.

1998-01-01

Peripheral blood mononuclear cells (PBMC) from immune cattle proliferate in the presence of autologous Cowdria ruminantium-infected endothelial cells and monocytes. Endothelial cells required treatment with T-cell growth factors to induce class II major histocompatibility complex expression prior to infection and use as stimulators. Proliferative responses to both infected autologous endothelial cells and monocytes were characterized by expansion of a mixture of CD4+, CD8+, and γδ T cells. However, γδ T cells dominated following several restimulations. Reverse transcription-PCR analysis of cytokine expression by C. ruminantium-specific T-cell lines and immune PBMC revealed weak interleukin-2 (IL-2), IL-4, and gamma interferon (IFN-γ) transcripts at 3 to 24 h after stimulation. Strong expression of IFN-γ, tumor necrosis factor alpha (TNF-α), TNF-β, and IL-2 receptor α-chain mRNA was detected in T-cell lines 48 h after antigen stimulation. Supernatants from these T-cell cultures contained IFN-γ protein. Our findings suggest that in immune cattle a C. ruminantium-specific T-cell response is induced and that infected endothelial cells and monocytes may present C. ruminantium antigens to specific T lymphocytes in vivo during infection and thereby play a role in induction of protective immune responses to the pathogen. PMID:9573061

Clinical and Laboratory Differences between Lymphocyte- and Neutrophil-Predominant Pleural Tuberculosis

PubMed Central

Kim, Kang; Kim, Sukyeon; Oh, Ki-Jong; Jeong, Suk Hyeon; Jung, Woo Jin; Shin, Beomsu; Jhun, Byung Woo; Lee, Hyun; Park, Hye Yun; Koh, Won-Jung

2016-01-01

Pleural tuberculosis (TB), a form of extrapulmonary TB, can be difficult to diagnose. High numbers of lymphocytes in pleural fluid have been considered part of the diagnostic criteria for pleural TB; however, in many cases, neutrophils rather than lymphocytes are the predominant cell type in pleural effusions, making diagnosis more complicated. Additionally, there is limited information on the clinical and laboratory characteristics of neutrophil-predominant pleural effusions caused by Mycobacterium tuberculosis (MTB). To investigate clinical and laboratory differences between lymphocyte- and neutrophil-predominant pleural TB, we retrospectively analyzed 200 patients with the two types of pleural TB. Of these patients, 9.5% had neutrophil-predominant pleural TB. Patients with lymphocyte-predominant and neutrophil-predominant pleural TB showed similar clinical signs and symptoms. However, neutrophil-predominant pleural TB was associated with significantly higher inflammatory serum markers, such as white blood cell count (P = 0.001) and C-reactive protein (P = 0.001). Moreover, MTB was more frequently detected in the pleural fluid from patients in the neutrophil-predominant group than the lymphocyte-predominant group, with the former group exhibiting significantly higher rates of positive results for acid-fast bacilli in sputum (36.8 versus 9.4%, P = 0.003), diagnostic yield of MTB culture (78.9% versus 22.7%, P < 0.001) and MTB detected by polymerase chain reaction (31.6% versus 5.0%, P = 0.001). Four of seven patients with repeated pleural fluid analyses revealed persistent neutrophil-predominant features, which does not support the traditional viewpoint that neutrophil-predominant pleural TB is a temporary form that rapidly develops into lymphocyte-predominant pleural TB. In conclusion, neutrophil-predominant pleural TB showed a more intense inflammatory response and a higher positive rate in microbiological testing compared to lymphocyte-predominant pleural TB

[Laboratory diagnosis of lymphocytic meningitis].

PubMed

Marí, José María Navarro; Ruiz, Mercedes Pérez; Anza, Diego Vicente

2010-01-01

Lymphocytic meningitis, mainly those with an acute and benign course, are caused by viruses. In our area, the most commonly involved agents are enteroviruses, herpes simplex, varicella zoster and Toscana viruses. Nucleic acids amplification techniques (NAAT) are the methods of choice to diagnose viral meningitis from cerebrospinal fluid (CSF) samples. They are more rapid and sensitive, and indeed, they are not influenced by the viability of the virus in the clinical specimen as traditional methods are. The development of commercial equipments, the degree of automation, and the use of real-time polymerase chain reaction (PCR) systems are the most important premises to choose the molecular method in each laboratory. Recently, commercial kits of real-time PCR are available for the detection of enteroviruses and herpesviruses, which are the most frequently viruses involved in meningitis. Although NAAT from the clinical sample have replaced cell culture for diagnostic purposes, the combination of both methods remain useful. When the detection of the causal agent from the CSF sample is not possible, other specimens (pharyngeal exudates, stools) or serological methods can be used. Serology is the reference method for meningitis caused by West Nile virus and lymphocytic choriomeningitis virus, which are less frequently detected in our area. 2010 Elsevier España S.L. All rights reserved.

Gastrocnemius tendon strain in a dog treated with autologous mesenchymal stem cells and a custom orthosis.

PubMed

Case, J Brad; Palmer, Ross; Valdes-Martinez, Alex; Egger, Erick L; Haussler, Kevin K

2013-05-01

To report clinical findings and outcome in a dog with gastrocnemius tendon strain treated with autologous mesenchymal stem cells and a custom orthosis. Clinical report. A 4-year-old spayed female Border Collie. Bone-marrow derived, autologous mesenchymal stem cells were transplanted into the tendon core lesion. A custom, progressive, dynamic orthosis was fit to the tarsus. Serial orthopedic examinations and ultrasonography as well as long-term force-plate gait analysis were utilized for follow up. Lameness subjectively resolved and peak vertical force increased from 43% to 92% of the contralateral pelvic limb. Serial ultrasonographic examinations revealed improved but incomplete restoration of normal linear fiber pattern of the gastrocnemius tendon. Findings suggest that autologous mesenchymal stem cell transplantation with custom, progressive, dynamic orthosis may be a viable, minimally invasive technique for treatment of calcaneal tendon injuries in dogs. © Copyright 2013 by The American College of Veterinary Surgeons.

Effects of dendritic cells from hepatitis B virus transgenic mice-stimulated autologous lymphocytes on hepatitis B virus replication: a study on the impact of specific sensitized effector cells on in vitro virus replication.

PubMed

Shen, Zhong-Yang; Zheng, Wei-Ping; Liu, Tao; Yang, Yang; Song, Hong-Li

2015-03-01

The objective of this study was to explore the effects of dendritic cells (DCs) from hepatitis B virus (HBV) transgenic mice-stimulated autologous lymphocytes on in vitro HBV replication. DCs from HBV transgenic mice were induced to maturity by lipopolysaccharide, followed by incubation with hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in vitro. Mature DCs and autologous lymphocytes were co-stimulated to form specific sensitized immune effector cells (IEC), which were then co-cultured with the human hepatoma cell line HepG2.2.15. Changes in morphology and activity of hepatocytes were then observed, as well as analysis of changes in liver enzyme, and HBV DNA and inflammatory cytokine levels in the culture supernatant. Intracellular HBV DNA and covalently closed circular DNA (cccDNA) concentration were measured by real-time polymerase chain reaction. Co-stimulation by mature DCs and IEC showed no impact on the morphology and liver enzyme expression level of HepG2.2.15 cells, but the supernatant HBV DNA and intracellular HBV DNA and cccDNA levels decreased significantly compared with those cells co-cultured with immature DCs. Secretion of inflammatory cytokines in the supernatant showed that when HBV DNA was highly expressed, the concentration of IFN-γ and IL-2 decreased, while IL-10 increased. Contrastingly, when HBV DNA had low expression, the concentration of IFN-γ and IL-2 increased and IL-10 decreased. Co-stimulation of HBV-related antigen-induced mature DCs and autologous lymphocytes showed inhibitory effects on ex vivo HBV replication, and cytokines were suggested to mediate this effect.

Renal Allograft Survival in Nonhuman Primates Infused with Donor Antigen-Pulsed Autologous Regulatory Dendritic Cells

PubMed Central

Ezzelarab, M.B.; Raich-Regue, D.; Lu, L.; Zahorchak, A.F.; Perez-Gutierrez, A.; Humar, A.; Wijkstrom, M.; Minervini, M.; Wiseman, R.W.; Cooper, D.K.C.; Morelli, A.E.; Thomson, A.W.

2017-01-01

Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg pre-loaded with cell membrane vesicles from allogeneic PBMC, induce T cell hyporesponsiveness to donor alloAg in vitro. These donor alloAg-pulsed autologous DCreg (1.4–3.6 x 106/kg) were administered intravenously, one day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 [CTLA4] Ig) and tapered rapamycin. Prolongation of graft median survival time from 39.5 days (no DCreg infusion; n=6 historical controls) and 29 days with control unpulsed DCreg (n=2), to 56 days with donor Ag-pulsed DCreg (n=5), was associated with evidence of modulated host CD4+ and CD8+ T cell responses to donor Ag and attenuation of systemic IL-17 production. Circulating anti-donor antibody (Ab) was not detected until CTLA4Ig withdrawal. One monkey treated with donor Ag-pulsed DCreg rejected its graft in association with progressively elevated anti-donor Ab, 525 days post-transplant (160 days after withdrawal of immunosuppression). These findings indicate a modest but not statistically significant beneficial effect of donor Ag-pulsed autologous DCreg infusion on NHP graft survival when administered with a minimal immunosuppressive drug regimen. PMID:28009481

Interleukin-6 and vascular endothelial growth factor release by renal cell carcinoma cells impedes lymphocyte-dendritic cell cross-talk.

PubMed

Cabillic, F; Bouet-Toussaint, F; Toutirais, O; Rioux-Leclercq, N; Fergelot, P; de la Pintière, C Thomas; Genetet, N; Patard, J-J; Catros-Quemener, V

2006-12-01

Anti-tumour T cell response requires antigen presentation via efficient immunological synapse between antigen presenting cells, e.g. dendritic cells (DC), and specific T cells in an adapted Th1 cytokine context. Nine renal cell carcinoma (RCC) primary culture cells were used as sources of tumour antigens which were loaded on DC (DC-Tu) for autologous T cell activation assays. Cytotoxic activity of lymphocytes stimulated with DC-Tu was evaluated against autologous tumour cells. Assays were performed with 75 grays irradiated tumour cells (Tu irr) and with hydrogen peroxide +/- heat shock (Tu H(2)O(2) +/- HS) treated cells. DC-Tu irr failed to enhance cytotoxic activity of autologous lymphocytes in seven of 13 assays. In all these defective assays, irradiated tumour cells displayed high interleukin (IL)-6 and vascular endothelial growth factor (VEGF) release. Conversely, when tumour cells released low IL-6 levels (n = 4), DC-Tu irr efficiently enhanced CTL activity. When assays were performed with the same RCC cells treated with H(2)O(2) + HS, DC-Tu stimulation resulted in improved CTL activity. H(2)O(2) + HS treatment induced post-apoptotic cell necrosis of tumour cells, totally abrogated their cytokine release [IL-6, VEGF, transforming growth factor (TGF)-beta1] and induced HSP70 expression. Taken together, data show that reduction in IL-6 and VEGF release in the environment of the tumour concomitantly to tumour cell HSP expression favours induction of a stronger anti-tumour CTL response.

Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor.

PubMed

Zhao, Yangbing; Moon, Edmund; Carpenito, Carmine; Paulos, Chrystal M; Liu, Xiaojun; Brennan, Andrea L; Chew, Anne; Carroll, Richard G; Scholler, John; Levine, Bruce L; Albelda, Steven M; June, Carl H

2010-11-15

Redirecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor-reactive T lymphocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production have limited clinical application of T cells expressing chimeric antigen receptors (CAR). T lymphocytes can be gene modified by RNA electroporation without integration-associated safety concerns. To establish a safe platform for adoptive immunotherapy, we first optimized the vector backbone for RNA in vitro transcription to achieve high-level transgene expression. CAR expression and function of RNA-electroporated T cells could be detected up to a week after electroporation. Multiple injections of RNA CAR-electroporated T cells mediated regression of large vascularized flank mesothelioma tumors in NOD/scid/γc(-/-) mice. Dramatic tumor reduction also occurred when the preexisting intraperitoneal human-derived tumors, which had been growing in vivo for >50 days, were treated by multiple injections of autologous human T cells electroporated with anti-mesothelin CAR mRNA. This is the first report using matched patient tumor and lymphocytes showing that autologous T cells from cancer patients can be engineered to provide an effective therapy for a disseminated tumor in a robust preclinical model. Multiple injections of RNA-engineered T cells are a novel approach for adoptive cell transfer, providing flexible platform for the treatment of cancer that may complement the use of retroviral and lentiviral engineered T cells. This approach may increase the therapeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors. Copyright © 2010 AACR.

Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor

PubMed Central

Zhao, Yangbing; Moon, Edmund; Carpenito, Carmine; Paulos, Chrystal M.; Liu, Xiaojun; Brennan, Andrea L; Chew, Anne; Carroll, Richard G.; Scholler, John; Levine, Bruce L.; Albelda, Steven M.; June, Carl H.

2010-01-01

Redirecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor reactive T lymphocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production have limited clinical application of T cells expressing chimeric antigen receptors (CARs). T lymphocytes can be gene modified by RNA electroporation without integration-associated safety concerns. To establish a safe platform for adoptive immunotherapy, we first optimized the vector backbone for RNA in vitro transcription to achieve high level transgene expression. CAR expression and function of RNA-electroporated T cells could be detected up to a week post electroporation. Multiple injections of RNA CAR electroporated T cells mediated regression of large vascularized flank mesothelioma tumors in NOD/scid/γc(−/−) mice. Dramatic tumor reduction also occurred when the pre-existing intraperitoneal human-derived tumors, that had been growing in vivo for over 50 days, were treated by multiple injections of autologous human T cells electroporated with anti-mesothelin CAR mRNA. This is the first report using matched patient tumor and lymphocytes demonstrating that autologous T cells from cancer patients can be engineered to provide an effective therapy for a disseminated tumor in a robust preclinical model. Multiple injections of RNA engineered T cells are a novel approach for adoptive cell transfer, providing flexible platform for the treatment of cancer that may complement the use of retroviral and lentiviral engineered T cells. This approach may increase the therapeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors. PMID:20926399

Persistent non-union of the humeral shaft treated by plating and autologous bone grafting.

PubMed

Pollon, Tristan; Reina, Nicolas; Delclaux, Stéphanie; Bonnevialle, Paul; Mansat, Pierre; Bonnevialle, Nicolas

2017-02-01

Surgical treatment of persistent non-union of the humeral shaft is a complex situation because of the risk of failure and surgery-related complications. The primary objective of this study was to evaluate clinical and radiological results of a continuous series of persistent non-union treated with plating and bone grafting. The secondary objective was to expose factors contributing to the failure of prior bone union attempts. Sixteen patients (average age of 52 years) were treated for persistent non-union of the humeral shaft in our department; six of these patients had predisposing comorbidities or addictions. The persistent non-union was treated by plating with autologous bone graft from the iliac crest in a single-stage procedure in 12 cases and a two-stage procedure in three cases; one case was treated with plating and vascularized fibula graft. At a minimum follow-up of 12 months (average 78 months), four (25 %) failed to heal. The 12 other patients had bone union after an average of eight months. The average QuickDASH score was 48 points (18-72). A retrospective analysis of the prior attempts to treat the non-union revealed three cases of unstable fixation, four cases with no osteogenic supply and seven cases of positive microbiological cultures at the non-union site. Plating and autologous bone grafting resulted in union in only 75 % of persistent non-union of the humeral shaft. The persistent nature of the humeral shaft non-union could be attributed to deviating from validated rules for surgical treatment and/or the presence of a surgical site infection.

Human T-Cell Clones from Autoimmune Thyroid Glands: Specific Recognition of Autologous Thyroid Cells

NASA Astrophysics Data System (ADS)

Londei, Marco; Bottazzo, G. Franco; Feldmann, Marc

1985-04-01

The thyroid glands of patients with autoimmune diseases such as Graves' disease and certain forms of goiter contain infiltrating activated T lymphocytes and, unlike cells of normal glands, the epithelial follicular cells strongly express histocompatability antigens of the HLA-DR type. In a study of such autoimmune disorders, the infiltrating T cells from the thyroid glands of two patients with Graves' disease were cloned in mitogen-free interleukin-2 (T-cell growth factor). The clones were expanded and their specificity was tested. Three types of clones were found. One group, of T4 phenotype, specifically recognized autologous thyroid cells. Another, also of T4 phenotype, recognized autologous thyroid or blood cells and thus responded positively in the autologous mixed lymphocyte reaction. Other clones derived from cells that were activated in vivo were of no known specificity. These clones provide a model of a human autoimmune disease and their analysis should clarify mechanisms of pathogenesis and provide clues to abrogating these undesirable immune responses.

Deficiency of the autologous mixed lymphocyte reactions of non-T/T and T/T type in intravenous drug abusers infected by the human immunodeficiency virus (HIV).

PubMed

Puppo, F; Pierri, I; Rogna, S; Pattarini, R; Piovano, P L; Catellani, S; Varnier, O E; Indiveri, F

1987-01-01

In the present study both responsiveness and stimulatory capacity in autologous mixed lymphocyte reactions (AMLRs) of non-T/T and T/T type, as well as in allogeneic mixed lymphocyte reaction (MLR), were evaluated in 30 intravenous drug abusers (IDAs) infected by the human immunodeficiency virus (HIV) and in 10 HIV-negative IDAs. The production of interleukin 2 (IL2), and the expression of HLA Class II antigens and IL2 receptors by PHA-activated T lymphocytes were also evaluated. A severe impairment of both responsiveness and stimulatory capacity in MLR and AMLRs was found in the HIV-positive IDAs and not in the HIV-negative IDAs. The HIV-positive IDAs showed also a defective expression of HLA Class II antigens, whereas the IL2 production and the IL2 receptor expression were in the normal range. The present data are consistent with similar observations in male homosexuals with AIDS-related complex and confirm that the HIV infection induces a broad spectrum of immunological abnormalities leading to a progressive derangement of the immunocompetence.

Recovery of autologous sickle cells by hypotonic wash.

PubMed

Wilson, Emily; Kezeor, Kelly; Crosby, Monica

2018-01-01

It is important to isolate autologous red blood cells (RBCs) from transfused RBCs in samples from recently transfused patients to ensure that accurate serologic results are obtained. Typically, this isolation can be performed using methods that separate patient reticulocytes from transfused, older donor RBCs. Patients with sickle cell disease (SCD), however, characteristically have RBCs with altered membrane and morphological features, causing their RBCs to take on a sickle-shape appearance different from the biconcave disc-shape appearance of "normal" RBCs. These characteristics enable the use of hypotonic saline solution to lyse normal RBCs while allowing "sickle cells" to remain intact. Because many patients with SCD undergo frequent transfusions to treat their condition, the use of hypotonic saline solution provides a rapid method to obtain autologous RBCs for serologic testing from this patient population using standard laboratory equipment and supplies.

The Role of T Lymphocytes in Cancer Patients Undergoing Immunotherapy with Autologous Dendritic Cells

PubMed Central

Rodrigues, Cláudia M.; Matias, Bruna F.; Murta, Eddie F.C.; Michelin, Márcia A.

2011-01-01

Introduction: Cancer stems from mutations in specific genes that induce uncontrolled cell proliferation. Dendritic cells (DCs) are important immunologic cells and play a crucial role in the induction of an antitumour response. Patients and methods: We examined the immune response mediated by T lymphocytes, helper T cells, cytotoxic T cells, and regulatory T cells, as well as the cytokines [interleukin (IL)-2, IL-12, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and IL-10], produced by these cell populations, in cancer patients (N = 7) undergoing immunotheraphy with autologous DCs. Results: We observed an initial increase in T helper cells (CD4+) expressing IL-2, IFN-γ, IL-12, TNF-α, and IL-10 after initiation of treatment, with statistically significant for the cytokines IL-2, TNF-α and IL-10. A similar significant effect was observed for IL-2-expressing cytotoxic T cells (CD8+). The percentage of total T cells (CD3+) remained elevated throughout immunotherapy. Regulatory T cells (CD25+/FOXP3+) only showed high percentage of their maximum value when analyzed the pretreatment levels, with statistically significant. Conclusion: Immunotherapy with DCs stimulated the immune response, as evidenced by an increase in percent fluorescence of most cell populations investigated during the specified treatment period. PMID:21603246

The role of T lymphocytes in cancer patients undergoing immunotherapy with autologous dendritic cells.

PubMed

Rodrigues, Cláudia M; Matias, Bruna F; Murta, Eddie F C; Michelin, Márcia A

2011-01-01

Cancer stems from mutations in specific genes that induce uncontrolled cell proliferation. Dendritic cells (DCs) are important immunologic cells and play a crucial role in the induction of an antitumour response. We examined the immune response mediated by T lymphocytes, helper T cells, cytotoxic T cells, and regulatory T cells, as well as the cytokines [interleukin (IL)-2, IL-12, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and IL-10], produced by these cell populations, in cancer patients (N = 7) undergoing immunotheraphy with autologous DCs. We observed an initial increase in T helper cells (CD4+) expressing IL-2, IFN-γ, IL-12, TNF-α, and IL-10 after initiation of treatment, with statistically significant for the cytokines IL-2, TNF-α and IL-10. A similar significant effect was observed for IL-2-expressing cytotoxic T cells (CD8+). The percentage of total T cells (CD3+) remained elevated throughout immunotherapy. Regulatory T cells (CD25+/FOXP3+) only showed high percentage of their maximum value when analyzed the pretreatment levels, with statistically significant. Immunotherapy with DCs stimulated the immune response, as evidenced by an increase in percent fluorescence of most cell populations investigated during the specified treatment period.

Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

ClinicalTrials.gov

2013-07-01

B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

Renal Allograft Survival in Nonhuman Primates Infused With Donor Antigen-Pulsed Autologous Regulatory Dendritic Cells.

PubMed

Ezzelarab, M B; Raich-Regue, D; Lu, L; Zahorchak, A F; Perez-Gutierrez, A; Humar, A; Wijkstrom, M; Minervini, M; Wiseman, R W; Cooper, D K C; Morelli, A E; Thomson, A W

2017-06-01

Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg preloaded with cell membrane vesicles from allogeneic peripheral blood mononuclear cells induce T cell hyporesponsiveness to donor alloantigen (alloAg) in vitro. These donor alloAg-pulsed autologous DCreg (1.4-3.6 × 10 6 /kg) were administered intravenously, 1 day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 immunoglobulin [CTLA4] Ig) and tapered rapamycin. Prolongation of graft median survival time from 39.5 days (no DCreg infusion; n = 6 historical controls) and 29 days with control unpulsed DCreg (n = 2), to 56 days with donor Ag-pulsed DCreg (n = 5) was associated with evidence of modulated host CD4 + and CD8 + T cell responses to donor Ag and attenuation of systemic IL-17 production. Circulating anti-donor antibody (Ab) was not detected until CTLA4 Ig withdrawal. One monkey treated with donor Ag-pulsed DCreg rejected its graft in association with progressively elevated anti-donor Ab, 525 days posttransplant (160 days after withdrawal of immunosuppression). These findings indicate a modest but not statistically significant beneficial effect of donor Ag-pulsed autologous DCreg infusion on NHP graft survival when administered with a minimal immunosuppressive drug regimen. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

The Benefit of Microskin in Combination With Autologous Keratinocyte Suspension to Treat Full Skin Loss In Vivo.

PubMed

Yuru, Shang; Dawei, Li; Chuanan, Shen; Kai, Yin; Li, Ma; Longzhu, Li; Dongxu, Zhao; Wenfeng, Cheng

Patients with extensive deep burns often lack enough autologous skin to cover the wounds. This study explores a new method using microskin in combination with autologous keratinocytes in the treatment of extensive deep burn. Wounds in the combination group were treated with automicroskin at an area expansion ratio of 20:1 (wound area to automicroskin area) and autologous keratinocyte suspension, which were compared with the following treatments: no autotransplant, only allografts (control group); autologous keratinocyte suspension only (keratinocyte only group); automicroskin at an area expansion ratio of 20:1 (20:1 group); and automicroskin at an area expansion ratio of 10:1 (10:1 group, positive control). The authors used epithelialization rate (epithelialized area on day 21 divided by original wound area), hematoxylin and eosin staining, laminin, and type IV collagen immunohistochemistry to assess wound healing. The epithelialization rate of combination group (74.2% ± 8.0%) was similar to that of 10: 1 group (84.3% ± 11.9%, P = .085) and significantly (P < .05) higher than that of 20:1 group (59.2% ± 10.8%), keratinocyte only group (53.8% ± 11.5%), and control group (22.7% ± 5.5%). The hematoxylin and eosin staining and immunohistochemistry showed the epithelialization in the combination group was better than that in the keratinocyte only group and control group. Microskin in combination with autologous keratinocyte suspension can promote the reepithelialization of full-thickness wounds and reduce the requirements for automircoskin, and it is a useful option in the treatment of extensive deep burns.

Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis

PubMed Central

Abrahamsson, Sofia V.; Angelini, Daniela F.; Dubinsky, Amy N.; Morel, Esther; Oh, Unsong; Jones, Joanne L.; Carassiti, Daniele; Reynolds, Richard; Salvetti, Marco; Calabresi, Peter A.; Coles, Alasdair J.; Battistini, Luca; Martin, Roland; Burt, Richard K.

2013-01-01

Autologous haematopoietic stem cell transplantation has been tried as one experimental strategy for the treatment of patients with aggressive multiple sclerosis refractory to other immunotherapies. The procedure is aimed at ablating and repopulating the immune repertoire by sequentially mobilizing and harvesting haematopoietic stem cells, administering an immunosuppressive conditioning regimen, and re-infusing the autologous haematopoietic cell product. ‘Non-myeloablative’ conditioning regimens to achieve lymphocytic ablation without marrow suppression have been proposed to improve safety and tolerability. One trial with non-myeloablative autologous haematopoietic stem cell transplantation reported clinical improvement and inflammatory stabilization in treated patients with highly active multiple sclerosis. The aim of the present study was to understand the changes in the reconstituted immune repertoire bearing potential relevance to its mode of action. Peripheral blood was obtained from 12 patients with multiple sclerosis participating in the aforementioned trial and longitudinally followed for 2 years. We examined the phenotype and function of peripheral blood lymphocytes by cell surface or intracellular staining and multi-colour fluorescence activated cell sorting alone or in combination with proliferation assays. During immune reconstitution post-transplantation we observed significant though transient increases in the proportion of CD4+FoxP3+ T cells and CD56high natural killer cell subsets, which are cell subsets associated with immunoregulatory function. CD8+CD57+ cytotoxic T cells were persistently increased after therapy and were able to suppress CD4+ T cell proliferation with variable potency. In contrast, a CD161high proinflammatory CD8+ T cell subset was depleted at all time-points post-transplantation. Phenotypic characterization revealed that the CD161highCD8+ T cells were mucosal-associated invariant T cells, a novel cell population originating

Technical manual for manufacturing autologous fibrin tissue adhesive.

PubMed

Park, J J; Cintron, J R; Siedentop, K H; Orsay, C P; Pearl, R K; Nelson, R L; Abcarian, H

1999-10-01

The aim of this article is to provide a concise and simple technical manual for manufacturing autologous fibrin tissue adhesive derived from the precipitation of fibrinogen using a combination of ethanol and freezing for surgery. All materials and equipment needed to manufacture ethanol-based autologous fibrin tissue adhesive are listed. In addition, step-by-step instructions are provided to allow for easy and rapid fibrin adhesive production. Ethanol-based autologous fibrin tissue adhesive can be manufactured in under 60 minutes. Furthermore, at our institution the startup cost for manufacturing ethanol-based autologous fibrin tissue adhesive was under $2,500.00. Ethanol-based autologous fibrin tissue adhesive is a safe, reliable, and easily manufactured autologous fibrin tissue adhesive that can be made by a trained technician in any blood bank, pharmacy, or surgical laboratory.

Obatoclax, Fludarabine, and Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2013-09-27

B-cell Chronic Lymphocytic Leukemia; Leukemia; Prolymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

Isolation and partial characterization of melanoma-associated antigens identified by autologous antibody.

PubMed

Vlock, D R; Scalise, D; Meglin, N; Kirkwood, J M; Ballou, B

1988-06-01

The study of the autologous immune response to cancer avoids the difficulties encountered in the use of xenoantisera and may identify antigens of physiological relevance. However, the low titer and incidence of autologous antibody to melanoma have hampered further evaluation. By utilizing acid dissociation and ultrafiltration of serum, we have been able to augment the detectable autologous immune response to melanoma in the majority of patients studied. In autologous system Y-Mel 84:420, serum S150 demonstrated a rise in titer from 1:32 in native sera to 1:262,044 after dissociation. The antigen detected by S150 was found to be broadly represented on melanoma, glioma, renal cell carcinoma, neuroblastoma, and head and neck carcinoma cell lines. It did not react with bladder or colon carcinoma, fetal fibroblasts, pooled platelets, lymphocytes and red blood cells, or autologous cultured lymphocytes. Using polyacrylamide gel electrophoresis, S150 detects a 66,000-mol wt antigen in spent tissue culture media and serum ultrafiltrate. In cell lysate two bands between 20,000 and 30,000 mol wt are detected by S150. The 66,000-mol wt antigen is sensitive to trypsin digestion and but is resistant to pepsin and heat inactivation. Exposure of spent media to trypsin results in the development of a 24,000-mol wt band that appears to correspond to the antigen detected in the cell lysate. The difference between the antigens detected in the cell lysate as compared with spent media and serum ultrafiltrate may be due to degradation during cell lysis. We conclude that melanoma-associated antigens are present in the serum of patients with melanoma and are shed or secreted by their tumor cells.

Colony formation by normal and malignant human B-lymphocytes.

PubMed Central

Izaguirre, C. A.; Minden, M. D.; Howatson, A. F.; McCulloch, E. A.

1980-01-01

A method is described that permits colony formation in culture by B lymphocytes from normal blood and from blood, marrow or lymph nodes of patients with myeloma or lymphoma. The method depends on: (1) exhaustively depleting cell suspensions of T lymphocytes, (2) a medium conditioned by T lymphocytes in the presence of phytohaemagglutinin (PHA-TCM), and (3) irradiated autologous or homologous T lymphocytes. Under these conditions the assay is linear. Cellular development of B lymphocytes can be followed; differentiation to plasma cells is seen in cultures of cells from normal individuals and myeloma patients, but not lymphoma patients. Malignant B lymphocytes in culture produced immunoglobulin of the class identified in the patient's blood, or in freshly obtained cells. We conclude that the assay is suitable for studying the growth, differentiation and regulation of normal and malignant B lymphocytes in culture. Images Fig. 1 Fig. 2 PMID:6968572

Autologous hematopoietic stem cell transplantation in lymphoma patients is associated with a decrease in the double strand break repair capacity of peripheral blood lymphocytes.

PubMed

Lacoste, Sandrine; Bhatia, Smita; Chen, Yanjun; Bhatia, Ravi; O'Connor, Timothy R

2017-01-01

Patients who undergo autologous hematopoietic stem cell transplantation (aHCT) for treatment of a relapsed or refractory lymphoma are at risk of developing therapy related- myelodysplasia/acute myeloid leukemia (t-MDS/AML). Part of the risk likely resides in inherent interindividual differences in their DNA repair capacity (DRC), which is thought to influence the effect chemotherapeutic treatments have on the patient's stem cells prior to aHCT. Measuring DRC involves identifying small differences in repair proficiency among individuals. Initially, we investigated the cell model in healthy individuals (primary lymphocytes and/or lymphoblastoid cell lines) that would be appropriate to measure genetically determined DRC using host-cell reactivation assays. We present evidence that interindividual differences in DRC double-strand break repair (by non-homologous end-joining [NHEJ] or single-strand annealing [SSA]) are better preserved in non-induced primary lymphocytes. In contrast, lymphocytes induced to proliferate are required to assay base excision (BER) or nucleotide excision repair (NER). We established that both NHEJ and SSA DRCs in lymphocytes of healthy individuals were inversely correlated with the age of the donor, indicating that DSB repair in lymphocytes is likely not a constant feature but rather something that decreases with age (~0.37% NHEJ DRC/year). To investigate the predictive value of pre-aHCT DRC on outcome in patients, we then applied the optimized assays to the analysis of primary lymphocytes from lymphoma patients and found that individuals who later developed t-MDS/AML (cases) were indistinguishable in their DRC from controls who never developed t-MDS/AML. However, when DRC was investigated shortly after aHCT in the same individuals (21.6 months later on average), aHCT patients (both cases and controls) showed a significant decrease in DSB repair measurements. The average decrease of 6.9% in NHEJ DRC observed among aHCT patients was much higher

Apolizumab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

ClinicalTrials.gov

2013-07-15

Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Small Lymphocytic Lymphoma

Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

ClinicalTrials.gov

2014-10-30

Hematopoietic/Lymphoid Cancer; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

Neutrophil-to-lymphocyte ratio decreases in obstructive sleep apnea treated with mandibular advancement devices.

PubMed

Al-Halawani, Moh'd; Naik, Sreelatha; Chan, Michael; Kreinin, Iouri; Meiers, Jonathan; Kryger, Meir

2018-02-07

Obstructive sleep apnea has been associated with chronic inflammation triggered by nocturnal hypoxemia. The neutrophil-to-lymphocyte ratio (NLR) is a measure of subclinical systemic inflammation. We hypothesize that NLR levels would improve as chronic inflammation diminishes in obstructive sleep apnea (OSA) patients treated with mandibular advancement devices (MADs). We studied patients with OSA who were treated with MAD as a first-line treatment or because they could not tolerate CPAP. We obtained pre-treatment and post-treatment complete blood counts. NLR was calculated by dividing the number of neutrophils by the number of lymphocytes obtained from the CBCs. Patients with other conditions known to affect NLR were excluded from the study. We compared the values of NLR and oxygen desaturation index (ODI) before and after treatment with MAD in 22 patients who met inclusion criteria and completed the study protocol. There was a significant difference in NLR before and after treatment (p = 0.01). There was also a significant difference in the 3% ODI and 4% ODI before and after treatment with MAD (p = 0.014, 0.007), respectively. A subgroup analysis compared NLR in two groups of patients, the optimally treated and suboptimally treated. There was a significant decrease in the NLR in the optimally treated group (n = 10) (p < 0.01), whereas it did not change in the suboptimally treated group (n = 12) (p = 0.349). The neutrophil-to-lymphocyte ratio may be useful in documenting improvement in inflammation for OSA patients treated with mandibular advancement devices. Our results specifically suggest that the NLR values are associated with the decrease in the ODI.

Adoptive T-cell Therapy Using Autologous Tumor-infiltrating Lymphocytes for Metastatic Melanoma: Current Status and Future Outlook

PubMed Central

Wu, Richard; Forget, Marie-Andree; Chacon, Jessica; Bernatchez, Chantale; Haymaker, Cara; Chen, Jie Qing; Hwu, Patrick; Radvanyi, Laszlo

2012-01-01

Immunotherapy using autologous T-cells has emerged to be a powerful treatment option for patients with metastatic melanoma. These include the adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL), T-cells transduced with high-affinity T-cell receptors (TCR) against major melanosomal tumor antigens, and T cells transduced with chimeric antigen receptors (CAR) composed of hybrid immunoglobulin light chains with endo-domains of T-cell signaling molecules. Among these and other options for T-cell therapy, TIL together with high-dose IL-2 has had the longest clinical history with multiple clinical trials in centers across the world consistently demonstrating durable clinical response rates near 50% or more. A distinct advantage of TIL therapy making it still the T-cell therapy of choice is the broad nature of the T-cell recognition against both defined as well as un-defined tumors antigens against all possible MHC, rather than the single specificity and limited MHC coverage of the newer TCR and CAR transduction technologies. In the past decade, significant inroads have been made in defining the phenotypes of T cells in TIL mediating tumor regression. CD8+ T cells are emerging to be critical, although the exact subset of CD8+ T cells exhibiting the highest clinical activity in terms of memory and effector markers is still controversial. We present a model in which both effector-memory and more differentiated effector T cells ultimately may need to cooperate to mediate long-term tumor control in responding patients. Although TIL therapy has shown great potential to treat metastatic melanoma, a number of issues have emerged that need to be addressed to bring it more into the mainstream of melanoma care. First, we have a reached the point where a pivotal phase II or phase III trials are needed in an attempt to gain regulatory approval of TIL as standard-of-care. Second, improvements in how we expand TIL for therapy are needed, that minimize the time the T

A parathyroid-hormone-related-protein (PTH-rP)-specific cytotoxic T cell response induced by in vitro stimulation of tumour-infiltrating lymphocytes derived from prostate cancer metastases, with epitope peptide-loaded autologous dendritic cells and low-dose IL-2

PubMed Central

Correale, P; Micheli, L; Vecchio, M T Del; Sabatino, M; Petrioli, R; Pozzessere, D; Marsili, S; Giorgi, G; Lozzi, L; Neri, P; Francini, G

2001-01-01

Bone metastases are one of the most common events in patients with prostate carcinoma. PTH-rP, a protein produced by prostate carcinoma and other epithelial cancers, is a key agent for the development of bone metastases. A PTH-rP-derived peptide, designated PTR-4 was identified, which is capable to bind HLA-A2.1 molecules and to generate PTH-rP-specific cytotoxic T cell (CTL) lines from healthy HLA-A2.1+ individual peripheral-blood-mononuclear-cells (PBMC). In this model, we investigated the in vitro possibility of generating an efficient PTH-rP specific CTL response by cyclical stimulations with IL-2 and PTR-4 peptide-pulsed autologous dendritic cells (DC), of HLA-A2.1+ tumour infiltrating lymphocytes (TIL) derived from a patient with metastatic prostate carcinoma. A T cell line generated in this way (called TM-PTR-4) had a CD3+, CD5+, CD4−, CD8+, CD45Ro+, CD56− immunophenotype and a HLA-A2.1 restricted cytotoxic activity to PTR-4-peptide pulsed CIR-A2 (HLA-A2.1+) target cells, PTH-rP+/HLA-A2.1+ CIR-A2 transfected with PTH-rP gene, prostate carcinoma LNCaP cells, and autologous metastatic prostate cancer cells (M-CaP). These lymphocytes were not cytotoxic to HLA-A2.1+ targets not producing PTH-rP, such as peptide-unpulsed CIR-A2 and colon carcinoma SW-1463, cell lines. Our results provide evidence that PTR-4 peptide-pulsed autologous DC may break the tolerance of human TIL against the autologous tumour by inducing a PTH-rP-specific CTL immune reaction. In conclusion PTR-4 peptide-pulsed autologous DC may be a promising approach for vaccine-therapy and antigen-specific CTL adoptive immunotherapy of hormone-resistant prostrate cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11742494

Correcting Nasojugal Groove with Autologous Cultured Fibroblast Injection: A Pilot Study.

PubMed

Moon, Kyung-Chul; Lee, Hyun-Su; Han, Seung-Kyu; Chung, Ho-Yun

2018-06-01

A new commercial drug that contains autologous cultured fibroblasts has been developed and approved by the United States Food and Drug Administration for improving the appearance of nasolabial folds. However, the treatment requires three sessions every 3-6 weeks. It is known that the skin overlying the nasojugal groove is thinner, and the wrinkle is generally shallower than nasolabial folds. Therefore, we hypothesized that the nasojugal groove could be improved by just one treatment session. Therefore, the purpose of this study was to evaluate the efficacy and safety of autologous cultured fibroblast injection to correct nasojugal grooves. Forty-six subjects with nasojugal grooves were enrolled in this study. They were injected with autologous cultured fibroblasts or placebo in one session. Blinded evaluators and subjects assessed the efficacy using a validated wrinkle assessment scale at 4, 12, and 24 weeks after the injection. Information of adverse events was collected at each visit. Based on the evaluators' assessment at 24 weeks after the injection, 76% of subjects treated with autologous cultured fibroblasts showed improvement whereas 0% of subjects treated with placebo showed improvement (P < 0.0001). Based on self-assessment at 24 weeks after the injection, 72% of subjects treated with autologous cultured fibroblasts and 45% of subjects treated with placebo showed improvement (P = 0.0662). There were no serious adverse events related to autologous cultured fibroblast injection. Autologous cultured fibroblast injection might be effective and safe to correct nasojugal grooves. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Reprogramming of Melanoma Tumor-Infiltrating Lymphocytes to Induced Pluripotent Stem Cells

PubMed Central

Saito, Hidehito; Okita, Keisuke; Fusaki, Noemi; Sabel, Michael S.; Chang, Alfred E.; Ito, Fumito

2016-01-01

Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients hold great promise for autologous cell therapies. One of the possible applications of iPSCs is to use them as a cell source for producing autologous lymphocytes for cell-based therapy against cancer. Tumor-infiltrating lymphocytes (TILs) that express programmed cell death protein-1 (PD-1) are tumor-reactive T cells, and adoptive cell therapy with autologous TILs has been found to achieve durable complete response in selected patients with metastatic melanoma. Here, we describe the derivation of human iPSCs from melanoma TILs expressing high level of PD-1 by Sendai virus-mediated transduction of the four transcription factors, OCT3/4, SOX2, KLF4, and c-MYC. TIL-derived iPSCs display embryonic stem cell-like morphology, have normal karyotype, express stem cell-specific surface antigens and pluripotency-associated transcription factors, and have the capacity to differentiate in vitro and in vivo. A wide variety of T cell receptor gene rearrangement patterns in TIL-derived iPSCs confirmed the heterogeneity of T cells infiltrating melanomas. The ability to reprogram TILs containing patient-specific tumor-reactive repertoire might allow the generation of patient- and tumor-specific polyclonal T cells for cancer immunotherapy. PMID:27057178

Two-Year Outcome of a Patient Treated With Phototherapeutic Keratectomy and Autologous SMILE Lenticule Transplantation for Flap-Related Complications Following LASIK.

PubMed

Zhao, Jing; Zhao, Feng; Huang, Jinrong; Xu, Haipeng; Chen, Yingjun; Zhou, Xingtao

2018-04-01

To describe a patient with flap complications after LASIK who was subsequently treated using phototherapeutic keratectomy (PTK) and an autologous lenticule transplant obtained via small incision lenticule extraction (SMILE). A 23-year-old man experienced free flap and partial flap loss in the left eye following LASIK, resulting in corneal stroma opacity 1 month later. The manifest refraction was -3.25 diopters sphere (DS)/-0.50 diopters cylinder (DC) × 100° in the right eye and +2.50 DS/-1.25 DC × 155° in the left eye. His left eye was treated with PTK and transplantation of an autologous lenticule obtained from his right eye using the SMILE procedure. At the 2-year follow-up visit, the uncorrected distance visual acuity of the left eye had improved from 20/100 to 20/22 and the corrected distance visual acuity had improved from 20/25 to 20/18. Central corneal thickness had increased from 464 to 499 µm. The mean keratometry value had decreased from 45.00 diopters (D) at the 1-month follow-up visit to 39.40 D at the 2-year follow-up visit. Optical coherence tomography examination revealed that the lenticule remained transparent and exhibited a visible demarcation line. The transplantation of an autologous lenticule obtained via SMILE combined with PTK improved uncorrected and corrected acuity in this patient with flap loss after LASIK. [J Refract Surg. 2018;34(4):281-285.]. Copyright 2018, SLACK Incorporated.

Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

ClinicalTrials.gov

2015-11-10

Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

Antitumor killer lymphocytes in the peripheral blood of a patient with transitional cell carcinoma of the bladder.

PubMed

Kim, C J; Yuasa, T; Kushima, R; Tomoyoshi, T; Seto, A

1998-05-01

Peripheral blood lymphocytes (PBL) from patients with bladder cancer also contain cells possessing cytotoxic activity against autologous tumor cells. These cells are phenotypically heterogenous and include natural killer (NK) and cytotoxic T cells. This study investigated the role of cytotoxic lymphocytes directed against autologous bladder cancer cells. PBL were obtained at intervals before and after surgery and analyzed for cytotoxic activity against autologous bladder cancer cells in 4-hour 51Cr release assay. PBL stimulated with autologous tumor cells were also transformed with human T-lymphotropic virus type-1, establishing a cell line (KB31) which was analyzed for phenotype and cytotoxic activity against the autologous tumor cells. PBL preoperative cytotoxic activity was low, but increased after surgery. Cytotoxic activity was found not only against autologous bladder cancer cells, but also against heterologous bladder cancer (KK-47) and myeloid leukemia (K562) cells, with the highest activity against the heterologous cell lines. The cytotoxic activity of KB31 was 40% against autologous tumor cells 6 weeks after initiation of the cell line, but decreased to 5% by 6 months. This activity was lower than that against the other cell lines, and was similar to that of PBL in short-term culture. Fluorescence-activated cell sorter (FACS) analysis demonstrated that in KB31 cells at 6 weeks, CD8+ cells were dominant, but CD56+ cells predominated at 6 months. These results suggest that the presence of cytotoxic activity in the peripheral blood of the patient was due to both cytotoxic T cells and NK cells. The cytotoxic activity was lowest prior to surgery and increased postoperatively.

Vorinostat, Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

ClinicalTrials.gov

2018-01-12

Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

Outcomes in relapsed Hodgkin's lymphoma treated with autologous and allogeneic hematopoietic cell transplantation at the Pontificia Universidad Católica de Chile

PubMed Central

Ramirez, Pablo; Ocqueteau, Mauricio; Rodriguez, Alejandra; Garcia, Maria Jose; Sarmiento, Mauricio; Ernst, Daniel; Jara, Veronica; Bertin, Pablo

2015-01-01

Introduction Hodgkin's lymphoma is a highly curable disease. Autologous and reduced intensity allogeneic hematopoietic cell transplantations are alternatives to treat relapsed patients. Here, we report on the results of one service using these procedures. Methods All patients who underwent transplantations in our institution between 1996 and 2014 were retrospectively studied and demographics, toxicities and survival rate were analyzed. Results This study evaluated 24 autologous and five reduced intensity allogeneic transplantations: the median ages of the patients were 29 and 32 years, respectively. At the time of autologous transplantation, ten patients were in complete remission, nine had chemosensitive disease but were not in complete remission, three had refractory disease and the status of two is unknown. In the allogeneic group, two were in complete remission and three had chemosensitive disease. The 5-year overall survival after autologous transplantation was 42% (66% patients were in complete remission, 37% had chemosensitive disease with incomplete remission and 0% had refractory disease) and 1-year overall survival after allogeneic transplantation was 80%. Transplant-related mortality was 0% in patients conditioned with the ifosfamide/carboplatin/etoposide (ICE), carmustine/etoposide/cyclophosphamide (BEC) and carmustine/etoposide/cytarabine/melphalan (BEAM) regimens, 37% in patients conditioned with busulfan-based regimens and 20% in allogeneic transplantations. Conclusions Hematopoietic cell transplantation for relapsed Hodgkin's lymphoma is a potentially curative procedure especially in patients in complete remission at the time of autologous transplantations, and possibly after allogeneic transplantations. Further studies are necessary to clarify the role of allogeneic transplantations in the treatment of relapsed Hodgkin's lymphoma. PMID:26041421

Venetoclax in Patients with Previously Treated Chronic Lymphocytic Leukemia.

PubMed

Roberts, Andrew W; Stilgenbauer, Stephan; Seymour, John F; Huang, David C S

2017-08-15

Venetoclax is the first BCL2 inhibitor to enter routine clinical practice. It is an orally bioavailable small molecule that binds BCL2 very specifically. Acting as a pharmacologic mimic of the proteins that initiate apoptosis (a so-called BH3 mimetic), venetoclax rapidly induces apoptosis in chronic lymphocytic leukemia (CLL) cells, which express high levels of BCL2 and rely on it to maintain their survival. As a single agent, daily venetoclax treatment induced durable responses in 79% of patients with relapsed or refractory CLL or small lymphocytic lymphoma in a phase I study, including complete remissions in 20% of patients. Its use was approved by the FDA in April 2016 for patients with previously treated del(17p) CLL on the basis of a single-arm phase II trial demonstrating a 79% response rate and an estimated 1-year progression-free survival of 72% with 400 mg/day continuous therapy. This review focuses on venetoclax, its mechanism of action, pharmacology, and clinical trial data and seeks to place it in the context of rapid advances in therapy for patients with relapsed CLL, especially those with del(17p) CLL. Clin Cancer Res; 23(16); 4527-33. ©2017 AACR . ©2017 American Association for Cancer Research.

[T and B lymphocytes and serum alpha 1-antitrypsin activity in children with bronchial asthma treated with broncho-vaxom].

PubMed

Wartenberg, J; Lewandowska, J; Pilarek, M; Piltz, D

The aim of this study was to evaluate an effect of Broncho-Vaxom treatment on T and B lymphocytes and serum alpha 1AT in children treated at "Zuch" sanatorium in Szczawno-spa. The trial involved 46 school aged children suffering from infectious or infectious-atopic asthma. The post-Broncho-Vaxom treatment values for T lymphocytes were significantly higher in infectious, and significantly lower for B lymphocytes in infectious-atopic asthma. Serum alpha 1AT activity in children suffering from infectious asthma decreased significantly after the treatment. A correlation between the efficacy of the treatment and the lymphocyte percentage was observed. In children with very effective clinical results of Broncho-Vaxom treatment, the significant increase in T lymphocyte, and decrease in B lymphocyte populations was observed. Changes in T and B lymphocyte percentage were analysed in respect to alpha 1AT pre-treatment activity. In children with high alpha 1AT value, T lymphocytes after the treatment increased significantly in infectious, and B lymphocytes decreased significantly in infectious-atopic group.

Expansion of tumor-infiltrating lymphocytes and their potential for application as adoptive cell transfer therapy in human breast cancer.

PubMed

Lee, Hee Jin; Kim, Young-Ae; Sim, Chan Kyu; Heo, Sun-Hee; Song, In Hye; Park, Hye Seon; Park, Suk Young; Bang, Won Seon; Park, In Ah; Lee, Miseon; Lee, Jung Hoon; Cho, Yeon Sook; Chang, Suhwan; Jung, Jaeyun; Kim, Jisun; Lee, Sae Byul; Kim, Sung Youl; Lee, Myeong Sup; Gong, Gyungyub

2017-12-26

Adoptive cell transfer (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs) has been successful in treating a considerable proportion of patients with metastatic melanoma. In addition, some patients with several other solid tumors were recently reported to have benefited clinically from such ACT. However, it remains unclear whether ACT using TILs is broadly applicable in breast cancer, the most common cancer in women. In this study, the utility of TILs as an ACT source in breast cancers was explored by deriving TILs from a large number of breast cancer samples and assessing their biological potentials. We successfully expanded TILs ex vivo under a standard TIL culture condition from over 100 breast cancer samples, including all breast cancer subtypes. We also found that the information about the percentage of TIL and presence of tertiary lymphoid structure in the tumor tissues could be useful for estimating the number of obtainable TILs after ex vivo culture. The ex vivo expanded TILs contained a considerable level of central memory phenotype T cells (about 20%), and a large proportion of TIL samples were reactive to autologous tumor cells in vitro . Furthermore, the in vitro tumor-reactive autologous TILs could also function in vivo in a xenograft mouse model implanted with the primary tumor tissue. Collectively, these results strongly indicate that ACT using ex vivo expanded autologous TILs is a feasible option in treating patients with breast cancer.

Expansion of tumor-infiltrating lymphocytes and their potential for application as adoptive cell transfer therapy in human breast cancer

PubMed Central

Lee, Hee Jin; Kim, Young-Ae; Sim, Chan Kyu; Heo, Sun-Hee; Song, In Hye; Park, Hye Seon; Park, Suk Young; Bang, Won Seon; Park, In Ah; Lee, Miseon; Lee, Jung Hoon; Cho, Yeon Sook; Chang, Suhwan; Jung, Jaeyun; Kim, Jisun; Lee, Sae Byul; Kim, Sung Youl; Lee, Myeong Sup; Gong, Gyungyub

2017-01-01

Adoptive cell transfer (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs) has been successful in treating a considerable proportion of patients with metastatic melanoma. In addition, some patients with several other solid tumors were recently reported to have benefited clinically from such ACT. However, it remains unclear whether ACT using TILs is broadly applicable in breast cancer, the most common cancer in women. In this study, the utility of TILs as an ACT source in breast cancers was explored by deriving TILs from a large number of breast cancer samples and assessing their biological potentials. We successfully expanded TILs ex vivo under a standard TIL culture condition from over 100 breast cancer samples, including all breast cancer subtypes. We also found that the information about the percentage of TIL and presence of tertiary lymphoid structure in the tumor tissues could be useful for estimating the number of obtainable TILs after ex vivo culture. The ex vivo expanded TILs contained a considerable level of central memory phenotype T cells (about 20%), and a large proportion of TIL samples were reactive to autologous tumor cells in vitro. Furthermore, the in vitro tumor-reactive autologous TILs could also function in vivo in a xenograft mouse model implanted with the primary tumor tissue. Collectively, these results strongly indicate that ACT using ex vivo expanded autologous TILs is a feasible option in treating patients with breast cancer. PMID:29371915

Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

ClinicalTrials.gov

2018-01-26

Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

Prechemotherapy neutrophil : lymphocyte ratio is superior to the platelet : lymphocyte ratio as a prognostic indicator for locally advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy.

PubMed

Ji, W H; Jiang, Y H; Ji, Y L; Li, B; Mao, W M

2016-07-01

prechemotherapy platelet to lymphocyte ratio ≤30 to preoperative platelet to lymphocyte ratio ≤130 group. In conclusions, prechemotherapy neutrophil to lymphocyte ratio is an independent prognostic factor for OS in patients with advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy, and, as an adverse prognostic predictor, increased prechemotherapy neutrophil to lymphocyte ratio is superior to platelet to lymphocyte ratio. Maintaining a low neutrophil to lymphocyte ratio and platelet to lymphocyte ratio throughout treatment is a predictor of better OS. © 2015 International Society for Diseases of the Esophagus.

Functional characterization of a regulatory human T-cell subpopulation increasing during autologous MLR.

PubMed Central

Cosulich, M E; Risso, A; Canonica, G W; Bargellesi, A

1986-01-01

The present study was undertaken to investigate the heterogeneity of helper T cells in humans using two different monoclonal antibodies: 5/9 and MLR4. The former identifies 15-20% of resting T lymphocytes from peripheral blood and corresponds to an anti-helper/inducer T cell. The second antibody, MLR4, recognizes 5% of total T lymphocytes and partially overlaps with the 5/9+ T cells. In order to investigate functional differences within the 5/9+ cells, we separated two different subsets (5/9+ MLR+ and 5/9+ MLR4-) by a rosetting technique. Although both subsets provide help for Ig synthesis in a PWM-stimulated culture, only the 5/9+ MLR4- fraction gave a proliferative response in both autologous and allogeneic MLR and to soluble protein antigens. The effect of radiation on the ability of the two subsets to provide help for Ig synthesis showed that the 5/9+ MLR4+ subset is highly radiation-sensitive, while 5/9+ MLR- is relatively radiation-resistant. In a further series of experiments, 5/9+ MLR4+ cells isolated after activation in an autologous MLR but not by Con A, were no longer able to induce T-cell differentiation but now showed a strong suppressor effect. The 5/9+ MLR4- subset separated from the same cultures did not display any suppressor function. These data demonstrate in fresh PBL the existence of a radiation-sensitive regulatory subset exerting a helper activity, and which acquires suppressor activity after activation in autologous MLR. PMID:2936679

Application of cytogenetic endpoints and comet assay on human lymphocytes treated with atorvastatin in vitro.

PubMed

Gajski, Goran; Garaj-Vrhovac, Vera

2008-01-01

This study investigated the genotoxic potential of atorvastatin on human lymphocytes using comet assay, structural chromosome aberrations (CA) and sister-chromatid exchange (SCE) analysis. Lymphocyte cultures were treated with a single drug at a concentration of 30.21 ng/mL. For comet assay, cells exposed to atorvastatin for 24 h, 48 h and 72 h were embedded in agarose slides, lysed with alkaline lysis solution and exposed to an electric field. DNA migrated within the agarose and formed comets whose length depends on the amount of DNA damage. For analysis of structural CA, cells were grown on medium for 48 h and for SCE analysis for 72 h. Structural CA did not induce significant damage to the genome, although a higher CA frequency was observed in cells treated with atorvastatin for 3 h, 20 h and 48 h than in control samples. Results of the SCE analysis did show statistically significant differences in the mean SCE number between atorvastatin-exposed and control human lymphocytes and between different exposure times. Comet assay also showed increased DNA damage caused in atorvastatin-exposed human lymphocytes than in corresponding control cells for exposure times of 24 h, 48 h and 72 h for the tail length and for 72 h for the tail moment. Results obtained in this study point to the significance of biological indicators providing information on the primary genome damage after long-term exposure, which can help to establish drug therapeutic concentrations that do not put patients with high blood cholesterol to a greater treatment-related risk.

Mastectomy Skin Necrosis After Breast Reconstruction: A Comparative Analysis Between Autologous Reconstruction and Implant-Based Reconstruction.

PubMed

Sue, Gloria R; Lee, Gordon K

2018-05-01

Mastectomy skin necrosis is a significant problem after breast reconstruction. We sought to perform a comparative analysis on this complication between patients undergoing autologous breast reconstruction and patients undergoing 2-stage expander implant breast reconstruction. A retrospective review was performed on consecutive patients undergoing autologous breast reconstruction or 2-stage expander implant breast reconstruction by the senior author from 2006 through 2015. Patient demographic factors including age, body mass index, history of diabetes, history of smoking, and history of radiation to the breast were collected. Our primary outcome measure was mastectomy skin necrosis. Fisher exact test was used for statistical analysis between the 2 patient cohorts. The treatment patterns of mastectomy skin necrosis were then analyzed. We identified 204 patients who underwent autologous breast reconstruction and 293 patients who underwent 2-stage expander implant breast reconstruction. Patients undergoing autologous breast reconstruction were older, heavier, more likely to have diabetes, and more likely to have had prior radiation to the breast compared with patients undergoing implant-based reconstruction. The incidence of mastectomy skin necrosis was 30.4% of patients in the autologous group compared with only 10.6% of patients in the tissue expander group (P < 0.001). The treatment of this complication differed between these 2 patient groups. In general, those with autologous reconstructions were treated with more conservative means. Although 37.1% of patients were treated successfully with local wound care in the autologous group, only 3.2% were treated with local wound care in the tissue expander group (P < 0.001). Less than half (29.0%) of patients in the autologous group were treated with an operative intervention for this complication compared with 41.9% in the implant-based group (P = 0.25). Mastectomy skin necrosis is significantly more likely to occur after

[Autologous epidermal sheets production for skin cellular therapy].

PubMed

Vacher, D

2003-05-01

Cell therapy is becoming a very interesting solution to replace degenerated or damaged tissues. In January 1998, Genevrier Laboratories inaugurated a new department especially designed for the production of cultured cells as therapeutic agents. Meeting clinician therapeutic needs by providing autologous keratinocytes and chondrocytes in the near future, represents the primary aim of the Biotechnology department. Concrete cell-based products are already being used for the treatment of burns and cutaneous chronic wounds such as the EPIBASE graft, which corresponds to an epidermis sheet composed of cultured autologous keratinocytes.

Frequencies of occurrence of all human chromosomes in micronuclei from normal and 5-azacytidine-treated lymphocytes as revealed by chromosome painting.

PubMed

Fauth, E; Scherthan, H; Zankl, H

1998-05-01

Chromosome painting with library DNA probes specific for all human chromosomes was used to study the chromosomal content of micronuclei (MN) in normal and 5-azacytidine (5-aza-C)-treated lymphocyte cultures. More than 60,000 normal lymphocytes were screened for associated MN after in situ hybridization. At least 50 MN were scored for each probe. With the exception of chromosomes 12 and 19, which did not occur in MN, all other chromosomes were detected in MN at frequencies varying from 1 to 11.5%. Treatment of lymphocyte cultures with 5-aza-C induced preferential exclusion of chromosomes 1 (34%), 9 (32%) and 16 (20%) material in MN, whereas chromosome 8, 10, 12-15 and 21 material was not detected in MN. The results obtained from normal lymphocytes allow for the first time an estimation of the frequency of occurrence of all chromosomes in spontaneously occurring MN in human cells. Data derived from 5-aza-C-treated lymphocytes are furthermore consistent with the view that undermethylation of heterochromatin may be associated with loss of specific chromosomes at metaphase.

Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2017-12-26

B-Cell Prolymphocytic Leukemia; Hypodiploidy; Loss of Chromosome 17p; Plasma Cell Leukemia; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; t(14;16); t(4;14); T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

Real world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in the United States.

PubMed

Mato, Anthony R; Thompson, Meghan; Allan, John N; Brander, Danielle M; Pagel, John M; Ujjani, Chaitra S; Hill, Brian T; Lamanna, Nicole; Lansigan, Frederick; Jacobs, Ryan; Shadman, Mazyar; Skarbnik, Alan P; Pu, Jeffrey J; Barr, Paul M; Sehgal, Alison R; Cheson, Bruce D; Zent, Clive S; Tuncer, Hande H; Schuster, Stephen J; Pickens, Peter V; Shah, Nirav N; Goy, Andre; Winter, Allison M; Garcia, Christine; Kennard, Kaitlin; Isaac, Krista; Dorsey, Colleen; Gashonia, Lisa M; Singavi, Arun K; Roeker, Lindsey E; Zelenetz, Andrew; Williams, Annalynn; Howlett, Christina; Weissbrot, Hanna; Ali, Naveed; Khajavian, Sirin; Sitlinger, Andrea; Tranchito, Eve; Rhodes, Joanna; Felsenfeld, Joshua; Bailey, Neil; Patel, Bhavisha; Burns, Timothy F; Yacur, Melissa; Malhotra, Mansi; Svoboda, Jakub; Furman, Richard R; Nabhan, Chadi

2018-06-07

Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with CLL treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV, 45% del(17p), and 26.8% complex karyotype (≥ 3 abnormalities). Prior to venetoclax initiation, 89% received a B-cell receptor antagonist. For tumor lysis syndrome prophylaxis, 93% received allopurinol, 92% normal saline, and 45% rasburicase. Dose escalation to the maximum recommended dose of 400 mg daily was achieved in 85% of patients. Adverse events of interest included neutropenia in 47.4%, thrombocytopenia in 36%, tumor lysis syndrome in 13.4%, neutropenic fever in 11.6%, and diarrhea in 7.3%. The overall response rate to venetoclax was 72% (19.4% complete remission). With a median follow up of 7 months, median progression free survival and overall survival for the entire cohort have not been reached. To date, 41 venetoclax treated patients have discontinued therapy and 24 have received a subsequent therapy, most commonly ibrutinib. In the largest clinical experience of venetoclax-treated chronic lymphocytic leukemia patients , the majority successfully completed and maintained a maximum recommended dose. Response rates and duration of response appear comparable to clinical trial data. Venetoclax was active in patients with mutations known to confer ibrutinib resistance. Optimal sequencing of newer chronic lymphocytic leukemia therapies requires further study. Copyright © 2018, Ferrata Storti Foundation.

Tositumomab and Iodine I 131 Tositumomab in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma in First Remission

ClinicalTrials.gov

2017-10-10

Lymphoid Leukemia in Remission; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

Therapeutic effects of autologous lymphocytes activated with trastuzumab for xenograft mouse models of human breast cancer.

PubMed

Nakagawa, Shinichiro; Matsuoka, Yusuke; Ichihara, Hideaki; Yoshida, Hitoji; Yoshida, Kenshi; Ueoka, Ryuichi

2013-01-01

Trastuzumab (TTZ) is molecular targeted drug used for metastatic breast cancer patients overexpressing human epidermal growth factor receptor 2 (HER2). Therapeutic effects of lymphocytes activated with TTZ (TTZ-LAK) using xenograft mouse models of human breast cancer (MDA-MB-453) cells were examined in vivo. Remarkable reduction of tumor volume in a xenograft mouse models intravenously treated with TTZ-LAK cells after the subcutaneously inoculated of MDA-MB-453 cells was verified in vivo. The migration of TTZ-LAK cells in tumor of mouse models subcutaneously inoculated MDA-MB-453 cells was observed on the basis of histological analysis using immunostaining with CD-3. Induction of apoptosis in tumor of xenograft mice treated with TTZ-LAK cells was observed in micrographs using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method. It was noteworthy that the therapeutic effects of TTZ-LAK cells along with apoptosis were obtained for xenograft mouse models of human breast tumor in vivo.

[Autologous bone marrow transplantation in intestinal carcinoma].

PubMed

Sebesta, C; Tiefengraber, E; Kier, P; Ruckser, R; Habertheuer, K H; Schmid, A; Hinterberger, W

1995-01-01

Although adjuvant chemotherapy has made some progress in the treatment of colorectal cancer, chemotherapy of metastatic disease remains disappointing. Autologous bone marrow or stem cell transplantation following supralethal chemotherapy is presently not of major significance in tumors of the intestine. The registry of the EBMT (European Cooperative Group for Blood and Marrow Transplantation) contains at March 1993 a total of 2085 cases of autotransplants for solid tumors, of which only 19 were performed for disseminated gastrointestinal cancer (15 gastric, 4 colon). It remains to be shown, whether the presently poor results can be improved upon inclusion of lymphokine-activated killer cells (LAK-cells) by use of cytokine combinations or by the use of tumor infiltrating lymphocytes (TIL) post transplantation.

Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes

NASA Astrophysics Data System (ADS)

Morgan, Richard A.; Dudley, Mark E.; Wunderlich, John R.; Hughes, Marybeth S.; Yang, James C.; Sherry, Richard M.; Royal, Richard E.; Topalian, Suzanne L.; Kammula, Udai S.; Restifo, Nicholas P.; Zheng, Zhili; Nahvi, Azam; de Vries, Christiaan R.; Rogers-Freezer, Linda J.; Mavroukakis, Sharon A.; Rosenberg, Steven A.

2006-10-01

Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.

Entospletinib and Obinutuzumab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-03-05

Anemia; B-Cell Prolymphocytic Leukemia; Fatigue; Fever; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Hairy Cell Leukemia; Lymphadenopathy; Lymphocytosis; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Night Sweats; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma; Richter Syndrome; Splenomegaly; Thrombocytopenia; Weight Loss

Hematopoietic stem cell transplantation for chronic lymphocytic leukemia.

PubMed

Gladstone, Douglas E; Fuchs, Ephraim

2012-03-01

Although hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many aggressive hematologic malignancies, the role of HSCT in chronic lymphocytic leukemia (CLL) has remained controversial. Now in the era of improved conventional treatment and better prognostication of long-term outcome, a review of autologous and allogeneic HSCT in CLL treatment is warranted. Despite an improved disease-free survival in some patients, multiple, prospective, randomized autologous HSCT CLL trials fail to demonstrate an overall survival benefit as compared to conventional therapy. Allogeneic bone marrow transplantation, although limited by donor availability, can successfully eradicate CLL with adverse prognostic features. In the older CLL patients, nonmyeloablative allogeneic transplants are better tolerated than myeloablative transplants. Nonmyeloablative allogeneic transplants are less effective in heavily diseased burdened patients. Outside of a clinical protocol, autologous HSCT for CLL cannot be justified. Nonmyeloablative allogeneic transplantation should be considered in high-risk populations early in the disease process, when disease burden is most easily controlled. Alternative donor selection using haploidentical donors and posttransplantation cyclophosphamide has the potential to vastly increase the availability of curative therapy in CLL while retaining a low treatment-related toxicity.

Molecular mechanisms of lymphocyte extravasation. II. Studies of in vitro lymphocyte adherence to high endothelial venules.

PubMed

Braaten, B A; Spangrude, G J; Daynes, R A

1984-07-01

Lymphocyte migration from the blood into the lymph nodes in most species occurs across post-capillary high endothelial venules (HEV). In a previous study, we proposed that lymphocyte extravasation involves receptor-mediated binding followed by adenylate cyclase-dependent activation of lymphocyte motility. This hypothesis was, in part, based on observations of in vitro lymphocyte adherence to HEV by employing pertussigen, which is a known inhibitor of lymphocyte recirculation. In vitro lymphocyte-HEV binding requires a cold (6 degrees C) incubation step and binding is poor to nil if the assay is attempted at room (23 degrees C) or physiologic temperature. We decided to investigate why this assay is temperature restricted, because of the possibility that pertussigen or fucoidin -treated lymphocytes might interact with HEV differently at higher temperatures. We now report that O.C.T. compound (OCT), the embedding matrix generally used to cut frozen lymph node sections, is toxic to lymphocytes at temperatures above 6 degrees C. Exclusion of OCT from the assay system will allow lymphocyte-HEV binding to occur at 23 degrees C and to a lesser extent at 37 degrees C. With this modified protocol, lymphocytes treated with either pertussigen, fucoidin , or neuraminidase were tested for adherence to HEV at 23 degrees C. No essential difference in binding properties was observed from what had been reported at 6 degrees C. In contrast, trypsin-treated lymphocytes that did not bind to HEV with the standard technique at 6 degrees C did adhere to a minimal extent to HEV at 23 degrees C using the modified procedure. We also report some preliminary work, using the modified assay, on in vitro lymphocyte-HEV binding of rat, rabbit, and guinea pig lymphocytes to sections of lymph nodes from the respective species.

Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

ClinicalTrials.gov

2013-06-03

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

Vaccination with Irradiated Autologous Melanoma Cells Engineered to Secrete Human Granulocyte--Macrophage Colony-Stimulating Factor Generates Potent Antitumor Immunity in Patients with Metastatic Melanoma

NASA Astrophysics Data System (ADS)

Soiffer, Robert; Lynch, Thomas; Mihm, Martin; Jung, Ken; Rhuda, Catherine; Schmollinger, Jan C.; Hodi, F. Stephen; Liebster, Laura; Lam, Prudence; Mentzer, Steven; Singer, Samuel; Tanabe, Kenneth K.; Benedict Cosimi, A.; Duda, Rosemary; Sober, Arthur; Bhan, Atul; Daley, John; Neuberg, Donna; Parry, Gordon; Rokovich, Joseph; Richards, Laurie; Drayer, Jan; Berns, Anton; Clift, Shirley; Cohen, Lawrence K.; Mulligan, Richard C.; Dranoff, Glenn

1998-10-01

We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte--macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte--macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.

Second-degree burns with six etiologies treated with autologous noncultured cell-spray grafting.

PubMed

Esteban-Vives, Roger; Choi, Myung S; Young, Matthew T; Over, Patrick; Ziembicki, Jenny; Corcos, Alain; Gerlach, Jörg C

2016-11-01

Partial and deep partial-thickness burn wounds present a difficult diagnosis and prognosis that makes the planning for a conservative treatment versus mesh grafting problematic. A non-invasive treatment strategy avoiding mesh grafting is often chosen by practitioners based on their clinical and empirical evidence. However, a delayed re-epithelialization after conservative treatment may extend the patient's hospitalization period, increase the risk of infection, and lead to poor functional and aesthetic outcome. Early spray grafting, using non-cultured autologous cells, is under discussion for partial and deep partial-thickness wounds to accelerate the re-epithelialization process, reducing the healing time in the hospital, and minimizing complications. To address planning for future clinical studies on this technology, suitable indications will be interesting. We present case information on severe second-degree injuries after gas, chemical, electrical, gasoline, hot water, and tar scalding burns showing one patient per indication. The treatment results with autologous non-cultured cells, support rapid, uncomplicated re-epithelialization with aesthetically and functionally satisfying outcomes. Hospital stays averaged 7.6±1.6 days. Early autologous cell-spray grafting does not preclude or prevent simultaneous or subsequent traditional mesh autografting when indicated on defined areas of full-thickness injury. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Genotoxic effect of Physalis angulata L. (Solanaceae) extract on human lymphocytes treated in vitro.

PubMed

Alves dos Santos, Raquel; Cabral, Teresinha Rosa; Cabral, Isabel Rosa; Antunes, Lusânia Maria; Pontes Andrade, Cristiane; Cerqueira dos Santos Cardoso, Plínio; de Oliveira Bahia, Marcelo; Pessoa, Claudia; Martins do Nascimento, José Luis; Rodríguez Burbano, Rommel; Takahashi, Catarina Satie

2008-08-01

Physalis angulata L (Solanaceae) is a medicinal plant from North of Brazil, whose different extracts and infusions are commonly used in the popular medicine for the treatment of malaria, asthma, hepatitis, dermatitis and rheumatism. However, the genotoxic effects of P. angulata on human cells is not well known. The main purpose of the present study was to evaluate the in vitro genotoxic effects of aqueous extract of P. angulata using the comet assay and the micronucleus assay in human lymphocytes provided from 6 healthy donors. Treatments with P. angulata extracts were performed in vitro in order to access the extent of DNA damage. The comet assay has shown that treatments with P. angulata at 0.5, 1.0, 2.0, 3.0 and 6.0 microg/mL in culture medium were genotoxic. Lymphocytes treated with P. angulata at the concentrations of 3.0 and 6.0 microg/mL in culture medium showed a statistically significant increase in the frequency of micronucleus (p<0.05), however, the cytokinesis blocked proliferation index (CBPI) was not decreased after P. angulata treatment. In conclusion, the present work demonstrated the genotoxic effects of P. angulata extract on human lymphocytes in vitro.

The use of decompression to simulate the effect of extravehicular activity on human lymphocyte transformation

NASA Technical Reports Server (NTRS)

Meehan, R. T.; Duncan, U.; Neale, L.; Waligora, J.; Taylor, G. R.

1986-01-01

Lymphocytes from 35 subjects participating in a chamber study simulating extravehicular activity (EVA) conditions were studied. No significant differences in H3 thymidine uptake between pre chamber and post chamber response to any mitogens autologous plasma, or among circulating mononuclear cells by flow cytometry are observed. The studies could not identify the subjects who developed venous bubbles. Data from eight subjects suggests that acute stress associated with participating in the study augments in vitro lymphocyte proliferation. Results indicate EVA exposure does not greatly influence space-flight induced alterations in immune effector cell function.

CD8+ lymphocytes are required to maintain virus suppression in SIV-infected macaques treated with short-term antiretroviral therapy

PubMed Central

Cartwright, Emily K.; Spicer, Lori; Smith, S. Abigail; Lee, David; Fast, Randy; Paganini, Sara; Lawson, Benton O.; Nega, Melon; Easley, Kirk; Schmitz, Joern E.; Bosinger, Steven E.; Paiardini, Mirko; Chahroudi, Ann; Vanderford, Thomas H.; Estes, Jacob D.; Lifson, Jeffrey D.; Derdeyn, Cynthia A.; Silvestri, Guido

2016-01-01

Infection with HIV persists despite suppressive antiretroviral therapy (ART) and treatment interruption results in rapid viral rebound. Antibody-mediated CD8+ lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows these cells contribute to virus control in untreated animals. However, the contribution of CD8+ lymphocytes to maintaining virus suppression under ART remains unknown. We showed that in SIV-infected RMs treated with short-term ART (i.e., 8-32 weeks), depletion of CD8+ lymphocytes resulted in increased plasma viremia in all animals, and that repopulation of CD8+ T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4+ T cells pre-depletion positively correlated with both peak and area-under-the-curve of viremia post-depletion. These results suggest a role for CD8+ T cells in controlling virus production during ART, thus providing rationale to explore immunotherapeutic approaches in ART-treated HIV-infected individuals. PMID:27653601

In vivo traffic of indium-111-oxine labeled human lymphocytes collected by automated apheresis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Read, E.J.; Keenan, A.M.; Carter, C.S.

1990-06-01

The in vivo traffic patterns of autologous lymphocytes were studied in five normal human volunteers using lymphocytes obtained by automated apheresis, separated on Ficoll-Hypaque gradients, and labeled ex vivo with {sup 111}In-oxine. Final lymphocyte infusions contained 1.8-3.1 X 10(9) cells and 270-390 microCi (9.99-14.43 MBq) {sup 111}In, or 11-17 microCi (0.41-0.63 MBq) per 10(8) lymphocytes. Gamma imaging showed transient lung uptake and significant retention of radioactivity in the liver and spleen. Progressive uptake of activity in normal, nonpalpable axillary and inguinal lymph nodes was seen from 24 to 96 hr. Accumulation of radioactivity also was demonstrated at the forearm skinmore » test site, as well as in its associated epitrochlear and axillary lymph nodes, in a subject who had been tested for delayed hypersensitivity with tetanus toxoid. Indium-111-oxine labeled human lymphocytes may provide a useful tool for future studies of normal and abnormal lymphocyte traffic.« less

Influence of immunotherapy with autologous dendritic cells on innate and adaptive immune response in cancer.

PubMed

Matias, Bruna F; de Oliveira, Tânia M; Rodrigues, Cláudia M; Abdalla, Douglas R; Montes, Letícia; Murta, Eddie F C; Michelin, Márcia A

2013-01-01

The objective of this study was to evaluate some of the mechanisms involved in the activation of the immune system in patients with advanced-stage cancer (n = 7) who received an autologous dendritic cell vaccine. We examined the immune response mediated by macrophages (CD14+), natural killer cells (CD56+), and B lymphocytes (CD19+) by flow cytometry and assessed the expression of Th1 (IFN-γ, TNF-α, IL-2, and IL-12), Th2 (IL-4), and Treg (TGF-β) cytokines by flow cytometry and an enzyme-linked immunosorbent assay. The CD14+ TNF-α+ population was significantly increased (P < 0.04) when patients received the vaccine; IL-2 expression in both NK cells and in B lymphocytes was increased after a transient initial increase showed a nearly significant decrease (P < 0.07 and P < 0.06 respectively), whereas the CD19+ and CD56+ populations did not show significant changes. Dendritic cell-based immunotherapy led to increased secretion of IFN-γ and IL-12 and reduced secretion of TGF-β. In conclusion, it is likely that the autologous dendritic cell vaccine stimulated the immune cells from the peripheral blood of patients with cancer and generally increased the production of Th1 cytokines, which are related to immunomodulatory responses against cancer.

Influence of Immunotherapy with Autologous Dendritic Cells on Innate and Adaptive Immune Response in Cancer

PubMed Central

Matias, Bruna F.; de Oliveira, Tânia M.; Rodrigues, Cláudia M.; Abdalla, Douglas R.; Montes, Letícia; Murta, Eddie F.C.; Michelin, Márcia A.

2013-01-01

The objective of this study was to evaluate some of the mechanisms involved in the activation of the immune system in patients with advanced-stage cancer (n = 7) who received an autologous dendritic cell vaccine. We examined the immune response mediated by macrophages (CD14+), natural killer cells (CD56+), and B lymphocytes (CD19+) by flow cytometry and assessed the expression of Th1 (IFN-γ, TNF-α, IL-2, and IL-12), Th2 (IL-4), and Treg (TGF-β) cytokines by flow cytometry and an enzyme-linked immunosorbent assay. The CD14+ TNF-α+ population was significantly increased (P < 0.04) when patients received the vaccine; IL-2 expression in both NK cells and in B lymphocytes was increased after a transient initial increase showed a nearly significant decrease (P < 0.07 and P < 0.06 respectively), whereas the CD19+ and CD56+ populations did not show significant changes. Dendritic cell-based immunotherapy led to increased secretion of IFN-γ and IL-12 and reduced secretion of TGF-β. In conclusion, it is likely that the autologous dendritic cell vaccine stimulated the immune cells from the peripheral blood of patients with cancer and generally increased the production of Th1 cytokines, which are related to immunomodulatory responses against cancer. PMID:23926442

Anterior cruciate ligament tears treated with percutaneous injection of autologous bone marrow nucleated cells: a case series

PubMed Central

Centeno, Christopher J; Pitts, John; Al-Sayegh, Hasan; Freeman, Michael D

2015-01-01

Introduction This was a prospective case series designed to investigate treatment for anterior cruciate ligament (ACL) tears using an injection of autologous bone marrow concentrate. Methods Consecutive adult patients presenting to a private outpatient interventional musculoskeletal and pain practice with knee pain, ACL laxity on exam, and magnetic resonance imaging (MRI) evidence of a grade 1, 2, or 3 ACL tears with less than 1 cm retraction were eligible for this study. Eligible patients were treated with an intraligamentous injection of autologous bone marrow concentrate, using fluoroscopic guidance. Pre- and postprocedural sagittal MRI images of the ACLs were analyzed using ImageJ software to objectively quantify changes between pre- and posttreatment scans. Five different types of measurement of ACL pixel intensity were examined as a proxy for ligament integrity. In addition pain visual analog scale (VAS) and Lower Extremity Functional Scale (LEFS) values were recorded at baseline and at 1 month, 3 months, 6 months, and annually postinjection. Objective outcomes measured were pre- to post-MRI measurement changes, as analyzed by the ImageJ software. Subjective outcomes measured were changes in the VAS and LEFS, and a self-rated percentage improvement. Results Seven of ten patients showed improvement in at least four of five objective measures of ACL integrity in their postprocedure MRIs. In the entire study group, the mean gray value, median, raw integrated density, and modal gray value all decreased toward low-signal ACLs (P=0.01, P=0.02, P=0.002, and P=0.08), indications of improved ligament integrity. Seven of ten patients responded to the self-rated metrics follow up. The mean VAS change was a decrease of 1.7 (P=0.25), the mean LEFS change was an increase of 23.3 (P=0.03), and mean reported improvement was 86.7%. Conclusion Based on this small case series, autologous bone marrow concentrate shows promise in the treatment of grade 1, 2, and possibly grade 3

Adoptive transfer of MART-1 T cell receptor transgenic lymphocytes and dendritic cell vaccination in patients with metastatic melanoma

PubMed Central

Chodon, Thinle; Comin-Anduix, Begonya; Chmielowski, Bartosz; Koya, Richard C; Wu, Zhongqi; Auerbach, Martin; Ng, Charles; Avramis, Earl; Seja, Elizabeth; Villanueva, Arturo; McCannel, Tara A.; Ishiyama, Akira; Czernin, Johannes; Radu, Caius G.; Wang, Xiaoyan; Gjertson, David W.; Cochran, Alistair J.; Cornetta, Kenneth; Wong, Deborah J.L.; Kaplan-lefko, Paula; Hamid, Omid; Samlowski, Wolfram; Cohen, Peter A.; Daniels, Gregory A.; Mukherji, Bijay; Yang, Lili; Zack, Jerome A.; Kohn, Donald B.; Heath, James R.; Glaspy, John A.; Witte, Owen N.; Baltimore, David; Economou, James S.; Ribas, Antoni

2014-01-01

Purpose It has been demonstrated that large numbers of tumor-specific T cells for adoptive cell transfer (ACT) can be manufactured by retroviral genetic engineering of autologous peripheral blood lymphocytes and expanding them over several weeks. In mouse models, this therapy is optimized when administered with dendritic cell (DC) vaccination. We developed a short one-week manufacture protocol to determine the feasibility, safety and antitumor efficacy of this double cell therapy. Experimnetal Design A clinical trial (NCT00910650) adoptively transferring MART-1 T cell receptor (TCR) transgenic lymphocytes together with MART-1 peptide pulsed DC vaccination in HLA-A2.1 patients with metastatic melanoma. Autologous TCR transgenic cells were manufactured in 6 to 7 days using retroviral vector gene transfer, and re-infused with (n = 10) or without (n = 3) prior cryopreservation. Results 14 patients with metastatic melanoma were enrolled and nine out of 13 treated patients (69%) showed evidence of tumor regression. Peripheral blood reconstitution with MART-1-specific T cells peaked within two weeks of ACT indicating rapid in vivo expansion. Administration of freshly manufactured TCR transgenic T cells resulted in a higher persistence of MART-1-specific T cells in the blood as compared to cryopreserved. Evidence that DC vaccination could cause further in vivo expansion was only observed with ACT using non-cryopreserved T cells. Conclusion Double cell therapy with ACT of TCR engineered T cells with a very short ex vivo manipulation and DC vaccines is feasible and results in antitumor activity, but improvements are needed to maintain tumor responses. PMID:24634374

Autologous hematopoietic stem cells for refractory Crohn's disease.

PubMed

DiNicola, C A; Zand, A; Hommes, D W

2017-05-01

Autologous hematopoietic stem cells are gaining ground as an effective and safe treatment for treating severe refractory Crohn's disease (CD). Autologous hematopoietic stem cell therapy (AHSCT) induces resetting of the immune system by de novo regeneration of T-cell repertoire and repopulation of epithelial cells by bone-marrow derived cells to help patients achieve clinical and endoscopic remission. Areas covered: Herein, the authors discuss the use of AHSCT in treating patients with CD. Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease. Clinical and endoscopic remission has been achieved in patients treated with AHSCT for CD. The only randomized trial published to date, the ASTIC Trial, did not support further use of AHSCT to treat CD. Yet, critics of this trial have deemed AHSCT as a promising treatment for severe refractory CD. Expert opinion: Even with the promising evidence presented for HSCT for refractory CD, protocols need to be refined through the collaboration of GI and hemato-oncology professionals. The goal is to incorporate safe AHSCT and restore tolerance by delivering an effective immune 'cease fire' as a treatment option for severe refractory CD.

Requirement for Innate Immunity and CD90+ NK1.1− Lymphocytes to Treat Established Melanoma with Chemo-Immunotherapy

PubMed Central

Moskalenko, Marina; Pan, Michael; Fu, Yichun; de Moll, Ellen H.; Hashimoto, Daigo; Mortha, Arthur; Leboeuf, Marylene; Jayaraman, Padmini; Bernardo, Sebastian; Sikora, Andrew G.; Wolchok, Jedd; Bhardwaj, Nina; Merad, Miriam; Saenger, Yvonne

2015-01-01

We sought to define cellular immune mechanisms of synergy between tumor-antigen–targeted monoclonal antibodies and chemotherapy. Established B16 melanoma in mice was treated with cytotoxic doses of cyclophosphamide in combination with an antibody targeting tyrosinase-related protein 1 (αTRP1), a native melanoma differentiation antigen. We find that Fcγ receptors are required for efficacy, showing that antitumor activity of combination therapy is immune mediated. Rag1−/− mice deficient in adaptive immunity are able to clear tumors, and thus innate immunity is sufficient for efficacy. Furthermore, previously treated wild-type mice are not significantly protected against tumor reinduction, as compared with mice inoculated with irradiated B16 alone, consistent with a primarily innate immune mechanism of action of chemo-immunotherapy. In contrast, mice deficient in both classical natural killer (NK) lymphocytes and nonclassical innate lymphocytes (ILC) due to deletion of the IL2 receptor common gamma chain IL2γc−/−) are refractory to chemo-immunotherapy. Classical NK lymphocytes are not critical for treatment, as depletion of NK1.1+ cells does not impair antitumor effect. Depletion of CD90+NK1.1− lymphocytes, however, both diminishes therapeutic benefit and decreases accumulation of macrophages within the tumor. Tumor clearance during combination chemo-immunotherapy with monoclonal antibodies against native antigen is mediated by the innate immune system. We highlight a novel potential role for CD90+NK1.1− ILCs in chemo-immunotherapy. PMID:25600438

Circulating lymphocyte levels and relationship with infection status in patients with relapsing-remitting multiple sclerosis treated with daclizumab beta.

PubMed

Giovannoni, Gavin; Wiendl, Heinz; Turner, Benjamin; Umans, Kimberly; Mokliatchouk, Oksana; Castro-Borrero, Wanda; Greenberg, Steven J; McCroskery, Peter; Giannattasio, Giorgio

2017-09-01

Reversible lymphocyte count reductions have occurred following daclizumab beta treatment for relapsing-remitting multiple sclerosis. To analyse total and differential lymphocyte levels and relationship with infection status. In DECIDE, blood samples were collected at 12-week intervals from daclizumab beta- ( n = 919) or intramuscular interferon beta-1a-treated ( n = 922) patients. Infections/serious infections were assessed proximate to grade 2/3 lymphopenia or low CD4 + /CD8 + T-cell counts. Total safety population (TSP) data were additionally analysed from the entire clinical development programme ( n = 2236). Over 96 weeks in DECIDE, mean absolute lymphocyte count (ALC), CD4 + and CD8 + T-cell counts decreased <10% (7.1% vs 1.6%, 9.7% vs 2.0%, 9.3% vs 5.9%: daclizumab beta vs interferon beta-1a, respectively); shifts to ALC below lower limit of normal occurred in 13% versus 15%, respectively. Grade 3 lymphopenia was uncommon (TSP: <1%) and transient. Lymphocyte changes generally occurred within 24 weeks after treatment initiation and were reversible within 12 weeks of discontinuation. In DECIDE, mean CD4 + /CD8 + T-cell counts were similar regardless of infection status. TSP data were consistent with DECIDE. When observed, ALC and CD4 + /CD8 + T-cell count decreases in daclizumab beta-treated patients were generally mild-to-modest, reversible upon treatment discontinuation and not associated with increased risk of infections, including opportunistic infections.

[Production of autologous keratinocytes for therapeutic purposes within a pharmaceutical company].

PubMed

Guillot, F L

2001-01-01

Because biotechnologies are growing and are becoming key players in the pharmaceutical industry scene, Genévrier Laboratories inaugurated in January 1998, a new department especially designed for the production of cultured cells as therapeutic agents. Meeting clinician therapeutic needs by providing autologous keratinocytes and chondrocytes in the near future, represents the primary aim of the Biotechnology department. Concrete cell-based products are already being used for the treatment of burns and cutaneous chronic wounds such as the EPIBASE graft, which corresponds to an epidermis sheet composed of cultured autologous keratinocytes.

Immunodeficiency with thymoma: failure to induce Ig production in immunodeficient lymphocytes cocultured with normal T cells. [X radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Litwin, S.D.

Blood mononuclear cells of two individuals having immunodeficiency with thymoma (ID-THY) were cocultured with normal mononuclear cells or treated mononuclear cell fractions in an attempt to correct an imbalance of regulatory cells postulated to be responsible for the failure of pokeweed mitogen-induced Ig synthesis in vitro. Treatment included abrogation of suppressor cell activity by irradiation or incubation with prednisolone in vitro. T cell help was provided by cocultivating lymphocytes of related and unrelated persons, and in some cases autologous treated cells. Ig secretion failed to be induced by any experimental maneuver suggesting that the primary problem in the above ID-THYmore » cells was related to defective or deficient B cells rather than an imbalance of T regulatory cells. Prednisolone treatment in vitro decreased suppressor cell activity in allogeneic cocultures of two ID-THY persons (S1 and S2) but not of an individual (S3) with variable immunodeficiency suggesting heterogeneity of suppressor cells.« less

Effect of autologous platelet-rich plasma on the chondrogenic differentiation of rabbit adipose-derived stem cells in vitro

PubMed Central

TANG, XIAO-BO; DONG, PEI-LONG; WANG, JIAN; ZHOU, HAI-YANG; ZHANG, HAI-XIANG; WANG, SHAN-ZHENG

2015-01-01

This study aimed to isolate rabbit adipose-derived stem cells (ADSCs) and explore the potential of platelet-rich plasma (PRP) in the chondrogenic differentiation of ADSCs, thereby potentially providing a new approach for the repair and regeneration of cartilage injury. Rabbit ADSCs were isolated and characterized by induction towards adipogenic, osteogenic and chondrogenic lineages in vitro. The isolated ADSCs were also cultured with or without 10% PRP. Immunofluorescence staining, toluidine blue staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect type II collagen (Col II) and aggrecan (AGC) expression. Col II immunofluorescence staining and toluidine blue staining indicated that following induction by autologous PRP, ADSCs manifested Col II and AGC expression. The expression of Col II and AGC mRNA was significantly upregulated in the PRP-treated cells when compared with that in control cells. Autologous PRP produced by laboratory centrifugation was able to promote the chondrogenic differentiation of rabbit ADSCs in vitro. PMID:26622340

Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies Can Be Effectively Treated With Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor

PubMed Central

Kochenderfer, James N.; Dudley, Mark E.; Kassim, Sadik H.; Somerville, Robert P.T.; Carpenter, Robert O.; Stetler-Stevenson, Maryalice; Yang, James C.; Phan, Giao Q.; Hughes, Marybeth S.; Sherry, Richard M.; Raffeld, Mark; Feldman, Steven; Lu, Lily; Li, Yong F.; Ngo, Lien T.; Goy, Andre; Feldman, Tatyana; Spaner, David E.; Wang, Michael L.; Chen, Clara C.; Kranick, Sarah M.; Nath, Avindra; Nathan, Debbie-Ann N.; Morton, Kathleen E.; Toomey, Mary Ann; Rosenberg, Steven A.

2015-01-01

Purpose T cells can be genetically modified to express an anti-CD19 chimeric antigen receptor (CAR). We assessed the safety and efficacy of administering autologous anti-CD19 CAR T cells to patients with advanced CD19+ B-cell malignancies. Patients and Methods We treated 15 patients with advanced B-cell malignancies. Nine patients had diffuse large B-cell lymphoma (DLBCL), two had indolent lymphomas, and four had chronic lymphocytic leukemia. Patients received a conditioning chemotherapy regimen of cyclophosphamide and fludarabine followed by a single infusion of anti-CD19 CAR T cells. Results Of 15 patients, eight achieved complete remissions (CRs), four achieved partial remissions, one had stable lymphoma, and two were not evaluable for response. CRs were obtained by four of seven evaluable patients with chemotherapy-refractory DLBCL; three of these four CRs are ongoing, with durations ranging from 9 to 22 months. Acute toxicities including fever, hypotension, delirium, and other neurologic toxicities occurred in some patients after infusion of anti-CD19 CAR T cells; these toxicities resolved within 3 weeks after cell infusion. One patient died suddenly as a result of an unknown cause 16 days after cell infusion. CAR T cells were detected in the blood of patients at peak levels, ranging from nine to 777 CAR-positive T cells/μL. Conclusion This is the first report to our knowledge of successful treatment of DLBCL with anti-CD19 CAR T cells. These results demonstrate the feasibility and effectiveness of treating chemotherapy-refractory B-cell malignancies with anti-CD19 CAR T cells. The numerous remissions obtained provide strong support for further development of this approach. PMID:25154820

Autologous cytokine-induced killer cell immunotherapy may improve overall survival in advanced malignant melanoma patients.

PubMed

Zhang, Yong; Zhu, Yu'nan; Zhao, Erjiang; He, Xiaolei; Zhao, Lingdi; Wang, Zibing; Fu, Xiaomin; Qi, Yalong; Ma, Baozhen; Song, Yongping; Gao, Quanli

2017-11-01

Our study was conducted to explore the efficacy of autologous cytokine-induced killer (CIK) cells in patients with advanced malignant melanoma. Materials & Methods: Here we reviewed 113 stage IV malignant melanoma patients among which 68 patients received CIK cell immunotherapy alone, while 45 patients accepted CIK cell therapy combined with chemotherapy. Results: We found that the median survival time in CIK cell group was longer than the combined therapy group (21 vs 15 months, p = 0.07). In addition, serum hemoglobin level as well as monocyte proportion and lymphocyte count were associated with patients' survival time. These indicated that CIK cell immunotherapy might extend survival time in advanced malignant melanoma patients. Furthermore, serum hemoglobin level, monocyte proportion and lymphocyte count could be prognostic indicators for melanoma.

Treatment of Refractory Filamentary Keratitis With Autologous Serum Tears.

PubMed

Read, Sarah P; Rodriguez, Marianeli; Dubovy, Sander; Karp, Carol L; Galor, Anat

2017-09-01

To report a case of filamentary keratitis (FK) successfully treated with autologous serum tears and to review the pathogenesis and management of FK. Case report including high-resolution anterior segment optical coherence tomography and filament histopathology. A 61-year-old Hispanic man presented with pain and photophobia of the right eye. He was found to have a corneal epithelial defect and a small peripheral infiltrate 4 months after Laser Assisted in situ Keratomileusis. After resolution of the epithelial defect, he developed FK. Over a 4-month period, conservative management with aggressive lubrication, lid hygiene, topical corticosteroids, topical cyclosporine, bandage contact lenses, and oral doxycycline failed to resolve the corneal filaments. Notably, treatment with 20% autologous serum tears, four times daily, led to a sustained resolution of the FK within 1 week. This case demonstrates the complexity of FK management and introduces autologous serum tears as a viable management option when conservative approaches to this condition fail.

Total lymphocyte count and subpopulation lymphocyte counts in relation to dietary intake and nutritional status of peritoneal dialysis patients.

PubMed

Grzegorzewska, Alicja E; Leander, Magdalena

2005-01-01

Dietary deficiency causes abnormalities in circulating lymphocyte counts. For the present paper, we evaluated correlations between total and subpopulation lymphocyte counts (TLC, SLCs) and parameters of nutrition in peritoneal dialysis (PD) patients. Studies were carried out in 55 patients treated with PD for 22.2 +/- 11.4 months. Parameters of nutritional status included total body mass, lean body mass (LBM), body mass index (BMI), and laboratory indices [total protein, albumin, iron, ferritin, and total iron binding capacity (TIBC)]. The SLCs were evaluated using flow cytometry. Positive correlations were seen between TLC and dietary intake of niacin; TLC and CD8 and CD16+56 counts and energy delivered from protein; CD4 count and beta-carotene and monounsaturated fatty acids 17:1 intake; and CD19 count and potassium, copper, vitamin A, and beta-carotene intake. Anorexia negatively influenced CD19 count. Serum albumin showed correlations with CD4 and CD19 counts, and LBM with CD19 count. A higher CD19 count was connected with a higher red blood cell count, hemoglobin, and hematocrit. Correlations were observed between TIBC and TLC and CD3 and CD8 counts, and between serum Fe and TLC and CD3 and CD4 counts. Patients with a higher CD19 count showed a better clinical-laboratory score, especially less weakness. Patients with a higher CD4 count had less expressed insomnia. Quantities of ingested vitamins and minerals influence lymphocyte counts in the peripheral blood of PD patients. Evaluation of TLC and SLCs is helpful in monitoring the effectiveness of nutrition in these patients.

Antibody-targeted interleukin 2 stimulates T-cell killing of autologous tumor cells.

PubMed Central

Gillies, S D; Reilly, E B; Lo, K M; Reisfeld, R A

1992-01-01

A genetically engineered fusion protein consisting of a chimeric anti-ganglioside GD2 antibody (ch14.18) and interleukin 2 (IL2) was tested for its ability to enhance the killing of autologous GD2-expressing melanoma target cells by a tumor-infiltrating lymphocyte line (660 TIL). The fusion of IL2 to the carboxyl terminus of the immunoglobulin heavy chain did not reduce IL2 activity as measured in a standard proliferation assay using either mouse or human T-cell lines. Antigen-binding activity was greater than that of the native chimeric antibody. The ability of resting 660 TIL cells to kill their autologous GD2-positive target cells was enhanced if the target cells were first coated with the fusion protein. This stimulation of killing was greater than that of uncoated cells in the presence of equivalent or higher concentrations of free IL2. Such antibody-cytokine fusion proteins may prove useful in targeting the biological effect of IL2 and other cytokines to tumor cells and in this way stimulate their immune destruction. Images PMID:1741398

Ibrutinib Improves Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia

Cancer.gov

A summary of results from an international phase III trial that compared ibrutinib (Imbruvica®) and ofatumumab (Arzerra®) for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for the treatment of persistent active EBV infection.

PubMed

Savoldo, Barbara; Huls, M Helen; Liu, Zhensheng; Okamura, Takayuki; Volk, Hans-Dieter; Reinke, Petra; Sabat, Robert; Babel, Nina; Jones, James F; Webster-Cyriaque, Jennifer; Gee, Adrian P; Brenner, Malcolm K; Heslop, Helen E; Rooney, Cliona M

2002-12-01

Chronic active Epstein-Barr virus (CAEBV) infection syndrome is a heterogeneous EBV-related disorder characterized by chronic fatigue, fever, lymphadenopathy, and/or hepatosplenomegaly, associated with abnormal patterns of antibody to EBV. CAEBV can range from disabling mild/moderate forms to rapidly lethal disorders. Even patients with mild/moderate disease frequently suffer adverse effects from long-term anti-inflammatory agents and have a quality of life that progressively deteriorates. It is still unknown why these individuals are unable to produce an effective immune response to control EBV, and no effective treatment is currently available. Since ex vivo-expanded EBV-specific cytotoxic T lymphocytes (EBV-CTLs) can safely restore EBV-specific cellular immune responses in immunodeficient patients, we assessed the possibility that adoptive immunotherapy might also effectively treat CAEBV infection. Following stimulation with irradiated EBV-transformed lymphoblastoid cell lines (LCLs), EBV-CTLs were successfully generated from 8 of 8 patients with the mild/moderate form of CAEBV infection. These CTLs were predominantly CD3(+) CD8(+) cells and produced specific killing of the autologous LCLs. There were 5 patients with 1- to 12-year histories of disease who were treated with 1 to 4 injections of EBV-CTLs. Following infusion, there was resolution of fatigue and malaise, disappearance of fever, and regression of lymphadenopathy and splenomegaly. The pattern and titers of anti-EBV antibodies also normalized. No toxicity was observed. There were 4 patients who did not show any relapse of disease within 6 to 36 months follow-up; one patient had recurrence of fatigue and myalgia one year after CTL infusion. We suggest that adoptive immunotherapy with autologous EBV-CTLs may represent a safe and feasible alternative treatment for patients affected with mild/moderate CAEBV infection and that this approach should be evaluated in the more severe forms of the disease.

Comparison of corticosteroid, autologous blood or sclerosant injections for chronic tennis elbow.

PubMed

Branson, R; Naidu, K; du Toit, C; Rotstein, A H; Kiss, R; McMillan, D; Fooks, L; Coombes, B K; Vicenzino, B

2017-06-01

To compare three different ultrasound-guided injections for chronic tennis elbow. Assessor-blinded, randomized controlled comparative trial. 44 patients with clinically diagnosed tennis elbow, confirmed by Doppler ultrasound, received under ultrasound guidance, a single corticosteroid injection (n=14), or two injections (separated by 4 weeks) of either autologous blood (n=14) or polidocanol (n=16). Clinical and ultrasound examination was performed at baseline, 4, 12 and 26 weeks. Complete recovery or much improvement was greater for corticosteroid injection than autologous blood and polidocanol at 4 weeks (p<0.001, number needed to treat 1 (95% CI 1-2)). In contrast, at 26 weeks corticosteroid was significantly worse than polidocanol (p=0.004, number needed to harm 2 (1-6)). Recurrence after corticosteroid injection was significantly higher than autologous blood or polidocanol (p=0.007, number needed to harm 2 (1-4)). Corticosteroid injection produced greater reduction in tendon thickness and vascularity than autologous blood at 4 weeks only. Compared to autologous blood, polidocanol reduced tendon thickness at 4 and 12 weeks and reduced echogenicity and hyperaemia after 12 or 26 weeks respectively. Injections of corticosteroid cannot be recommended over polidocanol or autologous blood, because despite beneficial short-term effect there were inferior long-term effects. Whether polidocanol or autologous blood injections are effective is unknown, especially as their global effect profiles are not unlike previously reported for wait-and-see. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Autologous engineering of cartilage

PubMed Central

Emans, Pieter J.; van Rhijn, Lodewijk W.; Welting, Tim J. M.; Cremers, Andy; Wijnands, Nina; Spaapen, Frank; Voncken, J. Willem; Shastri, V. Prasad

2010-01-01

Treatment of full-thickness damage to hyaline cartilage is hampered by the limited availability of autologous healthy cartilage and the lengthy, cost-prohibitive cell isolation and expansion steps associated with autologous cartilage implantation (ACI). Here we report a strategy for de novo engineering of ectopic autologous cartilage (EAC) within the subperiosteal space (in vivo bioreactor), through the mere introduction of a biocompatible gel that might promote hypoxia-mediated chondrogenesis, thereby effectively overcoming the aforementioned limitations. The EAC is obtained within 3 wk post injection of the gel, and can be press-fit into an osteochondral defect where it undergoes remodeling with good lateral and subchondral integration. The implanted EAC showed no calcification even after 9 mo and attained an average O’Driscoll score of 11 (versus 4 for controls). An “on demand” autologous source of autologous cartilage with remodeling capacity is expected to significantly impact the clinical options in repair of trauma to articular cartilage. PMID:20133690

Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS

PubMed Central

Madigan, Nicolas N.; Morris, Jonathan; Jentoft, Mark; Sorenson, Eric J.; Butler, Greg; Gastineau, Dennis; Dietz, Allan; Windebank, Anthony J.

2016-01-01

Objective: To determine the safety of intrathecal autologous adipose-derived mesenchymal stromal cell treatment for amyotrophic lateral sclerosis (ALS). Methods: Participants with ALS were enrolled and treated in this phase I dose-escalation safety trial, ranging from 1 × 107 (single dose) to 1 × 108 cells (2 monthly doses). After intrathecal treatments, participants underwent standardized follow-up, which included clinical examinations, revised ALS Functional Rating Scale (ALSFRS-R) questionnaire, blood and CSF sampling, and MRI of the neuroaxis. Results: Twenty-seven patients with ALS were enrolled and treated in this study. The safety profile was positive, with the most common side effects reported being temporary low back and radicular leg pain at the highest dose level. These clinical findings were associated with elevated CSF protein and nucleated cells with MRI of thickened lumbosacral nerve roots. Autopsies from 4 treated patients did not show evidence of tumor formation. Longitudinal ALSFRS-R questionnaires confirmed continued progression of disease in all treated patients. Conclusions: Intrathecal treatment of autologous adipose-derived mesenchymal stromal cells appears safe at the tested doses in ALS. These results warrant further exploration of efficacy in phase II trials. Classification of evidence: This phase I study provides Class IV evidence that in patient with ALS, intrathecal autologous adipose-derived mesenchymal stromal cell therapy is safe. PMID:27784774

Cord Blood Banking Standards: Autologous Versus Altruistic

PubMed Central

Armitage, Sue

2016-01-01

Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as “biological insurance” should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards. PMID:26779485

CCR 20th Anniversary Commentary: Autologous T Cells—The Ultimate Personalized Drug for the Immunotherapy of Human Cancer

PubMed Central

Rosenberg, Steven A.

2015-01-01

Summary The article by Rosenberg and colleagues, which was published in the July 1, 2011, issue of Clinical Cancer Research, demonstrated the power of the adoptive transfer of autologous antitumor T cells to mediate the complete, durable, and likely curative regression of cancer in patients with heavily pretreated metastatic melanoma. It also provided a stimulus to the development of cell transfer approaches for other cancer types using both natural and genetically engineered lymphocytes. PMID:26672082

External quality assessment for CD4 + T-lymphocyte count test: Performance of the Brazilian public health laboratories network.

PubMed

Gaspar, Pâmela Cristina; Wohlke, Bruna Lovizutto Protti; Brunialti, Milena Karina Coló; Pires, Ana Flávia; Kohiyama, Igor Massaki; Salomão, Reinaldo; Alonso Neto, José Boullosa; Júnior, Orlando da Costa Ferreira; Franchini, Miriam; Bazzo, Maria Luiza; Benzaken, Adele Schwartz

2018-05-01

The National Network for CD4+ T-lymphocyte counting of Brazil comprises 93 laboratories. This study reports the laboratory performances achieved in external quality assessment (EQA) rounds provides by Ministry of Health to evaluate the quality of the kits used and the performance of test by the technicians.Ten EQA rounds were analyzed according the EQA criteria aimed to evaluate individual laboratory performance on the basis of the accuracy of their results compared to the general mean obtained by all participating laboratories and the reproducibility of the results obtained between 2 samples from the same donor.The percentage of approved and failed laboratories in the EQAs tends to follow a uniform pattern. Since 2011, approval has remained above 80% and the failure rate has never exceeded 15%.EQA is very important to evaluate the performance of the laboratories, to identify monitor, and to resolve errors as quickly as possible.

Intra-ligamentary autologous conditioned plasma and healing response to treat partial ACL ruptures.

PubMed

Koch, Matthias; Matteo, Berardo Di; Eichhorn, Jürgen; Zellner, Johannes; Mayr, Felix; Krutsch, Werner; Achenbach, Leonard; Woehl, Rebecca; Nerlich, Michael; Angele, Peter

2018-05-01

Conservative treatment of partial ACL ruptures is associated with a high failure rate, and often patients undergo ACL reconstruction. ACL preservation by trephination of the ACL origin and application of Autologous Conditioned Plasma (ACP) seems to be an intriguing new treatment option to favour ACL tissue healing and avoid traditional reconstruction. The aim of this study was to describe the mid-term outcomes of this new ACL preserving technique. Twenty-four patients (mean age 41.8 years) affected by partial rupture of one or both ACL bundles were included in the present trial. The partial ACL tears were arthroscopically assessed and classified according to a new five step grading system. All patients were treated by trephination of the femoral ACL stump and intra-ligamentary application of ACP. The postoperative outcome was evaluated by both subjective scores and stability testing up to a mean of 25.1 months' follow-up. Adverse events and failure rate were also documented. Clinical outcome was good to excellent with IKDC subjective 82.7 (SD 11.8), Lysholm 87.6 (SD 8.1), Tegner 5.3 (SD 2.1), Cincinnati 88.7 (SD 14.8). The failure rate (i.e. persisting knee instability assessed clinically or by rolimeter) was 12.5%. At objective measurements, knee joints showed a firm endpoint in Lachman test, negative pivot shift phenomenon and a significant reduction in AP-laxity compared to pre-operative status by rolimeter testing (p = 0.002). Return to sport practice was achieved after mean 4.8 months (SD 4.1). ACL stump trephination and concomitant intra-ligamentary application of ACP revealed promising results at mid-term follow-up to treat partial ACL lesions.

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes and high-dose interleukin-2 for metastatic melanoma: The surgeon’s perspective

PubMed Central

ZIPPEL, DOUGLAS B.; BESSER, MICHAL; SHAPIRA, RONI; BEN-NUN, ALON; GOITEIN, DAVID; DAVIDSON, TIMA; TREVES, ABRAHAM J.; MARKEL, GAL; SCHACHTER, JACOB; PAPA, MOSHE Z.

2012-01-01

Tumor-infiltrating lymphocytes (TILs) are produced by resecting tumor tissue and growing and expanding ex vivo large quantities of autologous T cells. Once the TILs are ready for infusion, the patient undergoes a non-myeloablative lympho-depleting course of chemotherapy and subsequent TIL infusion with high-dose bolus IL-2. This study reviews the surgical experience of the TIL program at the Chaim Sheba Cancer Research Center in Israel. Eligible patients underwent surgical consultation to determine what tumorectomy would be beneficial for harvesting appropriate tissue. Factors involved in the decision included tumor mass size, location and morbidity of the procedure. Between January 2006 and May 2010, 44 patients underwent 47 procedures of adoptive transfer of TILs. Three patients underwent the procedure twice for recurrence after initial good responses, including an additional surgical procedure to produce fresh tumor. Thirty-seven excisions were with general anesthesia and 10 were with local anesthesia. Of the 37 general anesthesia procedures, 27 were open procedures involving a thoracotomy, a laparotomy or dissection of a major lymph node basin. Ten used minimally invasive techniques such as thorascopy or laparoscopy. Tumorectomy sites included 18 lymph node metastasis, 13 subcutaneous nodules, 11 lung specimens and 5 abdominal visceral metastasis including 2 liver lesions. Surgical mortality and major morbidity was 0%. Minor morbidity included only wound complications. Maximal number of TILs were derived from lymph node specimens, while liver metastasis procured the fewest TILs. Adoptive cell transfer technology affords a maximal tumor response with minimal surgical morbidity in metastatic patients. PMID:22969990

Lymphocytic infiltration of bladder after local cellular immunotherapy.

PubMed

Ingram, M; Bishai, M B; Techy, G B; Narayan, K S; Saroufeem, R; Yazan, O; Marshall, C E

2000-01-01

This is a case report of a patient who received cellular immunotherapy, in the form of local injections of autologous stimulated lymphocytes (ASL) into individual tumors in the urinary bladder. A major consideration in cellular immunotherapy being the ability of immune cells to reach all target areas, we hypothesized that direct delivery of effector cells into individual bladder tumors might assure such access. ASL were generated by exposing the patient's PBL to phytohemagglutinin and culturing them in the presence of IL-2 to expand the population. ASL were injected into the base of individual bladder tumors three times at intervals of 3 weeks. The patient died of a myocardial infarct, unrelated to cell therapy, 20 days after the third injection. An autopsy was performed. Histological sections of the bladder showed extensive lymphocytic infiltration of virtually the entire organ. No conclusions about the therapeutic efficacy of local immunotherapy using ASL are possible. Nevertheless, the observations reported, taken together with reports of therapeutic efficacy of other immunotherapy regimens in the management of bladder cancer, suggest that ready access of stimulated lymphocytes to all regions of the organ may account, in part, for the relatively high rate of therapeutic success reported for various immunotherapy regimens for this malignancy.

Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

ClinicalTrials.gov

2017-12-05

B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

T cell receptor (TCR) structure of autologous melanoma-reactive cytotoxic T lymphocyte (CTL) clones: tumor-infiltrating lymphocytes overexpress in vivo the TCR beta chain sequence used by an HLA-A2- restricted and melanocyte-lineage-specific CTL clone

PubMed Central

1993-01-01

HLA-A2+ melanomas express common melanoma-associated antigens (Ags) recognized in vitro by autologous cytotoxic T lymphocytes (CTL). However, it is not known whether tumor Ags can drive in vivo a selective accumulation/expansion of Ag-specific, tumor-infiltrating T lymphocytes (TIL). Therefore, to evaluate this possibility, 39 CTL clones isolated from several independent mixed lymphocyte tumor cultures (MLTC) of TIL and peripheral blood lymphocytes (PBL) of an HLA- A2+ melanoma patient and selected for T cell receptor (TCR)-dependent, HLA-restricted tumor lysis, were used for analysis of TCR alpha and beta chain structure by the cDNA polymerase chain reaction (PCR) technique with variable gene-specific primers followed by sequencing. Despite absence of oligoclonality in fresh TIL and PBL, as well as in T cells of day 28 MLTC (day of cloning), sequence analysis of TCR alpha and beta chains of TIL clones revealed a dominance of a major category of melanoma-specific, HLA-A2-restricted T cells expressing a V alpha 8.2/J alpha AP511/C alpha and V beta 2.1/D beta 1/J beta 1.1/C beta 1 TCR. The same TCR was also found in 2 out of 14 PBL clones. The other PBL clones employed a V alpha 2.1 gene segment associated with either V beta 13.2, 14, or w22. Clones A81 (V alpha 2.1/J alpha IGRJ alpha 04/C alpha and V beta 14/D beta 1/J beta 1.2/C beta 1) and A21 (V alpha 8.2/J alpha AP511/C alpha and V beta 2.1/D beta 1/J beta 1.1/C beta 1), representative of the two most frequent TCR of PBL and TIL, respectively, expressed different lytic patterns, but both were HLA-A2 restricted and lysed only HLA-A2+ melanomas and normal melanocytes, thus indicating recognition of two distinct HLA-A2-associated and tissue-related Ags. Finally, by the inverse PCR technique, the specific TCR beta chain (V beta 2.1/D beta 1/J beta 1.1/C beta 1) expressed by the dominant TIL clone was found to represent 19 and 18.4% of all V beta 2 sequences expressed in the fresh tumor sample and in the purified TIL

Autologous dental pulp stem cells in periodontal regeneration: a case report.

PubMed

Aimetti, Mario; Ferrarotti, Francesco; Cricenti, Luca; Mariani, Giulia Maria; Romano, Federica

2014-01-01

Histologic findings in animal models suggest that the application of dental pulp stem cells (DPSCs) may promote periodontal regeneration in infrabony defects. This case report describes the clinical and radiographic regenerative potential of autologous DPSCs in the treatment of human noncontained intraosseous defects. A chronic periodontitis patient with one vital third molar requiring extraction was surgically treated. The third molar was extracted and used as an autologous DPSCs source to regenerate the infrabony defect on the mandibular right second premolar. At the 1-year examination, the defect was completely filled with bonelike tissue as confirmed through the reentry procedure.

Lymphocyte-to-monocyte ratio is associated with survival in pembrolizumab-treated metastatic melanoma patients.

PubMed

Failing, Jarrett J; Yan, Yiyi; Porrata, Luis F; Markovic, Svetomir N

2017-12-01

The peripheral blood lymphocyte-to-monocyte ratio (LMR) has been associated with prognosis in many malignancies including metastatic melanoma. However, it has not been studied in patients treated with immune checkpoint inhibitors. In this study, we analyzed the baseline LMR with progression-free survival (PFS) and overall survival (OS) in metastatic melanoma patients treated with pembrolizumab. A total of 133 patients with metastatic melanoma treated with pembrolizumab were included in this retrospective study. LMR was calculated from pretherapy peripheral blood counts and the optimal cutoff value was determined by a receiver operator characteristic curve. PFS and OS were evaluated using the Kaplan-Meier method and multivariate Cox proportional hazard modeling. Patients with an LMR of at least 1.7 showed improved PFS (hazard ratio=0.55; 95% confidence interval: 0.34-0.92; P=0.024) and OS (hazard ratio=0.29; 95% confidence interval: 0.15-0.59; P=0.0007). The baseline LMR is associated with PFS and OS in metastatic melanoma patients treated with pembrolizumab, and could represent a convenient and cost-effective prognostic biomarker. Validation of these findings in an independent cohort is needed.

Autologous blood transfusion in total knee replacement surgery.

PubMed

Sarkanović, Mirka Lukić; Gvozdenović, Ljiljana; Savić, Dragan; Ilić, Miroslav P; Jovanović, Gordana

2013-03-01

Total knee replacement (TKR) surgery is one of the most frequent and the most extensive procedures in orthopedic surgery, accompanied with some serious complications. Perioperative blood loss is one of the most serious losses, so it is vital to recognize and treat such losses properly. Autologous blood transfusion is the only true alternative for the allogeneic blood. The aim of this study was to to examine if autologous blood transfusion reduces usage of allogenic blood in total knee replacement surgery, as well as to examine possible effect of autologous blood transfusion on postoperative complications, recovery and hospital stay of patients after total knee replacement surgery. During the controlled, prospective, randomised study we compared two groups of patients (n = 112) with total prosthesis implanted in their knee. The group I consisted of the patients who received the transfusion of other people's (allogeneic) blood (n = 57) and the group II of the patients whose blood was collected postoperatively and then given them [their own (autologous) blood] (n = 55). The transfusion trigger for both groups was hemoglobin level of 85 g/L. In the group of patients whose blood was collected perioperatively only 9 (0.9%) of the patients received transfusion of allogeneic blood, as opposed to the control group in which 98.24% of the patients received the transfusion of allogeneic blood (p < or = 0.01). The patients whose blood was collected stayed in hospital for 6.18 days, while the patients of the control group stayed 7.67 days (p < 0.01). Autologous blood transfusion is a very effective method for reducing consumption of allogenic blood and thus, indirectly for reducing all complications related to allogenic blood transfusion. There is also a positive influence on postoperative recovery after total knee replacement surgery due to the reduction of hospital stay, and indirectly on the reduction of hospital costs.

Autologous Cartilage Chip Transplantation Improves Repair Tissue Composition Compared With Marrow Stimulation.

PubMed

Christensen, Bjørn Borsøe; Olesen, Morten Lykke; Lind, Martin; Foldager, Casper Bindzus

2017-06-01

Repair of chondral injuries by use of cartilage chips has recently demonstrated clinical feasibility. To investigate in vivo cartilage repair outcome of autologous cartilage chips compared with marrow stimulation in full-thickness cartilage defects in a minipig model. Controlled laboratory study. Six Göttingen minipigs received two 6-mm chondral defects in the medial and lateral trochlea of each knee. The two treatment groups were (1) autologous cartilage chips embedded in fibrin glue (ACC) (n = 12) and (2) marrow stimulation (MST) (n = 12). The animals were euthanized after 6 months, and the composition of repair tissue was quantitatively determined using histomorphometry. Semiquantitative evaluation was performed by means of the International Cartilage Repair Society (ICRS) II score. Collagen type II staining was used to further evaluate the repair tissue composition. Significantly more hyaline cartilage was found in the ACC (17.1%) compared with MST (2.9%) group ( P < .01). Furthermore, the ACC group had significantly less fibrous tissue (23.8%) compared with the MST group (41.1%) ( P < .01). No significant difference in fibrocartilage content was found (54.7% for ACC vs 50.8% for MST). The ACC group had significantly higher ICRS II scores for tissue morphological characteristics, matrix staining, cell morphological characteristics, surface assessment, mid/deep assessment, and overall assessment ( P < .05). The ACC-treated defects had significantly more collagen type II staining (54.5%) compared with the MST-treated defects (28.1%) ( P < .05). ACC transplant resulted in improved quality of cartilage repair tissue compared with MST at 6 months postoperatively. Further studies are needed to investigate ACC as a possible alternative first-line treatment for focal cartilage injuries in the knee.

Autologous fat graft as treatment of post short stature surgical correction scars.

PubMed

Maione, Luca; Memeo, Antonio; Pedretti, Leopoldo; Verdoni, Fabio; Lisa, Andrea; Bandi, Valeria; Giannasi, Silvia; Vinci, Valeriano; Mambretti, Andrea; Klinger, Marco

2014-12-01

Surgical limb lengthening is undertaken to correct pathological short stature. Among the possible complications related to this procedure, painful and retractile scars are a cause for both functional and cosmetic concern. Our team has already shown the efficacy of autologous fat grafting in the treatment of scars with varying aetiology, so we decided to apply this technique to scars related to surgical correction of dwarfism. A prospective study was conducted to evaluate the efficacy of autologous fat grafting in the treatment of post-surgical scars in patients with short-limb dwarfism using durometer measurements and a modified patient and observer scar assessment scale (POSAS), to which was added a parameter to evaluate movement impairment. Between January 2009 and September 2012, 36 children (28 female and 8 male) who presented retractile and painful post-surgical scars came to our unit and were treated with autologous fat grafting. Preoperative and postoperative mean durometer measurements were analysed using the analysis of variance (ANOVA) test and POSAS parameters were studied using the Wilcoxon rank sum test. There was a statistically significant reduction in all durometer measurements (p-value <0.05) and in all but one of the POSAS parameters (p-value <0.05) following treatment with autologous fat grafting. Surgical procedures to camouflage scars on lower limbs are not often used as a first approach and non-surgical treatments often lead to unsatisfactory results. In contrast, our autologous fat grafting technique in the treatment of post-surgical scars has been shown to be a valuable option in patients with short-limb dwarfism. There was a reduction of skin hardness and a clinical improvement of all POSAS parameters in all patients treated. Moreover, the newly introduced POSAS parameter appears to be reliable and we recommend that it is included to give a more complete evaluation of patient perception. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effectiveness and safety of autologous fat grafting to the soft palate alone.

PubMed

Boneti, Cristiano; Ray, Peter D; Macklem, Elizabeth B; Kohanzadeh, Som; de la Torre, Jorge; Grant, John H

2015-06-01

Posterior pharyngeal augmentation is an accepted method of treating velopharyngeal insufficiency (VPI). Techniques using autologous fat harvest, preparation, and grafting are well described. Based on the complications from retropharyngeal injection, we performed augmentation of the nasal surface of the palate to reduce hypernasality with decreased risks. After Institutional Review Board approval, a chart review from 2010 to 2013 identified 46 patients with cleft palate, subjective and nasoendoscopic evidence of VPI treated with autologous fat grafting to the soft palate. Speech evaluation of velopharyngeal function was compared before and after autologous fat grafting. A total of 61 autologous fat grafting procedures were performed in 46 patients. The average age of the study population is 5.59 ± 2.05 years. The majority underwent a single procedure (32/46 or 69.6%), 13 of 46 patients (28.2%) had 2 fat grafting procedures and only 1 patient (2.2%) had 3 fat grafting procedures. The fat was injected primarily in the soft palate. The recorded volume of fat grafted averaged 2.4 ± 1.1 mL. Average operative time was 39 ± 12.55 minutes. There were no local or donor site complications. Four patients were lost to follow-up. Of 34 patients with adequate speech follow-up, including Pittsburgh Weighted Speech Scale (PWSS) assessment, the average preoperative score of 8.17 ± 3.59 was reduced to 5.17 ± 3.14 postoperatively. Although 26 of 34 patients (76.5%) had an improvement in their PWSS score, only 13 of 34 patients (38.23%) saw an improvement in their PWSS category. Autologous fat grafting to the soft palate is a safe operation with minimal risks. Speech outcomes are subjectively enhanced in the majority of patients, with a full PWSS category improvement seen in 40% of the cases. Patient selection criteria to optimize results are provided.

Lymphocyte Functions in Microgravity

NASA Technical Reports Server (NTRS)

Pellis, Neal R.; Risin, Diane; Sundaresan, A.; Cooper, D.; Dawson, David L. (Technical Monitor)

1999-01-01

To understand the mechanism of immunity impairment in space it is important to analyze the direct effects of space-related conditions on different lymphocytes functions. Since 1992, we are investigating the effect of modeled and true microgravity (MG) on numerous lymphocyte functions. We had shown that modeled (MMG) and true microgravity inhibit lymphocyte locomotion through type I collagen. Modeled microgravity also suppresses polyclonal and antigen-specific lymphocyte activation. Polyclonal activation of lymphocytes prior to exposure to MMG abrogates the MG-induced inhibition of lymphocyte locomotion. The relationship between activation deficits and the loss of locomotion in MG was investigated using PKC activation by phorbol ester (PMA) and calcium ionophore (ionomycin). Direct activation of PKC by PMA substantially restored the MMG-inhibited lymphocyte locomotion and PHA-induced lymphocyte activation lonomycin by itself did not restore either locomotion or activation of the lymphocytes, indicating that these changes are not related to the impairment in the calcium flux in MMG. Treatment of lymphocytes with PMA before exposure to MMG prevented the loss of locomotion. It was observed that DNA synthesis is not necessary for restoration of locomotion since mitomicin C treated and untreated cells recovered their locomotion to the same level after PKC activation. Our recent data indicate that microgravity may selectively effect the expression of novel Ca2+ independent isoforms of PKC, in particularly PKC sigma and delta. This provides a new insight in understanding of the mechanisms of MG-sensitive cellular functions.

CCR 20th Anniversary Commentary: Autologous T Cells-The Ultimate Personalized Drug for the Immunotherapy of Human Cancer.

PubMed

Rosenberg, Steven A

2015-12-15

The article by Rosenberg and colleagues, which was published in the July 1, 2011, issue of Clinical Cancer Research, demonstrated the power of the adoptive transfer of autologous antitumor T cells to mediate the complete, durable, and likely curative regression of cancer in patients with heavily pretreated metastatic melanoma. It also provided a stimulus to the development of cell transfer approaches for other cancer types using both natural and genetically engineered lymphocytes. ©2015 American Association for Cancer Research.

[The Influence of UV-Light on the Sub-Populational Composition and Expression of Membrane Markers of Lymphocytes of Donor Blood].

PubMed

Artyukhov, V G; Basharina, O V; Zemchenkova, O V; Ryazantsev, S V

2016-01-01

The influence of UV-light (240-390 nm) at dozes of 151 and 755 J/m2 on the content of membrane markers of lymphocytes using the method of flow cytometry was investigated. It was demonstrated that during incubation of UV-irradiated lymphocytes the change of their populational and sub-populational composition occurs. Expression of complexes of CD3, CD 19,.CD8, CD 16, CD25 and CD95 increased. This increase was caused mainly by de novo synthesis. UV-light had immunostimulating effect on CD8+ T-lymphocyte population. Together with the increase of cytotoxic cells and NK-cells, activation of lymphocytes (increased amount of CD25+ and CD95+ cells) took place. Amount of cells undergone apoptosis or necrosis increased proportionally to the dosage. These changes were more expressed during incubation of lymphocytes in nutrition medium without autological blood serum, e.g. under deficiency of growth factors and antioxidants.

Human Herpesvirus-6 cytopathic inclusions: an exceptional and recognizable finding on skin biopsy during HHV6 reactivation after autologous stem-cell transplantation.

PubMed

Roux, Jennifer; Battistella, Maxime; Fornecker, Luc; Legoff, Jérôme; Deau, Bénédicte; Houhou, Nadira; Bouaziz, Jean-David; Thieblemont, Catherine; Janin, Anne

2012-08-01

Skin rash are common in immunocompromised patients, particularly after bone marrow transplantation. Human herpes virus 6 (HHV6) reactivation is often suspected, but its clinical presentation and the routine laboratory tests may be unspecific, thus leading to late diagnosis. In this case, we report specific intralymphocytic cytopathic inclusions on skin biopsy as a sign of systemic HHV6 reactivation. A 56-year-old patient presented progressive erythroderma and fever occurring after autologous hematopoietic stem-cell transplantation for mantle cell lymphoma. The skin biopsy showed a perivascular infiltrate of medium-to-large lymphocytes with irregular nuclei containing a large central basophilic inclusion surrounded by a clear halo. High levels of HHV-6 genomic in skin biopsy confirm HHV-6-induced cytopathic effect. The clinical course improved with intravenous foscavir. The specific histopathological findings encountered in this case are exceptional but recognizable, and along with HHV-6 DNA detection allow a prompt recognition of HHV6 skin rash.

Lenalidomide, Ibrutinib, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma That Is Metastatic or Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-04-13

Ann Arbor Stage III Small Lymphocytic Lymphoma; Ann Arbor Stage IV Small Lymphocytic Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma

ClinicalTrials.gov

2018-02-12

Prolymphocytic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

Early autologous stem cell transplantation for chronic lymphocytic leukemia: long-term follow-up of the German CLL Study Group CLL3 trial.

PubMed

Dreger, Peter; Döhner, Hartmut; McClanahan, Fabienne; Busch, Raymonde; Ritgen, Matthias; Greinix, Hildegard; Fink, Anna-Maria; Knauf, Wolfgang; Stadler, Michael; Pfreundschuh, Michael; Dührsen, Ulrich; Brittinger, Günter; Hensel, Manfred; Schetelig, Johannes; Winkler, Dirk; Bühler, Andreas; Kneba, Michael; Schmitz, Norbert; Hallek, Michael; Stilgenbauer, Stephan

2012-05-24

The CLL3 trial was designed to study intensive treatment including autologous stem cell transplantation (autoSCT) as part of first-line therapy in patients with chronic lymphocytic leukemia (CLL). Here, we present the long-term outcome of the trial with particular focus on the impact of genomic risk factors, and we provide a retrospective comparison with patients from the fludarabine-cyclophosphamide-rituximab (FCR) arm of the German CLL Study Group (GCLLSG) CLL8 trial. After a median observation time of 8.7 years (0.3-12.3 years), median progression-free survival (PFS), time to retreatment, and overall survival (OS) of 169 evaluable patients, including 38 patients who did not proceed to autoSCT, was 5.7, 7.3, and 11.3 years, respectively. PFS and OS were significantly reduced in the presence of 17p- and of an unfavorable immunoglobulin heavy variable chain mutational status, but not of 11q-. Five-year nonrelapse mortality was 6.5%. When 110 CLL3 patients were compared with 126 matched patients from the FCR arm of the CLL8 trial, 4-year time to retreatment (75% vs 77%) and OS (86% vs 90%) was similar despite a significant benefit for autoSCT in terms of PFS. In summary, early treatment intensification including autoSCT can provide very effective disease control in poor-risk CLL, although its clinical benefit in the FCR era remains uncertain. The trial has been registered with www.clinicaltrials.gov as NCT00275015.

A comparison of treating Unicameral bone cyst using steroids and percutaneous autologous bone marrow aspiration injection.

PubMed

Akram, Muhammad; Farooqi, Faheem Mubashir; Shahzad, Muhammad Latif; Awais, Syed Muhammad

2015-11-01

To compare the results of percutaneous autologous bone aspiration injection and steroids injections in the treatment of unicameral bone cyst. The prospective study was conducted at Mayo Hospital, Lahore, from January 2008 to March 2014, and comprised patients diagnosed radiologically as a case of unicameral bone cyst. The patients were divided into two groups, with group 1 being treated with bone marrow aspiration injection, while group 2 was given steroids injection. Aspiration of bone marrow was done from tibial tuberosity. The 30 patients in the study were divided into two groups of 15(50%) each. In group 1, 8(53.34%) patients and in group 2, 3 (20%) patients achieved healing after the first injection (p<0.05), while overall success rates were 13(86.67%) in group 1, and 11(73.33%) in group 2 (p> 0.05). The mean number of procedures required in group 1 was 1.57± 0.495 (range: 01-3) and for 2.19 ± 1.076 (range: 1-5) in group 2 (p<0.05), and mean interval-to-healing was 14.3 months ± 8.705 (range: 7-36) for group 1 and 12.5 months ± 7.88 (range: 4-32) for group 2 (p> 0.05). Bone marrow aspiration injection was better than steroids in treating unicameral bone cyst.

Infused autograft lymphocyte-to-monocyte ratio and survival in T-cell lymphoma post-autologous peripheral blood hematopoietic stem cell transplantation.

PubMed

Porrata, Luis F; Inwards, David J; Ansell, Stephen M; Micallef, Ivana N; Johnston, Patrick B; Hogan, William J; Markovic, Svetomir N

2015-07-03

The infused autograft lymphocyte-to-monocyte ratio (A-LMR) is a prognostic factor for survival in B-cell lymphomas post-autologous peripheral hematopoietic stem cell transplantation (APHSCT). Thus, we set out to investigate if the A-LMR is also a prognostic factor for survival post-APHSCT in T-cell lymphomas. From 1998 to 2014, 109 T-cell lymphoma patients that underwent APHSCT were studied. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to identify the optimal cut-off value of A-LMR for survival analysis and k-fold cross-validation model to validate the A-LMR cut-off value. Univariate and multivariate Cox proportional hazard models were used to assess the prognostic discriminator power of A-LMR. ROC and AUC identified an A-LMR ≥ 1 as the best cut-off value and was validated by k-fold cross-validation. Multivariate analysis showed A-LMR to be an independent prognostic factor for overall survival (OS) and progression-free survival (PFS). Patients with an A-LMR ≥ 1.0 experienced a superior OS and PFS versus patients with an A-LMR < 1.0 [median OS was not reached vs 17.9 months, 5-year OS rates of 87% (95% confidence interval (CI), 75-94%) vs 26% (95% CI, 13-42%), p < 0.0001; median PFS was not reached vs 11.9 months, 5-year PFS rates of 72% (95% CI, 58-83%) vs 16% (95% CI, 6-32%), p < 0.0001]. A-LMR is also a prognostic factor for clinical outcomes in patients with T-cell lymphomas undergoing APHSCT.

Autologous fat transplantation for the treatment of linear scleroderma en coup de sabre.

PubMed

Ibler, Kristina S; Gramkow, Christina; Siemssen, Peter A

2015-01-01

Scleroderma en coup de sabre is a disfiguring disease for which only limited therapeutic options exist. Three cases of facial linear scleroderma treated with autologous fat transplantation with acceptable results are presented. Autologous fat transplantation was preferred to corrective surgery because of the extent of the lesions and absence of any associated facial distortion. Fat as a filler was chosen to reduce the risk of adverse effects. Adipocytes are suggested to have wider biological effects than other fillers and may offer more durable results. At least two transplantations were needed to evoke a significant effect.

Autologous Platelet-Rich Plasma Preparations

PubMed Central

Schippinger, Gert; Prüller, Florian; Divjak, Manuela; Mahla, Elisabeth; Fankhauser, Florian; Rackemann, Steve; Raggam, Reinhard Bernd

2015-01-01

Background Autologous platelet-rich plasma (PRP) has been widely used for the treatment of sports injuries. It has been associated with improved healing and regeneration of soft tissues in elite athletes. Athletes are commonly receiving nonsteroidal anti-inflammatory drugs (NSAIDs). As yet, the effect of these drugs on platelet function in PRP formulations has not been taken into consideration. Hypothesis The function of platelets in PRP produced under the influence of NSAIDs is inhibited and may lessen a possible healing effect on the site of injury. Study Design Controlled laboratory study. Methods PRP was collected from patients receiving NSAIDs after elective orthopaedic surgery, and platelet function was evaluated using light transmission aggregometry (LTA). Results were compared with those obtained from healthy volunteers without a history of NSAID intake during the previous 2 weeks. Two different systems for blood collection and PRP production (Arthrex ACP double-syringe system and standard 4.5-mL sodium citrate blood collection tubes) were used and compared regarding the quality of PRP that was produced. Results For both groups, the baseline platelet counts of whole blood and the platelet counts of PRP formulations were found to be in the normal range. Both collection systems for PRP produced comparable results without significant differences between the groups. Platelet function testing with LTA revealed significantly impaired platelet aggregation in both PRP preparations, obtained from patients taking NSAIDs, irrespective of the type of NSAID (P < .001). All subjects from the control group showed normal platelet aggregation patterns when tested with LTA. Conclusion Autologous PRP produced from subjects after NSAID medication shows significantly impaired platelet function and may result in lower quality regarding the content of bioactive compounds. Clinical Relevance If required, the administration of NSAIDs should be performed after blood collection for

[EFFECTIVENESS COMPARISON OF CORACOCLAVICULAR LIGAMENT RECONSTRUCTION BETWEEN BY AUTOLOGOUS AND ALLOGENEIC TENDON GRAFTS COMBINED WITH HOOK PLATE FIXATION FOR TREATING ACROMIOCLAVICULAR JOINT DISLOCATION].

PubMed

Yin, Fei; Sun, Zhenzhong; Wei, Xuming; Liu, Xueguang; Zhou, Ming; Zhuang, Yin; Song, Sheng

2016-05-08

To compare the effectiveness of coracoclavicular ligament reconstruction between by using autologous plantaris tendon graft combined with hook plate fixation and allogeneic tendon graft combined with hook plate fixation for treating acromiocavicular joint dislocation. Thirty-three patients with acromioclavicular joint dislocation who accorded with the inclusion criteria between January 2013 and June 2014 were assigned into 2 groups. The patients were treated with autologous plantaris tendon graft combined with hook plate fixation in group A ( n =17), and with allogeneic tendon graft combined with hook plate fixation in group B ( n =16). Thirteen-one patients was followed up more than 12 months (15 in group A and 16 in group B). There was no significant difference in gender, age, cause of injury, sides, time between injury and surgery, and type of dislocation ( P >0.05). The assessments included operation time, hospitalization time, hospitalization expenses, shoulder range of motion, gap of acromioclavicular, Constant-Murley scores, and visual analogue scale (VAS) for pain. The operation time of group A was significantly longer than that of group B, and the hospitalization expense was significantly lower than that of group B ( P <0.05). There was no significant difference in hospitalization time ( t =1.046, P =0.316). The incisions healed by first intention, and hook plate was removed after 3 months. The mean follow-up time was 21.3 months (range, 19-34 months) in group A and was 23.7 months (range, 18-37 months) in group B. X-ray examination showed no osteolysis. There was no significant difference in gap of acromiocavicular between 2 groups at preoperation, 1 week after operation, and last follow-up ( P >0.05). No redislocation of acromioclavicular joint and rejection reaction occurred during follow-up. At last follow-up, there was no significant difference in shoulder range of motion, Constant-Murley score, and VAS score between 2 groups ( P >0

Regeneration of Tissues and Organs Using Autologous Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anthony Atala

The Joint Commission for Health Care Organizations recently declared the shortage of transplantable organs and tissues a public health crisis. As such, there is about one death every 30 seconds due to organ failure. Complications and rejection are still significant albeit underappreciated problems. It is often overlooked that organ transplantation results in the patient being placed on an immune suppression regimen that will ultimate shorten their life span. Patients facing reconstruction often find that surgery is difficult or impossible due to the shortage of healthy autologous tissue. In many cases, autografting is a compromise between the condition and the curemore » that can result in substantial diminution of quality of life. The national cost of caring for persons who might benefit from engineered tissues or organs has reached $600 billion annually. Autologous tissue technologies have been developed as an alternative to transplantation or reconstructive surgery. Autologous tissues derived from the patient's own cells are capable of correcting numerous pathologies and injuries. The use of autologous cells eliminates the risks of rejection and immunological reactions, drastically reduces the time that patients must wait for lifesaving surgery, and negates the need for autologous tissue harvest, thereby eliminating the associated morbidities. In fact, the use of autologous tissues to create functional organs is one of the most important and groundbreaking steps ever taken in medicine. Although the basic premise of creating tissues in the laboratory has progressed dramatically, only a limited number of tissue developments have reached the patients to date. This is due, in part, to the several major technological challenges that require solutions. To that end, we have been in pursuit of more efficient ways to expand cells in vitro, methods to improve vascular support so that relevant volumes of engineered tissues can be grown, and constructs that can mimic the

Induction of polyclonal antibody synthesis by human allogeneic and autologous helper factors

PubMed Central

1979-01-01

Human helper factors were obtained from supernates of 48 h unidirectional allogeneic and autologous mixed lymphocyte reactions. These supernates were shown to induce the production of large amounts of immunoglobulin by tonsillar and peripheral blood mononuclear cells. Abundant polyclonal activation to antibody production occurred in these cultures in the absence of antigenic challenge which was similar in degree to that produced by pokeweed mitogen. This was documented by quantitating plasma cells, specific plaque-forming cells, and secreted immunoglobulin. In addition, the supplementation of companion cultures with sheep erythrocytes resulted in a significant enhancement of the specific plaque-forming cell response without an appreciable change in plasma cell number of secreted Ig. PMID:156242

Correlation between radio-induced lymphocyte apoptosis measurements obtained from two French centres.

PubMed

Mirjolet, C; Merlin, J L; Dalban, C; Maingon, P; Azria, D

2016-07-01

In the era of modern treatment delivery, increasing the dose delivered to the target to improve local control might be modulated by the patient's intrinsic radio-sensitivity. A predictive assay based on radio-induced lymphocyte apoptosis quantification highlighted the significant correlation between CD4 and CD8 T-lymphocyte apoptosis and grade 2 or 3 radiation-induced late toxicities. By conducting this assay at several technical platforms, the aim of this study was to demonstrate that radio-induced lymphocyte apoptosis values obtained from two different platforms were comparable. For 25 patients included in the PARATOXOR trial running in Dijon the radio-induced lymphocyte apoptosis results obtained from the laboratory of Montpellier (IRCM, Inserm U1194, France), considered as the reference (referred to as Lab 1), were compared with those from the laboratory located at the Institut de cancérologie de Lorraine (ICL, France), referred to as Lab 2. Different statistical methods were used to measure the agreement between the radio-induced lymphocyte apoptosis data from the two laboratories (quantitative data). The Bland-Altman plot was used to identify potential bias. All statistical tests demonstrated good agreement between radio-induced lymphocyte apoptosis values obtained from both sites and no major bias was identified. Since radio-induced lymphocyte apoptosis values, which predict tolerance to radiotherapy, could be assessed by two laboratories and showed a high level of robustness and consistency, we can suggest that this assay be extended to any laboratories that use the same technique. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Survival of Mexican children with acute myeloid leukaemia who received early intensification chemotherapy and an autologous transplant.

PubMed

Jiménez-Hernández, Elva; Dueñas-González, María Teresa; Arellano-Galindo, José; Medrano-Ortíz-De-Zárate, María Elena; Bekker-Méndez, Vilma Carolina; Berges-García, Adolfina; Solís-Labastida, Karina; Sánchez-Jara, Berenice; Tiznado-García, Héctor Manuel; Jaimes-Reyes, Ethel Zulie; García-Jiménez, Xochiketzalli; Espinoza-Hernández, Laura; Núñez-Villegas, Nora Nancy; Franco-Ornelas, Sergio; Pérez-Casillas, Ruy Xavier; Villegas, Octavio Martínez; Palomares, Teresa Marin; Mejía-Aranguré, Juan Manuel

2015-01-01

In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005-2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999-2004, was treated as Group A, but without the early intensified chemotherapy. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy.

Autologous bone marrow transplantation in relapsed adult acute leukemia.

PubMed

Dicke, K A; Zander, A R; Spitzer, G; Verma, D S; Peters, L J; Vellekoop, L; Thomson, S; Stewart, D; Hester, J P; McCredie, K B

1979-01-01

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%), when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.

Autologous bone marrow transplantation in relapsed adult acute leukemia.

PubMed

Dicke, K A; Zander, A R; Spitzer, G; Verma, D S; Peters, L; Vellekoop, L; Thomson, S; Stewart, D; McCredie, K B

1980-01-01

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%) when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.

[Dynamic changes of MMP-1, MMP-9 and TIMP-1 in the refractory diabetic dermal ulcers treated by autologous Platelet-rich gel].

PubMed

He, Li-Ping; Wang, Chun; Chen, Da-Wei; Li, Xiu-Jun; Ran, Xing-wu

2012-09-01

To investigate the dynamic changes of matrix metalloproteinase-1,-9 (MMP-1, MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1 ) in the refractory diabetic dermal ulcers treated with autologous platelet-rich gel (APG). 86 patients with nonhealing diabetic dermal ulcers were randomly assigned to two groups treated with standard procedures and APG (standard care plus topic application of autologous platelet-rich gel). The granulation tissues were collected at d0, d3, d6, d9, and d15 in patients in the APG group and at d0, d6, d15 in patients in the standard care group. The areas of ulcers were measured. The protein levels of MMP-1, MMP-9 and TIMP-1 in the tissues were determined with ELISA. The ratio of MMP-9/TIMP-1 and its relationship with the areas of ulcers were examined. The areas of ulcers of patients in the APG group decreased significantely (vs. do, P < 0.05). The concentrations of MMP-1 in the granulation tissues of patients treated with APG fluctuated and reached the lowest level at d15 (vs. d6, P < 0.05). The concentrations of MMP-9 in the patients treated with AGP decreased from d3 to d15, but without statistical significance compared with d0 (P > 0.05). The concentrations of TIMP-1 in the patients treated with AGP increased from d3 and reached the peak at d6 (P < 0.05). The ratio of MMP-9/TIMP-1 at both d6 and d15 decreased significantly compared with d0 (P < 0.05) in the patients treated with AGP. The areas of ulcers in the patients with standard care decreased significantly at d15 (vs. d6, P < 0.05). The concentrations of MMP-1 reached the peak at d6 (P < 0.05) and then decreased in the patients with standard care but was still higher than the patients treated with APG (P < 0.05). The concentrations of MMP-9 decreased significantly at d15 compared with d0 in the patients treated with standard care (P < 0.05), but the change of TIMP-1 was not significant. The ratio of MMP-9/TIMP-1 in the patients with standard care decreased at d15 compared with

Impact of the use of autologous stem cell transplantation at first relapse both in naïve and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study

PubMed Central

Le Gouill, Steven; De Guibert, Sophie; Planche, Lucie; Brice, Pauline; Dupuis, Jehan; Cartron, Guillaume; Van Hoof, Achiel; Casasnovas, Olivier; Gyan, Emmanuel; Tilly, Hervé; Fruchart, Christophe; Deconinck, Eric; Fitoussi, Olivier; Gastaud, Lauris; Delwail, Vincent; Gabarre, Jean; Gressin, Rémy; Blanc, Michel; Foussard, Charles; Salles, Gilles

2011-01-01

Background We analyzed detailed characteristics and salvage treatment in 175 follicular lymphoma patients from the FL2000 study who were in progression after first-line therapy with or without addition of rituximab to chemotherapy and interferon. Design and Methods The impact of using autologous stem cell transplantation and/or rituximab administration at first progression was investigated, taking into account initial therapy. With a median follow up of 31 months, 3-year event free and overall survival rates after progression were 50% (95%CI 42–58%) and 72% (95%CI 64–78%), respectively. Results The 3-year event free rate of rituximab re-treated patients (n=112) was 52% (95%CI 41–62%) versus 40% (95%CI 24–55%) for those not receiving rituximab second line (n=53) (P=0.075). There was a significant difference in 3-year overall survival between patients receiving autologous stem cell transplantation and those not: 92% (95%CI 78–97%) versus 63% (95%CI 51–72%) (P=0.0003), respectively. In multivariate analysis, both autologous stem cell transplantation and period of progression/relapse affected event free and overall survival. Conclusions Regardless of front-line rituximab exposure, this study supports incorporating autologous stem cell transplantation in the therapeutic approach at first relapse for follicular lymphoma patients. PMID:21486862

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

PubMed Central

Saint-Jean, Mélanie; Volteau, Christelle; Quéreux, Gaëlle; Peuvrel, Lucie; Brocard, Anabelle; Saiagh, Soraya; Nguyen, Jean-Michel; Bedane, Christophe; Basset-Seguin, Nicole

2018-01-01

Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs). This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2) regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous metastasis, TILs were produced according to a previously described method and then infused into the patient who also received a complementary subcutaneous IL-2 regimen. Nine women and 1 man were treated for unresectable stage IIIC (n = 4) or IV (n = 6) melanoma. All but 1 patient with unresectable stage III melanoma (1st line) had received at least 2 previous treatments, including anti-CTLA-4 antibody for 4. The number of TILs infused ranged from 0.23 × 109 to 22.9 × 109. Regarding safety, no serious adverse effect was reported. Therapeutic responses included a complete remission, a partial remission, 2 stabilizations, and 6 progressions. Among these 4 patients with clinical benefit, 1 is still alive with 9 years of follow-up and 1 died from another cause after 8 years of follow-up. Notably, patients treated with high percentages of CD4 + CD25 + CD127lowFoxp3+ T cells among their TILs had significantly shorter OS. The therapeutic effect of combining TILs with new immunotherapies needs further investigation. PMID:29750176

Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

ClinicalTrials.gov

2018-03-26

Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma; T-Cell Large Granular Lymphocyte Leukemia

Outcomes in Patients With Relapsed or Refractory Acute Promyelocytic Leukemia Treated With or Without Autologous or Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Pemmaraju, Naveen; Tanaka, Maria Florencia; Ravandi, Farhad; Lin, Heather; Baladandayuthapani, Veerabhadran; Rondon, Gabriela; Giralt, Sergio A.; Chen, Julianne; Pierce, Sherry; Cortes, Jorge; Kantarjian, Hagop; Champlin, Richard E.; De Lima, Marcos; Qazilbash, Muzaffar H.

2014-01-01

Outcomes in patients with acute promyelocytic leukemia have improved; however, a subset of patients relapse despite receiving all-trans-retinoic acid and/or arsenic-based therapies. Among 40 patients with acute promyelocytic leukemia who were treated at our institution (1980–2010), 24 received hematopoietic stem cell transplantation (HCT) (autologous HCT, 7; allogeneic HCT, 14; both, 3); 16 received chemotherapy only. All 3 strategies (autologous HCT, allogeneic HCT, chemotherapy) were feasible in patients with relapsed acute promyelocytic leukemia and result in long-term disease control in selected patients. Background Outcomes in patients with acute promyelocytic leukemia (APL) have improved; however, a significant number of patients still relapse despite receiving all-trans-retinoic acid (ATRA) and arsenic-based therapies. Patients and Methods Outcomes of patients with relapsed APL who were treated at our institution (1980–2010) and who received HCT were compared with those who received chemotherapy (CT) only. Results Among 40 patients, 24 received HCT (autologous [auto] HCT, 7; allogeneic [allo] HCT, 14; both, 3); 16 received CT only. The median age at diagnosis was 36 years (range, 13–50 years), 31 years (range, 16–58 years), and 44 years (range, 24–79 years) for the auto-HCT, allo-HCT, and CT groups, respectively. Ten (100%) patients who received auto-HCT and 12 (71%) who received allo-HCT were in complete remission at the time of the HCT. The median follow-ups in the auto-HCT, allo-HCT, and CT groups were 74 months (range, 26–135 months), 118 months (range, 28–284 months), and 122 months (range, 32–216 months), respectively. Transplantation-related mortality (1 year) after auto-HCT and allo-HCT were 10% and 29%, respectively. The 7-year event-free survival after auto-HCT and allo-HCT was 68.6% and 40.6%, respectively (P = .45). The 7-year overall survival was 85.7%, 49.4%, and 40% in the auto-HCT, allo-HCT, and CT groups, respectively (P

A clinical study on the usefulness of autologous plasma filler in the treatment of nasolabial fold wrinkles.

PubMed

Choi, Young-Jun; Kim, Han-Saem; Min, Joon Hong; Nam, Jae-Hui; Lee, Ga-Young; Kim, Won-Serk

2017-06-01

Recently, the efficacy of autologous plasma filler for the reduction of facial wrinkles has been demonstrated. The aim of our study is to validate the efficacy and safety of autologous plasma filler in treating nasolabial fold wrinkles. Twenty Korean patients with moderate-to-severe nasolabial fold wrinkles were enrolled. The patients were treated with one session of autologous plasma filler. The wrinkle improvement effects were evaluated at 1-week, 4-week, 8-week, and 12-week after the treatment. Three assessment methods were applied. First, two independent dermatologists assessed cosmetic results using a 5-point wrinkle assessment scale. Second, global aesthetic improvement score was used for assessment of the final cosmetic results. Third, patient satisfaction was surveyed. Also, the adverse effects associated to treatment were observed. Mean age of the patients was 44.5 years. The average 5-point wrinkle assessment scale score was significantly improved at 1, 4, 8, and 12 weeks after treatment, comparing to before treatment (p < 0.01). The patients' average global aesthetic improvement score also indicated better cosmetic outcomes. The clinical improvement with sufficient patients' satisfaction and no significant adverse events demonstrated that novel autologous plasma filler could be considered as efficient and safety treatment option for nasolabial fold wrinkles.

Preclinical Derivation and Imaging of Autologously Transplanted Canine Induced Pluripotent Stem Cells*

PubMed Central

Lee, Andrew S.; Xu, Dan; Plews, Jordan R.; Nguyen, Patricia K.; Nag, Divya; Lyons, Jennifer K.; Han, Leng; Hu, Shijun; Lan, Feng; Liu, Junwei; Huang, Mei; Narsinh, Kazim H.; Long, Charles T.; de Almeida, Patricia E.; Levi, Benjamin; Kooreman, Nigel; Bangs, Charles; Pacharinsak, Cholawat; Ikeno, Fumiaki; Yeung, Alan C.; Gambhir, Sanjiv S.; Robbins, Robert C.; Longaker, Michael T.; Wu, Joseph C.

2011-01-01

Derivation of patient-specific induced pluripotent stem cells (iPSCs) opens a new avenue for future applications of regenerative medicine. However, before iPSCs can be used in a clinical setting, it is critical to validate their in vivo fate following autologous transplantation. Thus far, preclinical studies have been limited to small animals and have yet to be conducted in large animals that are physiologically more similar to humans. In this study, we report the first autologous transplantation of iPSCs in a large animal model through the generation of canine iPSCs (ciPSCs) from the canine adipose stromal cells and canine fibroblasts of adult mongrel dogs. We confirmed pluripotency of ciPSCs using the following techniques: (i) immunostaining and quantitative PCR for the presence of pluripotent and germ layer-specific markers in differentiated ciPSCs; (ii) microarray analysis that demonstrates similar gene expression profiles between ciPSCs and canine embryonic stem cells; (iii) teratoma formation assays; and (iv) karyotyping for genomic stability. Fate of ciPSCs autologously transplanted to the canine heart was tracked in vivo using clinical positron emission tomography, computed tomography, and magnetic resonance imaging. To demonstrate clinical potential of ciPSCs to treat models of injury, we generated endothelial cells (ciPSC-ECs) and used these cells to treat immunodeficient murine models of myocardial infarction and hindlimb ischemia. PMID:21719696

Concurrent classical Hodgkin lymphoma and plasmablastic lymphoma in a patient with chronic lymphocytic leukemia/small lymphocytic lymphoma treated with fludarabine: a dimorphic presentation of iatrogenic immunodeficiency-associated lymphoproliferative disorder with evidence suggestive of multiclonal transformability of B cells by Epstein-Barr virus.

PubMed

Foo, Wen-Chi; Huang, Qin; Sebastian, Siby; Hutchinson, Charles B; Burchette, Jim; Wang, Endi

2010-12-01

A small fraction of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma develop Epstein-Barr virus-positive B-cell lymphoproliferative disorders. These Epstein-Barr virus-B-cell lymphoproliferative disorders are thought to be related to immune suppression induced by fludarabine/other chemotherapeutic regimens. As in other immunodeficiency-associated lymphoproliferative disorders, these disorders demonstrate a heterogeneous histological spectrum that ranges from polymorphic to monomorphic to classical Hodgkin lymphoma-like lesions. We report a case of concurrent classical Hodgkin lymphoma and plasmablastic lymphoma in a patient with chronic lymphocytic leukemia/small lymphocytic lymphoma treated with fludarabine. Both classical Hodgkin lymphoma and plasmablastic lymphoma were positive for Epstein-Barr virus-encoded RNA, whereas classical Hodgkin lymphoma was also positive for Epstein-Barr virus- latent membrane protein 1, suggesting a different viral latency. Immunoglobulin gene rearrangement studies demonstrated distinct clones in the plasmablastic lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. These findings suggest biclonal secondary lymphomas associated with iatrogenic immunodeficiency. Epstein-Barr virus-B-cell lymphoproliferative disorders in the setting of chronic lymphocytic leukemia/small lymphocytic lymphoma, in particular those arising after chemotherapy, should be separated from true Richter's transformation, and be categorized as (iatrogenic) immunodeficiency-associated lymphoproliferative disorder. Copyright © 2010 Elsevier Inc. All rights reserved.

Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells and down-regulates cardiac allograft rejection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, De-Hua; Dou, Li-Ping; Wei, Yu-Xiang

Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation ofmore » recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-{gamma} by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4{sup +}CD25{sup high}Foxp3{sup +} regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.« less

Adoptive transfer of Epstein-Barr virus-specific cytotoxic T-lymphocytes for the treatment of angiocentric lymphomas.

PubMed

Cho, Hyun-Il; Hong, Young Seon; Lee, Myung Ah; Kim, Eun-Kyung; Yoon, Sung-Hee; Kim, Chun-Choo; Kim, Tai-Gyu

2006-01-01

Angiocentric lymphoma, known as natural killer (NK)/T-cell non-Hodgkin's lymphoma, has been reported to be associated with the Epstein-Barr virus (EBV). We performed adoptive transfer of EBV-specific polyclonal T-cell lines in 3 patients with extranodal NK/T-cell lymphoma, nasal type, and evaluated the treatment for safety, immunologic reconstitution, and clinical outcomes. The tissue samples collected from the 3 patients were confirmed by polymerase chain reaction analysis to be EBV positive. In the cases of the first and second patients, EBV-transformed B-lymphoblastoid cell lines (LCLs) and T-cell lines were generated from peripheral lymphocytes of HLA-matched sibling donors. The third patient's T-cell lines were induced with autologous lymphocytes. Polyclonal T-cell infusion was carried out after high-dose radiotherapy because active relapsed disease remained in all of the patients. The first patient received 4 weekly infusions of 2 3 10(7) cells/m(2), and the second and third patients underwent treatment with 2 cycles of infusions of the same dosage. All T-cell lines showed >60% NK activity, cytotoxic T-lymphocyte (CTL) responses of >40% against autologous LCLs, and no CTL activity against patient-derived lymphoblasts. The level of cytotoxicity increased substantially in all patients after cell infusion. The 2 patients who received T-cell therapy twice had stabilized disease for more than 3 years. These safe treatments exhibited no severe inflammatory response, and no serious toxicity developed during T-cell therapy. Our findings demonstrate that adoptively transferred cells may provide reconstitution of EBV-specific CTL responses in patients with active relapsed angiocentric lymphoma. These results provide a rationale for the immunotherapy of angiocentric lymphoma.

Injection Pharyngoplasty With Autologous Fat as Treatment for Stress Velopharyngeal Insufficiency in Brass and Woodwind Musicians.

PubMed

Syamal, Mausumi N; Bryson, Paul C

2017-02-01

Stress velopharyngeal insufficiency (SVPI) is an uncommon but often career-threatening condition affecting professional brass and woodwind musicians. To review the evaluation of and treatment for SVPI in professional musicians with lipoinjection to the posterior pharyngeal wall. A retrospective medical record and literature review. Two professional musicians with SVPI treated with autologous lipoinjection to the posterior pharyngeal wall were included. Nasopharyngoscopy was performed while patients played their instrument both before and after injection. To assess the effectiveness of autologous fat injection to the posterior pharyngeal wall to treat stress velopharyngeal insufficiency in 2 professional instrumentalists. Successful treatment was the absence of VPI during playing as visualized by flexible nasopharyngoscopy. After autologous lipoinjection of the posterior pharyngeal wall, 1 patient resumed full play with complete resolution, now 3 years after lipoinjection pharyngoplasty. The other patient received temporary resolution. Both had no surgical complications. Stress VPI is often a career-threatening condition for professional brass and woodwind musicians, with a cited incidence of 34%. Various treatment options in the literature include observation, speech and language pathology referral for pharyngeal strengthening, lipoinjection of the soft palate, and more invasive options, such as sphincter pharyngoplasty, pharyngeal flaps and V-Y pushback. Autologous fat injection pharyngoplasty of the posterior pharyngeal wall may be a less invasive treatment option for musicians with SVPI.

Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

PubMed Central

Jiménez-Hernández, Elva; Dueñas-González, María Teresa; Arellano-Galindo, José; Medrano-Ortíz-De-Zárate, María Elena; Bekker-Méndez, Vilma Carolina; Berges-García, Adolfina; Solís-Labastida, Karina; Sánchez-Jara, Berenice; Tiznado-García, Héctor Manuel; Jaimes-Reyes, Ethel Zulie; García-Jiménez, Xochiketzalli; Espinoza-Hernández, Laura; Núñez-Villegas, Nora Nancy; Franco-Ornelas, Sergio; Pérez-Casillas, Ruy Xavier; Martínez Villegas, Octavio; Palomares, Teresa Marin; Mejía-Aranguré, Juan Manuel

2015-01-01

Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy. PMID:25821830

Randomized Selection Design Trial Evaluating CD8+-Enriched Versus Unselected Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy for Patients With Melanoma

PubMed Central

Dudley, Mark E.; Gross, Colin A.; Somerville, Robert P.T.; Hong, Young; Schaub, Nicholas P.; Rosati, Shannon F.; White, Donald E.; Nathan, Debbie; Restifo, Nicholas P.; Steinberg, Seth M.; Wunderlich, John R.; Kammula, Udai S.; Sherry, Richard M.; Yang, James C.; Phan, Giao Q.; Hughes, Marybeth S.; Laurencot, Carolyn M.; Rosenberg, Steven A.

2013-01-01

Purpose Adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TILs) and high-dose interleukin-2 (IL-2) administered to lymphodepleted patients with melanoma can cause durable tumor regressions. The optimal TIL product for ACT is unknown. Patients and Methods Patients with metastatic melanoma were prospectively assigned to receive unselected young TILs versus CD8+-enriched TILs. All patients received lymphodepleting chemotherapy and high-dose IL-2 therapy and were assessed for response, toxicity, survival, and immunologic end points. Results Thirty-four patients received unselected young TILs with a median of 8.0% CD4+ lymphocytes, and 35 patients received CD8+-enriched TILs with a median of 0.3% CD4+ lymphocytes. One month after TIL infusion, patients who received CD8+-enriched TILs had significantly fewer CD4+ peripheral blood lymphocytes (P = .01). Twelve patients responded to therapy with unselected young TILs (according to Response Evaluation Criteria in Solid Tumors [RECIST]), and seven patients responded to CD8+-enriched TILs (35% v 20%; not significant). Retrospective studies showed a significant association between response to treatment and interferon gamma secretion by the infused TILs in response to autologous tumor (P = .04), and in the subgroup of patients who received TILs from subcutaneous tumors, eight of 15 patients receiving unselected young TILs responded but none of eight patients receiving CD8+-enriched TILs responded. Conclusion A randomized selection design trial was feasible for improving individualized TIL therapy. Since the evidence indicates that CD8+-enriched TILs are not more potent therapeutically and they are more laborious to prepare, future studies should focus on unselected young TILs. PMID:23650429

Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

PubMed Central

Akita, Sadanori; Akino, Kozo; Hirano, Akiyoshi; Ohtsuru, Akira; Yamashita, Shunichi

2010-01-01

Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years. PMID:21151652

Treatment of pressure ulcers with autologous bone marrow nuclear cells in patients with spinal cord injury

PubMed Central

Sarasúa, J González; López, S Pérez; Viejo, M Álvarez; Basterrechea, M Pérez; Rodríguez, A Fernández; Gutiérrez, A Ferrero; Gala, J García; Menéndez, Y Menéndez; Augusto, D Escudero; Arias, A Pérez; Hernández, J Otero

2011-01-01

Context Pressure ulcers are especially difficult to treat in patients with spinal cord injury (SCI) and recurrence rates are high. Prompted by encouraging results obtained using bone marrow stem cells to treat several diseases including chronic wounds, this study examines the use of autologous stem cells from bone marrow to promote the healing of pressure ulcers in patients with SCI. Objective To obtain preliminary data on the use of bone marrow mononuclear cells (BM-MNCs) to treat pressure ulcers in terms of clinical outcome, procedure safety, and treatment time. Participants Twenty-two patients with SCI (19 men, 3 women; mean age 56.41 years) with single type IV pressure ulcers of more than 4 months duration. Interventions By minimally invasive surgery, the ulcers were debrided and treated with BM-MNCs obtained by Ficoll density gradient separation of autologous bone marrow aspirates drawn from the iliac crest. Results In 19 patients (86.36%), the pressure ulcers treated with BM-MNCs had fully healed after a mean time of 21 days. The number of MNCs isolated was patient dependent, although similar clinical outcomes were observed in each case. Compared to conventional surgical treatment, mean intra-hospital stay was reduced from 85.16 to 43.06 days. Following treatment, 5 minutes of daily wound care was required per patient compared to 20 minutes for conventional surgery. During a mean follow-up of 19 months, none of the resolved ulcers recurred. Conclusions Our data indicate that cell therapy using autologous BM-MNCs could be an option to treat type IV pressure ulcers in patients with SCI, avoiding major surgical intervention. PMID:21756569

Characterization of the CD4+ and CD8+ tumor infiltrating lymphocytes propagated with bispecific monoclonal antibodies.

PubMed

Wong, J T; Pinto, C E; Gifford, J D; Kurnick, J T; Kradin, R L

1989-11-15

To study the CD4+ and CD8+ tumor infiltrating lymphocytes (TIL) in the antitumor response, we propagated these subsets directly from tumor tissues with anti-CD3:anti-CD8 (CD3,8) and anti-CD3:anti-CD4 (CD3,4) bispecific mAb (BSMAB). CD3,8 BSMAB cause selective cytolysis of CD8+ lymphocytes by bridging the CD8 molecules of target lymphocytes to the CD3 molecular complex of cytolytic T lymphocytes with concurrent activation and proliferation of residual CD3+CD4+ T lymphocytes. Similarly, CD3,4 BSMAB cause selective lysis of CD4+ lymphocytes whereas concurrently activating the residual CD3+CD8+ T cells. Small tumor fragments from four malignant melanoma and three renal cell carcinoma patients were cultured in medium containing CD3,8 + IL-2, CD3,4 + IL-2, or IL-2 alone. CD3,8 led to selective propagation of the CD4+ TIL whereas CD3,4 led to selective propagation of the CD8+ TIL from each of the tumors. The phenotypes of the TIL subset cultures were generally stable when assayed over a 1 to 3 months period and after further expansion with anti-CD3 mAb or lectins. Specific 51Cr release of labeled target cells that were bridged to the CD3 molecular complexes of TIL suggested that both CD4+ and CD8+ TIL cultures have the capacity of mediating cytolysis via their Ti/CD3 TCR complexes. In addition, both CD4+ and CD8+ TIL cultures from most patients caused substantial (greater than 20%) lysis of the NK-sensitive K562 cell line. The majority of CD4+ but not CD8+ TIL cultures also produced substantial lysis of the NK-resistant Daudi cell line. Lysis of the autologous tumor by the TIL subsets was assessed in two patients with malignant melanoma. The CD8+ TIL from one tumor demonstrated cytotoxic activity against the autologous tumor but negligible lysis of allogeneic melanoma targets. In conclusion, immunocompetent CD4+ and CD8+ TIL subsets can be isolated and expanded directly from small tumor fragments of malignant melanoma and renal cell carcinoma using BSMAB. The resultant

The Effect of In Vivo Hydrocortisone on Subpopulations of Human Lymphocytes

PubMed Central

Fauci, Anthony S.; Dale, David C.

1974-01-01

This study was designed to determine the effect of in vivo hydrocortisone on subpopulations of lymphoid cells in normal humans. Subjects received a single intravenous dose of either 100 mg or 400 mg of hydrocortisone, and blood was drawn at hourly intervals for 6 h, and then again at 10 and 24 h after injection. Profound decreases in absolute numbers of circulating lymphocytes and monocytes occurred at 4-6 h after both 100 mg and 400 mg of hydrocortisone. Counts returned to normal by 24 h. The relative proportion of circulating thymus-derived lymphocytes as measured by the sheep red blood cell rosette assay decreased maximally by 4 h and returned to base line 24 h after hydrocortisone. There was a selective depletion of functional subpopulations of lymphocytes as represented by differential effects on in vitro stimulation with various mitogens and antigens. Phytohaemagglutinin response was relatively unaffected, while responses to concanavalin A were significantly diminished. Responses to pokeweed mitogen were unaffected by 100 mg of hydrocortisone, but greatly diminished by 400 mg of hydrocortisone. In vitro responses to the antigens streptokinase-streptodornase and tetanus toxoid were markedly diminished by in vivo hydrocortisone. Reconstitution of monocyte-depleted cultures with autologous monocytes partially corrected the diminished response to antigens. This transient selective depletion of monocytes and subsets of human lymphocytes by a single dose of hydrocortisone is most compatible with a redistribution of these cells out of the circulation into other body compartments. Images PMID:4808638

A high molecular weight-melanoma associated antigen-specific chimeric antigen receptor redirects lymphocytes to target human melanomas

PubMed Central

Burns, William R.; Zhao, Yangbing; Frankel, Timothy L.; Hinrichs, Christian S.; Zheng, Zhili; Xu, Hui; Feldman, Steven A.; Ferrone, Soldano; Rosenberg, Steven A.; Morgan, Richard A.

2011-01-01

Immunotherapy, particularly the adoptive cell transfer (ACT) of tumor infiltrating lymphocytes (TIL), is a very promising therapy for metastatic melanoma. Some patients unable to receive TIL have been successfully treated with autologous peripheral blood lymphocytes (PBL), genetically modified to express HLA class I antigen restricted, melanoma antigen-reactive T-cell receptors; however, substantial numbers of patients remain ineligible due to the lack of expression of the restricting HLA class I allele. We sought to overcome this limitation by designing a non-MHC-restricted, chimeric antigen receptor (CAR) targeting the high molecular weight-melanoma associated antigen (HMW-MAA), which is highly expressed on over 90% of human melanomas but has a restricted distribution in normal tissues. HMW-MAA-specific CARs containing an antigen recognition domain based on variations of the HMW-MAA-specific monoclonal antibody (mAb) 225.28S and a T-cell activation domain based on combinations of CD28, 4-1BB, and CD3ζ activation motifs were constructed within a retroviral vector to allow stable gene transfer into cells and their progeny. Following optimization of the HMW-MAA-specific CAR for expression and function in human PBL, these gene-modified T cells secreted cytokines, were cytolytic, and proliferated in response to HMW-MAA expressing cell lines. Furthermore, the receptor functioned in both CD4+ and CD8+ cells, was non-MHC-restricted, and reacted against explanted human melanomas. To evaluate this HMW-MAA-specific CAR in patients with metastatic melanoma, we developed a clinical-grade retroviral packaging line. This may represent a novel means to treat the majority of patients with advanced melanoma, most notably those unable to receive current ACT therapies. PMID:20395199

Disabling Immune Tolerance by Programmed Death-1 Blockade With Pidilizumab After Autologous Hematopoietic Stem-Cell Transplantation for Diffuse Large B-Cell Lymphoma: Results of an International Phase II Trial

PubMed Central

Armand, Philippe; Nagler, Arnon; Weller, Edie A.; Devine, Steven M.; Avigan, David E.; Chen, Yi-Bin; Kaminski, Mark S.; Holland, H. Kent; Winter, Jane N.; Mason, James R.; Fay, Joseph W.; Rizzieri, David A.; Hosing, Chitra M.; Ball, Edward D.; Uberti, Joseph P.; Lazarus, Hillard M.; Mapara, Markus Y.; Gregory, Stephanie A.; Timmerman, John M.; Andorsky, David; Or, Reuven; Waller, Edmund K.; Rotem-Yehudar, Rinat; Gordon, Leo I.

2013-01-01

Purpose The Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade. Patients and Methods We conducted an international phase II study of pidilizumab, an anti–PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of pidilizumab beginning 1 to 3 months after AHSCT. Results Sixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35 patients with measurable disease after AHSCT, the overall response rate after pidilizumab treatment was 51%. Treatment was associated with increases in circulating lymphocyte subsets including PD-L1E–bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab. Conclusion This is the first demonstration of clinical activity of PD-1 blockade in DLBCL. Given these results, PD-1 blockade after AHSCT using pidilizumab may represent a promising therapeutic strategy in this disease. PMID:24127452

Ex Vivo Induction of Multiple Myeloma-specific Immune Responses by Monocyte-derived Dendritic Cells Following Stimulation by Whole-tumor Antigen of Autologous Myeloma Cells.

PubMed

Vasileiou, Spyridoula; Baltadakis, Ioannis; Delimpasi, Sosanna; Karatza, Maria-Helena; Liapis, Konstantinos; Garofalaki, Maria; Tziotziou, Eirini; Poulopoulou, Zoe; Karakasis, Dimitri; Harhalakis, Nicholas

2017-09-01

The introduction of novel agents has significantly expanded treatment options for multiple myeloma (MM), albeit long-term disease control cannot be achieved in the majority of patients. Vaccination with MM antigen-loaded dendritic cells (DCs) represents an alternative strategy that is currently being explored. The aim of this study was to assess the immunogenic potential of ex vivo-generated monocyte-derived DCs (moDCs), following stimulation with the whole-antigen array of autologous myeloma cells (AMC). MoDCs were loaded with antigens of myeloma cells by 2 different methods: phagocytosis of apoptotic bodies from γ-irradiated AMC, or transfection with AMC total RNA by square-wave electroporation. Twenty patients with MM were enrolled in the study. Following stimulation and maturation, moDCs were tested for their capacity to induce T-helper 1 and cytotoxic T lymphocyte responses in vitro. Both strategies were effective in the induction of myeloma-specific cytotoxic T lymphocyte and T-helper 1 cells, as demonstrated by cytotoxicity and ELISpot assays. On the whole, T-cell responses were observed in 18 cases by either method of DC pulsing. We conclude that both whole-tumor antigen approaches are efficient in priming autologous antimyeloma T-cell responses and warrant further study aiming at the development of individualized DC vaccines for MM patients.

Improving therapy of chronic lymphocytic leukemia with chimeric antigen receptor T cells.

PubMed

Fraietta, Joseph A; Schwab, Robert D; Maus, Marcela V

2016-04-01

Adoptive cell immunotherapy for the treatment of chronic lymphocytic leukemia (CLL) has heralded a new era of synthetic biology. The infusion of genetically engineered, autologous chimeric antigen receptor (CAR) T cells directed against CD19 expressed by normal and malignant B cells represents a novel approach to cancer therapy. The results of recent clinical trials of CAR T cells in relapsed and refractory CLL have demonstrated long-term disease-free remissions, underscoring the power of harnessing and redirecting the immune system against cancer. This review will briefly summarize T-cell therapies in development for CLL disease. We discuss the role of T-cell function and phenotype, T-cell culture optimization, CAR design, and approaches to potentiate the survival and anti-tumor effects of infused lymphocytes. Future efforts will focus on improving the efficacy of CAR T cells for the treatment of CLL and incorporating adoptive cell immunotherapy into standard medical management of CLL. Copyright © 2016 Elsevier Inc. All rights reserved.

Loss of signal transduction and inhibition of lymphocyte locomotion in a ground-based model of microgravity

NASA Technical Reports Server (NTRS)

Sundaresan, Alamelu; Risin, Diana; Pellis, Neal R.; McIntire, L. V. (Principal Investigator)

2002-01-01

Inflammatory adherence to, and locomotion through the interstitium is an important component of the immune response. Conditions such as microgravity and modeled microgravity (MMG) severely inhibit lymphocyte locomotion in vitro through gelled type I collagen. We used the NASA rotating wall vessel bioreactor or slow-turning lateral vessel as a prototype for MMG in ground-based experiments. Previous experiments from our laboratory revealed that when lymphocytes (human peripheral blood mononuclear cells [PBMCs]) were first activated with phytohemaglutinin followed by exposure to MMG, locomotory capacity was not affected. In the present study, MMG inhibits lymphocyte locomotion in a manner similar to that observed in microgravity. Phorbol myristate acetate (PMA) treatment of PBMCs restored lost locomotory capacity by a maximum of 87%. Augmentation of cellular calcium flux with ionomycin had no restorative effect. Treatment of lymphocytes with mitomycin C prior to exposure to MMG, followed by PMA, restored locomotion to the same extent as when nonmitomycin C-treated lymphocytes were exposed to MMG (80-87%), suggesting that deoxyribonucleic acid replication is not essential for the restoration of locomotion. Thus, direct activation of protein kinase C (PKC) with PMA was effective in restoring locomotion in MMG comparable to the normal levels seen in Ig cultures. Therefore, in MMG, lymphocyte calcium signaling pathways were functional, with defects occurring at either the level of PKC or upstream of PKC.

Prognostic meaning of neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ration (LMR) in newly diagnosed Hodgkin lymphoma patients treated upfront with a PET-2 based strategy.

PubMed

Romano, Alessandra; Parrinello, Nunziatina Laura; Vetro, Calogero; Chiarenza, Annalisa; Cerchione, Claudio; Ippolito, Massimo; Palumbo, Giuseppe Alberto; Di Raimondo, Francesco

2018-06-01

Recent reports identify NLR (the ratio between absolute neutrophils counts, ANC, and absolute lymphocyte count, ALC), as predictor of progression-free survival (PFS) and overall survival (OS) in cancer patients. We retrospectively tested NLR and LMR (the ratio between absolute lymphocyte and monocyte counts) in newly diagnosed Hodgkin lymphoma (HL) patients treated upfront with a PET-2 risk-adapted strategy. NLR and LMR were calculated using records obtained from the complete blood count (CBC) from 180 newly diagnosed HL patients. PFS was evaluated accordingly to Kaplan-Meier method. Higher NLR was associated to advanced stage, increased absolute counts of neutrophils and reduced count of lymphocytes, and markers of systemic inflammation. After a median follow-up of 68 months, PFS at 60 months was 86.6% versus 70.1%, respectively, in patients with NLR ≥ 6 or NLR < 6. Predictors of PFS at 60 months were PET-2 scan (p < 0.0001), NLR ≥ 6.0 (p = 0.02), LMR < 2 (p = 0.048), and ANC (p = 0.0059) in univariate analysis, but only PET-2 was an independent predictor of PFS in multivariate analysis. Advanced-stage patients (N = 119) were treated according to a PET-2 risk-adapted protocol, with an early switch to BEACOPP regimen in case of PET-2 positivity. Despite this strategy, patients with positive PET-2 still had an inferior outcome, with PFS at 60 months of 84.7% versus 40.1% (negative and positive PET-2 patients, respectively, p < 0.0001). Independent predictors of PFS by multivariate analysis were PET-2 status and to a lesser extend NLR in advanced stage, while LMR maintained its significance in early stage. By focusing on PET-2 negative patients, we found that patients with NLR ≥ 6.0 or LMR < 2 had an inferior outcome compared to patients with both ratios above the cutoff (78.7 versus 91.9 months, p = 0.01). We confirm NLR as predictor of PFS in HL patients independently from stage at diagnosis

Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): study protocol of a phase I/II clinical trial.

PubMed

Niess, Hanno; von Einem, Jobst C; Thomas, Michael N; Michl, Marlies; Angele, Martin K; Huss, Ralf; Günther, Christine; Nelson, Peter J; Bruns, Christiane J; Heinemann, Volker

2015-04-08

Adenocarcinoma originating from the digestive system is a major contributor to cancer-related deaths worldwide. Tumor recurrence, advanced local growth and metastasis are key factors that frequently prevent these tumors from curative surgical treatment. Preclinical research has demonstrated that the dependency of these tumors on supporting mesenchymal stroma results in susceptibility to cell-based therapies targeting this stroma. TREAT-ME1 is a prospective, uncontrolled, single-arm phase I/II study assessing the safety and efficacy of genetically modified autologous mesenchymal stromal cells (MSC) as delivery vehicles for a cell-based gene therapy for advanced, recurrent or metastatic gastrointestinal or hepatopancreatobiliary adenocarcinoma. Autologous bone marrow will be drawn from each eligible patient after consent for bone marrow donation has been obtained (under a separate EC-approved protocol). In the following ~10 weeks the investigational medicinal product (IMP) is developed for each patient. To this end, the patient's MSCs are stably transfected with a gamma-retroviral, replication-incompetent and self-inactivating (SIN) vector system containing a therapeutic promoter - gene construct that allows for tumor-specific expression of the therapeutic gene. After release of the IMP the patients are enrolled after given informed consent for participation in the TREAT-ME 1 trial. In the phase I part of the study, the safety of the IMP is tested in six patients by three treatment cycles consisting of re-transfusion of MSCs at different concentrations followed by administration of the prodrug Ganciclovir. In the phase II part of the study, sixteen patients will be enrolled receiving IMP treatment. A subgroup of patients that qualifies for surgery will be treated preoperatively with the IMP to verify homing of the MSCs to tumors as to be confirmed in the surgical specimen. The TREAT-ME1 clinical study involves a highly innovative therapeutic strategy combining cell

Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells.

PubMed

Burkhardt, Ute E; Hainz, Ursula; Stevenson, Kristen; Goldstein, Natalie R; Pasek, Mildred; Naito, Masayasu; Wu, Di; Ho, Vincent T; Alonso, Anselmo; Hammond, Naa Norkor; Wong, Jessica; Sievers, Quinlan L; Brusic, Ana; McDonough, Sean M; Zeng, Wanyong; Perrin, Ann; Brown, Jennifer R; Canning, Christine M; Koreth, John; Cutler, Corey; Armand, Philippe; Neuberg, Donna; Lee, Jeng-Shin; Antin, Joseph H; Mulligan, Richard C; Sasada, Tetsuro; Ritz, Jerome; Soiffer, Robert J; Dranoff, Glenn; Alyea, Edwin P; Wu, Catherine J

2013-09-01

Patients with advanced hematologic malignancies remain at risk for relapse following reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a prospective clinical trial to test whether vaccination with whole leukemia cells early after transplantation facilitates the expansion of leukemia-reactive T cells and thereby enhances antitumor immunity. We enrolled 22 patients with advanced chronic lymphocytic leukemia (CLL), 18 of whom received up to 6 vaccines initiated between days 30 and 45 after transplantation. Each vaccine consisted of irradiated autologous tumor cells admixed with GM-CSF-secreting bystander cells. Serial patient PBMC samples following transplantation were collected, and the impact of vaccination on T cell activity was evaluated. At a median follow-up of 2.9 (range, 1-4) years, the estimated 2-year progression-free and overall survival rates of vaccinated subjects were 82% (95% CI, 54%-94%) and 88% (95% CI, 59%-97%), respectively. Although vaccination only had a modest impact on recovering T cell numbers, CD8+ T cells from vaccinated patients consistently reacted against autologous tumor, but not alloantigen-bearing recipient cells with increased secretion of the effector cytokine IFN-γ, unlike T cells from nonvaccinated CLL patients undergoing allo-HSCT. Further analysis confirmed that 17% (range, 13%-33%) of CD8+ T cell clones isolated from 4 vaccinated patients by limiting dilution of bulk tumor-reactive T cells solely reacted against CLL-associated antigens. Our studies suggest that autologous tumor cell vaccination is an effective strategy to advance long-term leukemia control following allo-HSCT. Clinicaltrials.gov NCT00442130. NCI (5R21CA115043-2), NHLBI (5R01HL103532-03), and Leukemia and Lymphoma Society Translational Research Program.

Ten-year follow-up of pediatric patients with non-Hodgkin lymphoma treated with allogeneic or autologous stem cell transplantation.

PubMed

Giulino-Roth, Lisa; Ricafort, Rosanna; Kernan, Nancy A; Small, Trudy N; Trippett, Tanya M; Steinherz, Peter G; Prockop, Susan E; Scaradavou, Andromachi; Chiu, Michelle; O'Reilly, Richard J; Boulad, Farid

2013-12-01

Autologous or allogeneic hematopoietic stem cell transplant (SCT) is often considered in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) but there are limited data on the use of SCT for the treatment of NHL in the pediatric setting. To evaluate the role of SCT for children with NHL, we reviewed 36 consecutive pediatric patients with NHL who underwent an allogeneic (n = 21) or autologous (n = 15) SCT at our institution between 1982 and 2004. Pathologic classification included: lymphoblastic lymphoma (n = 12), Burkitt lymphoma (BL) (n = 5), diffuse large B-cell lymphoma (n = 4), anaplastic large cell lymphoma (ALCL) (n = 13), peripheral T cell lymphoma (n = 1), and undifferentiated NHL (n = 1). Donor source for allogeneic-SCT recipients was an HLA-matched related donor (n = 15), a matched unrelated donor (n = 4), or a mismatched donor (related n = 1; unrelated n = 1). Twenty-eight patients (78%) had chemotherapy responsive disease at the time of transplant (either CR or PR). Overall survival (OS) and disease-free survival (DFS) were 55% and 53% with a median follow-up of 9.75 years. Outcomes were similar in patients receiving autologous and allogeneic-SCT (DFS 53% in both groups). Patients with ALCL had a DFS of 76.9%. In contrast, of five patients transplanted for BL, none survived. DFS among patients with chemotherapy sensitive disease was 61%, compared with 25% among patients with relapsed/refractory disease (P = 0.019). Allogeneic and autologous SCT offer the prospect of durable, disease-free survival for a significant proportion of pediatric patients with relapsed or refractory NHL. Survival is superior among patients with chemotherapy sensitive disease. © 2013 Wiley Periodicals, Inc.

ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity

PubMed Central

Beers, David R.; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R.; Alsuliman, Abdullah S.; Shpall, Elizabeth J.; Rezvani, Katy

2017-01-01

Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression. PMID:28289705

ALS patients' regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity.

PubMed

Beers, David R; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R; Alsuliman, Abdullah S; Shpall, Elizabeth J; Rezvani, Katy; Appel, Stanley H

2017-03-09

Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression.

Adipose tissue lymphocytes: types and roles.

PubMed

Caspar-Bauguil, S; Cousin, B; Bour, S; Casteilla, L; Castiella, L; Penicaud, L; Carpéné, C

2009-12-01

Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.

Studies of DNA and chromosome damage in skin fibroblasts and blood lymphocytes from psoriasis patients treated with 8-methoxypsoralen and UVA irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bredberg, A.; Lambert, B.; Lindblad, A.

1983-08-01

Exposure of human lymphocytes and skin fibroblasts in vitro to a single, clinically used dose of PUVA, i.e., 0.1 micrograms/ml of 8-methoxypsoralen (8-MOP) plus 0.9-4 J/cm2 of longwave ultraviolet radiation (UVA), lead to the formation of DNA damage as determined by alkaline elution, and to chromosome aberrations and sister chromatid exchanges (SCE). When lymphocyte-enriched plasma was obtained from psoriasis patients 2 h after oral intake of 8-MOP and then UVA irradiated (1.8-3.6 J/cm2) in vitro, an increased frequency of chromosome aberrations and SCE was observed. Normal levels of chromosome aberrations and SCE were found in lymphocytes of psoriasis patients aftermore » 3-30 weeks of PUVA treatment in vivo. A small but statistically significant increase in the SCE frequency was observed in the lymphocytes of psoriasis patients treated for 1-6 years with PUVA (mean 18.0 SCE/cell) as compared with before PUVA (mean 15.8, p less than 0.05). Skin fibroblasts of psoriasis patients analyzed 5 years after the start of PUVA treatment showed a normal number of SCE but a high fraction of filter-retained DNA in the alkaline elution assay, suggesting the presence of cross-linked DNA.« less

Peripheral blood lymphocyte/monocyte ratio as a useful prognostic factor in dogs with diffuse large B-cell lymphoma receiving chemoimmunotherapy.

PubMed

Marconato, Laura; Martini, Valeria; Stefanello, Damiano; Moretti, Pierangelo; Ferrari, Roberta; Comazzi, Stefano; Laganga, Paola; Riondato, Fulvio; Aresu, Luca

2015-11-01

Diffuse large B-cell lymphoma (DLBCL) is the most frequent canine lymphoid neoplasm. Despite treatment, the majority of dogs with DLBCL experience tumour relapse and consequently die, so practical models to characterise dogs with a poor prognosis are needed. This study examined whether the lymphocyte/monocyte ratio (LMR) can predict outcome in dogs with newly diagnosed DLBCL with regard to time-to-progression (TTP) and lymphoma specific survival (LSS). A retrospective study analysed the prognostic significance of LMR obtained at diagnosis by flow cytometry (based on morphological properties and CD45 expression) in 51 dogs that underwent complete staging and received the same treatment, comprising multi-agent chemotherapy and administration of an autologous vaccine. Dogs with an LMR ≤ 1.2 (30% of all cases) were found to have significantly shorter TTP and LSS, and it was concluded that LMR was a useful independent prognostic indicator with biological relevance in dogs with DLBCL treated with chemoimmunotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Metastatic Lung Lesions as a Preferred Resection Site for Immunotherapy With Tumor Infiltrating Lymphocytes.

PubMed

Ben-Avi, Ronny; Itzhaki, Orit; Simansky, David; Zippel, Dov; Markel, Gal; Ben Nun, Alon; Schachter, Jacob; Besser, Michal J

2016-06-01

Adoptive cell therapy with tumor infiltrating lymphocytes (TIL) yields 50% response rates in metastatic melanoma and shows promising clinical results in other solid tumors. Autologous TIL cultures are isolated from resected tumor tissue, expanded ex vivo to large numbers and reinfused to the preconditioned patient. In this prospective study, we validate the origin of the tumor biopsy and its effect on T-cell function and clinical response. One hundred forty-four patients underwent surgery and 79 patients were treated with TIL adoptive cell therapy. Cultures from lung tissue were compared with other origins. The success rate of establishing TIL culture from lung tissue was significantly higher compared with nonlung tissue (94% vs. 72%, respectively, P≤0.003). Lung-derived TIL cultures gave rise to higher cell numbers (P≤0.011) and exhibited increased in vitro antitumor reactivity. The average fold expansion for lung-derived TIL during a rapid expansion procedure was 1349±557 compared with 1061±473 for nonlung TIL (P≤0.038). Patients treated with TIL cultures of lung origin (compared with nonlung) had prolonged median overall survival (29 vs. 9.5 mo; P≤0.065). Given the remarkable advancement in minimally invasive thoracic surgery and the results of this study, we suggest efforts should be taken to resect lung metastasis rather than other sites to generate TIL cultures for clinical use.

Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens.

PubMed

Hessell, Ann J; Malherbe, Delphine C; Pissani, Franco; McBurney, Sean; Krebs, Shelly J; Gomes, Michelle; Pandey, Shilpi; Sutton, William F; Burwitz, Benjamin J; Gray, Matthew; Robins, Harlan; Park, Byung S; Sacha, Jonah B; LaBranche, Celia C; Fuller, Deborah H; Montefiori, David C; Stamatatos, Leonidas; Sather, D Noah; Haigwood, Nancy L

2016-04-01

Advancement in immunogen selection and vaccine design that will rapidly elicit a protective Ab response is considered critical for HIV vaccine protective efficacy. Vaccine-elicited Ab responses must therefore have the capacity to prevent infection by neutralization-resistant phenotypes of transmitted/founder (T/F) viruses that establish infection in humans. Most vaccine candidates to date have been ineffective at generating Abs that neutralize T/F or early variants. In this study, we report that coimmunizing rhesus macaques with HIV-1 gp160 DNA and gp140 trimeric protein selected from native envelope gene sequences (envs) induced neutralizing Abs against Tier 2 autologous viruses expressing cognate envelope (Env). The Env immunogens were selected from envs emerging during the earliest stages of neutralization breadth developing within the first 2 years of infection in two clade B-infected human subjects. Moreover, the IgG responses in macaques emulated the targeting to specific regions of Env known to be associated with autologous and heterologous neutralizing Abs developed within the human subjects. Furthermore, we measured increasing affinity of macaque polyclonal IgG responses over the course of the immunization regimen that correlated with Tier 1 neutralization. In addition, we report firm correlations between Tier 2 autologous neutralization and Tier 1 heterologous neutralization, as well as overall TZM-bl breadth scores. Additionally, the activation of Env-specific follicular helper CD4 T cells in lymphocytes isolated from inguinal lymph nodes of vaccinated macaques correlated with Tier 2 autologous neutralization. These results demonstrate the potential for native Env derived from subjects at the time of neutralization broadening as effective HIV vaccine elements. Copyright © 2016 by The American Association of Immunologists, Inc.

Impact of prestorage leucoreduction of autologous whole blood on length of hospital stay with a subgroup analysis in bilateral hip arthroplasty.

PubMed

Sawamura, Y; Ohto, H; Ikeda, K; Kanno, T; Suzuki, Y; Gonda, K; Tasaki, T; Nollet, K E; Takahashi, H; Aota, S

2018-06-20

Although prestorage leucoreduction (LR) of blood components for transfusion has gained favour around the world, evidence of its beneficial clinical effects is ambiguous. To reveal whether leucocytes and/or platelets in transfused blood are related to transfusion-related adverse effects, a prospective randomized crossover study was performed on patients who donated autologous blood prior to elective surgery. Among 1487 primary enrolees, a total of 192 patients undergoing two-stage, bilateral total hip arthroplasty were randomized to receive autologous blood that was either prestorage leucoreduced, or not, for the first procedure. For the second procedure, each patient was crossed over to receive alternatively processed autologous blood. Length of hospital stay served as a primary end-point, with perioperative infectious/thrombotic complications, pre- and postoperative laboratory values, and body temperature serving as secondary endpoints. No significant differences emerged between prestorage LR and non-LR cohorts in length of hospital stay, as well as perioperative infectious/thrombotic complications, postoperative body temperature and duration of fever. Postoperative laboratory values including white blood cell counts and C-reactive protein levels had no significant differences. This study could not prove any superiority of prestorage LR over non-LR for autologous whole blood among patients who underwent total hip arthroplasty. © 2018 International Society of Blood Transfusion.

Fate of lymphocytes after withdrawal of tofacitinib treatment.

PubMed

Piscianz, Elisa; Valencic, Erica; Cuzzoni, Eva; De Iudicibus, Sara; De Lorenzo, Elisa; Decorti, Giuliana; Tommasini, Alberto

2014-01-01

Tofacitinib (Tofa) is an inhibitor of Janus Kinase 3, developed for the treatment of autoimmune diseases and for the prevention of transplant rejection. Due to its selective action on proliferating cells, Tofa can offer a way to block T cell activation, without toxic effects on resting cells. However, few studies have investigated the effects of Tofa on lymphocyte activation in vitro. Our aim was to study the action of Tofa on different lymphocyte subsets after in vitro stimulation and to track the behaviour of treated cells after interruption of the treatment. Peripheral blood lymphocytes were stimulated in vitro with mitogen and treated with two concentrations of Tofa. After a first period in culture, cells were washed and further incubated for an additional time. Lymphocyte subsets, activation phenotype and proliferation were assessed at the different time frames. As expected, Tofa was able to reduce the activation and proliferation of lymphocytes in the first four days of treatment. In addition the drug led to a relative decrease of Natural Killer, B cells and CD8 T cells compared to CD4 T cells. However, treated cells were still viable after the first period in culture and begun to proliferate, strikingly, in a dose dependent manner when the drug was removed from the environment by replacing the culture medium. This novel data does not necessarily predict a similar behaviour in vivo, but can warn about the clinical use of this drug when a discontinuation of treatment with Tofa is considered for any reason.

Fate of Lymphocytes after Withdrawal of Tofacitinib Treatment

PubMed Central

Piscianz, Elisa; Valencic, Erica; Cuzzoni, Eva; De Iudicibus, Sara; De Lorenzo, Elisa; Decorti, Giuliana; Tommasini, Alberto

2014-01-01

Tofacitinib (Tofa) is an inhibitor of Janus Kinase 3, developed for the treatment of autoimmune diseases and for the prevention of transplant rejection. Due to its selective action on proliferating cells, Tofa can offer a way to block T cell activation, without toxic effects on resting cells. However, few studies have investigated the effects of Tofa on lymphocyte activation in vitro. Our aim was to study the action of Tofa on different lymphocyte subsets after in vitro stimulation and to track the behaviour of treated cells after interruption of the treatment. Peripheral blood lymphocytes were stimulated in vitro with mitogen and treated with two concentrations of Tofa. After a first period in culture, cells were washed and further incubated for an additional time. Lymphocyte subsets, activation phenotype and proliferation were assessed at the different time frames. As expected, Tofa was able to reduce the activation and proliferation of lymphocytes in the first four days of treatment. In addition the drug led to a relative decrease of Natural Killer, B cells and CD8 T cells compared to CD4 T cells. However, treated cells were still viable after the first period in culture and begun to proliferate, strikingly, in a dose dependent manner when the drug was removed from the environment by replacing the culture medium. This novel data does not necessarily predict a similar behaviour in vivo, but can warn about the clinical use of this drug when a discontinuation of treatment with Tofa is considered for any reason. PMID:24416411

Preliminary clinical trial of immunotherapy for malignant glioma.

PubMed

Ingram, M; Shelden, C H; Jacques, S; Skillen, R G; Bradley, W G; Techy, G B; Freshwater, D B; Abts, R M; Rand, R W

1987-10-01

An immunotherapy protocol based on intracranial implantation of stimulated, autologous lymphocytes into the tumor bed following surgical debulking of malignant glioma is described. Phase I clinical trials in human patients are now in progress. Preliminary data representing the first 39 patients treated are presented briefly.

Long-term follow-up of 2 patients treated with 90 Y-rituximab Radioimmunotherapy for relapse of nodular lymphocyte-predominant Hodgkin lymphoma.

PubMed

Golstein, S; Muylle, K; Vercruyssen, M; Spilleboudt, C; de Wind, A; Bron, D

2018-05-02

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma (< 5% of Hodgkin's lymphomas) predominantly affecting the middle-aged man, with an indolent behavior. Given the rare occurrence of this lymphoma, there are currently no clear guidelines for initial treatment or relapse. In this report, we present the follow up of two patients treated by radioimmunotherapy for first relapse of their NLPHL. Both patients were initially treated with rituximab and relapsed 1 year after the end of their treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Prognostic value of baseline absolute lymphocyte concentration and neutrophil/lymphocyte ratio in dogs with newly diagnosed multi-centric lymphoma.

PubMed

Mutz, M; Boudreaux, B; Kearney, M; Stroda, K; Gaunt, S; Shiomitsu, K

2015-12-01

Canine multi-centric B-cell lymphoma shares similarities with diffuse large B-cell (Non-Hodgkin's) lymphoma (NHL) in people. In people with NHL, lymphopenia at diagnosis and first relapse and neutrophil/lymphocyte ratio (N:L) > 3.5 are negative prognostic factors for survival. The objective of this study was to determine if lymphocyte concentration at diagnosis and first relapse and N:L were prognostic for survival in dogs with newly diagnosed multi-centric lymphoma. Medical records of 77 dogs with multi-centric lymphoma treated with a CHOP-based chemotherapy protocol were retrospectively evaluated. Absolute lymphocyte concentration and N:L ratio at presentation of dogs pre-treated with steroids was not significantly different from dogs who had not received steroids. On multivariate analysis, only immunophenotype remained significant for progression-free survival (PFS), whereas no variables remained significant for ST. A prospective study of these haematologic variables is warranted to assess their true significance. © 2013 John Wiley & Sons Ltd.

Clinical value of Pro-GRP and T lymphocyte subpopulation for the assessment of immune functions of lung cancer patients after DC-CIK biological therapy.

PubMed

He, Lijie; Wang, Jing; Chang, Dandan; Lv, Dandan; Li, Haina; Zhang, Heping

2018-02-01

The present study investigated the aptness of assessing the levels of progastrin-releasing peptide (Pro-GRP) in addition to the T lymphocyte subpopulation in lung cancer patients prior to and after therapy for determining immune function. A total of 45 patients with lung cancer were recruited and stratified in to a non-small cell lung cancer (NSCLC) and an SCLC group. Prior to and after treatment by combined biological therapy comprising chemotherapy or chemoradiotherapy followed by three cycles of retransformation of autologous dendritic cells-cytokine-induced killer cells (DC-CIK), the peripheral blood was assessed for populations of CD3 + , CD4 + , CD8 + and regulatory T cells (Treg) by flow cytometry, and for the levels of pro-GRP, carcinoembryonic antigen, neuron-specific enolase and Cyfra 21-1. The results revealed that in NSCLC patients, CD8 + T lymphocytes and Treg populations were decreased, and that CD3 + and CD4 + T lymphocytes as well as the CD4 + /CD8 + ratio were increased after therapy; in SCLC patients, CD3 + , CD4 + and CD8 + T lymphocytes were increased, while Treg cells were decreased after treatment compared with those at baseline. In each group, Pro-GRP was decreased compared with that prior to treatment, and in the SCLC group only, an obvious negative correlation was identified between Pro-GRP and the T lymphocyte subpopulation. Furthermore, a significant correlation between Pro-GRP and Tregs was identified in each group. In conclusion, the present study revealed that the immune function of the patients was improved after biological therapy. The results suggested a significant correlation between Pro-GRP and the T lymphocyte subpopulation in SCLC patients. Detection of Pro-GRP may assist the early clinical diagnosis of SCLC and may also be used to assess the immune regulatory function of patients along with the T lymphocyte subpopulation. Biological therapy with retransformed autologous DC-CIK was indicated to enhance the specific elimination

Activation of NK Cells in Mixed Cultures of Wharton's Jelly Mesenchymal Stromal Cells and Peripheral Blood Lymphocytes.

PubMed

Svirshchevskaya, E V; Poltavtsev, A M; Os'mak, G Zh; Poltavtseva, R A

2018-01-01

Mesenchymal stromal cells possess immunosuppressive properties that might be used for the therapy of inflammatory diseases of various geneses. The effects of mesenchymal stromal cells depend on their lifetime in the recipient tissues. During heterologous transplantation, mesenchymal stromal cells are eliminated by NK cells. We studied NK cell formation in mixed cultures of Wharton's jelly mesenchymal stromal cells and peripheral blood lymphocytes from an autologous donor. Lymphocytes were activated by a mitogen or IL-2. The lifetime of mesenchymal stromal cells was estimated by MTT test. Cytotoxic activity and phenotype of NK cells were evaluated by flow cytometry. It was found that activation of NK cells depended on IL-2 and was registered on day 2 of incubation with IL-2. In cultures with mitogen-activated lymphocytes, cytotoxicity was observed after 5-6 days. Cytotoxicity of NK correlated with significant decrease in CD16+ and increase in CD56+ NK and with reduction of mesenchymal stromal cell viability. Thus, the main mechanism of elimination of mesenchymal stromal cells is cytotoxicity of NK cells that depended on IL-2 production.

Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer.

PubMed

Bagley, Stephen J; Kothari, Shawn; Aggarwal, Charu; Bauml, Joshua M; Alley, Evan W; Evans, Tracey L; Kosteva, John A; Ciunci, Christine A; Gabriel, Peter E; Thompson, Jeffrey C; Stonehouse-Lee, Susan; Sherry, Victoria E; Gilbert, Elizabeth; Eaby-Sandy, Beth; Mutale, Faith; DiLullo, Gloria; Cohen, Roger B; Vachani, Anil; Langer, Corey J

2017-04-01

Efficient use of nivolumab in non-small-cell lung cancer (NSCLC) has been limited by the lack of a definitive predictive biomarker. In patients with metastatic melanoma treated with ipilimumab, a pretreatment neutrophil-to-lymphocyte ratio (NLR)<5 has been associated with improved survival. This retrospective cohort study aimed to determine whether the pretreatment NLR was associated with outcomes in NSCLC patients treated with nivolumab. We reviewed the medical records of all patients with previously treated advanced NSCLC who received nivolumab between March 2015 and March 2016 outside of a clinical trial at the University of Pennsylvania. Patients were dichotomized according to pretreatment NLR<5 vs. ≥5. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment NLR on overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). 175 patients were treated. Median age was 68 (range, 33-88); 54% were female. Twenty-five percent of patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2; 46% had received ≥2 prior systemic therapies. In multivariate analyses, pretreatment neutrophil-to-lymphocyte ratio (NLR) ≥5 was independently associated with inferior OS (median 5.5 vs. 8.4 months; HR 2.07, 95% CI 1.3-3.3; p=0.002) and inferior PFS (median 1.9 vs. 2.8 months; HR 1.43, 95% CI 1.02-2.0; p=0.04). In a cohort of patients with NSCLC treated with nivolumab in routine practice, pretreatment NLR≥5 was associated with inferior outcomes. It is unclear whether this marker is predictive or prognostic. Prospective studies are warranted to determine the utility of NLR in the context of other biomarkers of programmed death-1 (PD-1) therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Photochemical inactivation of lymphocytes by riboflavin with visible light for TA-GVHD prevention.

PubMed

Mo, Qin; Huang, Yuwen; Wang, Li; Cheng, Zhenzhen; Wu, Xiaofei; Jia, Yao; Wang, Xun; Zhang, Bo

2017-09-01

Transfusion-associated graft-versus-host disease (TA-GVHD) is a life-threatening complication caused by the input of a number of immunocompetent allogeneic lymphocytes. This study focus on the photochemical effects of riboflavin excited by visible light (RB+L) treatment on human lymphocytes, to study the feasibility of using RB+L treatment to prevent adverse immune reactions caused by transfused lymphocytes. 100μM riboflavin was added to lymphocyte suspensions. After exposure to 400-580nm visible light with a total energy of 40J/mL, cells were cultured and the ability of proliferation and cytokine secretion were assayed upon stimuli. Meanwhile, lymphocytes were also treated by gamma-irradiation as parallel to testify the inactivation effect of RB+L. Results showed that γ-irradiation and RB+L treated cells showed a decline in cell viability. After stimulation of phytohemagglutinin (PHA) or anti-CD3 together with anti-CD28, proliferative ability of RB+L treated cells was strongly inhibited when compared to untreated cells. The inhibitive rates of proliferation in RB+L group were also higher than those of cells treated by γ-irradiation. Results of CFSE assays also illustrated hardly any cell division of RB+L and γ-irradiation treated lymphocytes. Besides low level productions of IL-4 and IL-12, cytokine production of TNF-α, IFN-γ and IL-10 by incubation with PHA or IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α and IFN-γ stimulated by anti-CD3 plus anti-CD28 were suppressed after treatment of RB+L significantly. It was suggested that RB+L/γ-irradiation treatment induced cell apoptosis. These results indicated that RB+L treatment functionally inactivated lymphocytes by inhibiting cell proliferation and cytokine production. RB+L might be an alternative for TA-GVHD prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

Terminally differentiated CD8+ T cells and CD57−FOXP3+CD8+ T cells are highly associated with the efficacy of immunotherapy using activated autologous lymphocytes

PubMed Central

Akagi, Junji; Baba, Hideo; Sekine, Teruaki; Ogawa, Kenji

2018-01-01

Treatment with activated autologous lymphocytes (AALs) has demonstrated mixed results for cancer treatment. Preliminary results revealed that the proportion of cluster of differentiation (CD)8+CD57+ T cells is significantly increased in AALs, indicating that they are able to determine treatment outcome. Therefore, the role of CD8+CD57+ T cells in AAL efficacy was investigated. T lymphocytes were isolated from 35 patients with stage IV gastric carcinomas (17 men and 18 women; aged 41–84 years) receiving immunotherapy using AALs (IAAL). Using fluorescence activated cell sorting, CD8, CD27, CD57, and forkhead box protein 3 (FOXP3) expression was investigated on CD8+ T cell populations in CD8+ T cell differentiation prior to and following in vitro culture. The association between these populations and progression-free survival (PFS) was analyzed using Cox univariate, and multivariate analyses and Kaplan-Meier survival analysis. CD57 expression was negative in early-differentiated CD8+ T cells (CD27+CD8+CD57−), and positive in intermediate- (CD27+CD8+CD57+) and terminal- (CD27−CD8+CD57+) differentiated CD8+ T cells. Univariate analysis revealed a significant association between terminal-CD8+ T cells and longer PFS times (P=0.035), whereas CD57−FOXP3+CD8+ T cells were associated with shorter PFS times. Multivariate analysis revealed that CD57−FOXP3+CD8+ T cells was an independent poor prognostic factor, whereas CD57+FOXP3+CD8+ T cells were not associated with PFS. Although IAAL increased the proportion of terminal-CD8+ T cells relative to the pre-culture proportions, patients with a high CD57−FOXP3+CD8+ T cell percentage exhibited repressed terminal-CD8+ T cell induction, leading to poor patient prognosis. Terminally differentiated CD27−CD8+CD57+ T cells were responsible for the effectiveness of AALs; however, CD57−FOXP3+CD8+ T cells abrogated their efficacy, possibly by inhibiting their induction.

Influence of the bystander phenomenon on the chromosome aberration pattern in human lymphocytes induced by in vitro alpha-particle exposure.

PubMed

Schmid, Ernst; Roos, H

2009-04-01

A recent publication on both chromosome-type and chromatid-type aberrations in lymphocytes of patients during treatment with radium-224 for ankylosing spondilitis has revived the question of whether the chromatid-type aberrations may be the consequence of factors released by irradiated cells. Therefore, the aim of the present study was to investigate the influence of such a bystander phenomenon on the chromosome aberration pattern of lymphocytes. Monolayers of human lymphocytes were irradiated with 1 Gy of alpha-particles from an americium-241 source in the absence or presence of whole blood, autologous plasma or culture medium. In the presence of any liquid covering the monolayer during irradiation, the chromatid-type aberrations were, contrary to expectation, elevated. Whereas the intercellular distribution of dicentrics was significantly overdispersed, the chromatid-type aberrations showed a regular dispersion. It can be concluded that the enhanced frequency of chromatid aberrations is the result of a damage signal or a bystander phenomenon released by irradiated cells.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

MedlinePlus

... Impact Support LRF Subscribe About Lymphoma Chronic Lymphocytic Leukemia Home » About Lymphoma » Chronic Lymphocytic Leukemia Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Chronic lymphocytic leukemia Disease generally ...

Improving Therapy of Chronic Lymphocytic Leukemia (CLL) with Chimeric Antigen Receptor (CAR) T Cells

PubMed Central

Fraietta, Joseph A.; Schwab, Robert D.; Maus, Marcela V.

2016-01-01

Adoptive cell immunotherapy for the treatment of chronic lymphocytic leukemia (CLL) has heralded a new era of synthetic biology. The infusion of genetically-engineered, autologous chimeric antigen receptor (CAR) T cells directed against CD19 expressed by normal and malignant B cells represents a novel approach to cancer therapy. The results of recent clinical trials of CAR T cells in relapsed and refractory CLL have demonstrated long-term disease-free remissions, underscoring the power of harnessing and re-directing the immune system against cancer. This review will briefly summarize T cell therapies in development for CLL disease. We discuss the role of T cell function and phenotype, T cell culture optimization, CAR design, and approaches to potentiate the survival and anti-tumor effects of infused lymphocytes. Future efforts will focus on improving the efficacy of CAR T cells for the treatment of CLL and incorporating adoptive cell immunotherapy into standard medical management of CLL. PMID:27040708

Outcomes of Adoptive Cell Transfer With Tumor-infiltrating Lymphocytes for Metastatic Melanoma Patients With and Without Brain Metastases.

PubMed

Mehta, Gautam U; Malekzadeh, Parisa; Shelton, Thomas; White, Donald E; Butman, John A; Yang, James C; Kammula, Udai S; Goff, Stephanie L; Rosenberg, Steven A; Sherry, Richard M

2018-06-01

Brain metastases cause significant morbidity and mortality in patients with metastatic melanoma. Although adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) can achieve complete and durable remission of advanced cutaneous melanoma, the efficacy of this therapy for brain metastases is unclear. Records of patients with M1c melanoma treated with ACT using TIL, including patients with treated and untreated brain metastases, were analyzed. Treatment consisted of preparative chemotherapy, autologous TIL infusion, and high-dose interleukin-2. Treatment outcomes, sites of initial tumor progression, and overall survival were analyzed. Among 144 total patients, 15 patients with treated and 18 patients with untreated brain metastases were identified. Intracranial objective responses (OR) occurred in 28% patients with untreated brain metastases. The systemic OR rates for patients with M1c disease without identified brain disease, treated brain disease, and untreated brain disease, and were 49%, 33% and 33%, respectively, of which 59%, 20% and 16% were durable at last follow-up. The site of untreated brain disease was the most likely site of initial tumor progression (61%) in patients with untreated brain metastases. Overall, we found that ACT with TIL can eliminate small melanoma brain metastases. However, following TIL therapy these patients frequently progress in the brain at a site of untreated brain disease. Patients with treated or untreated brain disease are less likely to achieve durable systemic ORs following TIL therapy compared with M1c disease and no history of brain disease. Melanoma brain metastases likely require local therapy despite the systemic effect of ACT.

Comparison between sensitivity of autologous skin serum test and autologous plasma skin test in patients with Chronic Idiopathic Urticaria for detection of antibody against IgE or IgE receptor (FcεRIα).

PubMed

Sajedi, Vahid; Movahedi, Masoud; Aghamohammadi, Asghar; Aghamohamadi, Asghar; Gharagozlou, Mohammad; Ghareguzlou, Mohammad; Shafiei, Alireza; Soheili, Habib; Sanajian, Nahal

2011-06-01

Intradermal injection of autologous serum and plasma elicit a cutaneous reactivity in almost 45-60% of patients with Chronic Idiopathic Urticaria (CIU). This reactivity is associated with the presence of auto antibodies against IgE or IgE receptors. This study was carried out to compare the cutaneous reactivity of autologous serum and plasma skin tests in a series of patients with CIU for diagnosis of auto antibodies against IgE or IgE receptor. Fifty eight patients with CIU were injected intradermally with autologous serum and plasma (anticoagulated by citrate). Histamine was used as positive control and normal saline as negative control. The study group was checked by routine laboratory tests (CBC, U/A etc), allergens with skin prick tests, and serum IgE level, and auto antibodies against thyroid as well. Duration of urticaria was another factor which was assessed.There was no significant difference between positive ASST and positive APST patients for the above mentioned tests. 77.6% of the patients were Positive for APST and 65.5% were ASST positive. Duration of urticaria was longer in patients with positive ASST and APST than ASST and APST negative patients, although the difference was not statistically significant.Autologus serum skin test (ASST) and autologous plasma skin test (APST) could be used for estimation of duration and severity of urticaria and planning for the treatment.

Use of autologous platelet rich plasma to treat gingival recession in esthetic periodontal surgery

PubMed Central

Naik, Archana R.; Ramesh, Alampalli V.; Dwarkanath, C. D.; Naik, Madhukeshwara S.; Chinnappa, A. B.

2013-01-01

Background: Multiple approaches have been used to replace lost, damaged or diseased gingival tissues. Coronally advanced flap (CAF) and the use of guided tissue regeneration are among the successfully used surgical techniques to treat gingival recession. Platelet rich plasma (PRP), containing autologous growth factors, has been shown to promote soft-tissue healing. Therefore, the purpose of this study was to evaluate the efficacy of PRP in combination with CAF in the treatment of gingival recession. Materials and Methods: A total of 15 systemically healthy patients with buccal Miller's class I and class II gingival recession in cuspids or premolars participated in the study. CAF procedure was performed and PRP with collagen sponge was placed over the defect. Clinical parameters such as recession depth, recession width, surface area, width of keratinized gingival (KG), clinical attachment level (CAL), probing depth, plaque index and gingival index were evaluated at 3, 6 and 9 months post-surgery. The percentage of root coverage was calculated. Results: The results of this study suggest that the CAF procedure provides a predictable and simple technique in the treatment of localized Class I and Class II gingival recession. The additional application of PRP does significantly increase the width of KG and gain in clinical attachment. Conclusion: CAF procedure is a predictable and simple technique in the treatment of gingival recession and the additional application of PRP does significantly increase the width of KG and gain in CAL. The long-term benefits following surgical treatment of such defects needs to be determined further. PMID:24049336

Pevonedistat and Ibrutinib in Treating Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia or Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-03-20

B-Cell Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Marginal Zone Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; Richter Syndrome

NEUTROPHIL/LYMPHOCYTE RATIO AND PLATELET/LYMPHOCYTE RATIO IN PATIENTS WITH NSCLC

PubMed Central

Cukic, Vesna

2016-01-01

Objective: to compare neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in patients with NSCLC (Non- Small- Cell Lung Cancer): with and without metastases at the time of diagnosis to find out if there is the importance of these cell ratios in the assessment of severity NSCLC. Material and Methods: this is the retrospective analysis of NRL and PRL in patients with NSCLC at the time of the diagnosis of disease before any anti tumor treatment (chemotherapy, radiotherapy, surgery). 57 of patients with NSCLC treated in the first three months of 2016. year were chosen at random regardless of sex and age. We examined full blood count cells (FBC), calculated NLR and PLR in every patient and compared obtained values in patients with and patients without metastases. Results: In 57 patients with NSCLC there were 15 males with metastases, 28 without metastases, and 8 females with metastases, 6 without metastases. Since there was no regularity in the distribution of obtained values of NLR and PLR we made the Mann-Whitney U test. Mean values are presented with a median and interquartile percentiles. There was no significant difference in NLR between patients without and with metastases (p = 0.614; p = NS) as well as in PLR (p=0,068; p=NS). Conclusion: There must be a link between the immune status of the organism and lung cancer development. Immune cells have become of interest in recent years and much work has been done to study their role in the genesis of cancer but it did not give satisfactory results. Further clinical studies on large number of patients and further laboratory examination of the role of immune cells in cancer development and suppression are required. PMID:27999489

Single-Stage Cartilage Repair Using Platelet-Rich Fibrin Scaffolds With Autologous Cartilaginous Grafts.

PubMed

Wong, Chin-Chean; Chen, Chih-Hwa; Chan, Wing P; Chiu, Li-Hsuan; Ho, Wei-Pin; Hsieh, Fon-Jou; Chen, You-Tzung; Yang, Tsung-Lin

2017-11-01

To avoid complicated procedures requiring in vitro chondrocyte expansion for cartilage repair, the development of a culture-free, 1-stage approach combining platelet-rich fibrin (PRF) and autologous cartilage grafts may be the solution. To develop a feasible 1-step procedure to combine PRF and autologous cartilage grafts for articular chondral defects. Controlled laboratory study Methods: The chemotactic effects of PRF on chondrocytes harvested from the primary culture of rabbit cartilage were evaluated in vitro and ex vivo. The rabbit chondrocytes were cultured with different concentrations of PRF media and evaluated for their cell proliferation, chondrogenic gene expression, cell viability, and extracellular matrix synthesis abilities. For the in vivo study, the chondral defects were created on established animal models of rabbits. The gross anatomy, histology, and objective scores were evaluated to validate the treatment results. PRF improved the chemotaxis, proliferation, and viability of the cultured chondrocytes. The gene expression of the chondrogenic markers, including type II collagen and aggrecan, revealed that PRF induced the chondrogenic differentiation of cultured chondrocytes. PRF increased the formation and deposition of the cartilaginous matrix produced by cultured chondrocytes. The efficacy of PRF on cell viability was comparable with that of fetal bovine serum. In animal disease models, morphologic, histological, and objectively quantitative evaluation demonstrated that PRF combined with cartilage granules was feasible in facilitating chondral repair. PRF enhances the migration, proliferation, viability, and differentiation of chondrocytes, thus showing an appealing capacity for cartilage repair. The data altogether provide evidence to confirm the feasibility of 1-stage, culture-free method of combining PRF and autologous cartilage graft for repairing articular chondral defects. The single-stage, culture-free method of combining PRF and autologous

Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group

PubMed Central

Winqvist, Maria; Asklid, Anna; Andersson, PO; Karlsson, Karin; Karlsson, Claes; Lauri, Birgitta; Lundin, Jeanette; Mattsson, Mattias; Norin, Stefan; Sandstedt, Anna; Hansson, Lotta; Österborg, Anders

2016-01-01

Ibrutinib, a Bruton’s tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine health-care are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy ≥10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression-free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richter’s transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia. PMID:27198718

Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group.

PubMed

Winqvist, Maria; Asklid, Anna; Andersson, P O; Karlsson, Karin; Karlsson, Claes; Lauri, Birgitta; Lundin, Jeanette; Mattsson, Mattias; Norin, Stefan; Sandstedt, Anna; Hansson, Lotta; Österborg, Anders

2016-12-01

Ibrutinib, a Bruton's tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine health-care are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy ≥10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression-free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richter's transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia. Copyright© Ferrata Storti Foundation.

Hyaline cartilage degenerates after autologous osteochondral transplantation.

PubMed

Tibesku, C O; Szuwart, T; Kleffner, T O; Schlegel, P M; Jahn, U R; Van Aken, H; Fuchs, S

2004-11-01

Autologous osteochondral grafting is a well-established clinical procedure to treat focal cartilage defects in patients, although basic research on this topic remains sparse. The aim of the current study was to evaluate (1) histological changes of transplanted hyaline cartilage of osteochondral grafts and (2) the tissue that connects the transplanted cartilage with the adjacent cartilage in a sheep model. Both knee joints of four sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the contralateral femoral condyle. The animals were sacrificed after three months and the received knee joints were evaluated histologically. Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to Mankin revealed significantly more and more severe signs of degeneration than the adjacent cartilage, such as cloning of chondrocytes and irregularities of the articular surface. We found no connecting tissue between the transplanted and the adjacent cartilage and histological signs of degeneration of the transplanted hyaline cartilage. In the light of these findings, long-term results of autologous osteochondral grafts in human beings have to be followed critically.

What is autologous blood transfusion?

PubMed

Sansom, A

1993-07-01

The word autologous is Greek in origin. The definition is exact 'autos' means self and 'logus' means relation. Thus, the meaning is 'related to self'. Autologous blood transfusion, which also is referred to frequently but incorrectly and imprecisely as auto transfusion, designates the reinfusion of blood or blood components to the same individual from whom they were taken. Homologous blood is blood or blood components, from another human donor, taken and stored for later transfusion as required.

Immune monitoring with a lymphocyte adenosine triphosphate assay in kidney transplant recipients treated with a calcineurin inhibitor.

PubMed

Sugiyama, Kentaro; Tsukaguchi, Mahoto; Toyama, Akira; Satoh, Hiroshi; Saito, Kazuhide; Nakagawa, Yuki; Takahashi, Kota; Tanaka, Sachiko; Onda, Kenji; Hirano, Toshihiko

2014-06-01

The adenosine triphosphate assay using peripheral lymphocytes may be useful to evaluate the risks of acute rejection and infection in kidney transplant patients. We used the adenosine triphosphate assay to evaluate differences between recipients who were treated with cyclosporine- or tacrolimus-based immunosuppressive therapy. Adenosine triphosphate levels were measured in peripheral CD4+ cells before and after transplant and were correlated with clinical outcomes in 45 kidney transplant recipients. These recipients received immunosuppressive therapy with either cyclosporine (23 patients) or tacrolimus (22 patients). Adenosine triphosphate levels were significantly lower in the cyclosporine- than tacrolimus-based therapy groups from 2 to 6 weeks after transplant. Adenosine triphosphate levels were similar between these groups before and 1 week after transplant. The frequency of cytomegalovirus infection was greater in the recipients who received cyclosporine (17 patients [74%]) than tacrolimus (6 patients [27%]; P ≦ .003). The frequency of acute rejection episodes was similar between the cyclosporine and tacrolimus groups. These observations suggest that cyclosporine-based immunosuppressive therapy causes excessive immunosuppression compared with tacrolimus-based therapy, evidenced by the lymphocyte adenosine triphosphate levels. The adenosine triphosphate assay using peripheral CD4+ cells may be a useful method for predicting the occurrence of cytomegalovirus infections in kidney transplant recipients.

Clinical analysis of thoracoscopic surgery combined with intraoperative autologous blood transfusion in the treatment of traumatic hemothorax.

PubMed

Ma, Hu-Sai; Ma, Ju-Hua; Xue, Feng-Lai; Fu, Xiang-Ning; Zhang, Ni

2016-12-01

From January 2013 to January 2015, 19 patients of traumatic hemothorax with hemorrhagic shock were treated in our department by thoracoscopic surgery combined with autologous blood transfusion. This study retrospectively analyzed the therapeutic effect and shared our experience. The average amount of blood transfused back was 662.41 ml ± 269.15 ml. None of the patients developed transfusion reaction and were all discharged uneventfully. Thoracoscopic surgery combined with autologous blood trans- fusion is effective in the rescue of patients with progressive hemothorax and hemorrhagic shock. When corresponding indications are well managed, treatment for these patients is quicker, safer, and more effective.

To the nucleolar bodies (nucleoli) in cells of the lymphocytic lineage in patients suffering from B - chronic lymphocytic leukemia.

PubMed

Smetana, K; Karban, J; Trneny, M

2010-01-01

The present study was undertaken to provide more information on nucleoli in lymphocytes of B - chronic lymphocytic leukemia. The computer assisted nucleolar and cytoplasmic RNA image densitometry, reflecting the nucleolar and cytoplasmic RNA concentration at the single cell level, demonstrated a remarkable stability during the differentiation and maturation of B- lymphocytes. In contrast, as it was expected, the nucleolar diameter during the lymphocytic development markedly decreased. Thus the nucleolar RNA content of leukemic B-lymphocytes was apparently related to the nucleolar size. In both immature and mature lymphocytes, the cytostatic treatment increased the incidence of micronucleoli, which represent the "inactive" type of nucleoli. However, the decreased values of the nucleolar diameter were statistically significant only in mature lymphocytes of treated patients. On the other hand, despite such observation, it must be mentioned that "large active" and "ring shaped resting" nucleoli were still present in immature and mature lymphocytes after the cytostatic therapy and such cells might represent a potential pool of proliferating cells. As it is generally accepted "large active nucleoli" with multiple fibrillar centers are known to be characteristic for proliferating cells. "Ring shaped resting nucleoli" are present in sleeping cells, which may be stimulated to return to the cell cycle and to proliferate again. In addition, the nucleolar RNA distribution also indicated that Gumprecht ghosts mostly originated from mature lymphocytes. Increased ratio of the nucleolar to cytoplasmic RNA density in Gumprecht ghosts or apoptotic cells and apoptotic bodies of the lymphocytic origin was related to the decreased cytoplasmic RNA concentration. The increased nucleolar size together with the markedly decreased cytoplasmic RNA concentration characteristic for Gumprecht ghosts just reflected the spreading of lymphocytes during smear preparations. In apoptotic cells or

Lenalidomide With or Without Rituximab in Treating Patients With Progressive or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Prolymphocytic Leukemia, or Non-Hodgkin Lymphoma Previously Treated With Donor Stem Cell Transplant

ClinicalTrials.gov

2017-07-24

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Establishment of autologous embryonic stem cells derived from preantral follicle culture and oocyte parthenogenesis.

PubMed

Lee, Seung Tae; Choi, Mun Hwan; Lee, Eun Ju; Gong, Seung Pyo; Jang, Mi; Park, Sang Hyun; Jee, Hyang; Kim, Dae Yong; Han, Jae Yong; Lim, Jeong Mook

2008-11-01

To evaluate whether autologous embryonic stem cells can be established without generating clone embryos. Prospective model study. Gamete and stem cell biotechnology laboratory in Seoul National University, Seoul, Korea. F1 hybrid B6D2F1 mice. Preantral follicles were cultured, and oocytes matured in the follicles were parthenogenetically activated. Preimplantation development and stem cell characterization. More intrafollicular oocytes that were retrieved from secondary follicles matured and developed into blastocysts after parthenogenesis than those that were retrieved from primary follicles. Of those 35 blastocysts derived from 193 parthenotes, one line of colony-forming cells was established from the culturing of early secondary follicles. The established cells were positive for embryonic stem cell-specific markers and had normal diploid karyotype and telomerase activity. They differentiated into embryoid bodies in vitro and teratomas in vivo. Inducible differentiation of the established cells into neuronal lineage cells also was possible. Autologous embryonic stem cells can be established by preantral follicle culture and oocyte parthenogenesis. A combined technique of follicle culture and oocyte parthenogenesis that does not use developmentally competent oocytes has the potential to replace somatic cell nuclear transfer for autologous cell therapy.

[Efficacy of coarctation resection and aortoplasty with autologous pulmonary artery patch strategy for treating coarctation of the aorta combined with hypoplastic aortic arch in infants].

PubMed

Ma, Z L; Yan, J; Li, S J; Hua, Z D; Yan, F X; Wang, X; Wang, Q

2018-03-24

Objective: To investigate the outcomes of coarctation resection and aortoplasty with autologous pulmonary artery patch for treating coarctation of the aorta combined with hypoplastic aortic arch in infants. Methods: Clinical data of 21 infants with coarctation of the aorta and hypoplastic aortic arch, who underwent coarctation resection and aortoplasty with autologous pulmonary artery patch in Fuwai hospital from January 2009 to June 2016 were retrospectively analyzed. The age of the patients was 4 (2, 5) months,and the body weight of the patients was (5.3±1.6) kg. The patients were followed up to observe the surgery effect. Results: No perioperative death and serious complications occurred. When the patients were discharged,the systolic blood pressure of the right upper limb was lower than the preoperative systolic blood pressure ((85.7±5.9) mmHg(1 mmHg=0.133 kPa) vs. (100.7±16.6) mmHg, P< 0.001),and the systolic blood pressure of the right lower limb was higher than the preoperative systolic blood pressure ((98.7±13.3) mmHg vs. (85.6±20.8) mmHg, P< 0.001). The pressure gradient of aortic coarctation detected by echocardiography was lower than the preoperative pressure gradient ((13.1±3.8) mmHg vs. (46.2±17.1) mmHg, P< 0.001). No restenosis was detected by echocardiography at discharge. Follow-up data were obtained in 19 patients, and the follow-up time was 18 (8, 45) months.The patients grew well, and no death occurred. Restenosis occurred in 3 cases, 1 patient underwent aortic balloon dilatation and the remaining 2 patients were under follow up observation. Computed tomography angiography showed that the morphology of aortic arch was normal without signs of aortic aneurysm. Conclusion: Coarctation resection with autologous pulmonary artery patch aortoplastystrategy is considered as a safe and effective surgical method for management of infant coarctation with hypoplastic aortic arch, and this surgery method is related with satisfactory early and mid

Genetically Engineered Lymphocyte Therapy in Treating Patients With Lymphoma That is Resistant or Refractory to Chemotherapy

ClinicalTrials.gov

2015-09-27

Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

Prevalence and correlates of hospital-based autologous blood programs: a statewide survey.

PubMed

Hull, A L; Neuhauser, D V; Goodnough, L T

1992-05-01

To identify potential barriers to use of autologous blood procurement to minimize homologous blood transfusion needs during elective surgery, the authors conducted a telephone survey of 120 blood bank directors, representing 138 Ohio hospitals. The prevalence of autologous blood procurement facilities, estimated volume of autologous blood, and attitudes and perceptions of the directors toward autologous blood predeposit programs were assessed. Analysis of the data indicated that 30% of Ohio hospitals have autologous blood procurement facilities; larger hospitals were more likely to have this facility. Overall, 5.5% of transfusions involve predeposited autologous blood. No significant differences were found according to hospital bed size or whether the hospital had a procurement facility. Blood bank directors perceived surgeons to be knowledgeable about autologous predeposit; patient demand and surgical practice were felt to be more effective in promoting the use of autologous blood at the hospital than were blood bank efforts. Directors who had autologous predeposit procurement facilities perceived that the facility provided a marketing advantage. Respondents from larger hospitals were more likely to perceive that these programs could be financially self-sufficient. The authors conclude that an economic cost-benefit analysis of hospital-based autologous blood procurement programs is important. Positive findings may influence transfusion services to adopt autologous blood procurement programs, whereas negative findings may convince hospitals that community blood donor facilities can provide better autologous blood procurement.

A novel minimally invasive, dorsolateral, tubular partial odontoidectomy and autologous bone augmentation to treat dens pseudarthrosis: cadaveric, 3D virtual simulation study and technical report.

PubMed

Archavlis, Eleftherios; Serrano, Lucas; Schwandt, Eike; Nimer, Amr; Molina-Fuentes, Moisés Felipe; Rahim, Tamim; Ackermann, Maximilian; Gutenberg, Angelika; Kantelhardt, Sven Rainer; Giese, Alf

2017-02-01

OBJECTIVE The goal of this study was to demonstrate the clinical and technical nuances of a minimally invasive, dorsolateral, tubular approach for partial odontoidectomy, autologous bone augmentation, and temporary C1-2 fixation to treat dens pseudarthrosis. METHODS A cadaveric feasibility study, a 3D virtual reality reconstruction study, and the subsequent application of this approach in 2 clinical cases are reported. Eight procedures were completed in 4 human cadavers. A minimally invasive, dorsolateral, tubular approach for odontoidectomy was performed with the aid of a tubular retraction system, using a posterolateral incision and an oblique approach angle. Fluoroscopy and postprocedural CT, using 3D volumetric averaging software, were used to evaluate the degree of bone removal of C1-2 lateral masses and the C-2 pars interarticularis. Two clinical cases were treated using the approach: a 23-year-old patient with an odontoid fracture and pseudarthrosis, and a 35-year-old patient with a history of failed conservative treatment for odontoid fracture. RESULTS At 8 cadaveric levels, the mean volumetric bone removal of the C1-2 lateral masses on 1 side was 3% ± 1%, and the mean resection of the pars interarticularis on 1 side was 2% ± 1%. The median angulation of the trajectory was 50°, and the median distance from the midline of the incision entry point on the skin surface was 67 mm. The authors measured the diameter of the working channel in relation to head positioning and assessed a greater working corridor of 12 ± 4 mm in 20° inclination, 15° contralateral rotation, and 5° lateral flexion to the contralateral side. There were no violations of the dura. The reliability of C-2 pedicle screws and C-1 lateral mass screws was 94% (15 of 16 screws) with a single lateral breach. The patients treated experienced excellent clinical outcomes. CONCLUSIONS A minimally invasive, dorsolateral, tubular odontoidectomy and autologous bone augmentation combined with C1

The effect of smoking on neutrophil/lymphocyte and platelet/lymphocyte ratio and platelet ındices: a retrospective study.

PubMed

Tulgar, Y K; Cakar, S; Tulgar, S; Dalkilic, O; Cakiroglu, B; Uyanik, B S

2016-07-01

Smoking commonly leads to death. Although the neutrophil/lymphocyte Ratio, platelet/lymphocyte ratio and platelet indices have been shown to be important for the diagnosis, prognosis and severity of some diseases, the smoking status of patients in these studies has not been well defined. In this study, we compared ratios derived from complete blood count and platelet indices to smoking status and length in smokers and non-smokers. The data of healthy males and females aged between 18-60 years who presented to our institute for a routine check-up were collected, and subjects were divided in two groups - smokers and non-smokers. The presence of medical history or laboratory results which could affect inflammatory response, formed our exclusion criteria. All complete blood count results were noted and persons' smoking habits were calculated as pack/years. White blood cell, neutrophil, basophil and eosinophil counts; mean corpuscular volume, red cell distribution width and neutrophil/lymphocyte ratio were significantly higher in smokers when compared to non-smokers (p<0.05). When smokers were grouped according to smoking habits; positive linear correlations were detected between pack/year and Neutrophil/lymphocyte ratio and also pack/year and plateletcrit in smokers (p<0.05). Neutrophil/lymphocyte ratio increases in correlation with pack/year while platelet/lymphocyte ratio is not affected and platelet distribution width is increased in smokers. If smokers are not excluded from studies evaluating neutrophil/lymphocyte ratio and platelet distribution width, the relationship between smoking status as well as pack/year must be determined and reported.

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

PubMed Central

Lipsky, Andrew H.; Farooqui, Mohammed Z.H.; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M.; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U.; Herman, Sarah E. M.; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M.; Lozier, Jay N.; Wiestner, Adrian

2015-01-01

Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733 PMID

Measurement of sulphated glycosaminoglycans production after autologous 'chondrocytes-fibrin' constructs implantation in sheep knee joint.

PubMed

Munirah, S; Samsudin, O C; Chen, H C; Salmah, S H Sharifah; Aminuddin, B S; Ruszymah, B H I

2008-07-01

Chondrocytes were isolated from articular cartilage biopsy and were cultivated in vitro. Approximately 30 million of cultured chondrocytes per ml were incorporated with autologous plasma-derived fibrin to form three-dimensional construct. Full-thickness punch hole defects were created in lateral and medial femoral condyles. The defects were implanted either with the autologous 'chondrocytes-fibrin' construct (ACFC), autologous chondrocytes (ACI) or fibrin blank (AF). Sheep were euthanized after 12 weeks. The gross morphology of all defects treated with ACFC implantation, ACI and AF exhibited median scores which correspond to a nearly normal appearance according to the International Cartilage Repair Society (ICRS) classification. ACFC significantly enhanced cartilage repair compared to ACI and AF in accordance with the modified O'Driscoll histological scoring scale. The relative sulphated glycosaminoglycans content (%) was significantly higher (p < 0.05) in ACFC when compared to control groups; ACI vs. fibrin only vs. untreated (blank). Results showed that ACFC implantation exhibited superior cartilage-like tissue regeneration compared to ACI. If the result is applicable to the human, it possibly will improve the existing treatment approaches for cartilage restoration in orthopaedic surgery.

Unicameral bone cysts: a comparison of injection of steroid and grafting with autologous bone marrow.

PubMed

Cho, H S; Oh, J H; Kim, H-S; Kang, H G; Lee, S H

2007-02-01

Open surgery is rarely justified for the initial treatment of a unicameral bone cyst, but there is some debate concerning the relative effectiveness of closed methods. This study compared the results of steroid injection with those of autologous bone marrow grafting for the treatment of unicameral bone cysts. Between 1990 and 2001, 30 patients were treated by steroid injection and 28 by grafting with autologous bone marrow. The overall success rates were 86.7% and 92.0%, respectively (p>0.05). The success rate after the initial procedure was 23.3% in the steroid group and 52.0% in those receiving autologous bone marrow (p<0.05), and the respective cumulative success rates after second injections were 63.3% and 80.0% (p>0.05). The mean number of procedures required was 2.19 (1 to 5) and 1.57 (1 to 3) (p<0.05), the mean interval to healing was 12.5 months (4 to 32) and 14.3 months (7 to 36) (p>0.05), and the rate of recurrence after the initial procedure was 41.7% and 13.3% in the steroid and in the autologous bone marrow groups, respectively (p<0.05). Although the overall rates of success of both methods were similar, the steroid group had higher recurrence after a single procedure and required more injections to achieve healing.

Comparative Efficacy of Autologous Stromal Vascular Fraction and Autologous Adipose-Derived Mesenchymal Stem Cells Combined With Hyaluronic Acid for the Treatment of Sheep Osteoarthritis.

PubMed

Lv, Xiaoteng; He, Jiyin; Zhang, Xue; Luo, Xuan; He, Na; Sun, Zhongwei; Xia, Huitang; Liu, Victor; Zhang, Li; Lin, Xiangming; Lin, Liping; Yin, Huabin; Jiang, Dong; Cao, Wei; Wang, Richard; Zhou, Guangdong; Wang, Wen

2018-01-01

The current study explored whether intra-articular (IA) injection of autologous adipose mesenchymal stem cells (ASCs) combined with hyaluronic acid (HA) achieved better therapeutic efficacy than autologous stromal vascular fraction (SVF) combined with HA to prevent osteoarthritis (OA) progression and determined how long autologous ASCs combined with HA must remain in the joint to observe efficacy. OA models were established by performing anterior cruciate ligament transection (ACLT) and medial meniscectomy (MM). Autologous SVF (1×10 7 mononuclear cells), autologous low-dose ASCs (1×10 7 ), and autologous high-dose ASCs (5×10 7 ) combined with HA, and HA alone, or saline alone were injected into the OA model animals at 12 and 15 weeks after surgery, respectively. Compared with SVF+HA treatment, low-dose ASC+HA treatment yielded better magnetic resonance imaging (MRI) scores and macroscopic results, while the cartilage thickness of the tibial plateau did not differ between low, high ASC+HA and SVF+HA treatments detected by micro-computed tomography (µCT). Immunohistochemistry revealed that high-dose ASC+HA treatment rescued hypertrophic chondrocytes expressing collagen X in the deep area of articular cartilage. Western blotting analysis indicated the high- and low-dose ASC+HA groups expressed more collagen X than did the SVF+HA group. Enzyme-linked immunosorbent assay showed treatment with both ASC+HA and SVF+HA resulted in differing anti-inflammatory and trophic effects. Moreover, superparamagnetic iron oxide particle (SPIO)-labeled autologous ASC signals were detected by MRI at 2 and 18 weeks post-injection and were found in the lateral meniscus at 2 weeks and in the marrow cavity of the femoral condyle at 18 weeks post-injection. Thus, IA injection of autologous ASC+HA may demonstrate better efficacy than autologous SVF+HA in blocking OA progression and promoting cartilage regeneration, and autologous ASCs (5×10 7 cells) combined with HA potentially survive

Treatment of chronic non-healing ulcers using autologous platelet rich plasma: a case series.

PubMed

Suthar, Manish; Gupta, Saniya; Bukhari, Suhail; Ponemone, Venkatesh

2017-02-27

Non-healing ulcers are a major health problem worldwide and have great impact at personal, professional and social levels, with high cost in terms of human and material resources. Recalcitrant non-healing ulcers are inevitable and detrimental to the lower limb and are a major cause of non-traumatic lower limb amputations. Application of autologous Platelet Rich Plasma (PRP) has been a major breakthrough for the treatment of non-healing and diabetic foot ulcers, as it is an easy and cost-effective method, and provides the necessary growth factors that enhance tissue healing. PRP is a conglomeration of thrombocytes, cytokines and various growth factors which are secreted by α-granules of platelets that augment the rate of natural healing process with decrease in time. The purpose of this case series was to evaluate the safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers on the lower extremity. Autologous PRP was prepared from whole blood utilizing a rapid, intraoperative point-of-care system that works on the principle of density gradient centrifugation. Twenty Four (24) patients with non-healing ulcers of different etiologies, who met the inclusion criteria, were treated with single dose of subcutaneous PRP injections along with topical application of PRP gel under compassionate use. The mean age of the treated patients was 62.5 ± 13.53 years and they were followed-up for a period of 24 weeks. All the patients showed signs of wound healing with reduction in wound size, and the mean time duration to ulcer healing was 8.2 weeks. Also, an average five fold increase in the platelet concentrate was observed in the final PRP product obtained using the rapid point-of-care device, and the average platelet dose administered to the patients was 70.10 × 10 8 . This case series has demonstrated the potential safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers. NCT

Case Report: Industrial X-Ray Injury Treated With Non-Cultured Autologous Adipose-Derived Stromal Vascular Fraction (SVF).

PubMed

Iddins, C J; Cohen, S R; Goans, R E; Wanat, R; Jenkins, M; Christensen, D M; Dainiak, N

2016-08-01

Local cutaneous injuries induced by ionizing radiation (IR) are difficult to treat. Many have reported local injection of adipose-derived stromal vascular fraction (SVF), often with additional therapies, as an effective treatment of IR-induced injury even after other local therapies have failed. The authors report a case of a locally recurrent, IR-induced wound that was treated with autologous, non-cultured SVF without other concurrent therapy. A nondestructive testing technician was exposed to 130 kVp x rays to his non-dominant right thumb on 5 October 2011. The wound healed 4 mo after initial conservative therapy with oral/topical α-tocopherol, oral pentoxifylline, naproxen sodium, low-dose oral steroids, topical steroids, hyperbaric oxygen therapy (HBOT), oral antihistamines, and topical aloe vera. Remission lasted approximately 17 mo with one minor relapse in July 2012 after minimal trauma and subsequent healing. Aggressive wound breakdown during June 2013 required additional therapy with HBOT. An erythematous, annular papule developed over the following 12 mo (during which time the patient was not undergoing prescribed treatment). Electron paramagnetic resonance (EPR) done more than 2 mo after exposure to IR revealed dose estimates of 14 ± 3 Gy and 19 ± 6 Gy from two centers using different EPR techniques. The patient underwent debridement of the 0.5 cm papular area, followed by SVF injection into and around the wound bed and throughout the thumb without complication. Eleven months post SVF injection, the patient has been essentially asymptomatic with an intact integument. These results raise the possibility of prolonged benefit from SVF therapy without the use of cytokines. Since there is currently no consensus on the use of isolated SVF therapy in chronic, local IR-induced injury, assessment of this approach in an appropriately powered, controlled trial in experimental animals with local radiation injury appears to be indicated.

Chimeric autologous/allogeneic constructs for skin regeneration.

PubMed

Rasmussen, Cathy Ann; Tam, Joshua; Steiglitz, Barry M; Bauer, Rebecca L; Peters, Noel R; Wang, Ying; Anderson, R Rox; Allen-Hoffmann, B Lynn

2014-08-01

The ideal treatment for severe cutaneous injuries would eliminate the need for autografts and promote fully functional, aesthetically pleasing autologous skin regeneration. NIKS progenitor cell-based skin tissues have been developed to promote healing by providing barrier function and delivering wound healing factors. Independently, a device has recently been created to "copy" skin by harvesting full-thickness microscopic tissue columns (MTCs) in lieu of autografts traditionally harvested as sheets. We evaluated the feasibility of combining these two technologies by embedding MTCs in NIKS-based skin tissues to generate chimeric autologous/allogeneic constructs. Chimeric constructs have the potential to provide immediate wound coverage, eliminate painful donor site wounds, and promote restoration of a pigmented skin tissue possessing hair follicles, sweat glands, and sebaceous glands. After MTC insertion, chimeric constructs and controls were reintroduced into air-interface culture and maintained in vitro for several weeks. Tissue viability, proliferative capacity, and morphology were evaluated after long-term culture. Our results confirmed successful MTC insertion and integration, and demonstrated the feasibility of generating chimeric autologous/allogeneic constructs that preserved the viability, proliferative capacity, and structure of autologous pigmented skin. These feasibility studies established the proof-of-principle necessary to further develop chimeric autologous/allogeneic constructs for the treatment of complex skin defects. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Epstein-Barr virus-transformed B-cells as efficient antigen presenting cells to propagate Aspergillus-specific cytotoxic T-lymphocytes.

PubMed

Ramadan, Gamal

2008-01-01

To overcome the cytotoxic T-lymphocytes (CTL) expansion limitations imposed by the lack of sufficient dendritic cells (DC) alternative sources of autologous antigen presenting cells (APC) such as Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell lines (BLCL), which are easy to establish in vitro, have been considered and studied in the present work. Non-adherent peripheral blood mononuclear cells of three healthy donors were repeatedly primed with autologous Aspergillus fumigatus commercial culture-filtrate antigen-pulsed fast monocyte-derived DC (Aspf-CFA-DC) alone, Aspf-CFA-pulsed BLCL (Aspf-CFA-BLCL) alone or Aspf-CFA-BLCL after one, two, or three primings with Aspf-CFA-DC (1DC/BLCL, 2DC/BLCL or 3DCIBLCL; respectively). After 5th priming, lines generated by Aspf-CFA-BLCL only showed strong/weak lytic activity for EBV/Aspf; respectively. Aspf-specific lytic activity in all donors was increased by increasing the number of primings with Aspf-CFA-DC before switching to Aspf-CFA-BLCL (18.20 +/- 1.65% versus 35.67 +/- 1.02% and 40.03 +/- 1.41% in bulk cultures generated by 1DC/BLCL versus 2DC/BLCL and 3DC/BLCL, respectively). Bulk cultures generated by Aspf-CFA-BLCL after at least two primings with Aspf-CFA-DC showed approximately the same Aspf-specific lytic activity, effector cell phenotype, expansion level and percentage expression of IFN-gamma, CD69 and CD107a without any significant differences (p > 0.05) as standard bulk cultures generated by only Aspf-CFA-DC. Thus, this study explored the use of a combined DC/BLCL protocol to establish/propagate Aspf-specific CTL for adoptive immunotherapy to prevent or treat invasive pulmonary aspergillosis.

Outcome of Burns Treated With Autologous Cultured Proliferating Epidermal Cells: A Prospective Randomized Multicenter Intrapatient Comparative Trial.

PubMed

Gardien, Kim L M; Marck, Roos E; Bloemen, Monica C T; Waaijman, Taco; Gibbs, Sue; Ulrich, Magda M W; Middelkoop, Esther

2016-01-01

Standard treatment for large burns is transplantation with meshed split skin autografts (SSGs). A disadvantage of this treatment is that healing is accompanied by scar formation. Application of autologous epidermal cells (keratinocytes and melanocytes) may be a suitable therapeutic alternative, since this may enhance wound closure and improve scar quality. A prospective, multicenter randomized clinical trial was performed in 40 adult patients with acute full thickness burns. On two comparable wound areas, conventional treatment with SSGs was compared to an experimental treatment consisting of SSGs in combination with cultured autologous epidermal cells (ECs) seeded in a collagen carrier. The primary outcome measure was wound closure after 5-7 days. Secondary outcomes were safety aspects and scar quality measured by graft take, scar score (POSAS), skin colorimeter (DermaSpectrometer) and elasticity (Cutometer). Wound epithelialization after 5-7 days was significantly better for the experimental treatment (71%) compared to the standard treatment (67%) (p = 0.034, Wilcoxon), whereas the take rates of the grafts were similar. No related adverse events were recorded. Scar quality was evaluated at 3 (n = 33) and 12 (n = 28) months. The POSAS of the observer after 3 and 12 months and of the patient after 12 months were significantly better for the experimental area. Improvements between 12% and 23% (p ≤ 0.010, Wilcoxon) were detected for redness, pigmentation, thickness, relief, and pliability. Melanin index at 3 and 12 months and erythema index at 12 months were closer to normal skin for the experimental treatment than for conventional treatment (p ≤ 0.025 paired samples t-test). Skin elasticity showed significantly higher elasticity (p = 0.030) in the experimental area at 3 months follow-up. We showed a safe application and significant improvements of wound healing and scar quality in burn patients after treatment with ECs versus SSGs only

Allogeneic hematopoietic cell transplantation after failed autologous transplant for lymphoma using TLI and anti-thymocyte globulin conditioning.

PubMed

Rezvani, A R; Kanate, A S; Efron, B; Chhabra, S; Kohrt, H E; Shizuru, J A; Laport, G G; Miklos, D B; Benjamin, J E; Johnston, L J; Arai, S; Weng, W-K; Negrin, R S; Strober, S; Lowsky, R

2015-10-01

We describe 47 patients with lymphoma and failed prior autologous hematopoietic cell transplantation (HCT) who received TLI-ATG (anti-thymocyte globulin) conditioning followed by allogeneic HCT. Thirty-two patients had non-Hodgkin lymphoma (NHL; diffuse large B-cell lymphoma (n=19), T-cell NHL (n=6), mantle cell lymphoma (n=4) or other B-cell subtypes (n=3)), and 15 had Hodgkin lymphoma. The median follow-up was 4.9 (range, 2.1-11.9) years. The cumulative incidence of grade II-IV acute GvHD at day +100 was 12%, and the cumulative incidence of extensive chronic GvHD at 1 year was 36%. The 3-year cumulative incidences of overall survival (OS), PFS and non-relapse mortality (NRM) were 81%, 44% and 7%, respectively. Fifteen patients died (relapse, n=10; NRM, n=5). Among the 25 patients with relapse after allogeneic HCT, 11 (44%) achieved durable (>1 year) CRs following donor lymphocyte infusion or chemoradiotherapy. The majority of surviving patients (75%; n=24) were able to discontinue all immunosuppression. For patients with relapsed lymphoma after autologous HCT, allogeneic HCT using TLI-ATG conditioning is a well-tolerated, predominantly outpatient therapy with low NRM (7% at 3 years), a low incidence of GvHD, durable disease control and excellent OS (81% at 3 years).

Neutrophil-to-lymphocyte Ratio, Platelet-to-lymphocyte Ratio, and C-reactive Protein as New and Simple Prognostic Factors in Patients With Metastatic Renal Cell Cancer Treated With Tyrosine Kinase Inhibitors: A Systemic Review and Meta-analysis.

PubMed

Semeniuk-Wojtaś, Aleksandra; Lubas, Arkadiusz; Stec, Rafał; Syryło, Tomasz; Niemczyk, Stanisław; Szczylik, Cezary

2018-02-02

Inflammation plays a crucial role in cancer development. In this study, we evaluate the prognostic values of systemic inflammation markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) for the progression-free survival and overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. PubMed and the Cochrane Library databases were searched for published studies on the effect of NLR, PLR, and CRP in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. In the meta-analysis, NLR (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.27-3.18; P = .003) and PLR (HR, 6.96; 95% CI, 5.04-9.62; P < .001) had a significant influence on progression-free survival, whereas all considered proinflammatory markers had a significant impact on overall survival: NLR (HR, 2.14; 95% CI, 1.67-2.73; P < .001), PLR (HR, 14.67; 95% CI, 11.10-19.57; P < .001), and CRP (HR, 1.96; 95% CI, 1.26-3.05; P = .003). Inflammation markers such as NLR, PLR, and CRP are predictors of clinical outcome and could provide additional information to individualize treatment. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Chromosomal aberrations in lymphocytes of employees in transformer and generator production exposed to electromagnetic fields and mineral oil.

PubMed

Skyberg, K; Hansteen, I L; Vistnes, A I

2001-04-01

The objective was to study the risk of cytogenetic damage among high voltage laboratory workers exposed to electromagnetic fields and mineral oil. This is a cross sectional study of 24 exposed and 24 matched controls in a Norwegian transformer factory. The exposure group included employees in the high voltage laboratory and in the generator soldering department. Electric and magnetic fields and oil mist and vapor were measured. Blood samples were analyzed for chromosomal aberrations in cultured lymphocytes. In addition to conventional cultures, the lymphocytes were also treated with hydroxyurea and caffeine. This procedure inhibits DNA synthesis and repair in vitro, revealing in vivo genotoxic lesions that are repaired during conventional culturing. In conventional cultures, the exposure group and the controls showed similar values for all cytogenetic parameters. In the DNA synthesis- and repair-inhibited cultures, generator welders showed no differences compared to controls. Among high voltage laboratory testers, compared to the controls, the median number of chromatid breaks was doubled (5 vs. 2.5 per 50 cells; P<0.05) the median number of chromosome breaks was 2 vs. 0.5 (P>0.05) and the median number of aberrant cells was 5 vs. 3.5 (P<0.05). Further analysis of the inhibited culture data from this and a previous study indicated that years of exposure and smoking increase the risk of aberrations. We conclude that there was no increase in cytogenetic damage among exposed workers compared to controls in the conventional lymphocyte assay. In inhibited cultures, however, there were indications that electromagnetic fields in combination with mineral oil exposure may produce chromosomal aberrations. Copyright 2001 Wiley-Liss, Inc.

Nanofat-derived stem cells with platelet-rich fibrin improve facial contour remodeling and skin rejuvenation after autologous structural fat transplantation

PubMed Central

Liang, Zhi-Jie; Chen, Hai; Zhu, Mao-Guang; Xu, Fang-Tian; He, Ning; Wei, Xiao-Juan; Li, Hong-Mian

2017-01-01

Traditional autologous fat transplantation is a common surgical procedure for treating facial soft tissue depression and skin aging. However, the transplanted fat is easily absorbed, reducing the long-term efficacy of the procedure. Here, we examined the efficacy of nanofat-assisted autologous fat structural transplantation. Nanofat-derived stem cells (NFSCs) were isolated, mechanically emulsified, cultured, and characterized. Platelet-rich fibrin (PRF) enhanced proliferation and adipogenic differentiation of NFSCs in vitro. We then compared 62 test group patients with soft tissue depression or signs of aging who underwent combined nanofat, PRF, and autologous fat structural transplantation to control patients (77 cases) who underwent traditional autologous fat transplantation. Facial soft tissue depression symptoms and skin texture were improved to a greater extent after nanofat transplants than after traditional transplants, and the nanofat group had an overall satisfaction rate above 90%. These data suggest that NFSCs function similarly to mesenchymal stem cells and share many of the biological characteristics of traditional fat stem cell cultures. Transplants that combine newly-isolated nanofat, which has a rich stromal vascular fraction (SVF), with PRF and autologous structural fat granules may therefore be a safe, highly-effective, and long-lasting method for remodeling facial contours and rejuvenating the skin. PMID:28978136

Metformin Hydrochloride and Ritonavir in Treating Patients With Relapsed or Refractory Multiple Myeloma or Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2018-03-22

Anemia; Fatigue; Fever; Lymphadenopathy; Lymphocytosis; Night Sweats; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Refractory Chronic Lymphocytic Leukemia; Refractory Plasma Cell Myeloma; Splenomegaly; Thrombocytopenia; Weight Loss

Autologous bone graft versus demineralized bone matrix in internal fixation of ununited long bones.

PubMed

Pieske, Oliver; Wittmann, Alexandra; Zaspel, Johannes; Löffler, Thomas; Rubenbauer, Bianka; Trentzsch, Heiko; Piltz, Stefan

2009-12-15

Non-unions are severe complications in orthopaedic trauma care and occur in 10% of all fractures. The golden standard for the treatment of ununited fractures includes open reduction and internal fixation (ORIF) as well as augmentation with autologous-bone-grafting. However, there is morbidity associated with the bone-graft donor site and some patients offer limited quantity or quality of autologous-bone graft material. Since allogene bone-grafts are introduced on the market, this comparative study aims to evaluate healing characteristics of ununited bones treated with ORIF combined with either iliac-crest-autologous-bone-grafting (ICABG) or demineralized-bone-matrix (DBM). From 2000 to 2006 out of sixty-two consecutive patients with non-unions presenting at our Level I Trauma Center, twenty patients had ununited diaphyseal fractures of long bones and were treated by ORIF combined either by ICABG- (n = 10) or DBM-augmentation (n = 10). At the time of index-operation, patients of the DBM-group had a higher level of comorbidity (ASA-value: p = 0.014). Mean duration of follow-up was 56.6 months (ICABG-group) and 41.2 months (DBM-group). All patients were clinically and radiographically assessed and adverse effects related to bone grafting were documented. The results showed that two non-unions augmented with ICABG failed osseous healing (20%) whereas all non-unions grafted by DBM showed successful consolidation during the first year after the index operation (p = 0.146). No early complications were documented in both groups but two patients of the ICABG-group suffered long-term problems at the donor site (20%) (p = 0.146). Pain intensity were comparable in both groups (p = 0.326). However, patients treated with DBM were more satisfied with the surgical procedure (p = 0.031). With the use of DBM, the costs for augmentation of the non-union-site are more expensive compared to ICABG (calculated difference: 160 euro/case). Nevertheless, this study demonstrated that the

Simplified Screening Approach Identifies Mutated Proteins Expressed in Patient Tumors | Center for Cancer Research

Cancer.gov

Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) is a very effective treatment for patients with metastatic melanoma. In phase 2 clinical trials, up to 70 percent of patients with melanoma who received autologous TILs had considerable regressions of metastatic lesions. Recently, in another trial, 40 percent of patients treated had complete regressions of all

Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial.

PubMed

Chen, Fa-Ming; Gao, Li-Na; Tian, Bei-Min; Zhang, Xi-Yu; Zhang, Yong-Jie; Dong, Guang-Ying; Lu, Hong; Chu, Qing; Xu, Jie; Yu, Yang; Wu, Rui-Xin; Yin, Yuan; Shi, Songtao; Jin, Yan

2016-02-19

Periodontitis, which progressively destroys tooth-supporting structures, is one of the most widespread infectious diseases and the leading cause of tooth loss in adults. Evidence from preclinical trials and small-scale pilot clinical studies indicates that stem cells derived from periodontal ligament tissues are a promising therapy for the regeneration of lost/damaged periodontal tissue. This study assessed the safety and feasibility of using autologous periodontal ligament stem cells (PDLSCs) as an adjuvant to grafting materials in guided tissue regeneration (GTR) to treat periodontal intrabony defects. Our data provide primary clinical evidence for the efficacy of cell transplantation in regenerative dentistry. We conducted a single-center, randomized trial that used autologous PDLSCs in combination with bovine-derived bone mineral materials to treat periodontal intrabony defects. Enrolled patients were randomly assigned to either the Cell group (treatment with GTR and PDLSC sheets in combination with Bio-oss(®)) or the Control group (treatment with GTR and Bio-oss(®) without stem cells). During a 12-month follow-up study, we evaluated the frequency and extent of adverse events. For the assessment of treatment efficacy, the primary outcome was based on the magnitude of alveolar bone regeneration following the surgical procedure. A total of 30 periodontitis patients aged 18 to 65 years (48 testing teeth with periodontal intrabony defects) who satisfied our inclusion and exclusion criteria were enrolled in the study and randomly assigned to the Cell group or the Control group. A total of 21 teeth were treated in the Control group and 20 teeth were treated in the Cell group. All patients received surgery and a clinical evaluation. No clinical safety problems that could be attributed to the investigational PDLSCs were identified. Each group showed a significant increase in the alveolar bone height (decrease in the bone-defect depth) over time (p < 0.001). However

Assessing commercial opportunities for autologous and allogeneic cell-based products.

PubMed

Smith, Devyn M

2012-09-01

The two primary cell sources used to produce cell-based therapies are autologous (self-derived) and allogeneic (derived from a donor). This analysis attempts to compare and contrast the two approaches in order to understand whether there is an emerging preference in the market. While the current clinical trials underway are slightly biased to autologous approaches, it is clear that both cell-based approaches are being aggressively pursued. This analysis also breaks down the commercial advantages of each cell-based approach, comparing both cost of goods and the ideal indication type for each. While allogeneic therapies have considerable advantages over autologous therapies, they do have a distinct disadvantage regarding potential immunogenicity. The introduction of the hybrid autologous business model provides the ability for autologous-based therapies to mitigate some of the advantages that allogeneic cell-based therapies enjoy, including cost of goods. Finally, two case studies are presented that demonstrate that there is sufficient space for both autologous and allogeneic cell-based therapies within a single disease area.

Lymphocyte apheresis for chimeric antigen receptor T-cell manufacturing in children and young adults with leukemia and neuroblastoma.

PubMed

Ceppi, Francesco; Rivers, Julie; Annesley, Colleen; Pinto, Navin; Park, Julie R; Lindgren, Catherine; Mgebroff, Stephanie; Linn, Naomi; Delaney, Meghan; Gardner, Rebecca A

2018-06-01

The first step in the production of chimeric antigen receptor T cells is the collection of autologous T cells using apheresis technology. The procedure is technically challenging, because patients often have low leukocyte counts and are heavily pretreated with multiple lines of chemotherapy, marrow transplantation, and/or radiotherapy. Here, we report our experience of collecting T lymphocytes for chimeric antigen receptor T-cell manufacturing in pediatric and young adult patients with leukemia, non-Hodgkin lymphoma, or neuroblastoma. Apheresis procedures were performed on a COBE Spectra machine using the mononuclear cell program, with a collection target of 1 × 10 9 total mononuclear cells per kilogram. Data were collected regarding preapheresis and postapheresis blood counts, apheresis parameters, products, and adverse events. Ninety-nine patients (ages 1.3-25.7 years) and 102 apheresis events were available for analysis. Patients underwent apheresis at a variety of absolute lymphocyte cell counts, with a median absolute lymphocyte count of 944 cells/μL (range, 142-6944 cells/μL). Twenty-two patients (21.6%) had absolute lymphocyte counts less than 500 cells/μL. The mononuclear cell target was obtained in 100% of all apheresis harvests, and chimeric antigen receptor T-cell production was possible from the majority of collections (94%). Mononuclear cell collection efficiency was 65.4%, and T-lymphocyte collection efficiency was 83.4%. Ten patients (9.8%) presented with minor adverse events during the 102 apheresis procedures, with one exception of a severe allergy. Mononuclear cell apheresis for chimeric antigen receptor T-cell therapy is well tolerated and safe, and it is possible to obtain an adequate quantity of CD3+ lymphocytes for chimeric antigen receptor T-cell manufacturing in heavily pretreated patients who have low lymphocyte counts. © 2018 AABB.

Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study.

PubMed

Chanan-Khan, Asher; Cramer, Paula; Demirkan, Fatih; Fraser, Graeme; Silva, Rodrigo Santucci; Grosicki, Sebastian; Pristupa, Aleksander; Janssens, Ann; Mayer, Jiri; Bartlett, Nancy L; Dilhuydy, Marie-Sarah; Pylypenko, Halyna; Loscertales, Javier; Avigdor, Abraham; Rule, Simon; Villa, Diego; Samoilova, Olga; Panagiotidis, Panagiots; Goy, Andre; Mato, Anthony; Pavlovsky, Miguel A; Karlsson, Claes; Mahler, Michelle; Salman, Mariya; Sun, Steven; Phelps, Charles; Balasubramanian, Sriram; Howes, Angela; Hallek, Michael

2016-02-01

Most patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma relapse after initial therapy. Bendamustine plus rituximab is often used in the relapsed or refractory setting. We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma. The HELIOS trial was an international, double-blind, placebo-controlled, phase 3 study in adult patients (≥18 years of age) who had active chronic lymphocytic leukaemia or small lymphocytic lymphoma with measurable lymph node disease (>1·5 cm) by CT scan, and had relapsed or refractory disease following one or more previous lines of systemic therapy consisting of at least two cycles of a chemotherapy-containing regimen, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate bone marrow, liver, and kidney function. Patients with del(17p) were excluded because of known poor response to bendamustine plus rituximab. Patients who had received previous treatment with ibrutinib or other BTK inhibitors, refractory disease or relapse within 24 months with a previous bendamustine-containing regimen, or haemopoietic stem-cell transplant were also excluded. Patients were randomly assigned (1:1) by a web-based system to receive bendamustine plus rituximab given in cycles of 4 weeks' duration (bendamustine: 70 mg/m(2) intravenously on days 2-3 in cycle 1, and days 1-2 in cycles 2-6; rituximab: 375 mg/m(2) on day 1 of cycle 1, and 500 mg/m(2) on day 1 of cycles 2-6 for a maximum of six cycles) with either ibrutinib (420 mg daily orally) or placebo until disease progression or unacceptable toxicity. Patients were stratified according to whether they were refractory to purine analogues and by number of previous lines of therapy. The primary endpoint was independent review committee (IRC)-assessed progression

Modulation of radiation-induced and mitomycin C-induced chromosome damage by apigenin in human lymphocytes in vitro.

PubMed

Sharma, Narinder K

2013-09-01

Apigenin (APG), a flavone, is known to exhibit antioxidant, antimutagenic and antitumorigenic activity, both in vivo and in vitro. The aim of this study is to investigate the modulatory effects of APG on human lymphocytes after irradiation with gamma rays (3 Gy) or treatment with the antineoplastic agent, mitomycin C (MMC), in vitro. Cytogenetic biomarkers such as chromosome aberrations (CAs), sister chromatid exchanges (SCEs) and cytochalasin-B blocked micronuclei (CBMN), were studied in blood lymphocytes treated with radiation, or antineoplastic agent (MMC), and APG. Whole blood lymphocytes were cultured in vitro using a standard protocol. No significant differences were found in the frequency of CAs or micronuclei (MN) in human peripheral blood lymphocytes irradiated with gamma rays (3 Gy) and then post-treated with APG. There was an increase in the frequency of SCEs per cell in APG-treated samples compared with the controls. Lymphocytes treated with MMC in the presence of APG exhibited a significant decrease (P < 0.01) in the frequency of SCEs compared with MMC treatment alone. The data for the MN test indicated that APG treatment significantly reduced (P < 0.01) the frequency of MMC-induced MN.

Modulation of radiation-induced and mitomycin C-induced chromosome damage by apigenin in human lymphocytes in vitro

PubMed Central

Sharma, Narinder K.

2013-01-01

Apigenin (APG), a flavone, is known to exhibit antioxidant, antimutagenic and antitumorigenic activity, both in vivo and in vitro. The aim of this study is to investigate the modulatory effects of APG on human lymphocytes after irradiation with gamma rays (3 Gy) or treatment with the antineoplastic agent, mitomycin C (MMC), in vitro. Cytogenetic biomarkers such as chromosome aberrations (CAs), sister chromatid exchanges (SCEs) and cytochalasin-B blocked micronuclei (CBMN), were studied in blood lymphocytes treated with radiation, or antineoplastic agent (MMC), and APG. Whole blood lymphocytes were cultured in vitro using a standard protocol. No significant differences were found in the frequency of CAs or micronuclei (MN) in human peripheral blood lymphocytes irradiated with gamma rays (3 Gy) and then post-treated with APG. There was an increase in the frequency of SCEs per cell in APG-treated samples compared with the controls. Lymphocytes treated with MMC in the presence of APG exhibited a significant decrease (P < 0.01) in the frequency of SCEs compared with MMC treatment alone. The data for the MN test indicated that APG treatment significantly reduced (P < 0.01) the frequency of MMC-induced MN. PMID:23764456

Effective regeneration of dystrophic muscle using autologous iPSC-derived progenitors with CRISPR-Cas9 mediated precise correction.

PubMed

Hagan, Mackenzie; Ashraf, Muhammad; Kim, Il-Man; Weintraub, Neal L; Tang, Yaoliang

2018-01-01

Duchenne muscular dystrophy (DMD) is a lethal muscle wasting disease caused by a lack of dystrophin, which eventually leads to apoptosis of muscle cells and impaired muscle contractility. Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9) gene editing of induced pluripotent stem cells (IPSC) offers the potential to correct the DMD gene defect and create healthy IPSC for autologous cell transplantation without causing immune activation. However, IPSC carry a risk of tumor formation, which can potentially be mitigated by differentiation of IPSC into myogenic progenitor cells (MPC). We hypothesize that precise genetic editing in IPSC using CRISPR-Cas9 technology, coupled with MPC differentiation and autologous transplantation, can lead to safe and effective muscle repair. With future research, our hypothesis may provide an optimal autologous stem cell-based approach to treat the dystrophic pathology and improve the quality of life for patients with DMD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protective effect of hawthorn extract against genotoxicity induced by methyl methanesulfonate in human lymphocytes.

PubMed

Hosseinimehr, Seyed Jalal; Azadbakht, Mohammad; Tanha, Mohammad; Mahmodzadeh, Aziz; Mohammadifar, Sohila

2011-05-01

The preventive effect of hawthorn (Crataegus microphylla) fruit extract against genotoxicity induced by methyl methanesulfonate (MMS) has been investigated in human cultured blood lymphocytes. Peripheral blood samples were collected from human volunteers at 0 (10 minutes before), and at 1 and 2 hours after a single oral ingestion of 1 g hawthorn powder extract. At each time point, the whole blood was treated in vitro with MMS (200 µmol) at 24 hours after cell culture, and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cells. The lymphocytes treated with hawthorn and MMS to exhibit a significant decreasing in the incidence of micronucleated binucleated cells, as compared with similarly MMS-treated lymphocytes from blood samples collected at 0 hour. The maximum protection and decreasing in frequency of micronuclei (36%) was observed at 1 hour after ingestion of hawthorn extract. The high performance liquid chromatography (HPLC) analysis showed that hawthorn contained chlorogenic acid, epicatechin and hyperoside. It is obvious that hawthorn, particularly flavonoids constituents with antioxidative activity, reduced the oxidative stress and genotoxicity induced by toxic compounds. This set of data may have an important application for the protection of human lymphocyte from the genetic damage and side effects induced by chemicals hazardous in people.

Methodological considerations for implementation of lymphocyte subset analysis in a clinical reference laboratory.

PubMed

Muirhead, K A; Wallace, P K; Schmitt, T C; Frescatore, R L; Franco, J A; Horan, P K

1986-01-01

As the diagnostic utility of lymphocyte subset analysis has been recognized in the clinical research laboratory, a wide variety of reagents and cell preparation, staining and analysis methods have also been described. Methods that are perfectly suitable for analysis of smaller sample numbers in the biological or clinical research setting are not always appropriate and/or applicable in the setting of a high volume clinical reference laboratory. We describe here some of the specific considerations involved in choosing a method for flow cytometric analysis which minimizes sample preparation and data analysis time while maximizing sample stability, viability, and reproducibility. Monoclonal T- and B-cell reagents from three manufacturers were found to give equivalent results for a reference population of healthy individuals. This was true whether direct or indirect immunofluorescence staining was used and whether cells were prepared by Ficoll-Hypaque fractionation (FH) or by lysis of whole blood. When B cells were enumerated using a polyclonal anti-immunoglobulin reagent, less cytophilic immunoglobulin staining was present after lysis than after FH preparation. However, both preparation methods required additional incubation at 37 degrees C to obtain results concordant with monoclonal B-cell reagents. Standard reagents were chosen on the basis of maximum positive/negative separation and the availability of appropriate negative controls. The effects of collection medium and storage conditions on sample stability and reproducibility of subset analysis were also assessed. Specimens collected in heparin and stored at room temperature in buffered medium gave reproducible results for 3 days after specimen collection, using either FH or lysis as the preparation method. General strategies for instrument optimization, quality control, and biohazard containment are also discussed.

[Adoptive transfer of Epstein-Barr virus-specific T-lymphocytes in chronic active Epstein-Barr infection].

PubMed

Babel, N; Hammer, M H; Reinke, P

2003-03-14

A 27-year-old man was admitted because of intermittent fever, fatigue, lymphadenopathy and splenomegaly for 20 years. Chronic administration of 6 - 8 g aspirin per day (self-prescribed) resulted in limited control of symptoms and in the development of analgesic nephropathy. The patient had prominent splenomegaly and lymphadenopathy without histological signs of malignancy. Monocytosis and T-lymphopenia were also present. Infectious disease testing revealed IgG+/IgM- EBV serology and EA-EBV-mRNA nested PCR clearly demonstrated the presence of lytic EBV-proteins in PBMCs. As chronic active Epstein-Barr virus infection (CAEBV) was highly probable, treatment with aciclovir, gancilovir and steroids was started. Because treatment failed adoptive T-cell transfer with autologous EBV-specific T-cells was performed. After three consecutive infusions the patient responded with a complete remission of fever, fatigue, lymphadenopathy and splenomegaly without adverse effects. Retrospective real-time PCR analysis showed a decrease in viral load from 62847 copies/ microg DNA to 45 - 250 copies after treatment. The patient remains in stable remission without signs of CAEBV (> 4 years). Adoptive transfer of autologous, EBV-specific T-lymphocytes is a promising treatment in CAEBV.

Human monocyte-derived suppressor cells control graft-versus-host disease by inducing regulatory forkhead box protein 3-positive CD8+ T lymphocytes.

PubMed

Janikashvili, Nona; Trad, Malika; Gautheron, Alexandrine; Samson, Maxime; Lamarthée, Baptiste; Bonnefoy, Francis; Lemaire-Ewing, Stéphanie; Ciudad, Marion; Rekhviashvili, Khatuna; Seaphanh, Famky; Gaugler, Béatrice; Perruche, Sylvain; Bateman, Andrew; Martin, Laurent; Audia, Sylvain; Saas, Philippe; Larmonier, Nicolas; Bonnotte, Bernard

2015-06-01

Adoptive transfer of immunosuppressive cells has emerged as a promising strategy for the treatment of immune-mediated disorders. However, only a limited number of such cells can be isolated from in vivo specimens. Therefore efficient ex vivo differentiation and expansion procedures are critically needed to produce a clinically relevant amount of these suppressive cells. We sought to develop a novel, clinically relevant, and feasible approach to generate ex vivo a subpopulation of human suppressor cells of monocytic origin, referred to as human monocyte-derived suppressive cells (HuMoSCs), which can be used as an efficient therapeutic tool to treat inflammatory disorders. HuMoSCs were generated from human monocytes cultured for 7 days with GM-CSF and IL-6. The immune-regulatory properties of HuMoSCs were investigated in vitro and in vivo. The therapeutic efficacy of HuMoSCs was evaluated by using a graft-versus-host disease (GvHD) model of humanized mice (NOD/SCID/IL-2Rγc(-/-) [NSG] mice). CD33+ HuMoSCs are highly potent at inhibiting the proliferation and activation of autologous and allogeneic effector T lymphocytes in vitro and in vivo. The suppressive activity of these cells depends on signal transducer and activator of transcription 3 activation. Of therapeutic relevance, HuMoSCs induce long-lasting memory forkhead box protein 3-positive CD8+ regulatory T lymphocytes and significantly reduce GvHD induced with human PBMCs in NSG mice. Ex vivo-generated HuMoSCs inhibit effector T lymphocytes, promote the expansion of immunosuppressive forkhead box protein 3-positive CD8+ regulatory T cells, and can be used as an efficient therapeutic tool to prevent GvHD. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Scintigraphic detection of carotid atherosclerosis with indium-111-labeled autologous platelets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davis, H.H.; Siegel, B.A.; Sherman, L.A.

1980-05-01

Using autologous platelets labeled with indium-111-oxine, we studied the localization of platelets on arterial lesions by radionuclide scintigraphy in 34 patients with suspected cerebrovascular disease. The imaging results were compared with the findings of contrast angiography in 23 patients, 16 of whom were receiving antiplatelet and/or anticoagulant drugs during the platelet imaging study. Angiography demonstrated atherosclerotic lesions at 33 sites in the extracranial arteries of 16 of these patients. There was accumulation of /sup 111/In-platelets at 20 of these sites (61%) and at three other sites without definite angiographic abnormalities. Lesions with stenoses <50% were slightly more frequent than thosemore » with greater stenosis (68% vs 45%). The frequency of true-positive scintigraphic results was slightly higher in patients not treated with antithrombotic agents than in those on such drugs (70% vs 57%). Our results suggest that imaging with /sup 111/In-labeled autologous platelets may be useful for evaluating the pathophysiologic characteristics of atherosclerotic lesions in patients with cerebrovascular disease.« less

Synergistic action of protease-modulating matrix and autologous growth factors in healing of diabetic foot ulcers. A prospective randomized trial.

PubMed

Kakagia, Despoina D; Kazakos, Konstantinos J; Xarchas, Konstantinos C; Karanikas, Michael; Georgiadis, George S; Tripsiannis, Gregory; Manolas, Constantinos

2007-01-01

This study tests the hypothesis that addition of a protease-modulating matrix enhances the efficacy of autologous growth factors in diabetic ulcers. Fifty-one patients with chronic diabetic foot ulcers were managed as outpatients at the Democritus University Hospital of Alexandroupolis and followed up for 8 weeks. All target ulcers were > or = 2.5 cm in any one dimension and had been previously treated only with moist gauze. Patients were randomly allocated in three groups of 17 patients each: Group A was treated only with the oxidized regenerated cellulose/collagen biomaterial (Promogran, Johnson & Johnson, New Brunswick, NJ), Group B was treated only with autologous growth factors delivered by Gravitational Platelet Separation System (GPS, Biomet), and Group C was managed by a combination of both. All ulcers were digitally photographed at initiation of the study and then at change of dressings once weekly. Computerized planimetry (Texas Health Science Center ImageTool, Version 3.0) was used to assess ulcer dimensions that were analyzed for homogeneity and significance using the Statistical Package for Social Sciences, Version 13.0. Post hoc analysis revealed that there was significantly greater reduction of all three dimensions of the ulcers in Group C compared to Groups A and B (all P<.001). Although reduction of ulcer dimensions was greater in Group A than in Group B, these differences did not reach statistical significance. It is concluded that protease-modulating dressings act synergistically with autologous growth factors and enhance their efficacy in diabetic foot ulcers.

Beneficial Effects of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Naturally Occurring Tendinopathy

PubMed Central

Smith, Roger Kenneth Whealands; Werling, Natalie Jayne; Dakin, Stephanie Georgina; Alam, Rafiqul; Goodship, Allen E.; Dudhia, Jayesh

2013-01-01

Tendon injuries are a common age-related degenerative condition where current treatment strategies fail to restore functionality and normal quality of life. This disease also occurs naturally in horses, with many similarities to human tendinopathy making it an ideal large animal model for human disease. Regenerative approaches are increasingly used to improve outcome involving mesenchymal stem cells (MSCs), supported by clinical data where injection of autologous bone marrow derived MSCs (BM-MSCs) suspended in marrow supernatant into injured tendons has halved the re-injury rate in racehorses. We hypothesized that stem cell therapy induces a matrix more closely resembling normal tendon than the fibrous scar tissue formed by natural repair. Twelve horses with career-ending naturally-occurring superficial digital flexor tendon injury were allocated randomly to treatment and control groups. 1X107 autologous BM-MSCs suspended in 2 ml of marrow supernatant were implanted into the damaged tendon of the treated group. The control group received the same volume of saline. Following a 6 month exercise programme horses were euthanized and tendons assessed for structural stiffness by non-destructive mechanical testing and for morphological and molecular composition. BM-MSC treated tendons exhibited statistically significant improvements in key parameters compared to saline-injected control tendons towards that of normal tendons and those in the contralateral limbs. Specifically, treated tendons had lower structural stiffness (p<0.05) although no significant difference in calculated modulus of elasticity, lower (improved) histological scoring of organisation (p<0.003) and crimp pattern (p<0.05), lower cellularity (p<0.007), DNA content (p<0.05), vascularity (p<0.03), water content (p<0.05), GAG content (p<0.05), and MMP-13 activity (p<0.02). Treatment with autologous MSCs in marrow supernatant therefore provides significant benefits compared to untreated tendon repair in

Evaluation of subcutaneous infiltration of autologous platelet-rich plasma on skin-wound healing in dogs

PubMed Central

Farghali, Haithem A.; AbdElKader, Naglaa A.; Khattab, Marwa S.

2017-01-01

Platelet-rich plasma (PRP) is known to be rich in growth factors and cytokines, which are crucial to the healing process. This study investigate the effect of subcutaneous (S/C) infiltration of autologous PRP at the wound boundaries on wound epithelization and contraction. Five adult male mongrel dogs were used. Bilateral acute full thickness skin wounds (3 cm diameter) were created on the thorax symmetrically. Right side wounds were subcutaneously infiltrated with activated PRP at day 0 and then every week for three consecutive weeks. The left wound was left as control. Wound contraction and epithelization were clinically evaluated. Expression of collagen type I (COLI) A2, (COLIA2),histopathology and immunohistochemical (IHC) staining of COLI α1 (COLIA1) were performed on skin biopsies at first, second and third weeks. The catalase activity, malondialdehyde (MDA) concentration and matrix metalloproteinase (MMP) 9 (MMP-9) activity were assessed in wound fluid samples. All data were analysed statistically. The epithelization percent significantly increased in the PRP-treated wound at week 3. Collagen was well organized in the PRP-treated wounds compared with control wounds at week 3. The COLIA2 expression and intensity of COLIA1 significantly increased in PRP-treated wounds. MDA concentration was significantly decreased in PRP-treated wound at week 3. The catalase activity exhibited no difference between PRP treated and untreated wounds. The activity of MMP-9 reached its peak at the second week and was significantly high in the PRP-treated group. S/C infiltration of autologous PRP at the wound margins enhances the wound epithelization and reduces the scar tissue formation. PMID:28246352

Evaluation of subcutaneous infiltration of autologous platelet-rich plasma on skin-wound healing in dogs.

PubMed

Farghali, Haithem A; AbdElKader, Naglaa A; Khattab, Marwa S; AbuBakr, Huda O

2017-04-28

Platelet-rich plasma (PRP) is known to be rich in growth factors and cytokines, which are crucial to the healing process. This study investigate the effect of subcutaneous (S/C) infiltration of autologous PRP at the wound boundaries on wound epithelization and contraction. Five adult male mongrel dogs were used. Bilateral acute full thickness skin wounds (3 cm diameter) were created on the thorax symmetrically. Right side wounds were subcutaneously infiltrated with activated PRP at day 0 and then every week for three consecutive weeks. The left wound was left as control. Wound contraction and epithelization were clinically evaluated. Expression of collagen type I (COLI) A2, (COLIA2),histopathology and immunohistochemical (IHC) staining of COLI α1 (COLIA1) were performed on skin biopsies at first, second and third weeks. The catalase activity, malondialdehyde (MDA) concentration and matrix metalloproteinase (MMP) 9 (MMP-9) activity were assessed in wound fluid samples. All data were analysed statistically. The epithelization percent significantly increased in the PRP-treated wound at week 3. Collagen was well organized in the PRP-treated wounds compared with control wounds at week 3. The COLIA2 expression and intensity of COLIA1 significantly increased in PRP-treated wounds. MDA concentration was significantly decreased in PRP-treated wound at week 3. The catalase activity exhibited no difference between PRP treated and untreated wounds. The activity of MMP-9 reached its peak at the second week and was significantly high in the PRP-treated group. S/C infiltration of autologous PRP at the wound margins enhances the wound epithelization and reduces the scar tissue formation. © 2017 The Author(s).

Herpes simplex virus antigens directly activate NK cells via TLR2, thus facilitating their presentation to CD4 T lymphocytes.

PubMed

Kim, Min; Osborne, Naomi R; Zeng, Weiguang; Donaghy, Heather; McKinnon, Kay; Jackson, David C; Cunningham, Anthony L

2012-05-01

NK cells infiltrate human herpetic lesions, but their role has been underexplored. HSV can stimulate innate immune responses via surface TLR2, which is expressed on monocyte-derived dendritic cells (DCs) and NK cells. In this study, UV-inactivated HSV1/2 and immunodominant HSV2 glycoprotein D peptides conjugated to the TLR2 agonist dipalmitoyl-S-glyceryl cysteine stimulated CD4 T lymphocyte IFN-γ responses within PBMCs or in coculture with monocyte-derived DCs. NK cells contributed markedly to the PBMC responses. Furthermore, NK cells alone were activated directly by both Ags, also upregulating HLA-DR and HLA-DQ and then they activated autologous CD4 T lymphocytes. Using Transwells, Ag-stimulated NK cells and CD4 T lymphocytes were shown to interact through both cell-to-cell contact and cytokines, differing in relative importance in different donors. A distinct immunological synapse between Ag-stimulated NK cells and CD4 T lymphocytes was observed, indicating the significance of their cell-to-cell contact. A large proportion (57%) of NK cells was also in contact with CD4 T lymphocytes in the dermal infiltrate of human recurrent herpetic lesions. Thus, NK cells stimulated by TLR2-activating HSV Ags can present Ag alone or augment the role of DCs in vitro and perhaps in herpetic lesions or draining lymph nodes. In addition to DCs, NK cells should be considered as targets for adjuvants during HSV vaccine development.

[The present possibilities for routine use of blood-saving measures from the anesthesiologic point of view--theoretical bases and clinical practice. III. Autologous blood donation, autologous donation criteria and organizational measures].

PubMed

Singbartl, G; Schleinzer, W

1994-01-01

This third part of a review on "Autologous Transfusion" deals with preoperative autologous blood donation, with supplemental pharmaco-therapy, with election criteria of the patient as well as with the organizational measures to be taken into account if an intensive autologous predeposit programme is routinely applied. Donation of an autologous predeposit aims at supplying the patient with autologous blood and autologous plasma, respectively, according to the expected blood loss and in order to reduce the need for homologous transfusion. Important aspects, which have to be considered if applying a routine autologous donation programme refer both to the election criteria of the patient and to the organizational programme and measures to be considered. Data in the literature reveal, that the risk of side effects for the patient (who is both the donor and the receiver of the (autologous) blood) during and after donation of an autologous predeposit is definitely not greater than the risk reported for otherwise healthy homologous volunteers. In our opinion, this means, that a patient who has been declared eligible for an elective operative intervention which makes homologous transfusion very probable, can be considered eligible for donating an autologous predeposit; additionally, he should also be eligible for acute normovolemic hemodilution, as donating an autologous predeposit with accompanying volume substitution of the predeposit 'is under hemodynamic aspects' nothing else than an acute and preoperatively performed normovolemic hemodilution. Analysing the data so far reported, volume substitution of the autologous predeposit appears to be a very important component for the patient's safety.(ABSTRACT TRUNCATED AT 250 WORDS)

Autologous transplantation of bone marrow-derived mesenchymal stem cells: a promising therapeutic strategy for prevention of skin-graft contraction.

PubMed

Xu, Y; Huang, S; Fu, X

2012-07-01

Hypertrophic scars result from abnormal healing of severe burns, and are characterized by loss of the original structure and function of the skin. Transplantation of autologous split skin is the preferred treatment after scar excision; however, there will be some unavoidable degree of contraction within the grafts. To our knowledge, it is very rare that bone marrow-derived mesenchymal stem cells (BM-MSCs) have been used for the treatment of skin-graft contraction. However, in our clinics, we found that during a 2-year follow-up analysis, areas treated with autologous BM-MSCs combined with transplantation of split skin were less likely to have contraction of the skin grafts than areas treated with skin grafts alone. This result indicates that BM-MSCs may be a potential and promising treatment to prevent contraction of skin grafts. © The Author(s). CED © 2012 British Association of Dermatologists.

A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study.

PubMed

Peck, Yvonne; He, Pengfei; Chilla, Geetha Soujanya V N; Poh, Chueh Loo; Wang, Dong-An

2015-11-09

In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules, and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair.

A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study

PubMed Central

Peck, Yvonne; He, Pengfei; Chilla, Geetha Soujanya V. N.; Poh, Chueh Loo; Wang, Dong-An

2015-01-01

In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules, and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair. PMID:26549401

Comparison of the Efficacy of Homologous and Autologous Platelet-Rich Plasma (PRP) for Treating Androgenic Alopecia.

PubMed

Ince, Bilsev; Yildirim, Mehmet Emin Cem; Dadaci, Mehmet; Avunduk, Mustafa Cihat; Savaci, Nedim

2018-02-01

Androgenetic alopecia (AGA), the most common cause of hair loss in both sexes, accounts for 95% of all cases of hair loss. Although the literature has suggested that both nonactivated (n-PRP) and activated autologous (a-PRP) PRP can be used to treat AGA, we did not find any study investigating the use of homologous PRP (h-PRP) for this purpose. Also, to the best of our knowledge, there are no studies comparing the efficacy of h-PRP, a-PRP, or n-PRP on AGA therapy. The aim of this study was to compare the increase in hair density, average number of platelets, complications, preparation, and duration of application in the treatment of AGA using a-PRP, n-PRP, and h-PRP. Between 2014 and 2015, we studied male patients who had experienced increased hair loss in the last year. Patients were divided into three groups: Group 1 received n-PRP, Group 2 received active PRP, and Group 3 received h-PRP. For Group 1, PRP was prepared by a single centrifugation prepared from the patient's own blood. For Group 2, the PRP was prepared from the patient's own blood, but a second centrifugation was applied for platelet activation with calcium chloride. For Group 3, the PRP was prepared from pooled platelets with the same blood group as the patient from the blood center. PRP was injected at 1, 2, and 6 months. The hair density (n/cm 2 ) of each patient before and after injection was calculated. Each patient was assigned a fixed evaluation point at the time of application to calculate hair density. At 2, 6, and 12 months after the first treatment, the increase in hair density was calculated as 11.2, 26.1, and 32.4%, respectively, in Group 1; 8.1, 12.5, and 20.8%, respectively, in Group 2; and 16.09, 36.41, and 41.76%, respectively, in Group 3. The increase in hair density was statistically significantly greater in Group 1 than in Group 2 and more so in Group 3 than in both groups among all controls (p < 0.05). The efficacy of both PRPs was determined in AGA treatment in our study

Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes.

PubMed

Jiménez, G; López-Ruiz, E; Kwiatkowski, W; Montañez, E; Arrebola, F; Carrillo, E; Gray, P C; Izpisua Belmonte, J C; Choe, S; Perán, M; Marchal, J A

2015-11-13

Autologous chondrocyte implantation (ACI) depends on the quality and quantity of implanted cells and is hindered by the fact that chondrocytes cultured for long periods of time undergo dedifferentiation. Here we have developed a reproducible and efficient chondrogenic protocol to redifferentiate chondrocytes isolated from osteoarthritis (OA) patients. We used morphological, histological and immunological analysis together with a RT-PCR detection of collagen I and collagen II gene expression to show that chondrocytes isolated from articular cartilage biopsies of patients and subjected to long-term culture undergo dedifferentiation and that these cells can be redifferentiated following treatment with the chimeric Activin A/BMP2 ligand AB235. Examination of AB235-treated cell pellets in both in vitro and in vivo experiments revealed that redifferentiated chondrocytes synthesized a cartilage-specific extracellular matrix (ECM), primarily consisting of vertically-orientated collagen fibres and cartilage-specific proteoglycans. AB235-treated cell pellets also integrated into the surrounding subcutaneous tissue following transplantation in mice as demonstrated by their dramatic increase in size while non-treated control pellets disintegrated upon transplantation. Thus, our findings describe an effective protocol for the promotion of redifferentiation of autologous chondrocytes obtained from OA patients and the formation of a cartilage-like ECM that can integrate into the surrounding tissue in vivo.

Simplified Screening Approach Identifies Mutated Proteins Expressed in Patient Tumors | Center for Cancer Research

Cancer.gov

Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) is a very effective treatment for patients with metastatic melanoma. In phase 2 clinical trials, up to 70 percent of patients with melanoma who received autologous TILs had considerable regressions of metastatic lesions. Recently, in another trial, 40 percent of patients treated had complete regressions of all measurable lesions lasting more than five years after treatment. Identifying antigens associated with TIL-mediated tumor regression has been a difficult task due to the diversity of these large lymphocyte populations and the complexity of current screening approaches.

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib.

PubMed

Lipsky, Andrew H; Farooqui, Mohammed Z H; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U; Herman, Sarah E M; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M; Lozier, Jay N; Wiestner, Adrian

2015-12-01

Ibrutinib is associated with bleeding-related adverse events of grade ≤ 2 in severity, and infrequently with grade ≥ 3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤ 2 bleeding-related adverse events in 55% of 85 patients. No grade ≥ 3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤ 2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733

Autologous blood injection for treatment of chronic recurrent TMJ dislocation: is it successful? Is it safe enough? A systematic review.

PubMed

Varedi, Payam; Bohluli, Behnam

2015-09-01

The purpose of this article is to review the English literature about the efficacy and safety of autologous blood injection in treating patients suffering from chronic recurrent temporomandibular joint dislocation. In this article, we highlight the key trials and recent directions about this modality and discuss about the mechanism, advantages, and disadvantages of this approach. A literature search was performed using PubMed, Medline, and Ovid Medline databases to identify articles reporting on the injection of autologous blood for treatment of chronic recurrent dislocation of temporomandibular joint. Other references cited in the retrieved reports, as well as the "related articles" tool in PubMed Medline, were also checked to improve the search and, if relevant, were included in the study. The search was restricted to articles published in the English language. Seven studies meeting the inclusion criteria were reviewed. The selected articles included four prospective clinical trials and three case report articles. There are a few articles about the clinical use of autologous blood for treating patients with chronic recurrent temporomandibular joint dislocation. Reviewing of the literature shows that there are successful results about this modality, but there are still some concerns about it in terms of the effect of the injected blood on the articular cartilage and formation of fibrous or bony ankylosis.

Autologous bone marrow stem cell transplantation attenuates hepatocyte apoptosis in a rat model of ex vivo liver resection and liver autotransplantation.

PubMed

Xu, Tubing; Wang, Xiaojun; Chen, Geng; He, Yu; Bie, Ping

2013-10-01

To investigate the efficacy of autologous bone marrow stem cell (BMSC) transplantation in the treatment of hepatic injury in ex vivo liver resection and liver autotransplantation (ELRLA). Rat hepatic fibrosis was induced by intraperitoneal injection of 50% CCl4-olive oil solution at a dose of 2 mL/kg twice weekly for 4 wk. ELRLA was performed 3 d post the last injection of CCl4. Six rats in each group were killed 12, 24, 48, 72, and 168 h after the operation. Hepatocyte apoptosis was determined by TUNEL assay. The expression of Bcl-2, Bax, transforming growth factor (TGF) β1, TGFβ1 receptor1/2, and phosphorylated p38 MAPK were determined by Western blot. Autologous BMSC transplantation significantly inhibited the increase of alanine aminotransferease and aspartate aminotransferase at 12, 24, and 48 h post operation and attenuated ELRLA-induced hepatocyte apoptosis. In BMSC-treated rats, the expression of Bcl-2 was significantly upregulated, whereas there were no obvious changes in Bax level. The expression of TGFβ1 was significantly upregulated in the rat liver after the surgery. Autologous BMSC transplantation significantly downregulated the TGFβ1 levels at 48, 72, and 168 h post surgery. However, autologous BMSC transplantation showed little effect on the levels of TGFβ receptor 1/2 at all the time points observed. Furthermore, autologous BMSC transplantation significantly inhibited the activation of p38 MAPK. Autologous BMSC transplantation may reduce ELRLA-induced liver injury and improve survival rates in hepatic fibrosis rats. Autologous BMSC transplantation may be useful to improve the outcome of patients who undergo ELRLA. Copyright © 2013 Elsevier Inc. All rights reserved.

Cirmtuzumab inhibits Wnt5a-induced Rac1 activation in chronic lymphocytic leukemia treated with ibrutinib

PubMed Central

Yu, J; Chen, L; Cui, B; Wu, Christina; Choi, M Y; Chen, Y; Zhang, L; Rassenti, L Z; Widhopf II, G F; Kipps, T J

2017-01-01

Signaling via the B cell receptor (BCR) plays an important role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK) that can block BCR-signaling. However, ibrutinib cannot induce complete responses (CR) or durable remissions without continued therapy, suggesting alternative pathways also contribute to CLL growth/survival that are independent of BCR-signaling. ROR1 is a receptor for Wnt5a, which can promote activation of Rac1 to enhance CLL-cell proliferation and survival. In this study, we found that CLL cells of patients treated with ibrutinib had activated Rac1. Moreover, Wnt5a could induce Rac1 activation and enhance proliferation of CLL cells treated with ibrutinib at concentrations that were effective in completely inhibiting BTK and BCR-signaling. Wnt5a-induced Rac1 activation could be blocked by cirmtuzumab (UC-961), an anti-ROR1 mAb. We found that treatment with cirmtuzumab and ibrutinib was significantly more effective than treatment with either agent alone in clearing leukemia cells in vivo. This study indicates that cirmtuzumab may enhance the activity of ibrutinib in the treatment of patients with CLL or other ROR1+ B-cell malignancies. PMID:27904138

Cirmtuzumab inhibits Wnt5a-induced Rac1 activation in chronic lymphocytic leukemia treated with ibrutinib.

PubMed

Yu, J; Chen, L; Cui, B; Wu, Christina; Choi, M Y; Chen, Y; Zhang, L; Rassenti, L Z; Widhopf Ii, G F; Kipps, T J

2017-06-01

Signaling via the B cell receptor (BCR) plays an important role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK) that can block BCR-signaling. However, ibrutinib cannot induce complete responses (CR) or durable remissions without continued therapy, suggesting alternative pathways also contribute to CLL growth/survival that are independent of BCR-signaling. ROR1 is a receptor for Wnt5a, which can promote activation of Rac1 to enhance CLL-cell proliferation and survival. In this study, we found that CLL cells of patients treated with ibrutinib had activated Rac1. Moreover, Wnt5a could induce Rac1 activation and enhance proliferation of CLL cells treated with ibrutinib at concentrations that were effective in completely inhibiting BTK and BCR-signaling. Wnt5a-induced Rac1 activation could be blocked by cirmtuzumab (UC-961), an anti-ROR1 mAb. We found that treatment with cirmtuzumab and ibrutinib was significantly more effective than treatment with either agent alone in clearing leukemia cells in vivo. This study indicates that cirmtuzumab may enhance the activity of ibrutinib in the treatment of patients with CLL or other ROR1 + B-cell malignancies.

Transplantation of autologous differentiated urothelium in an experimental model of composite cystoplasty.

PubMed

Turner, Alex; Subramanian, Ramnath; Thomas, David F M; Hinley, Jennifer; Abbas, Syed Khawar; Stahlschmidt, Jens; Southgate, Jennifer

2011-03-01

Enterocystoplasty is associated with serious complications resulting from the chronic interaction between intestinal epithelium and urine. Composite cystoplasty is proposed as a means of overcoming these complications by substituting intestinal epithelium with tissue-engineered autologous urothelium. To develop a robust surgical procedure for composite cystoplasty and to determine if outcome is improved by transplantation of a differentiated urothelium. Bladder augmentation with in vitro-generated autologous tissues was performed in 11 female Large-White hybrid pigs in a well-equipped biomedical centre with operating facilities. Participants were a team comprising scientists, urologists, a veterinary surgeon, and a histopathologist. Urothelium harvested by open biopsy was expanded in culture and used to develop sheets of nondifferentiated or differentiated urothelium. The sheets were transplanted onto a vascularised, de-epithelialised, seromuscular colonic segment at the time of bladder augmentation. After removal of catheters and balloon at two weeks, voiding behaviour was monitored and animals were sacrificed at 3 months for immunohistology. Eleven pigs underwent augmentation, but four were lost to complications. Voiding behaviour was normal in the remainder. At autopsy, reconstructed bladders were healthy, lined by confluent urothelium, and showed no fibrosis, mucus, calculi, or colonic regrowth. Urothelial morphology was transitional with variable columnar attributes consistent between native and augmented segments. Bladders reconstructed with differentiated cell sheets had fewer lymphocytes infiltrating the lamina propria, indicating more effective urinary barrier function. The study endorses the potential for composite cystoplasty by (1) successfully developing reliable techniques for transplanting urothelium onto a prepared, vascularised, smooth muscle segment and (2) creating a functional urothelium-lined augmentation to overcome the complications of

Transplantation of Autologous Differentiated Urothelium in an Experimental Model of Composite Cystoplasty

PubMed Central

Turner, Alex; Subramanian, Ramnath; Thomas, David F.M.; Hinley, Jennifer; Abbas, Syed Khawar; Stahlschmidt, Jens; Southgate, Jennifer

2011-01-01

Background Enterocystoplasty is associated with serious complications resulting from the chronic interaction between intestinal epithelium and urine. Composite cystoplasty is proposed as a means of overcoming these complications by substituting intestinal epithelium with tissue-engineered autologous urothelium. Objective To develop a robust surgical procedure for composite cystoplasty and to determine if outcome is improved by transplantation of a differentiated urothelium. Design, setting, and participants Bladder augmentation with in vitro–generated autologous tissues was performed in 11 female Large-White hybrid pigs in a well-equipped biomedical centre with operating facilities. Participants were a team comprising scientists, urologists, a veterinary surgeon, and a histopathologist. Measurements Urothelium harvested by open biopsy was expanded in culture and used to develop sheets of nondifferentiated or differentiated urothelium. The sheets were transplanted onto a vascularised, de-epithelialised, seromuscular colonic segment at the time of bladder augmentation. After removal of catheters and balloon at two weeks, voiding behaviour was monitored and animals were sacrificed at 3 months for immunohistology. Results and limitations Eleven pigs underwent augmentation, but four were lost to complications. Voiding behaviour was normal in the remainder. At autopsy, reconstructed bladders were healthy, lined by confluent urothelium, and showed no fibrosis, mucus, calculi, or colonic regrowth. Urothelial morphology was transitional with variable columnar attributes consistent between native and augmented segments. Bladders reconstructed with differentiated cell sheets had fewer lymphocytes infiltrating the lamina propria, indicating more effective urinary barrier function. Conclusions The study endorses the potential for composite cystoplasty by (1) successfully developing reliable techniques for transplanting urothelium onto a prepared, vascularised, smooth muscle

Intradiscal Injection of Autologous Platelet-Rich Plasma Releasate to Treat Discogenic Low Back Pain: A Preliminary Clinical Trial.

PubMed

Akeda, Koji; Ohishi, Kohshi; Masuda, Koichi; Bae, Won C; Takegami, Norihiko; Yamada, Junichi; Nakamura, Tomoki; Sakakibara, Toshihiko; Kasai, Yuichi; Sudo, Akihiro

2017-06-01

Preliminary clinical trial. To determine the safety and initial efficacy of intradiscal injection of autologous platelet-rich plasma (PRP) releasate in patients with discogenic low back pain. PRP, which is comprised of autologous growth factors and cytokines, has been widely used in the clinical setting for tissue regeneration and repair. PRP has been shown in vitro and in vivo to potentially stimulate intervertebral disc matrix metabolism. Inclusion criteria for this study included chronic low back pain without leg pain for more than 3 months; one or more lumbar discs (L3/L4 to L5/S1) with evidence of degeneration, as indicated via magnetic resonance imaging (MRI); and at least one symptomatic disc, confirmed using standardized provocative discography. PRP releasate, isolated from clotted PRP, was injected into the center of the nucleus pulposus. Outcome measures included the use of a visual analog scale (VAS) and the Roland-Morris Disability Questionnaire (RDQ), as well as X-ray and MRI (T2-quantification). Data were analyzed from 14 patients (8 men and 6 women; mean age, 33.8 years). The average follow-up period was 10 months. Following treatment, no patient experienced adverse events or significant narrowing of disc height. The mean pain scores before treatment (VAS, 7.5±1.3; RDQ, 12.6±4.1) were significantly decreased at one month, and this was generally sustained throughout the observation period (6 months after treatment: VAS, 3.2±2.4, RDQ; 3.6±4.5 and 12 months: VAS, 2.9±2.8; RDQ, 2.8±3.9; p <0.01, respectively). The mean T2 values did not significantly change after treatment. We demonstrated that intradiscal injection of autologous PRP releasate in patients with low back pain was safe, with no adverse events observed during follow-up. Future randomized controlled clinical studies should be performed to systematically evaluate the effects of this therapy.

Preoperative autologous blood donation: clinical, economic, and ethical issues.

PubMed

Domen, R E

1996-09-01

Many patients are donating their own blood before surgery to avoid blood-borne infections, often on the advice of their physicians. But autologous blood transfusion, while safer than allogeneic transfusion, is not completely risk-free. It is also expensive, its benefits are difficult to assess, and its increasing popularity raises many difficult ethical issues, such as whether the benefit of allogeneic transfusion supports its additional expense. Record-keeping, collection, and transfusion errors are occasional risks of autologous transfusions. In addition, risks associated with blood donation, from mild dizziness to precipitation of angina, should be considered when high-risk patients are referred for autologous collection. Only approximately half of autologous units collected are actually used, and the cost per quality-adjusted year of life saved may be as high as $1 million, depending on the type of surgical procedure. Although recombinant human erythropoietin can stimulate red blood cell production before autologous donation and decrease the need for transfusion, it is not clear whether this strategy, which can cost thousands of dollars per patient, will be cost-effective. Perioperative hemodilution may become an important component in efforts to reduce patient exposure to allogeneic blood, but its use remains controversial.

Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune camouflage.

PubMed

Wang, Shuangyong; Li, Liangliang; Liu, Ying; Li, Chaoyang; Zhang, Min; Wang, Bowen; Huang, Zheqian; Gao, Xinbo; Wang, Zhichong

2015-03-01

We investigated the immune camouflage effects of methoxy polyethylene glycol succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel approach for reducing corneal antigenicity, thereby decreasing corneal graft rejection. Importantly, this approach did not alter normal local immunity. Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could shield major histocompatibility antigen class I molecules (RT1-A) of corneal grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co-cultured with autologous corneal grafts or untreated corneal grafts and PEGylated grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD rats with corneal neovascularisation were used as recipients for high-risk corneal transplantation and were randomly divided into four groups: autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The recipients received corneal grafts from Wistar rats. Corneal graft survival was prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG-SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA could immunologically camouflage corneal antigens to prolong corneal grafts survival in high-risk transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Laboratory-based performance evaluation of PIMA CD4+ T-lymphocyte count point-of-care by lay-counselors in Kenya.

PubMed

Zeh, Clement; Rose, Charles E; Inzaule, Seth; Desai, Mitesh A; Otieno, Fredrick; Humwa, Felix; Akoth, Benta; Omolo, Paul; Chen, Robert T; Kebede, Yenew; Samandari, Taraz

2017-09-01

CD4+ T-lymphocyte count testing at the point-of-care (POC) may improve linkage to care of persons diagnosed with HIV-1 infection, but the accuracy of POC devices when operated by lay-counselors in the era of task-shifting is unknown. We examined the accuracy of Alere's Pima™ POC device on both capillary and venous blood when performed by lay-counselors and laboratory technicians. In Phase I, we compared the perfomance of POC against FACSCalibur™ for 280 venous specimens by laboratory technicians. In Phase II we compared POC performance by lay-counselors versus laboratory technicians using 147 paired capillary and venous specimens, and compared these to FACSCalibur™. Statistical analyses included Bland-Altman analyses, concordance correlation coefficient, sensitivity, and specificity at treatment eligibility thresholds of 200, 350, and 500cells/μl. Phase I: POC sensitivity and specificity were 93.0% and 84.1% at 500cells/μl, respectively. Phase II: Good agreement was observed for venous POC results from both lay-counselors (concordance correlation coefficient (CCC)=0.873, bias -86.4cells/μl) and laboratory technicians (CCC=0.920, bias -65.7cells/μl). Capillary POC had good correlation: lay-counselors (CCC=0.902, bias -71.2cells/μl), laboratory technicians (CCC=0.918, bias -63.0cells/μl). Misclassification at the 500 cells/μl threshold for venous blood was 13.6% and 10.2% for lay-counselors and laboratory technicians and 12.2% for capillary blood in both groups. POC tended to under-classify the CD4 values with increasingly negative bias at higher CD4 values. Pima™ results were comparable to FACSCalibur™ for both venous and capillary specimens when operated by lay-counselors. POC CD4 testing has the potential to improve linkage to HIV care without burdening laboratory technicians in resource-limited settings. Published by Elsevier B.V.

RECEPTOR FOR THE FOURTH COMPONENT OF COMPLEMENT ON HUMAN B LYMPHOCYTES AND CULTURED HUMAN LYMPHOBLASTOID CELLS

PubMed Central

Bokisch, Viktor A.; Sobel, Alain T.

1974-01-01

This report describes receptors for C4b on human peripheral B lymphocytes. The simultaneous presence of C3b and C4b receptors on the same lymphocytes was demonstrated by the formation of mixed rosettes consisting of the lymphocytes, EAC14 and EAC1423. Furthermore, reduction of the number of EAC1423 rosette-forming lymphocytes in a lymphocyte population by albumin gradient centrifugation concomitantly reduced EAC14 rosette-forming lymphocytes. Binding of EAC14 intermediates to receptors on human lymphocytes and erythrocytes could be inhibited by equal amounts of soluble C3b or C4b, suggesting the presence of a single receptor for both ligands on those cells. In contrast, the results of the rosette assay with Raji cells, cultured human lymphoblastoid cells, EAC14 and EAC1423 suggested that the receptors for C4b and C3b are distinct entities, since Raji cells formed rosettes with EAC1423, but not with EAC14. Moreover, this report demonstrates a cooperation of erythrocyte-bound C4b and C3b in the binding of EAC1423 to B lymphocytes. In contrast to KAF-treated C3b, KAF-treated C4b did not bind to B lymphocytes, indicating that these cells lack a receptor for C4d. PMID:4547573

Autologous bone marrow purging with LAK cells.

PubMed

Giuliodori, L; Moretti, L; Stramigioli, S; Luchetti, F; Annibali, G M; Baldi, A

1993-12-01

In this study we will demonstrate that LAK cells, in vitro, can lyse hematologic neoplastic cells with a minor toxicity of the staminal autologous marrow cells. In fact, after bone marrow and LAK co-culture at a ratio of 1/1 for 8 hours, the inhibition on the GEMM colonies resulted to be 20% less compared to the untreated marrow. These data made LAK an inviting agent for marrow purging in autologous bone marrow transplantation.

Risk factors associated with a new pregnancy loss and perinatal outcomes in cases of recurrent miscarriage treated with lymphocyte immunotherapy.

PubMed

Cavalcante, Marcelo Borges; Costa, Fabrício da Silva; Araujo Júnior, Edward; Barini, Ricardo

2015-06-01

To assess the perinatal outcomes and risk factors for further pregnancy loss in patients with recurrent miscarriage treated with lymphocyte immunotherapy (LIT). We performed a retrospective observational study of women with a history of two or more consecutive miscarriages who underwent LIT. All patients had undergone investigation of the etiology of the pregnancy losses according to a specific protocol. These etiologic factors were compared between those whose pregnancy outcome was successful and those who had a further miscarriage. The comparison between the groups was performed by Kruskal-Wallis, Fisher exact and Chi-square tests. Perinatal outcome data were collected for the successful pregnancies. One-hundred six patients were included. The mean number (±SD) of previous pregnancies, deliveries and miscarriages in all patients were 2.73 ± 0.8, 0.19 ± 0.4 and 2.54 ± 0.6, respectively. A successful pregnancy outcome after lymphocyte therapy occurred in 82 patients (group I), while 24 (22.6%) sustained a further miscarriage (group II). There was no statistical difference in the genetic, anatomic and hormonal causes of miscarriage between the groups (p > 0.05). Antinuclear (ANA) and antithyroglobulin (TgAb) autoantibodies occurred more frequently in group II (p = 0.0010 and p = 0.0024, respectively). Of those with successful pregnancies, 11 women (13.4%) had a preterm delivery. The mean birth weight was 3036.4 ± 498.6 g. In patients with recurrent miscarriage treated with LIT, the presence of ANA and TgAb was a risk factor for further pregnancy loss. Perinatal outcomes in those whose pregnancies continued were favorable.

Prognostic significance of combined pretreatment lymphocyte counts and body mass index in patients with head and neck cancer treated with radiation therapy.

PubMed

Wu, Yao-Yu; Chang, Kai-Ping; Lin, Chien-Yu; Pai, Ping-Ching; Wang, Hung-Ming; Hsu, Cheng-Lung; Liao, Chun-Ta; Yen, Tzu-Chen; Fang, Tuan-Jen; Huang, Shiang-Fu; Kang, Chung-Jan; Fang, Ku-Hao; Lin, Wan-Ni; Wang, Yu-Chien; Hsin, Li-Jen; Tsang, Ngan-Ming

2018-05-23

We aimed to investigate the prognostic significance of combined pretreatment lymphocyte counts (LCs) and body mass index (BMI) in patients with head and neck cancer (HNC) treated with radiation therapy (RT). Nine hundred and twelve patients with HNC who were treated with RT were retrospectively reviewed. Survival was analyzed by stratifying the patients according to pretreatment LCs and BMI. Patients with low pretreatment LCs and BMI were characterized by a more advanced T stage, fewer nasopharyngeal subsites, less smoking and drinking, and fewer comorbidities. Patients with low pretreatment LCs and BMI had a significantly poorer overall and distant metastasis-free survival than those with high pretreatment LCs and BMI. No significant differences were observed in terms of local or regional recurrence-free survival. Combined pretreatment LCs and BMI may be more effective at predicting overall and distant metastasis-free survival in patients with HNC treated with RT. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Intrapleural instillation of autologous blood for persistent air leak in spontaneous pneumothorax in patients with advanced chronic obstructive pulmonary disease.

PubMed

Cao, Guo qiang; Kang, Jun; Wang, Fangwen; Wang, Hucheng

2012-05-01

We evaluated the safety and efficacy of increasing doses of autologous blood patch pleurodesis in treating persistent air leaks in patients with advanced chronic obstructive pulmonary disease (COPD). Forty-four patients with COPD and spontaneous pneumothorax (SP) on the 7th day after intercostal tube drainage were randomly assigned to 4 groups, with 11 patients in each group. Groups A, B, and C were given increasing doses of autologous blood--ie, 0.5 mL/kg, 1 mL/kg, 2 mL/kg, respectively--whereas group D was given 1 mL/kg normal saline only. The procedure was repeated if the air leak persisted on postoperative days 9 and 11. Patients in group D crossed over and received autologous blood as in group B if the air leak was still present on the 13th postoperative day. No patient died in the study. The air leak was sealed by the 13th postoperative day only in patients with air leaks smaller than size 3. Air leaks were classified as 0 to 3 [12], ie, size 0=no air leak; size 1=air leak on vigorous coughing only; size 2=small continuous air leak on gentle respiration; and size 3=large continuous air leak on gentle respiration. The success rates by the 13th postoperative day in groups A, B, C, and D were 27%, 82%, 82%, and 9%, respectively. The success rate (82%) was significantly higher in groups B and C than in group A (p=0.003) and D (p>0.01). Using autologous blood to treat secondary spontaneous pneumothorax (SSP) in patients with advanced COPD is easy, safe, and effective. The dose of blood required for autologous blood patch pleurodesis should be dependent on the body weight, and 1 mL/kg blood may be efficient. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Development of autologous blood cell therapies

PubMed Central

Kim, Ah Ram; Sankaran, Vijay G.

2016-01-01

Allogeneic hematopoietic stem cell transplantation and blood cell transfusions are commonly performed in patients with a variety of blood disorders. Unfortunately, these donor-derived cell therapies are constrained due to limited supplies, infectious risk factors, a lack of appropriately matched donors, and the risk of immunologic complications from such products. The use of autologous cell therapies has been proposed to overcome these shortcomings. One can derive such therapies directly from hematopoietic stem and progenitor cells of individuals, which can then be manipulated ex vivo to produce desired modifications or differentiated to produce a particular target population. Alternatively, pluripotent stem cells, which have a theoretically unlimited self-renewal capacity and an ability to differentiate into any desired cell type, can be used as an autologous starting source for such manipulation and differentiation approaches. In addition, such cell products can also be used as a delivery vehicle for therapeutics. In this review, we highlight recent advances and discuss ongoing challenges for the in vitro generation of autologous hematopoietic cells that can be used for cell therapy. PMID:27345108

Autologous cell therapies: challenges in US FDA regulation.

PubMed

McAllister, Todd N; Audley, David; L'Heureux, Nicolas

2012-11-01

Cell-based therapies (CBTs) have been hailed for the last two decades as the next pillar of healthcare, yet the clinical and commercial potential of regenerative medicine has yet to live up to the hype. While recent analysis has suggested that regenerative medicine is maturing into a multibillion dollar industry, examples of clinical and commercial success are still relatively rare. With 30 years of laboratory and clinical efforts fueled by countless billions in public and private funding, one must contemplate why CBTs have not made a greater impact. The current regulatory environment, with its zero-risk stance, stymies clinical innovation while fueling a potentially risky medical tourism industry. Here, we highlight the challenges the US FDA faces and present talking points for an improved regulatory framework for autologous CBTs.

Ovarian hyperstimulation syndrome in gonadotropin-treated laboratory South African clawed frogs (Xenopus laevis).

PubMed

Green, Sherril L; Parker, John; Davis, Corrine; Bouley, Donna M

2007-05-01

Ovarian hyperstimulation syndrome (OHS) is a rare but sometimes fatal iatrogenic complication of ovarian stimulation associated with the administration of exogenous gonadotropins to women undergoing treatment for infertility. Laboratory Xenopus spp are commonly treated with human chorionic gonadotropin (hCG) to stimulate ovulation and optimize the number of oocytes harvested for use in biomedical research. Here we report cases of OHS in 2 gonadotropin-treated laboratory Xenopus laevis. After receiving hCG, the frogs developed severe subcutaneous accumulation of fluid, coelomic distention, and whole-body edema and were unable to dive, although they continued to eat and swim. At postmortem examination, extensive subcutaneous edema was present; ascites and massive numbers of free-floating eggs were found in the coelomic cavity and in aberrant locations: around the heart-sac and adhered to the liver capsule. Whole-body edema, gross enlargement of the ovaries, ascites, and abdominal distention are findings comparable to those observed in women with OHS. The pathophysiology of OHS is thought to be related to hormonally induced disturbances of vasoactive mediators, one of which may be vascular endothelial growth factor secreted by theca and granulosa cells. We know of no other report describing OHSlike symptoms in gonadotropin-treated frogs, and the cases described here are 2 of the 3 we have observed at our respective institutions over the last 6 y. According to these results, OHS appears to be rare in gonadotropin-treated laboratory Xenopus. However, the condition should be included in the differential diagnosis for the bloated frog.

Office-Based Autologous Fat Injection Laryngoplasty for Glottic Insufficiency in Patients Under 50 Years Old.

PubMed

Hu, Hao-Chun; Hung, Yi-Ting; Lin, Shu-Yi; Tung, Tao-Hsin; Chang, Shyue-Yih

2018-04-17

We sought to determine the outcomes of office-based autologous fat injection laryngoplasty in the treatment of patients under 50 years old with glottic insufficiency but without neurological problems or acquired organic lesions in the vocal fold. We conducted a retrospective chart review of consecutive patients under 50 years of age who underwent office-based autologous fat injection laryngoplasty for glottic insufficiency. None of the patients presented neurological problems or acquired organic lesions in the vocal fold. Videolaryngostroboscopic data, objective voice assessment, perceptual measurements of vocal quality, and subjective ratings of voice quality were evaluated before and after treatment. The 23 patients (7 men and 16 women) in this study presented significant improvements in phonatory function in terms of maximum phonation time, jitter, grade, asthenia, and Voice Handicap Index-10 (VHI-10) values at 3 months. Significant improvements in terms of jitter, noise-to-harmonic ratio, grade, roughness, breathiness, asthenia, and the VHI-10 values were also observed at 6 months. Glottic insufficiency in younger patients without neurological problems or acquired organic lesions in the vocal fold can be treated effectively using office-based autologous fat injection laryngoplasty. Significant improvements in phonatory function were observed even 6 months after surgery. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia.

PubMed

Arthurs, Benjamin; Wunderle, Kathy; Hsu, Maylee; Kim, Suil

2017-01-01

We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus . Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.

Control of T lymphocyte morphology by the GTPase Rho

NASA Technical Reports Server (NTRS)

Woodside, Darren G.; Wooten, David K.; Teague, T. Kent; Miyamoto, Yuko J.; Caudell, Eva G.; Udagawa, Taturo; Andruss, Bernard F.; McIntyre, Bradley W.

2003-01-01

BACKGROUND: Rho family GTPase regulation of the actin cytoskeleton governs a variety of cell responses. In this report, we have analyzed the role of the GTPase Rho in maintenance of the T lymphocyte actin cytoskeleton. RESULTS: Inactivation of the GTPase Rho in the human T lymphocytic cell line HPB-ALL does not inhibit constitutively high adhesion to the integrin beta1 substrate fibronectin. It did however result in the aberrant extension of finger-like dendritic processes on the substrates VCAM-1, Fn, and mAb specific to beta1 integrins. Time-lapse video microscopy demonstrated that C3 induced extensions were primarily the result of an altered pseudopod elongation rather than retraction. Once the stellate pseudopodia extended, none retracted, and cells became completely immobile. Filipodial structures were absent and the dendritic-like processes in C3 treated cells were rich in filamentous actin. Immunolocalization of RhoA in untreated HPB-ALL cells spreading on fibronectin demonstrated a diffuse staining pattern within the pseudopodia. In C3 treated cells, clusters of RhoA were pronounced and localized within the altered extensions. CONCLUSIONS: GTPase Rho is actively involved in the regulation of T lymphocyte morphology and motility.

High-dose zinc oral supplementation after stem cell transplantation causes an increase of TRECs and CD4+ naïve lymphocytes and prevents TTV reactivation.

PubMed

Iovino, Lorenzo; Mazziotta, Francesco; Carulli, Giovanni; Guerrini, Francesca; Morganti, Riccardo; Mazzotti, Valentina; Maggi, Fabrizio; Macera, Lisa; Orciuolo, Enrico; Buda, Gabriele; Benedetti, Edoardo; Caracciolo, Francesco; Galimberti, Sara; Pistello, Mauro; Petrini, Mario

2018-05-02

Zinc plays an important role in thymic function and immune homeostasis. We performed a prospective clinical trial using a high-dose zinc oral supplementation to improve the immune reconstitution after hematopoietic stem cell transplant (HSCT). We enrolled 18 patients undergoing autologous HSCT for multiple myeloma. Nine patients were randomized to receive only a standard antimicrobial prophylaxis; whereas, nine patients received in addition 150 mg/day of zinc from day +5 to day +100 after transplant. CD4+ naïve lymphocytes and TRECs showed a significant increase from day +30 until day +100 only in the zinc-treated group. Moreover, the load of Torquetenovirus, a harmless virus that replicates in course of immunedepression, increased at day +100 only in the control group. No severe adverse events were reported during the zinc consumption. First data from the ZENITH trial suggest that high-dose zinc supplementation is safe and may enhance the thymic reconstitution after HSCT. Registered: http://Clinicaltrials.gov (NCT03159845); and EUDRACT: 2014-28 004499-47. Copyright © 2018 Elsevier Ltd. All rights reserved.

Débridement and Autologous Lipotransfer for Chronic Ulceration of the Diabetic Foot and Lower Limb Improves Wound Healing.

PubMed

Stasch, Tilman; Hoehne, Julius; Huynh, Tuan; De Baerdemaeker, Randy; Grandel, Siegfried; Herold, Christian

2015-12-01

The application of autologous lipotransfer (fat grafting, lipofilling) in reconstructive surgery is steadily becoming more popular as evidence of the regenerative and reparative effects of fat becomes better known. The authors investigated the use of autologous lipotransfer for treatment of chronic diabetic and other foot and lower limb ulcers. Twenty-six patients with nonhealing wounds were treated with surgical débridement and autologous lipotransfer (using the débridement and autologous lipotransfer method). The mean age of the wounds before intervention was 16.7 months. Wound size after débridement averaged 5.1 ± 2.6 cm2. On average, 7.1 ± 3.3 cc of lipoaspirate was transferred into the wound area. Twenty-two of 25 wounds (88 percent) healed completely within a mean of 68.0 ± 33.0 days. A reduction of wound size by 50 percent was achieved after an average of 4 weeks. In one patient with an ulcer within particularly scarred tissues on the lower limb, a repeated session of lipotransfer led to complete wound healing after another 4 weeks. The authors describe a simple and useful technique to improve wound healing in diabetic feet and chronic lower limb ulcers with a background of peripheral vascular disease, where other interventional options to achieve wound healing have failed.

Microvascular Complications in Type 1 Diabetes: A Comparative Analysis of Patients Treated with Autologous Nonmyeloablative Hematopoietic Stem-Cell Transplantation and Conventional Medical Therapy.

PubMed

Penaforte-Saboia, Jaquellyne G; Montenegro, Renan M; Couri, Carlos E; Batista, Livia A; Montenegro, Ana Paula D R; Fernandes, Virginia O; Akhtar, Hussain; Negrato, Carlos A; Malmegrim, Kelen Cristina Ribeiro; Moraes, Daniela Aparecida; Dias, Juliana B E; Simões, Belinda P; Gomes, Marilia Brito; Oliveira, Maria Carolina

2017-01-01

To explore the impact on microvascular complications, long-term preservation of residual B-cell function and glycemic control of patients with type 1 diabetes treated with autologous nonmyeloablative hematopoietic stem-cell transplantation (AHST) compared with conventional medical therapy (CT). Cross-sectional data of patients treated with AHST were compared with patients who received conventional therapy from the Brazilian Type 1 Diabetes Study Group, the largest multicenter observational study in type 1 diabetes mellitus in Brazil. Both groups of patients had diabetes for 8 years on average. An assessment comparison was made on the presence of microvascular complications, residual function of B cell, A1c, and insulin dose of the patients. After a median of 8 years of diagnosis, none of the AHST-treated patients ( n  = 24) developed microvascular complications, while 21.5% (31/144) had at least one ( p  < 0.005) complication in the CT group ( n  = 144). Furthermore, no case of nephropathy was reported in the AHST group, while 13.8% of CT group ( p  < 0.005) developed nephropathy during the same period. With regard of residual B-cell function, the percentage of individuals with predicted higher C-peptide levels (IDAA1C ≤ 9) was about 10-fold higher in the AHST group compared with CT (75 vs. 8.3%) ( p  < 0.001) group. Among AHST patients, 54.1% (13/24) had the HbA1c < 7.0 compared with 13.1% in the CT ( p  < 0.001) group. Patients with newly diagnosed type 1 diabetes treated with AHST presented lower prevalence of microvascular complications, higher residual B-cell function, and better glycemic control compared with the CT group.

[Effect of autologous platelet-rich plasma on heart infarction in sheep].

PubMed

Gallo, Ignacio; Sáenz, Alberto; Arévalo, Adolfo; Roussel, Sonia; Pérez-Moreiras, Ignacio; Artiñano, Edurne; Martínez-Peñuela, Ana; Esquide, Javier; Aspiroz, Antonio; Camacho, Ignacio

2013-01-01

Myocardial infarction is the most common cause of congestive heart failure. The objective of this work is to evaluate, in experimental animals, morphological and histological effects of the implantation of autologous platelet-rich plasma in infarcted heart sheep. Twenty-four ewes were used, they were surgically infarcted through left thoracotomy and two coronary arteries were ligated (first and second diagonal). After coronary artery ligation three sheep died of ventricular fibrillation. Three weeks after coronary ligation, sheep were reoperated through median sternotomy. Normal saline solution was injected in the infarcted zone in 6 of them (control group) whereas platelet gel was injected in 15 of them. All sheep were euthanized at 9 weeks of evolution of the second surgery. Noteworthy is the formation of new vessels in hematoxylin-eosin-stained sections and factor viii in plasma rich in growth-factors (PRGF)-treated hearts. Injection of platelet growth factors, PRGF, in previously infarcted sheep hearts promotes mitogenesis and angiogenesis. The use of autologous PRGF is simple and safe, causing no toxicity or immune-inflammatory reactions. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Autologous buccal mucosa graft augmentation for foreshortened vagina.

PubMed

Grimsby, Gwen M; Bradshaw, Karen; Baker, Linda A

2014-05-01

Vaginal foreshortening after pelvic surgery or radiotherapy may lead to dyspareunia and decreased quality of life. Unfortunately, little literature exists regarding treatment options for this debilitating problem. Autologous buccal mucosal grafting has been previously reported for creation of a total neovagina and the repair of postvaginoplasty vaginal stenosis. Autologous buccal mucosa offers several advantages as a replacement material for vaginal reconstruction. Vaginal and oral buccal mucosa are both hairless, moist, nonkeratinized stratified squamous epithelia. Buccal mucosa has a dense layer of elastic fibers, imparting both elasticity and strength, and acquires a robust neovascularity with excellent graft take. The graft material is readily available and donor site scars are hidden in the mouth. A 60-year-old woman had vaginal foreshortening to 4.5 cm 15 years after radical hysterectomy and brachytherapy for endometrial cancer. She was unable to have intercourse despite attempted vaginal dilation. Her foreshortened vagina was successfully augmented with autologous buccal mucosa grafting at the apex, increasing her vaginal length to 8 cm and permitting pain-free intercourse. Even in the face of an altered surgical field after radical hysterectomy and radiation, autologous buccal mucosa is an option for vaginal reconstruction for vaginal foreshortening.

Analysis by flow cytometry of the subpopulations of lymphocytes from the peripheral blood of procain or diethylaminoethanol treated rabbits.

PubMed

Vrăbiescu, A; Radu, D; Dolganiuc, A; Bordea, M; Olinescu, A

1998-01-01

The authors worked on 3 groups of 8 male rabbits, New Zealand race: 1) controls; 2) procain injected i.m., 15 mg/kg body weight, daily, for 30 days; 3) i.m. injected with diethylaminoethanol (DEAE), 15 mg/kg body weight, daily, for 35 days. The expression of the MHC I, MHC II, CD43, CD4 and IgM antigenic markers on the plasmatic membrane of the lymphocytes was studied using flow cytometry and monoclonal antibodies. Procain or DEAE treatment reduced the percentage of lymphocytes expressing I MHC, from 99.06 in the control group, to 94.51 in procain group and to 96.91 in the DEAE group. The intensity of expression of MHC complexes of class II decreases from 160.94 in the control group, to 107.21 in the procain group and to 104.05 in the DEAE group. No significant differences were noticed between the three groups of rabbits concerning the rate of lymphocytes that have on their surface expressed markers for CD43 (lymphocytes T), CD4 (Th), or IgM (lymphocytes B). Lymphocytosis induced in rabbits as a result of the DEAE treatment took place without a change in the proportions of lymphocyte subpopulations. The authors consider that owing to their capacity to reduce the expression of antigens MHC of class I and class II on the membrane of lymphocytes, procain and DEAE can have benefic effects in some autoimmune, autoaggression and inflammatory diseases.

Novel treatments for chronic lymphocytic leukemia and moving forward.

PubMed

Brown, Jennifer R; Porter, David L; O'Brien, Susan M

2014-01-01

The last several years have seen an explosion of novel therapies for chronic lymphocytic leukemia (CLL). These include the antibody obintutuzumab (GA-101), as well as small-molecule inhibitors of key pathways involved in the pathogenesis of CLL, specifically the B-cell receptor (BCR) pathway (especially Bruton's tyrosine kinase [BTK] and P13K), and the antiapoptotic pathway (especially BCL-2). We will consider each in turn, focusing on the molecules most advanced in clinical development. There has also been extensive development in rewiring the patient's own immune system to treat CLL. This has been done through modifying autologous T cells to express a chimeric antigen receptor (CAR). Thus far all CAR-T preparations have targeted the CD19 antigen. This is a good rational for B-cell malignancies as CD19 expression is limited to B-cell malignancies and normal B cells. The in vivo amplification of the transduced T cells relies on signaling and co-signaling domains and provides significant killing of CLL cells. As exciting as these novel agents and approaches are, they obviously beg the question, will chemotherapy as a treatment for CLL soon be obsolete? Although chemotherapy is associated with known short-term toxicities, it has the advantage of being completed in a short period of time and being relatively inexpensive in comparison to novel therapies. In addition, long-term follow-up of results with chemoimmunotherapy have now identified a group of patients whose remissions are maintained for more than 10 years. An important question that will arise going forward is how to incorporate novel agents without eliminating the long term benefits possible with chemoimmunotherapy in a subset of patients with CLL.

Development of an autologous canine cancer vaccine system for resectable malignant tumors in dogs.

PubMed

Yannelli, J R; Wouda, R; Masterson, T J; Avdiushko, M G; Cohen, D A

2016-12-01

While conventional therapies exist for canine cancer, immunotherapies need to be further explored and applied to the canine setting. We have developed an autologous cancer vaccine (K9-ACV), which is available for all dogs with resectable disease. K9-ACV was evaluated for safety and immunogenicity for a variety of cancer types in a cohort of companion dogs under veterinary care. The autologous vaccine was prepared by enzymatic digestion of solid tumor biopsies. The resultant single cell suspensions were then UV-irradiated resulting in immunogenic cell death of the tumor cells. Following sterility and endotoxin testing, the tumor cells were admixed with CpG ODN adjuvant and shipped to the participating veterinary clinics. The treating veterinarians then vaccinated each patient with three intradermal injections (10 million cells per dose) at 30-day intervals (one prime and two boost injections). In a cohort of 20 dogs completing the study, 17 dogs (85%) developed an augmented IgG response to autologous tumor antigens as demonstrated using western blot analysis of pre- and post-peripheral blood samples. We also report several dogs have lived beyond expected survival time based on previously published data. In summary, K9-ACV is an additional option to be considered for the treatment of dogs with resectable cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanical and chemical characteristics of an autologous glue.

PubMed

De Somer, Filip; Delanghe, Joris; Somers, Pamela; Debrouwere, Maarten; Van Nooten, Guido

2008-09-15

The study evaluates the mechanical and chemical characteristics of autologous surgical glue made by mixing ultrafiltered plasma with glutaraldehyde (GTA). Human albumin 200 g/L mixed with different concentrations of GTA (25, 50, 75, or 100 g/L) was used as a single protein set-up for testing tensile strength, elasticity, and rate of crosslinking. Subsequently, ultrafiltered canine or human plasma to obtain autologous glue replaced human albumin. BioGlue, a surgical glue, and Tissucol Duo, a fibrin sealant, were used as controls. Tensile strength of human albumin 200 g/L mixed with 75 g/L GTA is 825 +/- 109 N versus 672 +/- 167 N for BioGlue. Ultrafiltered canine plasma showed a maximum tensile strength of 634 +/- 137 N when mixed with GTA 75 g/L. For human plasma, the maximum tensile strength of 436 +/- 69 N was reached after mixing with GTA 25 g/L. Autologous glue had a higher elasticity of 144 +/- 66 N versus 322 +/- 104 N for BioGlue at maximum load. Autologous glues for vascular repair can be easily prepared out of the patient's plasma. The optimal characteristics, compared to BioGlue, are obtained for ultrafiltered canine and human plasma by mixing with a GTA concentration of 50-75 g/L and 25-50 g/L, respectively. The autologous glue will exert less tensile strength than BioGlue but has a better compliance. In case where no plasma can obtained from the patient, mixing human albumin 200 g/L with GTA 75 g/L can be an alternative to BioGlue.

CCI-779 in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2014-05-07

B-cell Chronic Lymphocytic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Malignant Neoplasm; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

[Agammaglobulinemia with the absence of circulating B-lymphocytes. 9 cases].

PubMed

Bejaoui, M; Barbouche, M R; Mellouli, F; Tirellil, N; Dellagi, K

1998-03-28

Agammaglobulinemia with absence of circulating B lymphocytes is a rare genetically transmitted immunodeficiency that appears in early childhood and affect mainly boys. The clinical manifestations of the disease are rather heterogeneous. Nine patients (7 boys and 2 girls) were diagnosed as suffering from agammaglobulinemia with absence of circulating B lymphocytes, over a period of 6 years. Quantitation of immunoglobulins and search for circulating B lymphocytes were respectively performed by the Mancini method and immunofluorescence using T specific (anti-CD3, anti-CD4 and anti-CD8) and B (anti-CD19) monoclonal antibody. The disease started to manifest clinically at the mean age of 8.7 months (4-16 months). The mean age at diagnosis is 4 years (1-11 years). The clinical manifestations were essentially recurrent infections of the lung and the gastrointestinal tract. However, bacterial meningitidis was observed in 3 patients. Severe complications such as an echovirus 27 meningoencephalitis and a chronic active hepatitis (1 patient) and a pericarditis (1 patient) were observed. All of our patients lacked circulating B lymphocytes and had low or null immunoglobulin levels. Five patients were treated by intravenous immunoglobulin (Ig) and 3 were treated by intramuscular immunoglobulin with a residual IgG level respectively of 5.5 g/l and 3.3 g/l. Recurrent infections are the principal manifestation of the agammaglobulinemia, early Ig treatment is the only therapy allowing improved.

Autologous Bone Plug Supplemented With Autologous Chondrocyte Implantation in Osteochondral Defects of the Knee.

PubMed

Bhattacharjee, Atanu; McCarthy, Helen S; Tins, Bernhard; Roberts, Sally; Kuiper, J H; Harrison, Paul E; Richardson, James B

2016-05-01

Structural and functional outcome of bone graft with first- or second-generation autologous chondrocyte implantation (ACI) in treating cartilage and subchondral bone defect has not been reported previously. To evaluate the outcome of simultaneous transplantation of an autologous bone plug with first- or second-generation ACI for restoration of concomitant subchondral bone and full-thickness cartilage defect in the femoral condyle of the knee. Case series; Level of evidence, 4. Seventeen patients (mean ± SD age, 27 ± 7 years; range, 17-40 years)-12 with osteochondritis dissecans (International Cartilage Repair Society [ICRS] grades 3 and 4) and 5 with an isolated osteochondral defect (ICRS grade 4)-had the defect reconstructed with implantation of a unicortical autologous bone graft combined with ACI (the OsPlug technique). Functional outcome was assessed with Lysholm scores obtained preoperatively and at 1 and 5 years postoperatively. The repair site was evaluated with the Oswestry Arthroscopy Score (OAS), MOCART score (magnetic resonance observation of cartilage repair tissue), and ICRS II histology score. Formation of a subchondral lamina and lateral integration of the bone grafts were evaluated from magnetic resonance imaging scans. The mean defect size was 4.5 ± 2.6 cm(2) (range, 1-9 cm(2)), and the mean depth was 11.3 ± 5 mm (range, 5-18 mm). The preoperative Lysholm score improved from 45 (interquartile range [IQR], 24; range, 16-79) to 77 (IQR, 28; range, 41-100) at 1 year (P = .001) and 70 (IQR, 35; range, 33-91) at 5 years (P = .009). The mean OAS of the repair site was 6.2 (range, 0-9) at a mean of 1.3 years. The mean MOCART score was 61 ± 22 (range, 20-85) at 2.6 ± 1.8 years. Histology demonstrated generally good integration of the repair cartilage with the underlying bone. Poor lateral integration of the bone graft, as assessed on magnetic resonance imaging scan, and a low OAS were significantly associated with a poor Lysholm score and failure. A

Differential influence of vemurafenib and dabrafenib on patients’ lymphocytes despite similar clinical efficacy in melanoma

PubMed Central

Schilling, B.; Sondermann, W.; Zhao, F.; Griewank, K. G.; Livingstone, E.; Sucker, A.; Zelba, H.; Weide, B.; Trefzer, U.; Wilhelm, T.; Loquai, C.; Berking, C.; Hassel, J.; Kähler, K. C.; Utikal, J.; Al Ghazal, P.; Gutzmer, R.; Goldinger, S. M.; Zimmer, L.; Paschen, A.; Hillen, U.; Schadendorf, D.

2014-01-01

Background Since the majority of melanomas eventually become resistant and progress, combining selective BRAF inhibitors (BRAFi) with immunotherapies has been proposed to achieve more durable treatment responses. Here, we explored the impact of selective BRAFi on the hosts' immune system. Patients and methods Clinical data, whole blood counts (WBC) and serum lactate dehydrogenase (LDH) of 277 vemurafenib- and 65 dabrafenib-treated melanoma patients were evaluated. The frequency and phenotype of lymphocyte subpopulations were determined by flow cytometry while T cell cytokine secretion was measured by multiplex assays. Results Progression-free survival (PFS) as well as overall survival (OS) were similar in patients treated with either BRAFi. High pretreatment LDH was associated with shorter PFS and OS in both groups. During therapy, peripheral lymphocytes decreased by 24.3% (median, P < 0.0001) in vemurafenib-treated patients but remained unchanged in dabrafenib-treated patients (+1.2%, P = 0.717). Differentiation of peripheral lymphocytes of vemurafenib-treated patients showed a significant decrease in CD4+ T cells (P < 0.05). Within CD4+ T cells obtained during treatment, an increase in CCR7+CD45RA+ (naïve) and a decrease in CCR7+CD45RA− (central memory) populations were found (P < 0.01 for both). Furthermore, secretion of interferon-γ and interleukin-9 by CD4+ T cells was significantly lower in samples obtained during vemurafenib treatment compared with baseline samples. Conclusion While both compounds have comparable clinical efficacy, vemurafenib but not dabrafenib decreases patients peripheral lymphocyte counts and alters CD4+ T cell phenotype and function. Thus, selective BRAFi can significantly affect patients' peripheral lymphocyte populations. Fully understanding these effects could be critical for successfully implementing combinatorial therapies of BRAFi with immunomodulatory agents. PMID:24504444

Comparison of cytotoxic T lymphocyte responses against pancreatic cancer induced by dendritic cells transfected with total tumor RNA and fusion hybrided with tumor cell

PubMed Central

Chen, Jiang; Li, Hong-Yu; Wang, Di; Shao, Xiao-Dong

2015-01-01

Pancreatic cancer (PC) is a deadly human malignancy. Dendritic cell (DC)-based immunotherapy with whole tumor antigens demonstrates potential efficiency in cancer treatment. Tumor RNA and tumor fusion hybrid cells are sources of whole tumor antigens for preparing DC tumor vaccines. However, the efficacy of these sources in eliciting immune responses against PC has not yet to be directly compared. In the present study, patient-derived PC cells and DCs were fused (DC–tumor hybrids) and primary cultured PC cell-derived total RNA was electroporated into autologous DCs (DC–tumor RNA). The antitumor immune responses induced by DC–tumor hybrids and DC–tumor RNA were compared directly. The results showed that both RNA and hybrid methodologies could induce tumor-specific cytotoxic T lymphocyte (CTL) responses, but pulsing DCs with total tumor RNA could induce a higher frequency of activated CTLs and T-helper cells than fusing DCs with autologous tumor cells. In addition, DC–tumor RNA triggered stronger autologous tumor cell lysis than DC–tumor hybrids. It could be concluded that DCs pulsed with whole tumor RNA are superior to those fused with tumor cells in priming anti-PC CTL responses. Electroporation with total tumor RNA may be more suitable for DC-based PC vaccination. PMID:25736302

Autologous patch graft in tube shunt surgery.

PubMed

Aslanides, I M; Spaeth, G L; Schmidt, C M; Lanzl, I M; Gandham, S B

1999-10-01

To evaluate an alternate method of covering the subconjunctival portion of the tube in aqueous shunt surgery. Evidence of tube erosion, graft-related infection, graft melting, or other associated intraocular complications were evaluated. A retrospective study of 16 patients (17 eyes) who underwent tube shunt surgery at Wills Eye Hospital between July 1991 and October 1996 was conducted. An autologous either "free" or "rotating" scleral lamellar graft was created to cover the subconjunctival portion of the tube shunt. All patients were evaluated for at least 6 months, with a mean follow-up of 14.8 months (range 6-62 months). All eyes tolerated the autologous graft well, with no clinical evidence of tube erosion, or graft-related or intraocular complications. Autologous patch graft in tube shunt surgery appears--in selected cases--to be an effective, safe and inexpensive surgical alternative to allogenic graft materials. It also offers ease of availability, and eliminates the risk of transmitting infectious disease.

Sequential monitoring and stability of ex vivo-expanded autologous and non-autologous regulatory T cells following infusion in non-human primates

PubMed Central

Zhang, H.; Guo, H.; Lu, L.; Zahorchak, A. F.; Wiseman, R. W.; Raimondi, G.; Cooper, D. K. C.; Ezzelarab, M. B.; Thomson, A. W.

2016-01-01

Ex vivo-expanded cynomolgus monkey CD4+CD25+CD127− regulatory T cells (Treg) maintained Foxp3 demethylation status at the Treg-Specific Demethylation Region (TSDR), and potently suppressed T cell proliferation through 3 rounds of expansion. When CFSE- or VPD450-labeled autologous (auto) and non-autologous (non-auto) expanded Treg were infused into monkeys, the number of labeled auto-Treg in peripheral blood declined rapidly during the first week, but persisted at low levels in both normal and anti-thymocyte globulin plus rapamycin-treated (immunosuppressed; IS) animals for at least 3 weeks. By contrast, MHC-mismatched non-auto-Treg could not be detected in normal monkey blood or in blood of two out of the three IS monkeys by day 6 post-infusion. They were also more difficult to detect than auto-Treg in peripheral lymphoid tissue. Both auto- and non-auto-Treg maintained Ki67 expression early after infusion. Sequential monitoring revealed that adoptively-transferred auto-Treg maintained similarly high levels of Foxp3 and CD25 and low CD127 compared with endogenous Treg, although Foxp3 staining diminished over time in these non-transplanted recipients. Thus, infused ex vivo-expanded auto-Treg persist longer than MHC-mismatched non-auto-Treg in blood of non-human primates and can be detected in secondary lymphoid tissue. Host lymphodepletion and rapamycin administration did not consistently prolong the persistence of non-auto-Treg in these sites. PMID:25783759

Combined application of autologous serum eye drops and silicone hydrogel lenses for the treatment of persistent epithelial defects.

PubMed

Choi, Jin A; Chung, So-Hyang

2011-11-01

We investigated the utility of a combination of autologous serum eye drops and a silicone-hydrogel (SH) lens in the treatment of persistent epithelial defects (PEDs). Eight patients who had distinct PED conditions were treated with 50% (v/v) autologous serum eye drops in combination with silicone hydrogel contact lenses and prospectively observed. The pathogenesis of PEDs included Sjogren-type dry eye syndrome, graft-versus-host disease, toxic keratitis, limbal cell deficiency, superior limbic keratoconjunctivitis, and neurotrophic keratitis. The patients had PEDs for 90±81.76 days (range: 30-240 days). Before the initiation of the combined treatment, three patients had already been unsuccessfully treated with SH lenses, and five patients had received serum eye drops alone. The PEDs of the eight eyes healed after a treatment period of 11.8±4.9 days. No visible deposits were noted on the surface of any contact lens. These findings demonstrate that the combination of an SH lens and serum eye drops may be effective in the treatment of intractable PEDs.

Cryopreservation of Autologous Blood (Red Blood Cells, Platelets and Plasma)

NASA Astrophysics Data System (ADS)

Ebine, Kunio

Prevention of post-transfusion hepatitis is still a problem in cardiovascular surgery. We initiated the cryopreservation of autologous blood for the transfusion in elective cardiovascular surgery since 1981. This study includes 152 surgical cases in which autologous frozen, allogeneic frozen, and/or allogeneic non-frozen blood were used. In the 152 surgical cases, there were 69 cases in which autologous blood only (Group I) was used; 12 cases with autologous and allogeneic frozen blood (Group II); 46 cases with autologous and allgeneic frozen plus allogeneic non-frozen blood (Group III); and 25 cases with allogeneic frozen plus allogeneic non-frozen blood (Group IV). No hepatitis developed in Groups I (0%) and II (0%), but there was positive hepatitis in Groups III (4.3%) and IV (8.0%) . In 357 cases of those who underwent surgery with allogeneic non-frozen whole blood during the same period, the incidence rate of hepatitis was 13.7% (49/357). Patients awaiting elective surgery can store their own blood in the frozen state. Patients who undergo surgery with the cryoautotransfusion will not produce any infections or immunologic reactions as opposed to those who undergo surgery with the allogeneic non-frozen blood.

AR-42 in Treating Patients With Advanced or Relapsed Multiple Myeloma, Chronic Lymphocytic Leukemia, or Lymphoma

ClinicalTrials.gov

2017-02-21

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large

Development of autologous blood cell therapies.

PubMed

Kim, Ah Ram; Sankaran, Vijay G

2016-10-01

Allogeneic hematopoietic stem cell transplantation and blood cell transfusions are performed commonly in patients with a variety of blood disorders. Unfortunately, these donor-derived cell therapies are constrained due to limited supplies, infectious risk factors, a lack of appropriately matched donors, and the risk of immunologic complications from such products. The use of autologous cell therapies has been proposed to overcome these shortcomings. One can derive such therapies directly from hematopoietic stem and progenitor cells of individuals, which can then be manipulated ex vivo to produce the desired modifications or differentiated to produce a particular target population. Alternatively, pluripotent stem cells, which have a theoretically unlimited self-renewal capacity and an ability to differentiate into any desired cell type, can be used as an autologous starting source for such manipulation and differentiation approaches. Such cell products can also be used as a delivery vehicle for therapeutics. In this review, we highlight recent advances and discuss ongoing challenges for the in vitro generation of autologous hematopoietic cells that can be used for cell therapy. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

Intraarticular injection autologous platelet-rich plasma and bone marrow concentrate in a goat osteoarthritis model.

PubMed

Wang, Zhen; Zhai, Chenjun; Fei, Hao; Hu, Junzheng; Cui, Weiding; Wang, Zhen; Li, Zeng; Fan, Weimin

2018-02-21

To evaluate the effects of intraarticular injections of autologous platelet-rich plasma (PRP) or bone marrow concentrate (BMC) on osteoarthritis (OA), 24 adult goats were equally divided into control (Ctrl), saline (NS), PRP, and BMC groups, and OA was induced by surgery in NS, PRP, and BMC groups. Autologous PRP and BMC were obtained from whole blood and bone marrow aspirates, respectively. The data revealed, platelets were increased in BMC by 1.8-fold, monocytes by 5.6-fold, TGF-β1 by 7.7-fold, and IGF-1 by 3.6-fold (p < 0.05), and platelets were increased in PRP by 2.9-fold, and TGF-β1 by 3.3-fold (p < 0.05). From the sixth week post-operation, saline, PRP, and BMC were administered by intraarticular injection once every 4 weeks, three consecutive times. After the animals were sacrificed, inflammatory cytokines in the synovial fluid was measured, and bone and cartilage degeneration progression was observed by macroscopy, histology, and immunohistochemistry. Compared with the NS group, the level of inflammatory cytokines was reduced in the PRP and BMC groups (p < 0.05). Histologically, delayed cartilage degeneration and higher levels of extracellular matrix (ECM) were observed in both PRP and BMC treated groups (p < 0.05). Furthermore, the BMC group showed greater cartilage protection and less ECM loss than the PRP group (p < 0.05). In summary, this study showed that intraarticular injection of autologous PRP and BMC has therapeutic efficacy in a goat osteoarthritis model, with the greater benefit in terms of cartilage protection being observed in the BMC-treated group than PRP. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Performance Evaluation of High Fluorescence Lymphocyte Count: Comparability to Atypical Lymphocyte Count and Clinical Significance.

PubMed

Tantanate, Chaicharoen; Klinbua, Cherdsak

2018-06-15

To investigate the association between high-fluorescence lymphocyte cell (HFLC) and atypical lymphocyte (AL) counts, and to determine the clinical significance of HFLC. We compared automated HFLC and microscopic AL counts and analyzed the findings. Patient clinical data for each specimen were reviewed. A total of 320 blood specimens were included. The correlation between HFLC and microscopic AL counts was 0.865 and 0.893 for absolute and percentage counts, respectively. Sensitivity, specificity, and accuracy of HFLC at the cutoff value of 0.1 × 109 per L for detection of AL were 0.8, 0.77, and 0.8, respectively. Studied patients were classified into 4 groups: infection, immunological disorders, malignant neoplasms, and others. Patients with infections had the highest HFLC. Most of those patients (67.7%) had dengue infection. HFLC counts were well-correlated with AL counts with the acceptable test characteristics. Applying HFLC flagging may alert laboratory staff to be aware of ALs.

[Morphometric analysis of lymphocyte nuclei in chronic lymphocytic leukemia].

PubMed

Ostapenko, V A; Kruchinskiĭ, N G; Smirnova, L A; Cherednik, A B; Nesterov, V N; Tepliakov, A I

1994-01-01

This work is dedicated to the study of use of quantitative analysis of cell nucleus structure for the analysis of peripheral blood lymphocytes in patients with chronic lymphocytic leukaemia. The structure of lymphocytic nuclei of healthy donors was evaluated by means of staining by toluidine blue purified cell suspensions smears. The preparations were analysed on the television measuring system "omnicon" with measurements of the following parameters: square of the nucleus, euchromatin, heterochromatin, and the ratio of heterochromatin and euchromatin squares. Actuarial analysis and nuclei classification of the previously mentioned parameters showed, that in peripheral blood of patients with chronic lymphocytic leukemia a large amount of atypical lymphocytes is present with reduced nucleus sizes. Atypical cells retain the ratio of structural components of chromatine, characteristic to normal cells, which show their low proliferative activity.

Autologous implantation of BMP2-expressing dermal fibroblasts to improve bone mineral density and architecture in rabbit long bones.

PubMed

Ishihara, Akikazu; Weisbrode, Steve E; Bertone, Alicia L

2015-10-01

Cell-mediated gene therapy may treat bone fragility disorders. Dermal fibroblasts (DFb) may be an alternative cell source to stem cells for orthopedic gene therapy because of their rapid cell yield and excellent plasticity with bone morphogenetic protein-2 (BMP2) gene transduction. Autologous DFb or BMP2-expressing autologous DFb were administered in twelve rabbits by two delivery routes; a transcortical intra-medullar infusion into tibiae and delayed intra-osseous injection into femoral drill defects. Both delivery methods of DFb-BMP2 resulted in a successful cell engraftment, increased bone volume, bone mineral density, improved trabecular bone microarchitecture, greater bone defect filling, external callus formation, and trabecular surface area, compared to non-transduced DFb or no cells. Cell engraftment within trabecular bone and bone marrow tissue was most efficiently achieved by intra-osseous injection of DFb-BMP2. Our results suggested that BMP2-expressing autologous DFb have enhanced efficiency of engraftment in target bones resulting in a measurable biologic response by the bone of improved bone mineral density and bone microarchitecture. These results support that autologous implantation of DFb-BMP2 warrants further study on animal models of bone fragility disorders, such as osteogenesis imperfecta and osteoporosis to potentially enhance bone quality, particularly along with other gene modification of these diseases. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

A comparative analysis of advanced techniques for skin reconstruction with autologous keratinocyte culture in severely burned children: own experience

PubMed Central

Nessler, Michał B.; Drukala, Justyna; Bartoszewicz, Marzenna; Mądry, Ryszard

2014-01-01

Introduction The local treatment in burns larger than 50% of total body surface area is still the great challenge for surgeons. Aim This paper presents a review of different solutions for deep burn wound healing in children and the early outcomes of treatment with combined autologous cell culture technique. Material and methods For this study, 20 children aged between 4 and 12 years with 55–65% of TBSA III grade burn injury were analyzed. A skin sample, 1 cm × 1 cm in size, for keratinocyte cultivation, was taken on the day of the burn. After necrotic tissue excision, the covering of the burned area with an isolated meshed skin graft was carried out between day 4 and 7. After 7 days of keratinocyte cultivation, the mentioned areas were covered with cells from the culture. We divided the burned regions, according to the way of wound closure, into 3 groups each consisting of 15 treated regions of the body. We used meshed split thickness skin grafts (SSG group), cultured autologous keratinocytes (CAC group), and both techniques applied in one stage (SSG + CAC group). Results In the SSG group, the mean time for complete closure of wounds was 12.7 days. Wounds treated with CAC only needed a non-significantly longer time to heal – 14.2 days (p = 0.056) when compared to SSG. The shortest time to heal was observed in the group treated with SSG + CAC – 8.5 days, and it was significantly shorter when compared to the SSG and CAC groups (p < 0.001). Conclusions This study suggests that cultured keratinocytes obtained after short-time multiplication, combined with meshed autologous split thickness skin grafts, constitute the optimal wound closure in burned children. PMID:25097488

Autologous chondrocyte implantation: superior biologic properties of hyaline cartilage repairs.

PubMed

Henderson, Ian; Lavigne, Patrick; Valenzuela, Herminio; Oakes, Barry

2007-02-01

Information regarding the quality of autologous chondrocyte implantation repair is needed to determine whether the current autologous chondrocyte implantation surgical technology and the subsequent biologic repair processes are capable of reliably forming durable hyaline or hyaline-like cartilage in vivo. We report and analyze the properties and qualities of autologous chondrocyte implantation repairs. We evaluated 66 autologous chondrocyte implantation repairs in 57 patients, 55 of whom had histology, indentometry, and International Cartilage Repair Society repair scoring at reoperation for mechanical symptoms or pain. International Knee Documentation Committee scores were used to address clinical outcome. Maximum stiffness, normalized stiffness, and International Cartilage Repair Society repair scoring were higher for hyaline articular cartilage repairs compared with fibrocartilage, with no difference in clinical outcome. Reoperations revealed 32 macroscopically abnormal repairs (Group B) and 23 knees with normal-looking repairs in which symptoms leading to arthroscopy were accounted for by other joint disorders (Group A). In Group A, 65% of repairs were either hyaline or hyaline-like cartilage compared with 28% in Group B. Autologous chondrocyte repairs composed of fibrocartilage showed more morphologic abnormalities and became symptomatic earlier than hyaline or hyaline-like cartilage repairs. The hyaline articular cartilage repairs had biomechanical properties comparable to surrounding cartilage and superior to those associated with fibrocartilage repairs.

What is the role of autologous blood transfusion in major spine surgery?

PubMed

Kumar, Naresh; Chen, Yongsheng; Nath, Chinmoy; Liu, Eugene Hern Choon

2012-06-01

Major spine surgery is associated with significant blood loss, which has numerous complications. Blood loss is therefore an important concern when undertaking any major spine surgery. Blood loss can be addressed by reducing intraoperative blood loss and replenishing perioperative blood loss. Reducing intraoperative blood loss helps maintain hemodynamic equilibrium and provides a clearer operative field during surgery. Homologous blood transfusion is still the mainstay for replenishing blood loss in major spine surgery across the world, despite its known adverse effects. These significant adverse effects can be seen in up to 20% of patients. Autologous blood transfusion avoids the risks associated with homologous blood transfusion and has been shown to be cost-effective. This article reviews the different methods of autologous transfusion and focuses on the use of intraoperative cell salvage in major spine surgery. Autologous blood transfusion is a proven alternative to homologous transfusion in major spine surgery, avoiding most, if not all of these adverse effects. However, autologous blood transfusion rates in major spine surgery remain low across the world. Autologous blood transfusion may obviate the need for homologous transfusion completely. We encourage spine surgeons to consider autologous blood transfusion wherever feasible.

Pegfilgrastim and Rituximab in Treating Patients With Untreated, Relapsed, or Refractory Follicular Lymphoma, Small Lymphocytic Lymphoma, or Marginal Zone Lymphoma

ClinicalTrials.gov

2017-09-08

Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

Open questions in the management of nodular lymphocyte predominant hodgkin lymphoma.

PubMed

Tyran, Marguerite; Gonzague, Laurence; Bouabdallah, Reda; Resbeut, Michel

2014-01-01

Localized Nodular Lymphocyte Predominant Hodgkin Lymphoma is a rare disease with an overall good prognosis but frequent late relapses. Due to it's rarity there is no standard therapeutic approach and pathological diagnosis may be hard. In this paper we discuss the technical aspects of the radiation therapy and histological issues. The new fields reductions proposed for classical Hodgkin lymphoma cannot be applied to early stages Nodular Lymphocyte Predominant Hodgkin lymphomas which are usually treated with radiation therapy without systemic chemotherapy.

Spectrum of Pig-a mutations in T lymphocytes of rats treated with procarbazine.

PubMed

Revollo, Javier; Bhalli, Javed A; Tebbe, Cameron; Noteboom, Jessica; Thomas, Demetria; McKinzie, Page; Felton, Nicholas; Pearce, Mason G; Dobrovolsky, Vasily N

2017-12-31

Procarbazine is a primary component of antineoplastic combination chemotherapy often used for the treatment of Hodgkin's lymphoma. It is believed that cytostatic and cytotoxic properties of procarbazine are mediated via its interaction with genomic DNA. Procarbazine is a carcinogen in animal models; it is classified as Group 2A compound by IARC. Also it is known as an in vitro and in vivo mutagen and genotoxicant. However, the molecular mechanism by which procarbazine induces mutations is not thoroughly understood and the spectrum of procarbazine-induced in vivo mutations is described insufficiently. We employed flow cytometry-based erythrocyte and T lymphocyte assays in order to quantify the frequencies of cells deficient in glycosylphosphatidyl inositol-anchored surface markers CD59 and CD48 (presumed mutants in the endogenous X-linked Pig-a gene) in rats. The rats were treated once daily with 100 mg/kg procarbazine HCl for 3 days. In addition, we sorted mutant-phenotype spleen T cells and immediately analysed their Pig-a gene using next generation sequencing of dual-indexed multiplex libraries and error-correcting data filtering. More than 100-fold increase in the frequencies of CD59-deficient RBCs was observed at Day 29 after the last administration, and a 10-fold increase in the frequency of CD48-deficient T cells was observed at Days 45 to 50. Sequencing revealed that, in T cells from procarbazine-treated rats, mutations in the Pig-a gene occurred predominantly at A:T basepairs when A was located on the non-transcribed DNA strand. A→T transversion was the most common mutation. Our results suggest that, at least for the transcribed X-linked Pig-a gene, in vivo methyl guanine adducts are not the major contributors to mutations induced by procarbazine. © The Author(s) 2017. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Autologous conditioned plasma as therapy of tendon and ligament lesions in seven horses

PubMed Central

Georg, Rindermann; Maria, Cislakova; Gisela, Arndt

2010-01-01

This case report describes the intralesional application of autologous conditioned plasma (ACP) in seven horses as treatment of severe tendinitis of the superficial digital flexor tendon, deep digital flexor tendon, or desmitis of the inferior check ligament. Follow-up data of the horses revealed a positive outcome in 10 to 13 months post injury. All horses treated with ACP were either performing in their previous work-load or were back in full training. Further studies with long-term follow-up will have to be performed to support these clinical intermediate-term observations. PMID:20458161

Safety and efficacy of cryopreserved autologous platelet concentrates in HLA-alloimmunized patients with hematologic malignancies.

PubMed

Gerber, Bernhard; Alberio, Lorenzo; Rochat, Sophie; Stenner, Frank; Manz, Markus G; Buser, Andy; Schanz, Urs; Stussi, Georg

2016-10-01

Curative chemotherapy approaches in patients with malignancies and platelet (PLT) transfusion refractoriness due to alloimmunization may be hampered by the lack of suitable PLT donors. For these patients, transfusion of cryopreserved autologous PLTs is an option, but is time- and resource-consuming. We aimed at further simplifying this process. A retrospective single-center analysis was conducted on the transfusion of cryopreserved autologous PLTs in nine female alloimmunized, PLT transfusion-refractory patients treated for acute leukemia (n = 8) and non-Hodgkin's lymphoma (n = 1). No additional processing was used before transfusion, and most notably, washing and centrifugation steps were omitted. Clinical efficacy and safety, as well as a flow cytometric assessment of structural and functional PLT changes, were analyzed. A total of 40 autologous PLT concentrates were thawed at bedside and transfused a median of 32 (range, 9 to 994) days after cryopreservation. No major bleeds and no severe dimethyl sulfoxide toxicity were observed. The median PLT count increments did not differ 1 and 18 to 24 hours after transfusion and reached 6 × 10 9 /L (interquartile range [IQR], 3 × 10 9 -7.5 × 10 9 /L) and 6 × 10 9 /L (IQR, 2.5 × 10 9 -9.5 × 10 9 /L), respectively. Cryopreservation resulted in partial activation of one-third of the PLTs. In vitro stimulation with strong agonists induced additional full activation of cryopreserved PLTs: median, 55% (IQR, 42%-60%) after thrombin and 39% (IQR, 36%-39%) after convulxin. The transfusion of cryopreserved autologous PLTs is feasible and safe. Despite the cryopreservation process, PLT functionality is partially maintained. © 2016 AABB.

Effectiveness of autologous serum as an alternative to fetal bovine serum in adipose-derived stem cell engineering.

PubMed

Choi, Jaehoon; Chung, Jee-Hyeok; Kwon, Geun-Yong; Kim, Ki-Wan; Kim, Sukwha; Chang, Hak

2013-09-01

In cell culture, medium supplemented with fetal bovine serum is commonly used, and it is widely known that fetal bovine serum supplies an adequate environment for culture and differentiation of stem cells. Nevertheless, the use of xenogeneic serum can cause several problems. We compared the effects of four different concentrations of autologous serum (1, 2, 5, and 10%) on expansion and adipogenic differentiation of adipose-derived stem cells using 10% fetal bovine serum as a control. The stem cells were grafted on nude mice and the in vivo differentiation capacity was evaluated. The isolation of adipose-derived stem cells was successful irrespective of the culture medium. The proliferation potential was statistically significant at passage 2, as follows: 10% autologous serum > 10% fetal bovine serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. The differentiation capacity appeared statistically significant at passage 4, as follows: 10% fetal bovine serum > 10% autologous serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. Ten percent autologous serum and 10% fetal bovine serum had greater differentiation capacity than 1 and 2% autologous serum in vivo, and no significant difference was observed between the groups at ≥ 5% concentration at 14 weeks. In conclusion, 10% autologous serum was at least as effective as 10% fetal bovine serum with respect to the number of adipose-derived stem cells at the end of both isolation and expansion, whereas 1 and 2% autologous serum was inferior.

[Distal Pancreatectomy with Autologous Fibrin Sealant - Implementation of an Established Concept of Tissue Sealing in Pancreatic Surgery].

PubMed

Luu, A M; Braumann, C; Belyaev, O; Janot, M; Uhl, W; Herzog, T

2016-12-01

Background: Postoperative pancreatic fistulas (POPF) remain a major concern after distal pancreatectomy. Irrespective of the technique to close the pancreatic remnant, pancreatic fistulas will occur in approximately 30 % of patients undergoing distal pancreatectomy. For the first time ever, autologous fibrin sealant (Vivostat®) was used to additionally seal the pancreatic remnant after a distal pancreatectomy. The aim was to analyse whether this changes the postoperative outcome. Patients/Material and Methods: In 2015, a technical case series was performed in 15 patients who underwent distal pancreatectomy. The pancreatic remnant was additionally sealed with autologous fibrin sealant (Vivostat®). Results: A postoperative pancreatic fistula (POPF) occurred in 5/15 patients (33 %). One patient had a POPF grade A (1/15, 6.7 %), whereas a POPF grade B occurred in 4/15 patients (26.7 %). 75 % (3/4) of the patients with a POPF grade B were sufficiently treated with antibiotics, whereas a CT-guided percutaneous drainage had to be placed only in one case. Conclusion: Autologous fibrin sealant is simple to apply and seems to be well tolerated. However, it does not seem to avoid the development of postoperative pancreatic fistulas after distal pancreatectomy. Georg Thieme Verlag KG Stuttgart · New York.

Autologous circulating angiogenic cells treated with osteopontin and delivered via a collagen scaffold enhance wound healing in the alloxan-induced diabetic rabbit ear ulcer model.

PubMed

O'Loughlin, Aonghus; Kulkarni, Mangesh; Vaughan, Erin E; Creane, Michael; Liew, Aaron; Dockery, Peter; Pandit, Abhay; O'Brien, Timothy

2013-01-01

Diabetic foot ulceration is the leading cause of amputation in people with diabetes mellitus. Peripheral vascular disease is present in the majority of patients with diabetic foot ulcers. Despite standard treatments there exists a high amputation rate. Circulating angiogenic cells previously known as early endothelial progenitor cells are derived from peripheral blood and support angiogenesis and vasculogenesis, providing a potential topical treatment for non-healing diabetic foot ulcers. A scaffold fabricated from Type 1 collagen facilitates topical cell delivery to a diabetic wound. Osteopontin is a matricellular protein involved in wound healing and increases the angiogenic potential of circulating angiogenic cells. A collagen scaffold seeded with circulating angiogenic cells was developed. Subsequently the effect of autologous circulating angiogenic cells that were seeded in a collagen scaffold and topically delivered to a hyperglycemic cutaneous wound was assessed. The alloxan-induced diabetic rabbit ear ulcer model was used to determine healing in response to the following treatments: collagen seeded with autologous circulating angiogenic cells exposed to osteopontin, collagen seeded with autologous circulating angiogenic cells, collagen alone and untreated wound. Stereology was used to assess angiogenesis in wounds. The cells exposed to osteopontin and seeded on collagen increased percentage wound closure as compared to other groups. Increased angiogenesis was observed with the treatment of collagen and collagen seeded with circulating angiogenic cells. These results demonstrate that topical treatment of full thickness cutaneous ulcers with autologous circulating angiogenic cells increases wound healing. Cells exposed to the matricellular protein osteopontin result in superior wound healing. The wound healing benefit is associated with a more efficient vascular network. This topical therapy provides a potential novel therapy for the treatment of non

Autologous Blood Versus Fibrin Glue in Pterygium Excision With Conjunctival Autograft Surgery.

PubMed

Nadarajah, Gaayathri; Ratnalingam, Vanitha Hema; Mohd Isa, Hazlita

2017-04-01

To evaluate graft stability and recurrence rate between fibrin glue and autologous blood in pterygium conjunctival autograft surgery. A prospective, randomized, single-blinded clinical trial to assess the efficacy of autologous blood in place of fibrin glue in pterygium surgery. A total of 120 eyes of 111 patients were randomized according to pterygium morphology, to undergo pterygium surgery with autografting using either autologous blood or fibrin glue. All patients were operated by a single surgeon; 58 eyes were operated using fibrin glue and 62 eyes had a conjunctival autograft with autologous blood. Patients were seen on postoperative day 1, 1 week, 1 month, 6 months, and 1 year after surgery. Graft stability and pterygium recurrence were graded by an independent observer who was masked to the method of treatment. All 120 eyes completed the 1-year follow-up. Graft loss was seen only in the autologous blood group. Of the 62 eyes in this group, a total of 15 (24.2%) grafts dislodged. Recurrence was calculated after excluding grafts that were dislodged. Of the 105 patients, there were a total of 7 recurrences, 2 (3.4%) from the fibrin adhesive method and 5 (10.6%) from the autologous blood method. This was not statistically significant (P = 0.238). Autologous blood does not exhibit similar graft stability seen with fibrin glue. Although the recurrence rate may not be significant, careful patient selection and a standard method needs to be laid out before the use of this method is widely accepted.

Further characterization of the circulating cell in chronic lymphocytic leukemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schutz, E.F.; Davis, S.; Rubin, A.D.

Peripheral lymphocytes from normal individuals and from patients with chronic lymphocytic leukemia (CLL) were cultured in vitro for 1-7 days. The growth response to phytohemagglutinin (PHA) was quantitated by the incorporation of tritiated uridine into RNA nucleotide during a 2-hr pulse with the radioisotope. While the maximum response in PHA-stimulated normal cultures appeared at 2-3 days, CLL cultures required 5-7 days to develop their maximal response, which was 50 percent-60 percent of the normal magnitude. Dilution of the number of normally reactive lymphocytes by culturing them with totally unreactive, mitomycin-treated cells produced a normal 72-hr maximal response, no matter whatmore » proportion of unreactive cells was included in the PHA-stimulated cultures. In addition, the response of peripheral lymphocytes from patients with myeloblastic leukemia, where large numbers of unreactive myeloblasts diluted the normal small lymphocytes, a depressed reaction occurred at the anticipated 2-3 days. Nylon fiber-adherent lymphocytes consisting of 85 percent immunoglobulin (Ig)-bearing cells responded minimally to PHA, but showed no evidence of a delay. When isolated from CLL patients, both fiber-adherent cells (ig-bearing) as well as non-fiber-adherent (sheep erythrocyte-rosetting) cells responded to PHA in a delayed fashion. Similarly, a case of CLL, in which 93.5 percent of the circulating lymphocytes bore sheep red blood cell receptors, showed its peak response to PHA at 7 days. Therefore, using surface marker criteria considered characteristic of normal T cells and B cells, the delayed response to PHA on the part of CLL lymphocytes was independent of thymic or nonthymic origin.« less

Efficacy of autologous platelets in macular hole surgery.

PubMed

Konstantinidis, Aristeidis; Hero, Mark; Nanos, Panagiotis; Panos, Georgios D

2013-01-01

The introduction of optical coherence tomography has allowed accurate measurement of the size of macular holes. A retrospective consecutive review was performed of 21 patients undergoing macular hole repair with vitrectomy, gas tamponade, and autologous platelet injection and we assessed the effect of macular hole parameters on anatomic and functional outcomes. We looked at the demographic features, final visual outcome, and anatomical closure. Twenty-one patients were included in the study. They underwent routine vitrectomy with gas tamponade (C3F8) and injection of autologous platelets. All patients were advised to maintain a facedown posture for 2 weeks. Anatomical closure was confirmed in all cases and 20 out of 21 of patients had improved postoperative visual acuity by two or more lines. In our series, the macular hole dimensions did not have much effect on the final results. The use of autologous platelets and strict facedown posture seems to be the deciding factor in good anatomical and visual outcome irrespective of macular hole dimensions.

Sulforaphane mitigates genotoxicity induced by radiation and anticancer drugs in human lymphocytes.

PubMed

Katoch, Omika; Kumar, Arun; Adhikari, Jawahar S; Dwarakanath, Bilikere S; Agrawala, Paban K

2013-12-12

Sulforaphane, present in cruciferous vegetables such as broccoli, is a dietary anticancer agent. Sulforaphane, added 2 or 20 h following phytohemaglutinin stimulation to cultured peripheral blood lymphocytes of individuals accidentally exposed to mixed γ and β-radiation, reduced the micronucleus frequency by up to 70%. Studies with whole blood cultures obtained from healthy volunteers confirmed the ability of sulforaphane to ameliorate γ-radiation-induced genotoxicity and to reduce micronucleus induction by other DNA-damaging anticancer agents, such as bleomycin and doxorubicin. This reduction in genotoxicity in lymphocytes treated at the G(0) or G(1) stage suggests a role for sulforaphane in modulating DNA repair. Sulforaphane also countered the radiation-induced increase in lymphocyte HDAC activity, to control levels, when cells were treated 2 h after exposure, and enhanced histone H4 acetylation status. Sulforaphane post-irradiation treatment enhanced the CD 34(+)Lin(-) cell population in culture. Sulforaphane has therapeutic potential for management of the late effects of radiation. Copyright © 2013 Elsevier B.V. All rights reserved.

Clinical observation of the application of autologous peripheral blood stem cell transplantation for the treatment of diabetic foot gangrene

PubMed Central

XU, SHI-MIN; LIANG, TING

2016-01-01

The aim of the present study was to investigate the optimal mobilization plan in autologous peripheral blood stem cell transplantation for the treatment of diabetic foot and to observe its clinical curative effect. A total of 127 patients with diabetic foot were treated with different doses of granulocyte colony stimulating factor (G-CSF) to mobilize their hematopoietic stem cells. Subsequently, the extracted stem cell suspension was injected into the ischemic lower extremities along the blood vessels in the areas presenting with pathological changes. Following the treatment, the intermittent claudication distance, skin temperature, ankle brachial index and pain scores of the patients were evaluated. In addition, the associations among the mobilization time, doses and peripheral blood CD34+ level were analyzed. The collection efficiency of the stem cells was associated with the dose of G-CSF and the mobilization time. Following the injection of the autologous peripheral blood stem cell suspension, the ischemic area of the patients was improved significantly. In conclusion, autologous peripheral blood stem cell transplantation can promote the establishment of collateral circulation in patients with diabetic foot, and the optimal time for gathering stem cells is closely correlated with the peripheral blood CD34+ level. PMID:26889255

The role of stem cell mobilization regimen on lymphocyte collection yield in patients with multiple myeloma.

PubMed

Hiwase, D K; Hiwase, S; Bailey, M; Bollard, G; Schwarer, A P

2008-01-01

The lymphocyte dose (LY-DO) infused during an autograft influences absolute lymphocyte (ALC) recovery and survival following autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Factors influencing lymphocyte yield (LY-C) during leukapheresis have been poorly studied. Factors that could influence survival, LY-C and CD34(+) cell yield were analyzed in 122 MM patients. Three mobilization regimens were used, granulocyte-colony-stimulating factor (G-CSF) alone (n=13), cyclophosphamide 1-2 g/m(2) plus G-CSF (LD-CY, n=62) and cyclophosphamide 3-4 g/m(2) and G-CSF (ID-CY, n=47). Using multivariate analysis, age, LY-C, ALC on day 30 (ALC-30) and International Staging System stage significantly influenced overall (OS) and progression-free survival (PFS) following ASCT. PFS (56 versus 29 months, P=0.05) and OS (72 versus 49 months; P=0.07) were longer in the LY-C>or=0.12x10(9)/kg group than the LY-C<0.12x10(9)/kg group. LY-C also influenced ALC on day 15 (ALC-15). Mobilization regimen, lymphocytes on the day of leukapheresis, prior radiotherapy and number of leukaphereses significantly influenced LY-C. Significantly higher LY-C was obtained with G-CSF alone compared with the LD-CY and ID-CY groups. CD34(+) count on the day of leukapheresis, prior chemotherapy with prednisone, cyclophosphamide, adriamycin and BCNU or melphalan, and stem cell mobilization regimen significantly influenced CD34(+) cell yield. LY-C influenced ALC-15 and survival following ASCT. Factors that influenced CD34(+) cell yield and LY-C during leukapheresis were different. Mobilization should be tailored to maximize the LY-C and CD34(+) cell yield.

Therapeutic Vaccination against Adjuvant Arthritis Using Autoimmune T Cells Treated with Hydrostatic Pressure

NASA Astrophysics Data System (ADS)

Lider, Ofer; Karin, Nathan; Shinitzky, Meir; Cohen, Irun R.

1987-07-01

An ideal treatment for autoimmune diseases would be a nontoxic means of specifically neutralizing the autoreactive lymphocytes responsible for the disease. This goal has been realized in experimental autoimmunity models by immunizing rats or mice against their own autoimmune cells such that the animals generate an immune response specifically repressive to the disease-producing lymphocytes. This maneuver, termed lymphocyte vaccination, was demonstrated to be effective using some, but not all, autoimmune helper T-lymphocyte lines. We now report that T lymphocytes, otherwise incapable of triggering an immune response, can be transformed into effective immunogens by treating the cells in vitro with hydrostatic pressure. Clone A2b, as effector clone that recognized cartilage proteoglycan and caused adjuvant arthritis in Lewis rats, is such a cell. Untreated A2b could not trigger an immune response, but inoculating rats with pressure-treated A2b induced early remission of established adjuvant arthritis as well as resistance to subsequent disease. Specific resistance to arthritis was associated with anti-idiotypic T-cell reactivity to clone A2b and could be transferred from vaccinated rats to naive recipients using donor lymphoid cells. Aggregation of T-lymphocyte membrane components appeared to be important for an immune response because the effects of hydrostatic pressure could be reproduced by treatment of A2b with chemical cross-linkers or with agents disrupting the cytoskeleton. Populations of lymph node cells from antigen-primed rats, when treated with hydrostatic pressure, could also induce suppression of disease. Thus, effective vaccines can be developed without having to isolate the autoimmune T lymphocytes as lines or clones. These results demonstrate that effector T lymphocytes suitably treated may serve as agents for specifically controlling the immune system.

Molecular Mechanisms of Particle Ration Induced Apoptosis in Lymphocyte

NASA Astrophysics Data System (ADS)

Shi, Yufang

Space radiation, composed of high-energy charged nuclei (HZE particles) and protons, has been previously shown to severely impact immune homeostasis in mice. To determine the molecular mechanisms that mediate acute lymphocyte depletion following exposure to HZE particle radiation mice were exposed to particle radiation beams at Brookhaven National Laboratory. We found that mice given whole body 5 6Fe particle irradiation (1GeV /n) had dose-dependent losses in total lymphocyte numbers in the spleen and thymus (using 200, 100 and 50 cGy), with thymocytes being more sensitive than splenocytes. All phenotypic subsets were reduced in number. In general, T cells and B cells were equally sensitive, while CD8+ T cells were more senstive than CD4+ T cells. In the thymus, immature CD4+CD8+ double-positive thymocytes were exquisitely sensitive to radiation-induced losses, single-positive CD4 or CD8 cells were less sensitive, and the least mature double negative cells were resistant. Irradiation of mice deficient in genes encoding essential apoptosis-inducing proteins revealed that the mechanism of lymphocyte depletion is independent of Fas ligand and TRAIL (TNF-ralated apoptosis-inducing ligand), in contrast to γ-radiation-induced lymphocyte losses which require the Fas-FasL pathway. Using inhibitors in vitro, lymphocyte apoptosis induced by HZE particle radiation was found to be caspase dependent, and not involve nitric oxide or oxygen free radicals.

A Novel Method of Orbital Floor Reconstruction Using Virtual Planning, 3-Dimensional Printing, and Autologous Bone.

PubMed

Vehmeijer, Maarten; van Eijnatten, Maureen; Liberton, Niels; Wolff, Jan

2016-08-01

Fractures of the orbital floor are often a result of traffic accidents or interpersonal violence. To date, numerous materials and methods have been used to reconstruct the orbital floor. However, simple and cost-effective 3-dimensional (3D) printing technologies for the treatment of orbital floor fractures are still sought. This study describes a simple, precise, cost-effective method of treating orbital fractures using 3D printing technologies in combination with autologous bone. Enophthalmos and diplopia developed in a 64-year-old female patient with an orbital floor fracture. A virtual 3D model of the fracture site was generated from computed tomography images of the patient. The fracture was virtually closed using spline interpolation. Furthermore, a virtual individualized mold of the defect site was created, which was manufactured using an inkjet printer. The tangible mold was subsequently used during surgery to sculpture an individualized autologous orbital floor implant. Virtual reconstruction of the orbital floor and the resulting mold enhanced the overall accuracy and efficiency of the surgical procedure. The sculptured autologous orbital floor implant showed an excellent fit in vivo. The combination of virtual planning and 3D printing offers an accurate and cost-effective treatment method for orbital floor fractures. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Retinoic acid postconsolidation therapy for high-risk neuroblastoma patients treated with autologous haematopoietic stem cell transplantation.

PubMed

Peinemann, Frank; van Dalen, Elvira C; Enk, Heike; Berthold, Frank

2017-08-25

Neuroblastoma is a rare malignant disease and mainly affects infants and very young children. The tumours mainly develop in the adrenal medullary tissue, with an abdominal mass as the most common presentation. About 50% of patients have metastatic disease at diagnosis. The high-risk group is characterised by metastasis and other features that increase the risk of an adverse outcome. High-risk patients have a five-year event-free survival of less than 50%. Retinoic acid has been shown to inhibit growth of human neuroblastoma cells and has been considered as a potential candidate for improving the outcome of patients with high-risk neuroblastoma. This review is an update of a previously published Cochrane Review. To evaluate the efficacy and safety of additional retinoic acid as part of a postconsolidation therapy after high-dose chemotherapy (HDCT) followed by autologous haematopoietic stem cell transplantation (HSCT), compared to placebo retinoic acid or to no additional retinoic acid in people with high-risk neuroblastoma (as defined by the International Neuroblastoma Risk Group (INRG) classification system). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2016, Issue 11), MEDLINE in PubMed (1946 to 24 November 2016), and Embase in Ovid (1947 to 24 November 2016). Further searches included trial registries (on 22 December 2016), conference proceedings (on 23 March 2017) and reference lists of recent reviews and relevant studies. We did not apply limits by publication year or languages. Randomised controlled trials (RCTs) evaluating additional retinoic acid after HDCT followed by HSCT for people with high-risk neuroblastoma compared to placebo retinoic acid or to no additional retinoic acid. Primary outcomes were overall survival and treatment-related mortality. Secondary outcomes were progression-free survival, event-free survival, early toxicity, late toxicity, and health-related quality of life. We used standard

BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties

PubMed Central

Haymaker, Cara L; Wu, Richard C; Ritthipichai, Krit; Bernatchez, Chantale; Forget, Marie-Andrée; Chen, Jie Qing; Liu, Hui; Wang, Ena; Marincola, Francesco; Hwu, Patrick; Radvanyi, Laszlo G

2015-01-01

In a recent adoptive cell therapy (ACT) clinical trial using autologous tumor-infiltrating lymphocytes (TILs) in patients with metastatic melanoma, we found an association between CD8+ T cells expressing the inhibitory receptor B- and T-lymphocyte attenuator (BTLA) and clinical response. Here, we further characterized this CD8+BTLA+ TIL subset and their CD8+BTLA− counterparts. We found that the CD8+ BTLA+ TILs had an increased response to IL-2, were less-differentiated effector-memory (TEM) cells, and persisted longer in vivo after infusion. In contrast, CD8+BTLA− TILs failed to proliferate and expressed genes associated with T-cell deletion/tolerance. Paradoxically, activation of BTLA signaling by its ligand, herpes virus entry mediator (HVEM), inhibited T-cell division and cytokine production, but also activated the Akt/PKB pathway thus protecting CD8+BTLA+ TILs from apoptosis. Our results point to a new role of BTLA as a useful T-cell differentiation marker in ACT and a dual signaling molecule that curtails T-cell activation while also conferring a survival advantage for CD8+ T cells. These attributes may explain our previous observation that BTLA expression on CD8+ TILs correlates with clinical response to adoptive T-cell therapy in metastatic melanoma. PMID:26405566

Perinatal outcomes after gestational surrogacy versus autologous IVF: analysis of national data.

PubMed

Sunkara, Sesh Kamal; Antonisamy, Belavendra; Selliah, Hepsy Y; Kamath, Mohan S

2017-12-01

Anonymized data were obtained from the Human Fertilization and Embryology Authority to determine whether gestational surrogacy influences perinatal outcomes compared with pregnancies after autologous IVF. A total of 103,160 singleton live births, including 244 after gestational surrogacy, 87,571 after autologous fresh IVF and intractyoplasmic sperm injection (ICSI) and 15,345 after autologous frozen embryo transfers were analysed. Perinatal outcomes of pretern birth (PTB), low birth weight (LBW) and high birth weight (HBW) were compared. No difference was found in the risk of PTB and LBW after gestational surrogacy compared with autologous fresh IVF-ICSI: PTB (adjusted OR 0.90, 95% CI 0.56 to 1.42), LBW (adjusted OR 0.90, 95% CI 0.57 to 1.43) and gestational surrogacy compared with autologous frozen embryo transfers: PTB (adjusted OR 0.96, 95% CI 0.58 to 1.60), LBW (adjusted OR 1.16, 95% CI 0.69 to 1.96). The incidence of HBW was significantly higher after gestational surrogacy compared with fresh IVF-ICSI (adjusted OR 1.94, 95% CI 1.38 to 2.75); no difference was found in HBW between gestational surrogacy and autologous frozen embryo transfers. The dataset is limited by lack of information on confounders, i.e. ethnicity, body mass index, underlying medical history, which could result in residual confounding. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Lymphocyte thymidine kinase and treatment response in acute lymphocytic leukemia.

PubMed

Russo, S A; Harris, M B; Greengard, O

1987-01-01

The activity of thymidine kinase (TK) and the proportion of its isozymes (TK1/TK2) were studied in peripheral lymphoid cells of 37 children with acute lymphocytic leukemia (ALL). The high TK in 25 untreated subjects (31.5 +/- 8.9) decreased during chemotherapy-induced remission to uniformly low (5.3 +/- 0.4) normal values, and rose again during relapse to a mean of (24.8 +/- 8.1). The proportion of isozyme 1 followed the same pattern but TK was a more sensitive indicator of disease state. The lymphocyte fractions' TK (per mg protein) correlated with the number (per ml blood) of WBCs, blasts and lymphocytes. Although the higher TK of blasts than of apparently normal lymphocytes was confirmed in cases permitting clean physical separation, the lymphocyte fraction of several untreated subjects with minimal blast counts also exhibited elevated TK. Moreover, this elevation was also seen in relapsed cases even if their blood (unlike bone marrow) was devoid of blasts. The results indicate that quantification of TK can reveal a subpopulation of maldifferentiated lymphocytes which are microscopically normal and that it may provide an objective parameter of prognostic differences between ALL subjects with similar hematological characteristics.

Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes

PubMed Central

Cho, Yoon Hee; Lee, Joong Won; Woo, Hae Dong; Lee, Sunyeong; Kim, Yang Jee; Lee, Younghyun; Shin, Sangah; Joung, Hyojee; Chung, Hai Won

2016-01-01

Following one of the world’s largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes. PMID:26907305

Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes.

PubMed

Cho, Yoon Hee; Lee, Joong Won; Woo, Hae Dong; Lee, Sunyeong; Kim, Yang Jee; Lee, Younghyun; Shin, Sangah; Joung, Hyojee; Chung, Hai Won

2016-02-19

Following one of the world's largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes.

The changes in the T-lymphocyte subsets in a population of Turkish children with puberty gingivitis.

PubMed

Demir, Turgut; Orbak, Recep; Tezel, Adnan; Canakç, Varol; Kaya, Hasan

2009-05-01

The aim of the study was to investigate the number of CD4 and CD8 T lymphocytes, analyse subjects with gingivitis and those without, and determine the role of T lymphocytes in the pathobiology of puberty gingivitis. Fifty individuals with and without puberty gingivitis were recruited for this study. The CD4(+) and CD8(+) T-lymphocyte counts were determined using flow cytometry on the biopsy samples, and the CD4(+)/CD8(+) ratio was calculated. At the same time, periodontal index scores were recorded to assess the periodontal status. Acquired data were analysed statistically using a paired t-test to compare laboratory values obtained before and after the treatment in individuals with puberty gingivitis and disease-free individuals. In addition, Pearson's correlation analysis was performed to investigate the relation between laboratory values and clinical measurements. The CD4(+)/CD8 ratio in gingival tissues obtained from test group was significantly higher (P < 0.05) than that found in the gingival tissue obtained from control group. We found that the CD4(+) and CD8(+) lymphocyte counts continued to increase significantly (P < 0.001) and the CD4(+)/CD8(+) ratio continued to drop significantly (P < 0.05) after treatment in test group. T lymphocytes could play a significant role in the pathobiology of puberty gingivitis.

A Pharmacokinetic/Pharmacodynamic Model of Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia Patients Treated with Flavopiridol

PubMed Central

Ji, Jia; Mould, Diane R.; Blum, Kristie A.; Ruppert, Amy S.; Poi, Ming; Zhao, Yuan; Johnson, Amy J.; Byrd, John C.; Grever, Michael R.; Phelps, Mitch A.

2013-01-01

Purpose Flavopiridol, the first clinically evaluated cyclin dependent kinase inhibitor, demonstrates activity in patients with refractory chronic lymphocytic leukemia, but prevalent and unpredictable tumor lysis syndrome (TLS) presents a major barrier to its broad clinical use. The purpose of this study was to investigate the relationships between pretreatment risk factors, drug pharmacokinetics, and TLS. Experimental Design A population pharmacokinetic/pharmacodynamic model linking drug exposure and TLS was developed. Plasma data of flavopiridol and its glucuronide metabolite (flavo-G) were obtained from 111 patients treated in early phase trials with frequent sampling following initial and/or escalated doses. TLS grading was modeled with logistic regression as a pharmacodynamic endpoint. Demographics, baseline disease status, and blood chemistry variables were evaluated as covariates. Results Gender was the most significant pharmacokinetic covariate, with females displaying higher flavo-G exposure than males. Glucuronide metabolite exposure was predictive of TLS occurrence, and bulky lymphadenopathy was identified as a significant covariate on TLS probability. The estimated probability of TLS occurrence in patients with baseline bulky lymphadenopathy < 10 cm or > 10 cm during the first two treatments was 0.111 (SE% 13.0%) and 0.265, (SE% 17.9%) respectively, when flavo-G area under the plasma concentration vs. time curve was at its median value in whole patient group. Conclusions This is the first population pharmacokinetic/pharmacodynamic model of TLS. Further work is needed to explore potential mechanisms and to determine if the associations between TLS, gender and glucuronide metabolites are relevant in CLL patients treated with other cyclin dependent kinase inhibitors. PMID:23300276

Evaluation of 230 patients with relapsed/refractory deletion 17p chronic lymphocytic leukaemia treated with ibrutinib from 3 clinical trials.

PubMed

Jones, Jeffrey; Mato, Anthony; Coutre, Steven; Byrd, John C; Furman, Richard R; Hillmen, Peter; Osterborg, Anders; Tam, Constantine; Stilgenbauer, Stephan; Wierda, William G; Heerema, Nyla A; Eckert, Karl; Clow, Fong; Zhou, Cathy; Chu, Alvina D; James, Danelle F; O'Brien, Susan M

2018-06-05

Patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) with deletion 17p [del(17p)] have poor outcomes with chemoimmunotherapy. Ibrutinib is indicated for the treatment of CLL/SLL, including del(17p) CLL/SLL, and allows for treatment without chemotherapy. This integrated analysis was performed to evaluate outcomes in 230 patients with relapsed/refractory del(17p) CLL/SLL from three ibrutinib studies. With a median of 2 prior therapies (range, 1-12), 18% and 79% of evaluable patients had del(11q) or unmutated IGHV, respectively. With a median follow-up of 28 months, overall response rate was 85% and estimated 30-month progression-free and overall survival rates were 57% [95% confidence interval (CI) 50-64] and 69% (95% CI 61-75), respectively. Patients with normal lactate dehydrogenase or no bulky disease had the most favourable survival outcomes. Sustained haematological improvements in haemoglobin, platelet count and absolute neutrophil count occurred in 61%, 67% and 70% of patients with baseline cytopenias, respectively. New onset severe cytopenias and infections decreased in frequency over time. Progression-free and overall survival with ibrutinib surpass those of other therapies for patients with del(17p) CLL/SLL. These results provide further evidence of the robust clinical activity of ibrutinib in difficult-to-treat CLL/SLL populations. © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Biologic activity of irradiated, autologous, GM-CSF-secreting leukemia cell vaccines early after allogeneic stem cell transplantation

PubMed Central

Ho, Vincent T.; Vanneman, Matthew; Kim, Haesook; Sasada, Tetsuro; Kang, Yoon Joong; Pasek, Mildred; Cutler, Corey; Koreth, John; Alyea, Edwin; Sarantopoulos, Stefanie; Antin, Joseph H.; Ritz, Jerome; Canning, Christine; Kutok, Jeffery; Mihm, Martin C.; Dranoff, Glenn; Soiffer, Robert

2009-01-01

Through an immune-mediated graft-versus-leukemia effect, allogeneic hematopoietic stem cell transplantation (HSCT) affords durable clinical benefits for many patients with hematologic malignancies. Nonetheless, subjects with high-risk acute myeloid leukemia or advanced myelodysplasia often relapse, underscoring the need to intensify tumor immunity within this cohort. In preclinical models, allogeneic HSCT followed by vaccination with irradiated tumor cells engineered to secrete GM-CSF generates a potent antitumor effect without exacerbating the toxicities of graft-versus-host disease (GVHD). To test whether this strategy might be similarly active in humans, we conducted a Phase I clinical trial in which high-risk acute myeloid leukemia or myelodysplasia patients were immunized with irradiated, autologous, GM-CSF-secreting tumor cells early after allogeneic, nonmyeloablative HSCT. Despite the administration of a calcineurin inhibitor as prophylaxis against GVHD, vaccination elicited local and systemic reactions that were qualitatively similar to those previously observed in nontransplanted, immunized solid-tumor patients. While the frequencies of acute and chronic GVHD were not increased, 9 of 10 subjects who completed vaccination achieved durable complete remissions, with a median follow-up of 26 months (range 12–43 months). Six long-term responders showed marked decreases in the levels of soluble NKG2D ligands, and 3 demonstrated normalization of cytotoxic lymphocyte NKG2D expression as a function of treatment. Together, these results establish the safety and immunogenicity of irradiated, autologous, GM-CSF-secreting leukemia cell vaccines early after allogeneic HSCT, and raise the possibility that this combinatorial immunotherapy might potentiate graft-versus-leukemia in patients. PMID:19717467

Lymphocyte-dependent antibodies in uveitis.

PubMed

Pápai, I; Lehrner, J

1976-01-01

Lymphocyte-dependent antibodies were revealed in the serum of patients suffering from uveitis of various aetiologies. The serum was incubated with normal uveal tissue and the binding of non-immune human lymphocytes was investigated. In three cases of sympathetic ophthalmitis the lymphocytes accumulated around the melanine granules, while in another 17 patients with uveitis cases the lymphocytes accumulated around the capillaries. Uveal tissue incubated with control sera failed to bound lymphocytes. The lymphocytic infiltration in certain cases of chronic uveitis suggested the role of lymphocyte-mediating antibodies in the aetiology of these cases.

Bioactivity of Autologous Irradiated Renal Cell Carcinoma Vaccines Generated by ex Vivo Granulocyte-Macrophage Colony-stimulating Factor Gene Transfer1

PubMed Central

Simons, Jonathan W.; Jaffee, Elizabeth M.; Weber, Christine E.; Levitsky, Hyam I.; Nelson, William G.; Carducci, Michael A.; Lazenby, Audrey J.; Cohen, Lawrence K.; Finn, Christy C.; Clift, Shirley M.; Hauda, Karen M.; Beck, Lisa A.; Leiferman, Kristen M.; Owens, Albert H.; Piantadosi, Steven; Dranoff, Glenn; Mulligan, Richard C.; Pardoll, Drew M.; Marshall, Fray F.

2014-01-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced, irradiated tumor vaccines induce potent, T-cell-mediated antitumor immune responses in preclinical models. We report the initial results of a Phase I trial evaluating this strategy for safety and the induction of immune responses in patients with metastatic renal cell carcinoma (RCC). Patients were treated in a randomized, double-blind dose-escalation study with equivalent doses of autologous, irradiated RCC vaccine cells with or without ex vivo human GM-CSF gene transfer. The replication-defective retroviral vector MFG was used for GM-CSF gene transfer. No dose-limiting toxicities were encountered in 16 fully evaluable patients. GM-CSF gene-transduced vaccines were equivalent in toxicity to nontransduced vaccines up to the feasible limits of autologous tumor vaccine yield. No evidence of autoimmune disease was observed. Biopsies of intradermal sites of injection with GM-CSF gene-transduced vaccines contained distinctive macrophage, dendritic cell, eosinophil, neutrophil, and T-cell infiltrates similar to those observed in preclinical models of efficacy. Histological analysis of delayed-type hypersensitivity responses in patients vaccinated with GM-CSF-transduced vaccines demonstrated an intense eosinophil infiltrate that was not observed in patients who received nontransduced vaccines. An objective partial response was observed in a patient treated with GM-CSF gene-transduced vaccine who displayed the largest delayed-type hypersensitivity conversion. No replication-competent retrovirus was detected in vaccinated patients. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous GM-CSF gene-transduced tumor vaccine for RCC patients. PMID:9108457

Neutrophil to lymphocyte ratio (NLR) improves the risk assessment of ISS staging in newly diagnosed MM patients treated upfront with novel agents.

PubMed

Romano, A; Parrinello, N L; Consoli, M L; Marchionni, L; Forte, S; Conticello, C; Pompa, A; Corso, A; Milone, G; Di Raimondo, F; Borrello, I

2015-11-01

Recent reports identify the ratio between absolute neutrophil count (ANC) and absolute lymphocyte count (ALC), called neutrophil to lymphocyte ratio (NLR), as a predictor of progression-free survival (PFS) and overall survival (OS) in various malignancies. We retrospectively examined the NLR in a cohort of 309 newly diagnosed multiple myeloma (MM) patients treated upfront with novel agents. NLR was calculated using data obtained from the complete blood count (CBC) at diagnosis and subsequently correlated with PFS and OS. The median NLR was 1.9 (range 0.4-15.9). Higher NLR was independent of international staging system (ISS) stage, plasma cell infiltration or cytogenetics. The 5-year PFS and OS estimates were, respectively, 18.2 and 36.4 % for patients with NLR ≥ 2 versus 25.5 and 66.6 % in patients with NLR < 2. Among younger patients (age <65 years, N = 179), NLR ≥ 2 had a negative prognostic impact on both PFS and OS, in all ISS stages. By combining ISS stage and NLR in a model limited to young patients, we found that 19 % of the patients were classified as very low risk, 70 % standard risk and 11 % very high risk. The 5-year estimates were 39.3, 19.4 and 10.9 % for PFS and 95.8, 50.9 and 23.6 % for OS for very low, standard-risk and very high-risk groups. We found NLR to be a predictor of PFS and OS in MM patients treated upfront with novel agents. NLR can be combined with ISS staging system to identify patients with dismal outcome. However, larger cohorts and prospective studies are needed to use NLR as additional parameter to personalise MM therapy in the era of novel agents.

Autologous Serum Therapy in Chronic Urticaria

PubMed Central

Patil, Sharmila; Sharma, Nidhi; Godse, Kiran

2013-01-01

Autologous serum therapy is a promising therapy for treatment resistant urticaria. This is useful in developing countries as this is economical option. Minimum instruments like centrifuge, syringe and needles are required for the procedure. PMID:23723475

Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF

PubMed Central

Alentorn-Geli, Eduard; Steinbacher, Gilbert; Álvarez-Díaz, Pedro; Cuscó, Xavier; Seijas, Roberto; Barastegui, David; Navarro, Jordi; Laiz, Patricia; García-Balletbó, Montserrat

2017-01-01

Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients. PMID:28798878

Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF.

PubMed

Cugat, Ramón; Alentorn-Geli, Eduard; Steinbacher, Gilbert; Álvarez-Díaz, Pedro; Cuscó, Xavier; Seijas, Roberto; Barastegui, David; Navarro, Jordi; Laiz, Patricia; García-Balletbó, Montserrat

2017-01-01

Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients.

Autologous fat grafting: use of closed syringe microcannula system for enhanced autologous structural grafting

PubMed Central

Alexander, Robert W; Harrell, David B

2013-01-01

Objectives Provide background for use of acquiring autologous adipose tissue as a tissue graft and source of adult progenitor cells for use in cosmetic plastic surgery. Discuss the background and mechanisms of action of closed syringe vacuum lipoaspiration, with emphasis on accessing adipose-derived mesenchymal/stromal cells and the stromal vascular fraction (SVF) for use in aesthetic, structural reconstruction and regenerative applications. Explain a proven protocol for acquiring high-quality autologous fat grafts (AFG) with use of disposable, microcannula systems. Design Explain the components and advantage of use of the patented super luer-lock and microcannulas system for use with the closed-syringe system. A sequential explanation of equipment selection for minimally traumatic lipoaspiration in small volumes is presented, including use of blunt injection cannulas to reduce risk of embolism. Results Thousands of AFG have proven safe and efficacious for lipoaspiration techniques for large and small structural fat grafting procedures. The importance and advantages of gentle harvesting of the adipose tissue complex has become very clear in the past 5 years. The closed-syringe system offers a minimally invasive, gentle system with which to mobilize subdermal fat tissues in a suspension form. Resulting total nuclear counting of undifferentiated cells of the adipose-derived -SVF suggests that the yield achieved is better than use of always-on, constant mechanical pump applied vacuum systems. Conclusion Use of a closed-syringe lipoaspiration system featuring disposable microcannulas offers a safe and effective means of harvesting small volumes of nonmanipulated adipose tissues and its accompanying progenitor cells within the SVF. Closed syringes and microcannulas are available as safe, sterile, disposable, compact systems for acquiring high-quality AFG. Presented is a detailed, step-by-step, proven protocol for performing quality autologous structural adipose

Investigation of the relationship between neutrophil-to-lymphocyte ratio and obstructive sleep apnoea syndrome.

PubMed

Yenigun, A; Karamanli, H

2015-09-01

To investigate the neutrophil-to-lymphocyte ratio and sleep apnoea severity relationship. Patients (n = 178) were assigned to five groups according to apnoea-hypopnea indices and continuous positive airway pressure use. White blood cell, neutrophil, lymphocyte and neutrophil-to-lymphocyte ratio values were compared for each group. The neutrophil-to-lymphocyte ratio values of severe obstructive sleep apnoea syndrome patients (group 4) were significantly higher than those of: control patients (group 1), mild obstructive sleep apnoea syndrome patients (group 2) and patients treated with continuous positive airway pressure (group 5) (p = 0.008, p = 0.008 and p = 0.003). Minimum oxygen saturation values of group 4 were significantly lower than those of groups 1, 2 and 5 (p = 0.0005, p = 0.011 and p = 0.001). There was a positive correlation between apnoea-hypopnea index and neutrophil-to-lymphocyte ratio (r = 0.758, p = 0.034), and a negative correlation between apnoea-hypopnea index and minimum oxygen saturation (r = -0.179, p = 0.012). Neutrophil-to-lymphocyte ratio may be used to determine disease severity, complementing polysomnography.

Ex-vivo expansion of CFU-GM and BFU-E in unselected PBMC cultures with Flt3L is enhanced by autologous plasma.

PubMed

Guo, M; Miller, W M; Papoutsakis, E T; Patel, S; James, C; Goolsby, C; Winter, J N

1999-01-01

Previous ex-vivo expansion studies in our laboratory, comparing unselected and CD34(+)-selected PBMC, have shown no advantage for CD34(+) cell selection, in terms of the expansion achieved. Our goal was to develop procedures for consistent generation of large numbers of hematopoietic progenitor and post-progenitor cells from unselected PBMC. Unselected PBMC, collected from cancer patients undergoing apheresis prior to high-dose chemotherapy and autologous stem cell rescue, were expanded ex vivo in static cultures, without a stromal layer, in the presence of Flt3 ligand (Flt3L), a recombinant GM-CSF/IL-3 fusion protein (PIXY321), G-CSF and GM-CSF for 10 days. The addition of 2% autologous plasma to this cytokine combination enhanced expansion of total cell numbers (3.2 fold versus 1.9 fold; p < 0.01), colony-forming units granulocyte-macrophage (CFU-GM) (22.0 fold versus 8.1 fold, p < 0.01) and burst-forming units erythroid (BFU-E) (17.6 fold versus 7.0 fold, 0.01 < p < 0.02). The optimal seeding density for a given specimen was inversely related to the frequency of CD34(+) cells in the sample. CFU-GM expansion with the Flt3L-containing cytokine cocktail was equivalent to that obtained with IL-3, IL-6, G-CSF and SCF, whether or not the cultures were supplemented with autologous plasma. In plasma-free cultures, BFU-E expansion was significantly higher with IL-3, IL-6, G-CSF and SCF than with Flt3L, PIXY321, G-CSF and GM-CSF. In the presence of autologous plasma, however BFU-E expansion was higher in the Flt3L-containing media. In comparison studies, autologous plasma suppressed BFU-E expansion in SCF-containing cultures. Consistent with our colony assay results, dual-parameter flow cytometric analysis of the expanded cell population revealed that supplementation with autologous plasma yielded a significant increase in the numbers of myeloid progenitors in Flt3L-containing cultures. Unselected PBMC from cancer patients can be effectively expanded ex vivo in Flt3L

Arachidonic acid metabolites in normal and autoimmune mice do not influence lymphocyte-high endothelial venule interactions.

PubMed

Manolios, N; Bakiera, B; Geczy, C L; Schrieber, L

1991-02-01

In peripheral lymphoid organs the number of lymphocytes and the proportion of functional lymphocyte subsets are regulated by multiple factors including the control of lymphocyte migration by selective lymphocyte-high endothelial venule (HEV) interactions. In this study, prostaglandin E2 (PGE2) levels from normal and autoimmune mouse lymph node cells were measured. The contribution of eicosanoids to lymphocyte-HEV interactions in normal (CBA/T6) and autoimmune (MRL/n) mice was examined. There was no association between PGE2 production in normal or autoimmune mice and the age of onset of disease activity in the latter strains. Arachidonic acid metabolites, in particular PGE2 and leukotriene B4 (LTB4), did not have any effects on lymphocyte-HEV binding. Likewise, lymphocytes treated in vivo and/or in vitro with arachidonic acid metabolite inhibitors (acetyl salicylic acid, indomethacin, BW755C) did not alter lymphocyte-HEV binding interactions in both normal and autoimmune mice. No clinical significance could be attributed to lymph node PGE2 production and the age of onset of autoimmune disease. In summary, these findings cast doubt on the role of arachidonic acid metabolites in lymphocyte-HEV binding interactions.

Endoscopic mucosal autograft for treating esophageal caustic strictures: preliminary human experience.

PubMed

He, Kexin; Zhao, Lili; Bu, Shoushan; Liu, Li; Wang, Xiang; Wang, Min; Fan, Zhining

2018-06-11

 Esophageal caustic stricture is a stubborn disease and postoperative restenosis limits the clinical efficacy of endoscopic dilation. Autologous mucosal grafts have been successfully applied in the treatment of urethral stricture and in the prevention of stricture after extensive mucosal resection. We aimed to use mucosal autografting performed endoscopically to treat refractory esophageal stricture. METHODS : Three patients with intractable corrosive esophageal stricture were treated endoscopically by combining dilation with autologous mucosal transplantation. RESULTS : All procedures were successful with no severe complications. Mucosal regeneration was shown at the transplanted segments. One patient was able to maintain a normal diet with complete remission after 1 year of follow-up. Intraluminal stenosis and dysphagia were significantly improved in another two patients. CONCLUSIONS : Mucosal autografting can achieve esophageal re-epithelialization, inhibit undesired fibrosis, prevent restenosis, and promote functional regeneration. © Georg Thieme Verlag KG Stuttgart · New York.

Preeclampsia in autologous and oocyte donation pregnancy: is there a different pathophysiology?

PubMed

Lashley, Lisa E E L O; Buurma, Aletta; Swings, Godelieve M J S; Eikmans, Michael; Anholts, Jacqueline D H; Bakker, Jaap A; Claas, Frans H J

2015-06-01

Oocyte donation (OD) is a specific method of artificial reproductive technology that is accompanied by a higher risk of preeclampsia during pregnancy. The pathophysiological mechanism underlying preeclampsia in OD pregnancies is thought to differ from preeclampsia in autologous pregnancies. As preeclampsia in autologous pregnancies is suggested to be associated with complement activation, we studied C4d deposition, circulating complement components and placental complement regulatory proteins in preeclamptic OD pregnancies. Women with uncomplicated and preeclamptic pregnancies after OD or spontaneous conception were selected. We stained the placentas for C4d, marker for complement activation, measured complement factors C1q, C3 and C4 in maternal sera and quantified the placental mRNA expression of complement regulatory proteins CD46, CD55 and CD59. A significantly (p < 0.03) higher incidence of C4d deposition was observed in placentas from women with preeclampsia compared with uncomplicated pregnancies, both OD and autologous. The level of complement factors in serum did not differ between the groups. Children born in the autologous preeclampsia group were significantly lower in birth weight (p < 10th percentile) compared with the preeclamptic OD group. In addition, the placental mRNA expression level of complement regulatory proteins was significantly lower in uncomplicated and preeclamptic OD compared with the autologous pregnancies. In line with autologous preeclampsia pregnancies, there is excessive activation of complement in preeclamptic OD pregnancies. However, in contrast to autologous pregnancies this is not associated with counterbalancing upregulation of complement regulatory proteins. Furthermore, C4d deposition in OD pregnancies is not related to the severity of preeclampsia, suggesting another trigger or regulatory mechanism of placental C4d deposition in preeclamptic OD pregnancies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Early immunotherapy using autologous adult stem cells reversed the effect of anti-pancreatic islets in recently diagnosed type 1 diabetes mellitus: preliminary results.

PubMed

Mesples, Alejandro; Majeed, Nasir; Zhang, Yun; Hu, Xiang

2013-10-14

Bone marrow stem cell treatment has been proven a promising therapeutic strategy and showed significant results given the strong immune modulating properties. We have investigated the safety and efficacy of autologous bone marrow stem cell transplantation through liver puncture in two patients with recently diagnosed type 1 diabetes mellitus. The procedure was approved by the Institutional Ethics Committee. In 2011, in three young patients, type 1 diabetes mellitus diagnosis was confirmed, with the presence of positive antibodies and ketoacidosis. Two patients was treated with autologous bone marrow stem cell stimulated with filgrastim and transplantation, through liver puncture, as immune modulators. One patients was treated with conventional treatment and participate in this experiment as a control group. The families of the patients signed the informed consent. No specific statistical analysis was performed. The patients had less than 8 years old, diagnosis of type 1 diabetes for less than 60 days, body mass index less than 22 kg/m2, normal complete blood count, coagulation and renal function, no lesions in target organs, glycosylated hemoglobin (HbA1c) level less than 13.70%, c-peptide level less than 0.67 ng/ml, positive results of Islets Cells Antibody (ICA), Glutamic Acid Decarboxylase (GAD) and insulin antibody. In two patients treated, the follow up at 12 months showed negative value in ICA, GAD and anti insulin antibody levels, with an increased levels of c peptide and decreased levels of blood glucose and HbA1c. Treatment with autologous bone marrow stem cells is easy and effective as it reversed the production and effect of anti pancreatic islet antibody and significantly resulted in an increased c-peptide concentration.

Licorice infusion: Chemical profile and effects on the activation and the cell cycle progression of human lymphocytes

PubMed Central

Cheel, José; Onofre, Gabriela; Vokurkova, Doris; Tůmová, Lenka; Neugebauerová, Jarmila

2010-01-01

A licorice infusion (LI) and its major constituents were investigated for their capacity to stimulate the activation and the cell cycle progression of human lymphocytes, measured by the CD69 expression and DNA content, respectively. The chemical profile of LI was determined by high-performance liquid chromatography-diode array detection (HPLC-DAD). Results: Two major components of LI were identified as liquiritin (1) and glycyrrhizin (2); total flavones and flavonols were shown as its minor constituents. The LI (100-800 μg/ml) stimulated the expression of CD69 on lymphocytes in a concentration-independent manner. Values of the activation index (AI) of total lymphocytes treated with LI (100-800 μg/ml) did not differ significantly among them (P < 0.05), but were 50% lower than the AI value exhibited by cells treated with phytohemagglutinin (PHA). The LI showed a similar effect on T cells, but on a lower scale. Compounds 1 and 2 (12-100 μg/ml) did not stimulate the CD69 expression on lymphocytes. The LI, 1 and 2 showed no meaningful effect on cell cycle progression of lymphocytes. The experimental data indicates that LI stimulates the activation of lymphocytes as a result of a proliferation-independent process. This finding suggests that LI could be considered as a potential specific immune stimulator. PMID:20548933

Inorganic arsenic represses interleukin-17A expression in human activated Th17 lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morzadec, Claudie; Macoch, Mélinda; Robineau, Marc

2012-08-01

Trivalent inorganic arsenic [As(III)] is an efficient anticancer agent used to treat patients suffering from acute promyelocytic leukemia. Recently, experimental studies have clearly demonstrated that this metalloid can also cure lymphoproliferative and/or pro-inflammatory syndromes in different murine models of chronic immune-mediated diseases. T helper (Th) 1 and Th17 lymphocytes play a central role in development of these diseases, in mice and humans, especially by secreting the potent pro-inflammatory cytokine interferon-γ and IL-17A, respectively. As(III) impairs basic functions of human T cells but its ability to modulate secretion of pro-inflammatory cytokines by differentiated Th lymphocytes is unknown. In the present study,more » we demonstrate that As(III), used at concentrations clinically achievable in plasma of patients, has no effect on the secretion of interferon-γ from Th1 cells but almost totally blocks the expression and the release of IL-17A from human Th17 lymphocytes co-stimulated for five days with anti-CD3 and anti-CD28 antibodies, in the presence of differentiating cytokines. In addition, As(III) specifically reduces mRNA levels of the retinoic-related orphan receptor (ROR)C gene which encodes RORγt, a key transcription factor controlling optimal IL-17 expression in fully differentiated Th17 cells. The metalloid also blocks initial expression of IL-17 gene induced by the co-stimulation, probably in part by impairing activation of the JNK/c-Jun pathway. In conclusion, our results demonstrate that As(III) represses expression of the major pro-inflammatory cytokine IL-17A produced by human Th17 lymphocytes, thus strengthening the idea that As(III) may be useful to treat inflammatory immune-mediated diseases in humans. -- Highlights: ► Arsenic inhibits secretion of IL-17A from human naïve and memory Th17 lymphocytes. ► Arsenic represses early expression of IL-17A gene in human activated T lymphocytes. ► Arsenic interferes with

Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody Mediated Rejection After Vascularized Composite Allotransplantation

DTIC Science & Technology

2017-10-01

Award Number: W81XWH-16-1-0664 TITLE: Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody-Mediated Rejection after...Annual 3. DATES COVERED 15 Sep 2016 – 14 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Autologous Hematopoietic Stem Cell Transplantation to...sensitization, autologous hematopoietic stem cell transplantation, antibody mediated rejection, donor specific antibodies 16. SECURITY CLASSIFICATION OF

The Effect of a Grape Seed Extract on Radiation-Induced DNA Damage in Human Lymphocytes

NASA Astrophysics Data System (ADS)

Dicu, Tiberius; Postescu, Ion D.; Foriş, Vasile; Brie, Ioana; Fischer-Fodor, Eva; Cernea, Valentin; Moldovan, Mircea; Cosma, Constantin

2009-05-01

Plant-derived antioxidants due to their phenolic compounds content are reported as potential candidates for reducing the levels of oxidative stress in living organisms. Grape seed extracts are very potent antioxidants and exhibit numerous interesting pharmacologic activities. Hydroethanolic (50/50, v/v) standardized extract was obtained from red grape seed (Vitis vinifera, variety Burgund Mare—BM). The total polyphenols content was evaluated by Folin-Ciocalteu procedure and expressed as μEq Gallic Acid/ml. The aim of this study was to evaluate the potential antioxidant effects of different concentrations of BM extract against 60Co γ-rays induced DNA damage in human lymphocytes. Samples of human lymphocytes were incubated with BM extract (12.5, 25.0 and 37.5 μEq GA/ml, respectively) administered at 30 minutes before in vitro irradiation with γ-rays (2 Gy). The DNA damage and repair in lymphocytes were evaluated using alkaline comet assay. Using the lesion score, the radiation-induced DNA damage was found to be significantly different (p<0.05) from control, both in the absence and presence of BM extract (except the lymphocytes treated with 37.5 μEq GA/ml BM extract). DNA repair analyzed by incubating the irradiated cells at 37° C and 5% CO2 atmosphere for 2 h, indicated a significant difference (p<0.05) in the lymphocytes group treated with 25.0 μEq GA/ml BM extract, immediately and two hours after irradiation. These results suggest radioprotective effects after treatment with BM extract in human lymphocytes.

Is Unilateral Implant or Autologous Breast Reconstruction Better in Obtaining Breast Symmetry?

PubMed

Cohen, Oriana; Small, Kevin; Lee, Christina; Petruolo, Oriana; Karp, Nolan; Choi, Mihye

2016-01-01

Unilateral breast reconstruction poses a special set of challenges to the reconstructive breast surgeon compared to bilateral reconstructions. No studies to date provide an objective comparison between autologous and implant based reconstructions in matching the contralateral breast. This study compares the quantitative postoperative results between unilateral implant and autologous flap reconstructions in matching the native breast in shape, size, and projection using three-dimensional (3D) imaging. Sixty-four patients who underwent unilateral mastectomy with tissue expander (TE)-implant (n = 34) or autologous microvascular free transverse rectus abdominus myocutaneous (TRAM; n = 18) or deep inferior epigastric artery perforator (DIEP; n = 12) flap (n = 30) reconstruction from 2007 to 2010 were analyzed. Key patient demographics and risk factors were collected. Using 3D scans of patients obtained during pre and postoperative visits including over 1 year follow-ups for both groups, 3D models were constructed and analyzed for total breast volume, anterior-posterior projection from the chest wall, and 3D comparison. No significant differences in mean age, body mass index, or total number of reconstructive surgeries were observed between the two groups (TE-implant: 52.2 ± 10, 23.9 ± 3.7, 3 ± 0.9; autologous: 50.7 ± 9.4, 25.4 ± 3.9, 2.9 ± 1.3; p > 0.05). The total volume difference between the reconstructed and contralateral breasts in the TE-implant group was insignificant: 27.1 ± 22.2 cc, similar to the autologous group: 29.5 ± 24.7 cc, as was the variance of breast volume from the mean. In both groups, the reconstructed breast had a larger volume. A-P projections were similar between the contralateral and the reconstructed breasts in the TE-implant group: 72.5 ± 3.21 mm versus 71.7 ± 3.5 mm (p > 0.05). The autologous reconstructed breast had statistically insignificant but less A-P projection compared to the contralateral breast (81.9 ± 16.1 mm versus 61

Effect of autologous platelet-rich plasma application on cutaneous wound healing in dogs.

PubMed

Jee, Cho-Hee; Eom, Na-Young; Jang, Hyo-Mi; Jung, Hae-Won; Choi, Eul-Soo; Won, Jin-Hee; Hong, Il-Hwa; Kang, Byeong-Teck; Jeong, Dong Wook; Jung, Dong-In

2016-03-01

This study was conducted to identify the effectiveness of platelet-rich plasma (PRP) and efficacy of intralesional injection as a method of application to acute cutaneous wounds in dogs. Healthy adult beagles (n = 3) were used in this study. Autologous PRP was separated from anticoagulant treated whole blood in three dogs. Cutaneous wounds were created and then treated by intralesional injection of PRP in the experimental group, while they were treated with saline in the control group on days 0, 2 and 4. The healing process was evaluated by gross examination throughout the experimental period and histologic examination on day 7, 14 and 21. In PRP treated wounds, the mean diameter was smaller and the wound closure rate was higher than in the control. Histological study revealed that PRP treated wounds showed more granulation formation and angiogenesis on day 7, and faster epithelialization, more granulation formation and collagen deposition were observed on day 14 than in control wounds. On day 21, collagen deposition and epithelialization were enhanced in PRP treated groups. Overall, PRP application showed beneficial effects in wound healing, and intralesional injection was useful for application of PRP and could be a good therapeutic option for wound management in dogs.

Effect of autologous platelet-rich plasma application on cutaneous wound healing in dogs

PubMed Central

Jee, Cho-Hee; Eom, Na-Young; Jang, Hyo-Mi; Jung, Hae-Won; Choi, Eul-Soo; Won, Jin-Hee; Hong, Il-Hwa; Kang, Byeong-Teck

2016-01-01

This study was conducted to identify the effectiveness of platelet-rich plasma (PRP) and efficacy of intralesional injection as a method of application to acute cutaneous wounds in dogs. Healthy adult beagles (n = 3) were used in this study. Autologous PRP was separated from anticoagulant treated whole blood in three dogs. Cutaneous wounds were created and then treated by intralesional injection of PRP in the experimental group, while they were treated with saline in the control group on days 0, 2 and 4. The healing process was evaluated by gross examination throughout the experimental period and histologic examination on day 7, 14 and 21. In PRP treated wounds, the mean diameter was smaller and the wound closure rate was higher than in the control. Histological study revealed that PRP treated wounds showed more granulation formation and angiogenesis on day 7, and faster epithelialization, more granulation formation and collagen deposition were observed on day 14 than in control wounds. On day 21, collagen deposition and epithelialization were enhanced in PRP treated groups. Overall, PRP application showed beneficial effects in wound healing, and intralesional injection was useful for application of PRP and could be a good therapeutic option for wound management in dogs. PMID:27051343

Chronic lymphocytic leukaemia

PubMed Central

Kipps, Thomas J.; Stevenson, Freda K.; Wu, Catherine J.; Croce, Carlo M.; Packham, Graham; Wierda, William G.; O’Brien, Susan; Gribben, John; Rai, Kanti

2017-01-01

Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5+ B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all. Several factors, including the immunoglobulin heavy-chain variable region gene (IGHV) mutational status, genomic changes, patient age and the presence of comorbidities, should be considered when defining the optimal management strategies, which include chemotherapy, chemoimmunotherapy and/or drugs targeting B cell receptor signalling or inhibitors of apoptosis, such as BCL-2. Research on the biology of CLL has profoundly enhanced our ability to identify patients who are at higher risk for disease progression and our capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL. How these and other advances have shaped our current understanding and treatment of patients with CLL is the subject of this Primer. PMID:28102226

Lumbar herniation following extended autologous latissimus dorsi breast reconstruction.

PubMed

Fraser, Sheila Margaret; Fatayer, Hiba; Achuthan, Rajgopal

2013-05-30

Reconstructive breast surgery is now recognized to be an important part of the treatment for breast cancer. Surgical reconstruction options consist of implants, autologous tissue transfer or a combination of the two. The latissimus dorsi flap is a pedicled musculocutaneous flap and is an established method of autologous breast reconstruction.Lumbar hernias are an unusual type of hernia, the majority occurring after surgery or trauma in this area. The reported incidence of a lumbar hernia subsequent to a latissimus dorsi reconstruction is very low. We present the unusual case of lumbar herniation after an extended autologous latissimus dorsi flap for breast reconstruction following a mastectomy. The lumbar hernia was confirmed on CT scanning and the patient underwent an open mesh repair of the hernia through the previous latissimus dorsi scar. Lumbar hernias are a rare complication that can occur following latissimus dorsi breast reconstruction. It should be considered in all patients presenting with persistent pain or swelling in the lumbar region.

Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia

PubMed Central

Porter, David L.; Hwang, Wei-Ting; Frey, Noelle V.; Lacey, Simon F.; Shaw, Pamela A.; Loren, Alison W.; Bagg, Adam; Marcucci, Katherine T.; Shen, Angela; Gonzalez, Vanessa; Ambrose, David; Grupp, Stephan A.; Chew, Anne; Zheng, Zhaohui; Milone, Michael C.; Levine, Bruce L.; Melenhorst, Jan J.; June, Carl H.

2018-01-01

Patients with multiply relapsed or refractory chronic lymphocytic leukemia (CLL) have a poor prognosis. Chimeric antigen receptor (CAR)–modified T cells targeting CD19 have the potential to improve on the low complete response rates with conventional therapies by inducing sustained remissions in patients with refractory B cell malignancies. We previously reported preliminary results on three patients with refractory CLL. We report the mature results from our initial trial using CAR-modified T cells to treat 14 patients with relapsed and refractory CLL. Autologous T cells transduced with a CD19-directed CAR (CTL019) lentiviral vector were infused into patients with relapsed/refractory CLL at doses of 0.14 × 108 to 11 × 108 CTL019 cells (median, 1.6 × 108 cells). Patients were monitored for toxicity, response, expansion, and persistence of circulating CTL019 T cells. The overall response rate in these heavily pretreated CLL patients was 8 of 14 (57%), with 4 complete remissions (CR) and 4 partial remissions (PR). The in vivo expansion of the CAR T cells correlated with clinical responses, and the CAR T cells persisted and remained functional beyond 4 years in the first two patients achieving CR. No patient in CR has relapsed. All responding patients developed B cell aplasia and experienced cytokine release syndrome, coincident with T cell proliferation. Minimal residual disease was not detectable in patients who achieved CR, suggesting that disease eradication may be possible in some patients with advanced CLL. PMID:26333935

Neutrophil-to-lymphocyte ratio in patients with severe tinnitus: prospective, controlled clinical study.

PubMed

Ozbay, I; Kahraman, C; Balikci, H H; Kucur, C; Kahraman, N K; Ozkaya, D P; Oghan, F

2015-06-01

To determine the relationship between severe tinnitus and inflammation using the neutrophil-to-lymphocyte ratio as a marker of stress. A total of 107 patients who had been suffering with severe tinnitus (tinnitus handicap inventory scale grades of 3-5) for at least 2 weeks were recruited. Patients underwent detailed ENT examinations and audiometric tests to exclude a relevant pathological cause of the tinnitus. Patients with systemic diseases, malignancy or inflammatory diseases that could alter neutrophil-to-lymphocyte ratio were excluded. A total of 107 age- and sex-matched healthy control participants were also recruited. Routine laboratory test results and neutrophil-to-lymphocyte ratio were compared between the patients and controls. Lipid profile, liver function, white blood cell count, haemoglobin level, mean corpuscular volume, and vitamin B12 and folate levels were similar among the patients and controls. However, mean neutrophil-to-lymphocyte ratio was significantly higher among the patients than the controls (p < 0.05). The findings of this novel study suggest that neutrophil-to-lymphocyte ratio should be considered during the evaluation of tinnitus patients as a potential clinical marker of tinnitus. Further studies are required to verify the findings.

Treatment of a Focal Articular Cartilage Defect of the Talus with Polymer-Based Autologous Chondrocyte Implantation: A 12-Year Follow-Up Period.

PubMed

Kreuz, Peter Cornelius; Kalkreuth, Richard Horst; Niemeyer, Philipp; Uhl, Markus; Erggelet, Christoph

Autologous chondrocyte implantation (ACI) is a first-line treatment option for large articular cartilage defects. Although well-established for cartilage defects in the knee, studies of the long-term outcomes of matrix-assisted ACI to treat cartilage defects in the ankle are rare. In the present report, we describe for the first time the long-term clinical and radiologic results 12 years after polymer-based matrix-assisted ACI treat a full-thickness talar cartilage defect in a 25-year-old male patient. The clinical outcome was assessed using the visual analog scale and Freiburg ankle score, magnetic resonance imaging evaluation using the Henderson-Kreuz scoring system and T2 mapping. Clinical assessment revealed improved visual analog scale and Freiburg ankle scores. The radiologic analysis and T2 relaxation time values indicated the formation of hyaline-like repair tissue. Polymer-based autologous chondrocytes has been shown to be a safe and clinically effective long-term treatment of articular cartilage defects in the talus. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

T lymphocyte subpopulations diverge in commercially raised chickens

PubMed Central

Bridle, Byram W.; Julian, Richard; Shewen, Patricia E.; Vaillancourt, Jean-Pierre

2006-01-01

Abstract To evaluate immunocompetence in commercially raised chickens, we immunophenotyped Dekalb Delta and H&N White Leghorn (WLH) hybrids, 20 chickens in each of 3 age groups (9 wk [juvenile], 25 wk [young adult], and 79 or 80 wk [adult]), for circulating CD3+, CD4+, CD8+, TCR1+, TCR2+, and TCR3+ lymphocytes. The proportion of CD3+ T cells, including CD4+ and CD8+ subsets, was increased in the hybrids as compared with published values for laboratory-raised outbred WLH chickens. The proportion of the TCR2+ (Vβ1) T cell subpopulation was also increased. An age-related decrease in the proportion of TCR1+ (γδ) T cells was noted in both hybrids. Further, a remarkably low CD4:CD8 ratio was evident in all age groups of both hybrids, indicating decreased immunocompetence. Overall, these experiments provide age-related proportions of various peripheral-blood T lymphocyte subpopulations in commercially raised Dekalb Delta and H&N chickens that diverge from the proportions in laboratory-raised outbred WLH chickens and suggest reduced immunocompetence. Such a decline in immunocompetence, including humoral immune capacity, could be attributed to genetic selection for production traits, environmental factors associated with commercial operations, and intense immunization. PMID:16850940

The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy.

PubMed

Cox, Samantha; Hurt, Christopher; Grenader, Tal; Mukherjee, Somnath; Bridgewater, John; Crosby, Thomas

2017-10-01

The derived neutrophil-lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial. 258 patients were randomised to receive dCRT±cetuximab. Kaplan-Meier's curves and both univariable and multivariable Cox regression models were calculated for overall survival (OS), progression free survival (PFS), local PFS inside the radiation volume (LPFSi), local PFS outside the radiation volume (LPFSo), and distant PFS (DPFS). An elevated pre-treatment dNLR≥2 was significantly associated with decreased OS in univariable (HR 1.74 [95% CI 1.29-2.35], p<0.001) and multivariable analyses (HR 1.64 [1.17-2.29], p=0.004). Median OS was 36months (95% CI 27.8-42.4) if dNLR<2 and 18.4months (95% CI 14.1-24.9) if dNLR≥2. All measures of PFS were also significantly reduced with an elevated dNLR. dNLR was prognostic for OS in cases of squamous cell carcinoma with a non-significant trend for adenocarcinoma/undifferentiated tumours. An elevated pre-treatment dNLR may be an independent prognostic biomarker for OS and PFS in oesophageal cancer patients treated with definitive CRT. dNLR is a simple, inexpensive and readily available tool for risk-stratification and should be considered for use in future oesophageal cancer clinical trials. The SCOPE1 trial was an International Standard Randomised Controlled Trial [number 47718479]. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers.

PubMed

Palma, Marzia; Gentilcore, Giusy; Heimersson, Kia; Mozaffari, Fariba; Näsman-Glaser, Barbro; Young, Emma; Rosenquist, Richard; Hansson, Lotta; Österborg, Anders; Mellstedt, Håkan

2017-03-01

Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T-cell defects. T-cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T-cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared them to healthy controls. In general, patients had higher absolute numbers of CD3 + cells and the CD8 + subset was particularly expanded in previously treated patients. Progressive patients had higher numbers of CD4 + and CD8 + cells expressing PD-1 compared to healthy controls, which was more pronounced in previously treated patients ( P =0.0003 and P =0.001, respectively). A significant increase in antigen-experienced T cells was observed in patients within both the CD4 + and CD8 + subsets, with a significantly higher PD-1 expression. Higher numbers of CD4 + and CD8 + cells with intracellular CTLA-4 were observed in patients, as well as high numbers of proliferating (Ki67 + ) and activated (CD69 + ) CD4 + and CD8 + cells, more pronounced in patients with active disease. The numbers of Th1, Th2, Th17 and regulatory T cells were substantially increased in patients compared to controls ( P <0.05), albeit decreasing to low levels in pre-treated patients. In conclusion, chronic lymphocytic leukemia T cells display increased expression of immune checkpoints, abnormal subset distribution, and a higher proportion of proliferating cells compared to healthy T cells. Disease activity and previous treatment shape the T-cell profile of chronic lymphocytic leukemia patients in different ways. Copyright© Ferrata Storti Foundation.

COMPARATIVE GENOTOXIC RESPONSES TO ARSENITE IN GUINEA PIG, MOUSE, RAT AND HUMAN LYMPHOCYTES

EPA Science Inventory

Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human
lymphocytes.

Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

Ocular surface epithelium induces expression of human mucosal lymphocyte antigen (HML-1) on peripheral blood lymphocytes

PubMed Central

Gomes, J A P; Dua, H S; Rizzo, L V; Nishi, M; Joseph, A; Donoso, L A

2004-01-01

Background/aims: Peripheral blood CD8+ lymphocytes that home to mucosal surfaces express the human mucosal lymphocyte antigen (HML-1). At mucosal surfaces, including the ocular surface, only intraepithelial CD8+ lymphocytes express HML-1. These lymphocytes are retained in the intraepithelial compartment by virtue of the interaction between HML-1 and its natural ligand, E-cadherin, which is expressed on epithelial cells. The purpose of this study was to determine whether ocular surface epithelial cells (ocular mucosa) could induce the expression of human mucosal lymphocyte antigen on peripheral blood lymphocytes. Methods: Human corneal and conjunctival epithelial cells were co-cultured with peripheral blood lymphocytes. Both non-activated and activated lymphocytes were used in the experiments. After 7 days of incubation, lymphocytes were recovered and analysed for the antigens CD8/HML-1, CD4/HML-1, CD3/CD8, CD3/CD4, CD3/CD25, CD8/CD25, and CD4/CD25 by flowcytometry. Results: Significant statistical differences were observed in the CD8/HML-1 expression when conjunctival epithelial cells were co-cultured with non-activated and activated lymphocytes (p = 0.04 for each) and when corneal epithelial cells were co-cultured with non-activated lymphocytes (p = 0.03). Significant statistical difference in CD4/HML-1 expression was observed only when conjunctival epithelial cells were co-cultured with activated lymphocytes (p = 0.02). Conclusion: Ocular surface epithelial cells can induce the expression of human mucosal lymphocyte antigen on CD8+ (and to some extent on CD4+) lymphocytes. This may allow the retention of CD8+ and CD4+ lymphocytes within the epithelial compartment of the conjunctiva and play a part in mucosal homing of lymphocytes. PMID:14736792

Autologous Platelet-Poor Plasma Gel for Injection Laryngoplasty

PubMed Central

Woo, Seung Hoon; Kim, Jin Pyeong; Park, Jung Je; Chung, Phil-Sang

2013-01-01

Purpose To overcome the potential disadvantages of the use of foreign materials and autologous fat or collagen, we introduce here an autologous plasma gel for injection laryngoplasty. The purpose of this study was to present a new injection material, a plasma gel, and to discuss its clinical effectiveness. Materials and Methods From 2 mL of blood, the platelet poor serum layer was collected and heated at 100℃ for 12 min to form a plasma gel. The plasma gel was then injected into a targeted site; the safety and efficacy thereof were evaluated in 30 rats. We also conducted a phase I/II clinical study of plasma gel injection laryngoplasty in 11 unilateral vocal fold paralysis patients. Results The plasma gel was semi-solid and an easily injectable material. Of note, plasma gel maintains the same consistency for up to 1 year in a sealed bottle. However, exposure to room air causes the plasma gel to disappear within 1 month. In our animal study, the autologous plasma gel remained in situ for 6 months in animals with minimal inflammation. Clinical study showed that vocal cord palsy was well compensated for with the plasma gel in all patients at two months after injection with no significant complications. Jitter, shimmer, maximum, maximum phonation time (MPT) and mean voice handicap index (VHI) also improved significantly after plasma gel injection. However, because the injected plasma gel was gradually absorbed, 6 patients needed another injection, while the gel remained in place in 2 patients. Conclusion Injection laryngoplasty with autologous plasma gel may be a useful and safe treatment option for temporary vocal cord palsy. PMID:24142660

Neoadjuvant Radiotherapy: Changing the Treatment Sequence to Allow Immediate Free Autologous Breast Reconstruction.

PubMed

Hughes, Kimberley; Neoh, Derek

2018-06-16

 Locally advanced breast cancer (LABC) is traditionally treated with a multimodal approach of chemotherapy, surgery, and postmastectomy radiotherapy (PMRT). The advantages of immediate breast reconstruction (IBR) are well described and include improved aesthetic outcomes, fewer surgical procedures, shorter treatment period, and a higher quality of life. However, this sequence makes immediate free autologous reconstruction more challenging as PMRT can have deleterious and unpredictable effects on the flap. We have reversed this treatment sequence with neoadjuvant chemotherapy and radiotherapy, followed by mastectomy and immediate free autologous reconstruction. To our knowledge, this is the first series to assess the outcomes of neoadjuvant radiotherapy on immediate free microvascular breast reconstruction.  A review of patients with LABC who underwent immediate free autologous breast reconstruction post neoadjuvant chemoradiotherapy between 2013 and 2017 was conducted. All reconstructions were performed by a single reconstructive team. The primary end points were flap failure and surgical complications. Secondary end points were pathological response rate and disease recurrence.  A total of 40 women with an average age of 48.1 (36-61) and average body mass index of 25.6 (18-37) were included. The most common choice of flap was immediate deep inferior epigastric perforator (DIEP, 31), followed by transverse or diagonal upper gracilis (5), muscle-sparing transversus abdominis (3), and stacked DIEP (1). Our major complication rate was 12.5% and minor complication 15%. There were no cases of local recurrence and only three cases (7.5%) of distant disease progression.  From our experience, this treatment sequence allows patients to have an immediate gold standard reconstruction without an increase in surgical morbidity. It affords the benefits of IBR without concern in delaying adjuvant therapy and appears to be safe from an oncological perspective. Thieme

Osteoinductive ceramics as a synthetic alternative to autologous bone grafting

PubMed Central

Yuan, Huipin; Fernandes, Hugo; Habibovic, Pamela; de Boer, Jan; Barradas, Ana M. C.; de Ruiter, Ad; Walsh, William R.; van Blitterswijk, Clemens A.; de Bruijn, Joost D.

2010-01-01

Biomaterials can be endowed with biologically instructive properties by changing basic parameters such as elasticity and surface texture. However, translation from in vitro proof of concept to clinical application is largely missing. Porous calcium phosphate ceramics are used to treat small bone defects but in general do not induce stem cell differentiation, which is essential for regenerating large bone defects. Here, we prepared calcium phosphate ceramics with varying physicochemical and structural characteristics. Microporosity correlated to their propensity to stimulate osteogenic differentiation of stem cells in vitro and bone induction in vivo. Implantation in a large bone defect in sheep unequivocally demonstrated that osteoinductive ceramics are equally efficient in bone repair as autologous bone grafts. Our results provide proof of concept for the clinical application of “smart” biomaterials. PMID:20643969

Validated Outcomes in the Grafting of Autologous Fat to the Breast: The VOGUE Study. Development of a Core Outcome Set for Research and Audit.

PubMed

Agha, Riaz A; Pidgeon, Thomas E; Borrelli, Mimi R; Dowlut, Naeem; Orkar, Ter-Er K; Ahmed, Maziyah; Pujji, Ojas; Orgill, Dennis P

2018-05-01

Autologous fat grafting is an important part of the reconstructive surgeon's toolbox when treating women affected by breast cancer and subsequent tumor extirpation. The debate over safety and efficacy of autologous fat grafting continues within the literature. However, work performed by the authors' group has shown significant heterogeneity in outcome reporting. Core outcome sets have been shown to reduce heterogeneity in outcome reporting. The authors' goal was to develop a core outcome set for autologous fat grafting in breast reconstruction. The authors published their protocol a priori. A Delphi consensus exercise among key stakeholders was conducted using a list of outcomes generated from their previous work. These outcomes were divided into six domains: oncologic, clinical, aesthetic and functional, patient-reported, process, and radiologic. In the first round, 55 of 78 participants (71 percent) completed the Delphi consensus exercise. Consensus was reached on nine of the 13 outcomes. The clarity of the results and lack of additional suggested outcomes deemed further rounds to be unnecessary. The VOGUE Study has led to the development of a much-needed core outcome set in the active research front and clinical area of autologous fat grafting. The authors hope that clinicians will use this core outcome set to audit their practice, and that researchers will implement these outcomes in their study design and reporting of autologous fat grafting outcomes. The authors encourage journals and surgical societies to endorse and encourage use of this core outcome set to help refine the scientific quality of the debate, the discourse, and the literature. Therapeutic, V.

Randomized phase II clinical trial of chemo-immunotherapy in advanced nonsmall cell lung cancer

PubMed Central

Lasalvia-Prisco, Eduardo; Garcia-Giralt, Emilio; Vázquez, Jesús; Aghazarian, Marta; Lasalvia-Galante, Eduardo; Larrañaga, Joshemaria; Spera, Gonzalo

2008-01-01

The purpose of this study was to compare chemotherapy-naive patients with stage IV nonsmall cell lung cancer patients treated with chemotherapy or chemoimmunotherapy. We tested doxetacel plus cisplatinum as chemotherapy protocol. An immunomodulatory adjuvant system was added as chemoimmunotherapy to the previously mentioned protocol. This system contains three well-known and complementary conditioners of protective immune-responses: cyclophosphamide low-dose, granulocyte macrophage-colony stimulant factor and magnesium silicate granuloma. Eighty-eight patients were randomly assigned to receive every 3-weeks one of the treatments under comparison. Patients received four cycles of treatment unless disease progression or unacceptable toxicity was documented. The maximum follow-up was one year. In each arm, tumor response (rate,duration), median survival time, 1-year overall survival, safety, and immunity modifications were assessed. Immunity was evaluated by submitting peripheral blood mononuclear cells to laboratory tests for nonspecific immunity: a) phytohemaglutinin-induced lymphocyte proliferation, b) prevalence of T-Regulatory (CD4+CD25+) cells and for specific immunity: a) lymphocyte proliferation induced by tumor-associated antigens (TAA) contained in a previously described autologous thermostable hemoderivative. The difference (chemotherapy vs. chemoimmunotherapy) in response rate induced by the two treatments (39.0% and 35.0%) was not statistically significant. However, the response duration (22 and 31 weeks), the median survival time (32 and 44 weeks) and 1-year survival (33.3% and 39.1%) were statistically higher with chemoimmunotherapy. No difference in toxicity between both arms was demonstrated. A switch in the laboratory immunity profile, nonspecific and specific, was associated with the chemoimmunotherapy treatment: increase of proliferative lymphocyte response, decrease of tolerogenic T-regulatory cells and eliciting TAA-sensitization. PMID:19707385

PRGF exerts more potent proliferative and anti-inflammatory effects than autologous serum on a cell culture inflammatory model.

PubMed

Anitua, E; Muruzabal, F; de la Fuente, M; Riestra, A; Merayo-Lloves, J; Orive, G

2016-10-01

Ocular graft versus host disease (oGVHD) is part of a systemic inflammatory disease that usually affects ocular surface tissues manifesting as a dry eye syndrome. Current treatments provide unsatisfactory results. Blood-derived products, like plasma rich in growth factors (PRGF) emerge as a potential therapy for this disease. The purpose of this study was to evaluate the tissue regeneration and anti-inflammatory capability of PRGF, an autologous platelet enriched plasma eye-drop, compared to autologous serum (AS) obtained from oGVHD patients on ocular surface cells cultured in a pro-inflammatory environment. PRGF and AS were obtained from four GVHD patients. Cell proliferation and inflammation markers, intercellular adhesion molecule-1 (ICAM-1) and cyclooxygenase-2 (COX-2), were measured in corneal and conjunctival fibroblastic cells cultured under pro-inflammatory conditions and after treatment with PRGF or AS eye drops. Moreover, cell proliferation increased after treatment with PRGF and AS, though this enhancement in the case of keratocytes was significantly higher with PRGF. PRGF eye drops showed a significant reduction of both inflammatory markers with respect to the initial inflammatory situation and to the AS treatment. Our results concluded that PRGF exerts more potent regenerative and anti-inflammatory effects than autologous serum on ocular surface fibroblasts treated with pro-inflammatory IL-1β and TNFα. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genome Therapy of Myotonic Dystrophy Type 1 iPS Cells for Development of Autologous Stem Cell Therapy.

PubMed

Gao, Yuanzheng; Guo, Xiuming; Santostefano, Katherine; Wang, Yanlin; Reid, Tammy; Zeng, Desmond; Terada, Naohiro; Ashizawa, Tetsuo; Xia, Guangbin

2016-08-01

Myotonic dystrophy type 1 (DM1) is caused by expanded Cytosine-Thymine-Guanine (CTG) repeats in the 3'-untranslated region (3' UTR) of the Dystrophia myotonica protein kinase (DMPK) gene, for which there is no effective therapy. The objective of this study is to develop genome therapy in human DM1 induced pluripotent stem (iPS) cells to eliminate mutant transcripts and reverse the phenotypes for developing autologous stem cell therapy. The general approach involves targeted insertion of polyA signals (PASs) upstream of DMPK CTG repeats, which will lead to premature termination of transcription and elimination of toxic mutant transcripts. Insertion of PASs was mediated by homologous recombination triggered by site-specific transcription activator-like effector nuclease (TALEN)-induced double-strand break. We found genome-treated DM1 iPS cells continue to maintain pluripotency. The insertion of PASs led to elimination of mutant transcripts and complete disappearance of nuclear RNA foci and reversal of aberrant splicing in linear-differentiated neural stem cells, cardiomyocytes, and teratoma tissues. In conclusion, genome therapy by insertion of PASs upstream of the expanded DMPK CTG repeats prevented the production of toxic mutant transcripts and reversal of phenotypes in DM1 iPS cells and their progeny. These genetically-treated iPS cells will have broad clinical application in developing autologous stem cell therapy for DM1.

Lymphocytic mural folliculitis and pancreatic carcinoma in a cat.

PubMed

Lobetti, Remo

2015-06-01

A 9-year-old castrated domestic shorthair cat was presented with a 6 week history of progressive non-pruritic alopecia, polyphagia and weight loss. A diagnosis of lymphocytic mural folliculitis was made and the cat was treated with a combination of prednisolone and ciclosporin; this produced an improvement in the alopecia but no resolution. Sixteen months after the initial assessment and diagnosis, the cat was re-evaluated for intermittent vomiting and weight loss with normal appetite. On examination the dermatopathy was still evident and a mass involving the duodenum and pancreas was present, which was diagnosed as a pancreatic carcinoma. From this case it would appear that lymphocytic mural folliculitis might be an early dermatological manifestation of pancreatic neoplasia. © ISFM and AAFP 2014.

Genetically Engineered Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Indolent B-Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2014-08-04

B-cell Chronic Lymphocytic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.

PubMed

Bradley, Todd; Fera, Daniela; Bhiman, Jinal; Eslamizar, Leila; Lu, Xiaozhi; Anasti, Kara; Zhang, Ruijung; Sutherland, Laura L; Scearce, Richard M; Bowman, Cindy M; Stolarchuk, Christina; Lloyd, Krissey E; Parks, Robert; Eaton, Amanda; Foulger, Andrew; Nie, Xiaoyan; Karim, Salim S Abdool; Barnett, Susan; Kelsoe, Garnett; Kepler, Thomas B; Alam, S Munir; Montefiori, David C; Moody, M Anthony; Liao, Hua-Xin; Morris, Lynn; Santra, Sampa; Harrison, Stephen C; Haynes, Barton F

2016-01-05

Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Implantation of Autologous Cartilage Chips Improves Cartilage Repair Tissue Quality in Osteochondral Defects: A Study in Göttingen Minipigs.

PubMed

Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Olesen, Morten Lykke; Hede, Kris Chadwick; Lind, Martin

2016-06-01

Osteochondral injuries have poor endogenous healing potential, and no standard treatment has been established. The use of combined layered autologous bone and cartilage chips for treatment of osteochondral defects has shown promising short-term clinical results. This study aimed to investigate the role of cartilage chips by comparing combined layered autologous bone and cartilage chips with autologous bone implantation alone in a Göttingen minipig model. The hypothesis was that the presence of cartilage chips would improve the quality of the repair tissue. Controlled laboratory study. Twelve Göttingen minipigs received 2 osteochondral defects in each knee. The defects were randomized to autologous bone graft (ABG) combined with autologous cartilage chips (autologous dual-tissue transplantation [ADTT]) or ABG alone. Six animals were euthanized at 6 months and 6 animals were euthanized at 12 months. Follow-up evaluation consisted of histomorphometry, immunohistochemistry, semiquantitative scoring (International Cartilage Repair Society II), and computed tomography. There was significantly more hyaline cartilage in the ADTT group (25.8%) compared with the ABG group (12.8%) at 6 months after treatment. At 12 months, the fraction of hyaline cartilage in the ABG group had significantly decreased to 4.8%, whereas the fraction of hyaline cartilage in the ADTT group was unchanged (20.1%). At 6 and 12 months, there was significantly more fibrocartilage in the ADTT group (44% and 60.8%) compared with the ABG group (24.5% and 41%). The fraction of fibrous tissue was significantly lower in the ADTT group compared with the ABG group at both 6 and 12 months. The implanted cartilage chips stained >75% positive for collagen type 4 and laminin at both 6 and 12 months. Significant differences were found in a number of International Cartilage Repair Society II subcategories. The volume of the remaining bone defect significantly decreased from 6 to 12 months in both treatment groups

Migration of lymphocytes on fibronectin-coated surfaces: temporal evolution of migratory parameters

NASA Technical Reports Server (NTRS)

Bergman, A. J.; Zygourakis, K.; McIntire, L. V. (Principal Investigator)

1999-01-01

Lymphocytes typically interact with implanted biomaterials through adsorbed exogenous proteins. To provide a more complete characterization of these interactions, analysis of lymphocyte migration on adsorbed extracellular matrix proteins must accompany the commonly performed adhesion studies. We report here a comparison of the migratory and adhesion behavior of Jurkat cells (a T lymphoblastoid cell line) on tissue culture treated and untreated polystyrene surfaces coated with various concentrations of fibronectin. The average speed of cell locomotion showed a biphasic response to substrate adhesiveness for cells migrating on untreated polystyrene and a monotonic decrease for cells migrating on tissue culture-treated polystyrene. A modified approach to the persistent random walk model was implemented to determine the time dependence of cell migration parameters. The random motility coefficient showed significant increases with time when cells migrated on tissue culture-treated polystyrene surfaces, while it remained relatively constant for experiments with untreated polystyrene plates. Finally, a cell migration computer model was developed to verify our modified persistent random walk analysis. Simulation results suggest that our experimental data were consistent with temporally increasing random motility coefficients.

Anterior debridement and fusion followed by posterior pedicle screw fixation in pyogenic spondylodiscitis: autologous iliac bone strut versus cage.

PubMed

Pee, Yong Hun; Park, Jong Dae; Choi, Young-Geun; Lee, Sang-Ho

2008-05-01

An anterior approach for debridement and fusion with autologous bone graft has been recommended as the gold standard for surgical treatment of pyogenic spondylodiscitis. The use of anterior foreign body implants at the site of active infection is still a challenging procedure for spine surgeons. Several authors have recently introduced anterior grafting with titanium mesh cages instead of autologous bone strut in the treatment of spondylodiscitis. The authors present their experience of anterior fusion with 3 types of cages followed by posterior pedicle screw fixation. They also compare their results with the use of autologous iliac bone strut. The authors retrospectively reviewed the cases of 60 patients with pyogenic spondylodiscitis treated by anterior debridement between January 2003 and April 2005. Fusion using either cages or iliac bone struts was performed during the same course of anesthesia followed by posterior fixation. Twenty-three patients underwent fusion with autologous iliac bone strut, and 37 patients underwent fusion with 1 of the 3 types of cages. The infections resolved in all patients, as noted by normalization of their erythrocyte sedimentation rates and C-reactive protein levels. Patients in both groups were evaluated in terms of their preoperative and postoperative clinical and imaging findings. Single-stage anterior debridement and cage fusion followed by posterior pedicle screw fixation can be effective in the treatment of pyogenic spondylodiscitis. There was no difference in clinical and imaging outcomes between the strut group and cage group except for the subsidence rate. The subsidence rate was higher in the strut group than in the cage group. The duration until subsidence was also shorter in the strut group than in the cage group.

Prospective randomized comparison of scar appearances between cograft of acellular dermal matrix with autologous split-thickness skin and autologous split-thickness skin graft alone for full-thickness skin defects of the extremities.

PubMed

Yi, Ju Won; Kim, Jae Kwang

2015-03-01

The purpose of this study was to evaluate the clinical outcomes of cografting of acellular dermal matrix with autologous split-thickness skin and autologous split-thickness skin graft alone for full-thickness skin defects on the extremities. In this prospective randomized study, 19 consecutive patients with full-thickness skin defects on the extremities following trauma underwent grafting using either cograft of acellular dermal matrix with autologous split-thickness skin graft (nine patients, group A) or autologous split-thickness skin graft alone (10 patients, group B) from June of 2011 to December of 2012. The postoperative evaluations included observation of complications (including graft necrosis, graft detachment, or seroma formation) and Vancouver Scar Scale score. No statistically significant difference was found regarding complications, including graft necrosis, graft detachment, or seroma formation. At week 8, significantly lower Vancouver Scar Scale scores for vascularity, pliability, height, and total score were found in group A compared with group B. At week 12, lower scores for pliability and height and total scores were identified in group A compared with group B. For cases with traumatic full-thickness skin defects on the extremities, a statistically significant better result was achieved with cograft of acellular dermal matrix with autologous split-thickness skin graft than with autologous split-thickness skin graft alone in terms of Vancouver Scar Scale score. Therapeutic, II.

Corticosteroid therapy in Epstein-Barr virus infection. Effect on lymphocyte class, subset, and response to early antigen.

PubMed

Brandfonbrener, A; Epstein, A; Wu, S; Phair, J

1986-02-01

Corticosteroid treatment of impending upper airway obstruction due to Epstein-Barr virus (EBV) infectious mononucleosis did not alter the pattern of lymphocyte changes induced by this viral infection during the first two weeks following administration of prednisone. By 12 weeks, 11 treated students had significantly fewer lymphocytes, including B, total T, helper, and T-suppressor cell numbers, than 11 untreated EBV-infected students, and values were closer to those noted in uninfected controls. Corticosteroid therapy did not alter the serologic response to early antigens of EBV. Fever and lymphadenopathy resolved somewhat more quickly in treated students.

Effect of Vibrio cholerae neuraminidase on the mitogen response of T lymphocytes. I. Enhancement of macrophage T-lymphocyte cooperation in concanavalin-A-induced lymphocyte activation.

PubMed

Knop, J

1980-12-01

Vibrio cholerae neuraminidase (VCN) enhances the immune response of lymphocytes in various systems, such as antigen- and mitogen-induced blastogenesis, mixed lymphocyte culture (MLC) and tumor-cell response. We used macrophage-depleted and reconstituted murine lymph-node T-cells to investigate the effect of VCN on macrophage-T-lymphocyte co-operation in Con-A-induced lymphocyte activation. In unfractionated lymph-node cells VCN enhanced the Con-A-induced lymphocyte activation as measured by 3H-thymidine (3H-dThd) incorporation. Removing macrophages from the cells resulted in a significantly diminished response. In addition the enhancing effect of VCN was greatly reduced. Reconstitution of the lymphocyte cultures with macrophages in increasing numbers and from various sources rstored the lymphocyte response and the enhancing effect of VCN. VCN proved to be most efficient in cultures reconstituted with normal peritoneal macrophages. Some effect was also observed using bone-marrow-derived (BM) macrophages. However, higher numbers of normal PE macrophages in the presence of VCN inhibited lymphocyte activation, and inhibition by thioglycollate-broth-induced macrophages was considerably increased by VCN. These results suggest that VCN acts by increasing the efficiency of macrophage-T lymphocyte interaction.

Cryptochrome-1 expression: a new prognostic marker in B-cell chronic lymphocytic leukemia.

PubMed

Lewintre, Eloisa Jantus; Martín, Cristina Reinoso; Ballesteros, Carlos García; Montaner, David; Rivera, Rosa Farrás; Mayans, José Ramón; García-Conde, Javier

2009-02-01

Chronic lymphocytic leukemia is an adult-onset leukemia with a heterogeneous clinical behavior. When chronic lymphocytic leukemia cases were divided on the basis of IgV(H) mutational status, widely differing clinical courses were revealed. Since IgV(H) sequencing is difficult to perform in a routine diagnostic laboratory, finding a surrogate for IgV(H) mutational status seems an important priority. In the present study, we proposed the use of Cryptochrome-1 as a new prognostic marker in early-stage chronic lymphocytic leukemia. Seventy patients (Binet stage A, without treatment) were included in the study. We correlated Cryptochrome-1 mRNA with well established prognostic markers such as IgV(H) mutations, ZAP70, LPL or CD38 expression and chromosomal abnormalities. High Cryptochrome-1 expression correlated with IgV(H) unmutated samples. In addition, Cryptochrome-1 was a valuable predictor of disease progression in early-stage chronic lymphocytic leukemia, therefore it can be introduced in clinical practice with the advantage of a simplified method of quantification.

Regulation of HSD17B1 and SRD5A1 in lymphocytes.

PubMed

Zhou, Z; Speiser, P W

1999-11-01

We previously reported lymphocyte expression of genes encoding enzymes required for steroid metabolism; however, only 17beta-HSD and 5alpha-reductase showed significant enzyme activity. We now investigate regulation of lymphocyte expression for genes encoding 17beta-HSD and 5alpha-reductase. Cultured human T and B lymphoid cell lines and peripheral blood mononuclear cells were treated with known regulators of steroidogenic gene expression including forskolin, PMA, ionomycin, various steroids, interleukin (IL)-4, and IL-6. Treatment with 10 or 50 microM forskolin resulted in a 20-60% reduction of expression for HSD17B1 (encoding 17beta-HSD I) in T and B lymphoid cell lines and peripheral blood mononuclear cells, although such a change was not observed in the expression of SRD5A1 (encoding 5alpha-reductase I). No significant changes were found when cells were treated for 24 h with various concentrations of PMA or ionomycin. Incubation with 10(-9) to 10(-7) M androstenedione or estradiol increased expression of HSD17B1, while testosterone decreased the expression of this gene. SRD5A1 expression was increased in the presence of 5alpha-DHT although no consistent changes were observed when the cells were treated with testosterone. Other steroids, including dexamethasone, progesterone, and 6-hydroxypregnanolone, produced no effects on expression of either HSD17B1 or SRD5A1. Treatment with 0.1-10 ng/ml of IL-4 or IL-6 also did not effect significant changes in gene expression. These data implicate the involvement of the cAMP-protein kinase signal transduction pathway in regulating lymphocyte expression of HSD17B1. Furthermore, it appears that lymphocyte HSD17B1 and SRD5A1 are regulated to some extent by specific steroids. Copyright 1999 Academic Press.

Foreskin-isolated keratinocytes provide successful extemporaneous autologous paediatric skin grafts.

PubMed

Mcheik, Jiad N; Barrault, Christine; Pedretti, Nathalie; Garnier, Julien; Juchaux, Franck; Levard, Guillaume; Morel, Franck; Lecron, Jean-Claude; Bernard, François-Xavier

2016-03-01

Severe burns in children are conventionally treated with split-thickness skin autografts or epidermal sheets. However, neither early complete healing nor quality of epithelialization is satisfactory. An alternative approach is to graft isolated keratinocytes. We evaluated paediatric foreskin and auricular skin as donor sources, autologous keratinocyte transplantation, and compared the graft efficiency to the in vitro capacities of isolated keratinocytes to divide and reconstitute epidermal tissue. Keratinocytes were isolated from surgical samples by enzymatic digestion. Living cell recovery, in vitro proliferation and epidermal reconstruction capacities were evaluated. Differentiation status was analysed, using qRT-PCR and immunolabelling. Eleven children were grafted with foreskin-derived (boys) or auricular (girls) keratinocyte suspensions dripped onto deep severe burns. The aesthetic and functional quality of epithelialization was monitored in a standardized way. Foreskin keratinocyte graft in male children provides for the re-epithelialization of partial deep severe burns and accelerates wound healing, thus allowing successful wound closure, and improves the quality of scars. In accordance, in vitro studies have revealed a high yield of living keratinocyte recovery from foreskin and their potential in terms of regeneration and differentiation. We report a successful method for grafting paediatric males presenting large severe burns through direct spreading of autologous foreskin keratinocytes. This alternative method is easy to implement, improves the quality of skin and minimizes associated donor site morbidity. In vitro studies have highlighted the potential of foreskin tissue for graft applications and could help in tissue selection with the prospect of grafting burns for girls. Copyright © 2013 John Wiley & Sons, Ltd.

Use of containers with sterilizing filter in autologous serum eyedrops.

PubMed

López-García, José S; García-Lozano, Isabel

2012-11-01

To assess the effect of the use of containers with an adapted sterilizing filter on the contamination of autologous serum eyedrops. Prospective, consecutive, comparative, and randomized study. Thirty patients with Sjögren syndrome. One hundred seventy-six autologous serum containers used in home therapy were studied; 48 of them included an adapted filter (Hyabak; Thea, Clermont-Ferrand, France), and the other 128 were conventional containers. Containers equipped with a filter were tested at 7, 14, 21, and 28 days of use, whereas conventional containers were studied after 7 days of use. In addition, testing for contamination was carried out in 14 conventional containers used during in-patient therapy every week for 4 weeks. In all cases, the preparation of the autologous serum was similar. Blood agar and chocolate agar were used as regular culture media for the microbiologic studies, whereas Sabouraud agar with chloramphenicol was the medium for fungal studies. Microbiologic contamination of containers with autologous serum eyedrops. Only one of the containers with an adapted sterilizing filter (2.1%) became contaminated with Staphylococcus epidermidis after 1 month of treatment, whereas the contamination rate among conventional containers reached 28.9% after 7 days of treatment. The most frequent germs found in the samples were coagulase-negative Staphylococcus (48.6%). With regard the containers used in the in-patient setting, 2 (14.3%) became contaminated after 2 weeks, 5 (35.7%) became contaminated after 3 weeks, and 5 (50%) became contaminated after 4 weeks, leaving 7 (50%) that did not become contaminated after 1 month of treatment. Using containers with an adapted filter significantly reduces the contamination rates in autologous serum eyedrops, thus extending the use of such container by the patients for up to 4 weeks with virtually no contamination risks. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

A clinical study on the feasibility of autologous cord blood transfusion for anemia of prematurity.

PubMed

Khodabux, Chantal M; von Lindern, Jeannette S; van Hilten, Joost A; Scherjon, Sicco; Walther, Frans J; Brand, Anneke

2008-08-01

The objective was to investigate the use of autologous red blood cells (RBCs) derived from umbilical cord blood (UCB), as an alternative for allogeneic transfusions in premature infants admitted to a tertiary neonatal center. UCB collection was performed at deliveries of less than 32 weeks of gestation and processed into autologous RBC products. Premature infants requiring a RBC transfusion were randomly assigned to an autologous or allogeneic product. The primary endpoint was an at least 50 percent reduction in allogeneic transfusion needs. Fifty-seven percent of the collections harvested enough volume (> or =15 mL) for processing. After being processed, autologous products (> or =10 mL/kg) were available for 36 percent of the total study population and for 27 percent of the transfused infants and could cover 58 percent (range, 25%-100%) of the transfusion needs within the 21-day product shelf life. Availability of autologous products depended most on the gestational age. Infants born between 24 and 28 weeks had the lowest availability (17%). All products, however, would be useful in view of their high (87%) transfusion needs. Availability was highest (48%) for the infants born between 28 and 30 weeks. For 42 percent of the infants with transfusion needs in this group, autologous products were available. For the infants born between 30 and 32 weeks, autologous products were available for 36 percent of the infants. Transfusion needs in this group were, however, much lower (19%) compared to the other gestational groups. Autologous RBCs derived from UCB could not replace 50 percent of allogeneic transfusions due to the low UCB volumes collected and subsequent low product availability.

Chimeric Human Skin Substitute Tissue: A Novel Treatment Option for the Delivery of Autologous Keratinocytes.

PubMed

Rasmussen, Cathy A; Allen-Hoffmann, B Lynn

2012-04-01

For patients suffering from catastrophic burns, few treatment options are available. Chimeric coculture of patient-derived autologous cells with a "carrier" cell source of allogeneic keratinocytes has been proposed as a means to address the complex clinical problem of severe skin loss. Currently, autologous keratinocytes are harvested, cultured, and expanded to form graftable epidermal sheets. However, epidermal sheets are thin, are extremely fragile, and do not possess barrier function, which only develops as skin stratifies and matures. Grafting is typically delayed for up to 4 weeks to propagate a sufficient quantity of the patient's cells for application to wound sites. Fully stratified chimeric bioengineered skin substitutes could not only provide immediate wound coverage and restore barrier function, but would simultaneously deliver autologous keratinocytes to wounds. The ideal allogeneic cell source for this application would be an abundant supply of clinically evaluated, nontumorigenic, pathogen-free, human keratinocytes. To evaluate this potential cell-based therapy, mixed populations of a green fluorescent protein-labeled neonatal human keratinocyte cell line (NIKS) and unlabeled primary keratinocytes were used to model the allogeneic and autologous components of chimeric monolayer and organotypic cultures. Relatively few autologous keratinocytes may be required to produce fully stratified chimeric skin substitute tissue substantially composed of autologous keratinocyte-derived regions. The need for few autologous cells interspersed within an allogeneic "carrier" cell population may decrease cell expansion time, reducing the time to patient application. This study provides proof of concept for utilizing NIKS keratinocytes as the allogeneic carrier for the generation of bioengineered chimeric skin substitute tissues capable of providing immediate wound coverage while simultaneously supplying autologous human cells for tissue regeneration.

Suppression of bovine lymphocyte function by treatment with physiologic concentrations of cortisone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ojo-Amaize, E.A.; Paape, M.J.; Guidry, A.J.

1986-03-01

The blastogenic response of peripheral blood lymphocytes (PBL) (8 cows) to capsular antigen extract of Staphylococcus aureus, PHA and LPS was measured in vitro using /sup 5/H-thymidine pulse labelling. isolated PBL were treated in vitro for 6-8 days with 10, 25 and 45 ng/ml cortisone. These concentrations simulate serum corticosteroid levels during environmental stress, acute clinical mastitis and ACTH therapy, respectively. To determine the minimal concentration of cortisone that would induce suppression, PBL were also incubated with increasing concentrations of cortisone starting at 10 pg/ml. All concentrations of cortisone caused a significant (P<0.01) depression of lymphocyte blastogenic response to S.more » aureus, PHA and LPS. Macrophage depletion experiments showed no macrophage suppressor effects. Both the blastogenic response of untreated peripheral blood lymphocytes to S. aureus, PHA and LPS and the degree to which that response was suppressed by cortisone differed significantly among cows. Results indicate that cortisone levels found during physiological stress and after therapeutic administration of ACTH can suppress lymphocyte function.« less

External quality assessment for CD4 + T-lymphocyte count test

PubMed Central

Gaspar, Pâmela Cristina; Wohlke, Bruna Lovizutto Protti; Brunialti, Milena Karina Coló; Pires, Ana Flávia; Kohiyama, Igor Massaki; Salomão, Reinaldo; Alonso Neto, José Boullosa; Júnior, Orlando da Costa Ferreira; Franchini, Miriam; Bazzo, Maria Luiza; Benzaken, Adele Schwartz

2018-01-01

Abstract The National Network for CD4+ T-lymphocyte counting of Brazil comprises 93 laboratories. This study reports the laboratory performances achieved in external quality assessment (EQA) rounds provides by Ministry of Health to evaluate the quality of the kits used and the performance of test by the technicians. Ten EQA rounds were analyzed according the EQA criteria aimed to evaluate individual laboratory performance on the basis of the accuracy of their results compared to the general mean obtained by all participating laboratories and the reproducibility of the results obtained between 2 samples from the same donor. The percentage of approved and failed laboratories in the EQAs tends to follow a uniform pattern. Since 2011, approval has remained above 80% and the failure rate has never exceeded 15%. EQA is very important to evaluate the performance of the laboratories, to identify monitor, and to resolve errors as quickly as possible. PMID:29794603

Autologous epidermal cells can induce wound closure of neurotrophic ulceration caused by trigeminal trophic syndrome.

PubMed

Schwerdtner, O; Damaskos, T; Kage, A; Weitzel-Kage, D; Klein, M

2005-06-01

Trigeminal trophic syndrome is an extremely rare complication following surgical ablation of the trigeminal nerve or after alcohol injection or thermocoagulation of the Gasserian ganglion. These lesions show a poor healing tendency and sometimes persist for years. The therapeutic results of local wound care with ointments and wound dressings are often unsatisfactory, and those of plastic surgery are variable. In the case presented, the skin area affected by neurotrophic ulceration is successfully treated with autologous cultivated epidermal cells. This form of tissue engineering is already a clinically established procedure for treating burns and chronic wounds. The results show for the first time that transplantation of in vitro cultivated epidermal cells can induce tissue regeneration and may be an effective tool in the treatment of neurotrophic ulcerations in the facial region.

[Cordyceps sinensis enhances lymphocyte proliferation and CD markers expression in simulated microgravity environment].

PubMed

Hao, Tong; Li, Jun-Jie; Du, Zhi-Yan; Duan, Cui-Mi; Wang, Yan-Meng; Wang, Chang-Yong; Song, Jing-Ping; Wang, Lin-Jie; Li, Ying-Hui; Wang, Yan

2012-10-01

This study was aimed to explore the effect of cordyceps sinensis enhancing lymphocyte proliferation and surface CD marker expression in simulated microgravity environment. The splenic lymphocytes were separated from mice and cultured in the rotary cell culture system simulated microgravity environment. The cells were treated with different concentration of cordyceps sinensis solution (0, 6.25, 12.5, 25 and 50 µg/ml) for 24, 48 and 72 h respectively, then the cells were harvested, and analyzed for cell proliferation and the expression of cell surface markers (CD4 and CD8). The results showed that under simulated microgravity environment, the lymphocyte proliferation was inhibited. When the concentration of cordyceps sinensis was 25 or 50 µg/ml, the lymphocyte proliferation, CD4 and CD8 expressions all increased, but 50 µg/ml cordyceps sinensis could inhibit the proliferation ability with the time prolonging. It is concluded that the suitable concentration of cordyceps sinensis displayed the ability to enhance the lymphocyte proliferation and CD marker expression in simulated microgravity environment. These results may be valuable for screening drugs which can be potentially against immunosuppression under simulated microgravity.

[Impact of topical application of autologous platelet-rich gel on medical expenditure and length of stay in hospitals in diabetic patients with refractory cutaneous ulcers].

PubMed

Li, Lan; Wang, Chun; Wang, Yan; He, Li-Ping; Yang, Yan-Zhi; Chen, Li-Hong; Chen, Da-Wei; Li, Xiu-Jun; Ran, Xing-Wu

2012-09-01

To evaluate the potential financial benefit of topical application of autologous platelet-rich gel (APG) in treating diabetic refractory cutaneous ulcers. A single-center prospective randomized controlled trial was undertaken, with 117 patients with proven diabetic refractory cutaneous ulcers participating in the study. The patients who gave informed consents were randomly assigned into standard care group (n = 58) or standard care plus topical application of APG treatment group (n = 59). The outcome of healing and the medical expenditur and length of stay in the patients were compared between the two groups. The APG-treated group had better healing outcomes than the standard-treated group. The APG-treated group had 84.750 (50/59) complete healing and 98.31% improvement, higher than the 68.97% (40/58) and 75.86%, respectively, in the standard-treated group (P = 0.026). The median length for healing in the APG-treated patients was 36 days, shorter than the 45 days in the standard-treated patients (P = 0.012). The total medical expenditure and length of stay in hospitals were not significantly different between APG-treated patients [yen 38223 (23070-57398); 57 (41-94) days] and standard-treated patients [yen 35070 (24436-53649); 58 (31.75-58.50) days) (P = 0.455 and 0.301 respectively). Spendings on items such as medicine, artificial treatment, materials, interventional operation, surgical procedures, laboratory tests and other auxiliary examination, accommodations, meals, nursing care and debridement and dressing change were similar between the two groups (P > 0.05). There is an advantage for the topical application of APG on diabetic refractory cutaneous ulcers in terms of the healing outcomes. APG is a cost-effective choice for patients with diabetic refractory cutaneous ulcers.

Impact of ibrutinib and idelalisib on the pharmaceutical cost of treating chronic lymphocytic leukemia at the individual and societal levels.

PubMed

Shanafelt, Tait D; Borah, Bijan J; Finnes, Heidi D; Chaffee, Kari G; Ding, Wei; Leis, Jose F; Chanan-Khan, Asher A; Parikh, Sameer A; Slager, Susan L; Kay, Neil E; Call, Tim G

2015-05-01

To evaluate the impact of approval of ibrutinib and idelalisib on pharmaceutical costs in the treatment of chronic lymphocytic leukemia (CLL) at the societal level and assess individual out-of-pocket costs under Medicare Part D. Average wholesale price of commonly used CLL treatment regimens was ascertained from national registries. Using the population of Olmsted County, Minnesota, we identified the proportion of patients with newly diagnosed CLL who experience progression to the point of requiring treatment. Using these data, total pharmaceutical cost over a 10-year period after diagnosis was estimated for a hypothetic cohort of 100 newly diagnosed patients under three scenarios: before approval of ibrutinib and idelalisib (historical scenario), after approval of ibrutinib and idelalisib as salvage therapy (current scenarios A and B), and assuming use of ibrutinib as first-line treatment (potential future scenario). Estimated 10-year pharmaceutical costs for 100 newly diagnosed patients were as follows: $4,565,929 (approximately $45,659 per newly diagnosed patient and $157,446 per treated patient) for the historical scenario, $7,794,843 (approximately $77,948 per newly diagnosed patient and $268,788 per treated patient) for current scenario A, $6,309,162 (approximately $63,092 per newly diagnosed patient and $217,557 per treated patient) for current scenario B, and $16,414,055 (approximately $164,141 per newly diagnosed patient and $566,002 per treated patient) for the potential future scenario. Total out-of-pocket cost for 100 patients with newly diagnosed CLL under Medicare Part D increased from $9,426 under the historical scenario (approximately $325 per treated patient) to $363,830 and $255,051 under current scenarios A and B (approximately $8,800 to $12,500 per treated patient) and to $1,031,367 (approximately $35,564 per treated patient) under the future scenario. Although ibrutinib and idelalisib are profound treatment advances, they will dramatically

Safety and effectiveness of predeposit autologous transfusions in preteen and adolescent children.

PubMed

Silvergleid, A J

1987-06-26

Although there is documentation in the literature of the safety and effectiveness of predeposit autologous transfusions among adult patients contemplating surgery, there are no comparable data for preteen and teenage children. We report our experience with 180 children between the ages of 8 and 18 years participating in a community blood center-based predeposit autologous transfusion program. Children as young as 8 years old and weighing as little as 27 kg predonated a prescribed amount of blood prior to elective orthopedic (169) or plastic (11) surgery. Only four children experienced a donor reaction; none of them was severe. No child was unable to donate the prescribed number of units. Eighty-eight percent of the children were able to supply their complete blood requirements, thus avoiding exposure to homologous blood. Our experience documents both the safety and effectiveness of predeposit autologous transfusions in preteen and adolescent children and should encourage existing predeposit autologous transfusion programs to extend participation to thousands of children for whom the opportunity to use their own blood is currently denied.

The Composite of Bone Marrow Concentrate and PRP as an Alternative to Autologous Bone Grafting

PubMed Central

Hakimi, Mohssen; Grassmann, Jan-Peter; Betsch, Marcel; Schneppendahl, Johannes; Gehrmann, Sebastian; Hakimi, Ahmad-Reza; Kröpil, Patric; Sager, Martin; Herten, Monika; Wild, Michael; Windolf, Joachim; Jungbluth, Pascal

2014-01-01

One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC). The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP) in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group). In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG), whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold) compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting. PMID:24950251

IIVP salvage regimen induces high response rates in patients with relapsed lymphoma before autologous stem cell transplantation.

PubMed

Abali, Huseyin; Oyan, Basak; Koc, Yener; Kars, Ayse; Barista, Ibrahim; Uner, Aysegul; Turker, Alev; Demirkazik, Figen; Tekin, Fatma; Tekuzman, Gulten; Kansu, Emin

2005-06-01

Patients with relapsed lymphoma can be cured with high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). New therapeutic approaches with better cytoreductive capacity are needed for relapsed patients to keep their chance for cure with transplantation. We report 30 patients with relapsed lymphoma, median age 43 years, treated with IIVP salvage regimen consisting of ifosfamide, mesna, idarubicin, and etoposide for 2 or 3 cycles. Seventeen patients had non-Hodgkin lymphoma (NHL) and 13 patients had Hodgkin disease (HD). Fourteen (47%) patients were at their first relapse. Overall response rate was 86.6% (n = 26) with 19 patients (63.3%) achieving complete response. Overall response rate was 92% in patients with HD and 82% in NHL. The most frequent side effects observed were grade III-IV neutropenia (87%) and thrombocytopenia (73%). IIVP regimen is a highly effective salvage therapy for patients with relapsed HD or NHL who are candidates for autologous HSCT. Close follow up is necessary because of the high incidence of grade III-IV hematologic toxicity.

High-dose therapy and autologous hematopoietic stem cell transplant in T-cell lymphoma: a single center experience.

PubMed

Cairoli, Anne; Ketterer, Nicolas; Barelli, Stefano; Duchosal, Michel A

2014-08-01

We report here the long-term outcome of autologous stem cell transplant in peripheral T-cell lymphoma (PTCL). Forty-three consecutive patients with PTCL diagnosed between 2000 and 2011 were treated with high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) in our center. Diagnoses included PTCL-not otherwise specified (n = 19), anaplastic large cell lymphoma (n = 11), angioimmunoblastic T-cell lymphoma (n = 5), enteropathy-associated T-cell lymphoma (n = 5) and other rare subtypes (n = 3). Thirty-six patients with a median age of 50 years (range 22-65) were transplanted in first response and seven after relapse. After a median follow-up of 63 months, estimated overall survival at 12 years was 40%, progression-free survival at 12 years was 34% and event-free survival at 12 years was 30%. On univariate analysis, age less than 50 years and no B symptoms at diagnosis were significantly associated with prolonged overall and progression-free-survival. HDCT/ASCT for peripheral T-cell lymphoma can lead to long-term survival for patients responding to induction chemotherapy.

Valvular Dysfunction in Lymphoma Survivors Treated With Autologous Stem Cell Transplantation: A National Cross-Sectional Study.

PubMed

Murbraech, Klaus; Wethal, Torgeir; Smeland, Knut B; Holte, Harald; Loge, Jon Håvard; Holte, Espen; Rösner, Assami; Dalen, Håvard; Kiserud, Cecilie E; Aakhus, Svend

2016-03-01

This study assessed the prevalence and associated risk factors for valvular dysfunction (VD) observed in adult lymphoma survivors (LS) after autologous hematopoietic stem cell transplantation (auto-HCT), and to determine whether anthracycline-containing chemotherapy (ACCT) alone in these patients is associated with VD. The prevalence of and risk factors for VD in LS after auto-HCT is unknown. Anthracyclines may induce heart failure, but any association with VD is not well-defined. This national cross-sectional study included all adult LS receiving auto-HCT from 1987 to 2008 in Norway. VD was defined by echocardiography as either more than mild regurgitation or any stenosis. Observations in LS were compared with a healthy age- and gender-matched (1:1) control group. In total, 274 LS (69% of all eligible) participated. Mean age was 56 ± 12 years, mean follow-up time after lymphoma diagnosis was 13 ± 6 years, and 62% of participants were males. Mean cumulative anthracycline dosage was 316 ± 111 mg/m(2), and 35% had received radiation therapy involving the heart (cardiac-RT). VD was observed in 22.3% of the LS. Severe VD was rare (n = 9; 3.3% of all LS) and mainly aortic stenosis (n = 7). We observed VD in 16.7% of LS treated with ACCT alone (n = 177), corresponding with a 3-fold increased VD risk (odds ratio: 2.9; 95% confidence interval: 1.5 to 5.8; p = 0.002) compared with controls. Furthermore, the presence of aortic valve degeneration was increased in the LS after ACCT alone compared with controls (13.0% vs. 2.9%; p < 0.001). Female sex, age >50 years at lymphoma diagnosis, ≥3 lines of chemotherapy before auto-HCT, and cardiac-RT >30 Gy were identified as independent risk factors for VD in the LS. In LS, ACCT alone was significantly associated with VD and related to valvular degeneration. Overall, predominantly moderate VD was prevalent in LS, and longer observation time is needed to clarify the clinical significance of this finding. Copyright © 2016

Laboratory measurements of radiance and reflectance spectra of dilute primary-treated sewage sludge

NASA Technical Reports Server (NTRS)

Usry, J. W.; Witte, W. G.; Whitlock, C. H.; Gurganus, E. A.

1977-01-01

The feasibility of remotely monitoring ocean dumping of waste products such as acid and sewage sludge is evaluated. The laboratory arrangement, solar simulator, and test results from three experiments conducted in the laboratory are described. Radiance and reflectance spectra are presented for primary-treated sewage sludge mixed with two types of base water. Results indicate that upwelled reflectance varies in a near-linear manner with concentration and that the sludge has a practically flat signal response between 420 and 970 nm. Well-defined upwelled reflectance spectra were obtained for the sewage-sludge mixtures at all wavelengths and concentrations. The spectral-reflectance values appeared to be influenced by the type of base water, but this influence was small, especially for the mixtures with low concentrations of sewage sludge.

Combination of medical needling and non-cultured autologous skin cell transplantation (ReNovaCell) for repigmentation of hypopigmented burn scars.

PubMed

Busch, K H; Bender, R; Walezko, N; Aziz, H; Altintas, M A; Aust, M C

2016-11-01

Burn scars remain a serious physical and psychological problem for the affected people. Clinical studies as well as basic scientific research have shown that medical needling can significantly increase the quality of burn scars with comparatively low risk and stress for the patient with regards to skin elasticity, moisture, erythema and transepidermal water loss. However, medical needling has no influence on repigmentation of large hypopigmented scars. The goal of this study is to evaluate whether two established methods - needling (for improvement of scar quality) and non-cultured autologous skin cell suspension (for repigmentation) - can be successfully combined. Twenty subjects with mean age of 33 years (6-60 years) with scars from deep second and third degree burns have been treated. The average treated surface area was 94cm 2 (15-250cm 2 ) and was focused on prominent areas such as the face, neck, chest and arm. Percutaneous collagen induction or "medical needling" was performed using a roller covered with 3mm long needles. The roller is vertically, horizontally and diagonally rolled over the scar, inducing microtrauma. Then, non-cultured autologous skin cell suspension (NCASCS) was produced and applied using the ReNovaCell Autologous Cell Harvesting Device (Avita Medical), according to the manufacturer's instructions. The patients were followed 12 months postoperatively. Pigmentation changes were measured objectively, as well as with patient and observer ratings. Patient satisfaction/preference was also obtained. Taken together, the pigmentation ratings and objective measures indicate individual improvement in 17 of the study participants. The melanin increases seen 12 months after NCASCS treatment are statistically significant. Medical needling in combination with NCASCS shows promise for repigmentation of burn cars. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Lymphocyte-conditioned medium in combination with interleukin-2 effectively induces antitumour autoimmunity by adoptive transfer of short activated killer (SHAK) cells.

PubMed

Buer, J; Hilse, R; Dallmann, I; Grosse, J; Kirchner, H; Zorn, U; Hänninen, E L; Franzke, A; Duensing, S; Poliwoda, H

1995-03-01

In this study, effective antitumour immunity was transferred by autologous short activated killer (SHAK) cells induced over four hours with lymphocyte conditioned medium (LCM) and recombinant interleukin-2 (rIL-2). Among eight patients with progressive metastatic renal cell carcinoma refractory to standard therapy, there were six objective tumour responses to SHAKs. Progression-free survival ranged from 0 to 8+ months, and overall survival ranged from 2 to 14+ months, with a median of 9+ months. Systemic toxicity of SHAKs was limited to flulike symptoms. Patient SHAKs provided a tumour-specific immunity, both cellular and humoral (expression and secretion of secondary cytokines, including IL-2, GM-CSF, INF-gamma and TNF-alpha), far superior to rIL-2 activated killer cells.

Failure of transplantation tolerance induction by autologous regulatory T cells in the pig-to-non-human primate islet xenotransplantation model.

PubMed

Shin, Jun-Seop; Min, Byoung-Hoon; Kim, Jong-Min; Kim, Jung-Sik; Yoon, Il Hee; Kim, Hyun Je; Kim, Yong-Hee; Jang, Jae Yool; Kang, Hee Jung; Lim, Dong-Gyun; Ha, Jongwon; Kim, Sang-Joon; Park, Chung-Gyu

2016-07-01

Islet allotransplantation is a promising way to treat some type 1 diabetic (T1D) patients with frequent hypoglycemic unawareness, and islet xenotransplantation is emerging to overcome the problem of donor organ shortage. Our recent study showing reproducible long-term survival of porcine islets in non-human primates (NHPs) allows us to examine whether autologous regulatory T-cell (Treg) infusion at peri-transplantation period would induce transplantation tolerance in xenotransplantation setting. Two diabetic rhesus monkeys were transplanted with porcine islets from wild-type adult Seoul National University (SNU) miniature pigs with immunosuppression by anti-thymoglobulin (ATG), cobra venom factor, anti-CD154 monoclonal antibody (mAb), and sirolimus. CD4(+) CD25(high) CD127(low) autologous regulatory T cells from the recipients were isolated, ex vivo expanded, and infused at the peri-transplantation period. Blood glucose and porcine C-peptide from the recipients were measured up to 1000 days. Maintenance immunosuppressants including a CD40-CD154 blockade were deliberately discontinued to confirm whether transplantation tolerance was induced by adoptively transferred Tregs. After pig islet transplantation via portal vein, blood glucose levels of diabetic recipients became normalized and maintained over 6 months while in immunosuppressive maintenance with a CD40-CD154 blockade and sirolimus. However, the engrafted pig islets in the long-term period were fully rejected by activated immune cells, particularly T cells, when immunosuppressants were stopped, showing a failure of transplantation tolerance induction by autologous Tregs. Taken together, autologous Tregs infused at the peri-transplantation period failed to induce transplantation tolerance in pig-to-NHP islet xenotransplantation setting. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Effect of Autologous Platelet Lysate Eye Drops: An In Vivo Confocal Microscopy Study

PubMed Central

Fea, Antonio M.; Testa, Valeria; Machetta, Federica; Parisi, Simone; D'Antico, Sergio; Spinetta, Roberta; Fusaro, Enrico; Grignolo, Federico M.

2016-01-01

Purpose. To determine the effectiveness of autologous platelet lysate (APL) eye drops in patients with primary Sjögren syndrome (SS) dry eye, refractory to standard therapy, in comparison with patients treated with artificial tears. We focused on the effect of APL on cornea morphology with the in vivo confocal microscopy (IVCM). Methods. Patients were assigned to two groups: group A used autologous platelet lysate QID, and group B used preservative-free artificial tears QID, for 90 days. Ophthalmological assessments included ocular surface disease index (OSDI), best corrected visual acuity (BCVA), Schirmer test, fluorescein score, and breakup time (BUT). A subgroup of patients in group A underwent IVCM: corneal basal epithelium, subbasal nerves, Langerhans cells, anterior stroma activated keratocytes, and reflectivity were evaluated. Results. 60 eyes of 30 patients were enrolled; in group A (n = 20 patients) mean OSDI, fluorescein score, and BUT showed significant improvement compared with group B (n = 10 patients). The IVCM showed a significant increase in basal epithelium cells density and subbasal nerve plexus density and number and a decrease in Langerhans cells density (p < 0.05). Conclusion. APL was found effective in the treatment of SS dry eye. IVCM seems to be a useful tool to visualize cornea morphologic modifications. PMID:27200376

The Effect of Autologous Platelet Lysate Eye Drops: An In Vivo Confocal Microscopy Study.

PubMed

Fea, Antonio M; Aragno, Vittoria; Testa, Valeria; Machetta, Federica; Parisi, Simone; D'Antico, Sergio; Spinetta, Roberta; Fusaro, Enrico; Grignolo, Federico M

2016-01-01

Purpose. To determine the effectiveness of autologous platelet lysate (APL) eye drops in patients with primary Sjögren syndrome (SS) dry eye, refractory to standard therapy, in comparison with patients treated with artificial tears. We focused on the effect of APL on cornea morphology with the in vivo confocal microscopy (IVCM). Methods. Patients were assigned to two groups: group A used autologous platelet lysate QID, and group B used preservative-free artificial tears QID, for 90 days. Ophthalmological assessments included ocular surface disease index (OSDI), best corrected visual acuity (BCVA), Schirmer test, fluorescein score, and breakup time (BUT). A subgroup of patients in group A underwent IVCM: corneal basal epithelium, subbasal nerves, Langerhans cells, anterior stroma activated keratocytes, and reflectivity were evaluated. Results. 60 eyes of 30 patients were enrolled; in group A (n = 20 patients) mean OSDI, fluorescein score, and BUT showed significant improvement compared with group B (n = 10 patients). The IVCM showed a significant increase in basal epithelium cells density and subbasal nerve plexus density and number and a decrease in Langerhans cells density (p < 0.05). Conclusion. APL was found effective in the treatment of SS dry eye. IVCM seems to be a useful tool to visualize cornea morphologic modifications.

Management of vocal fold scar with autologous fat implantation: perceptual results.

PubMed

Neuenschwander, M C; Sataloff, R T; Abaza, M M; Hawkshaw, M J; Reiter, D; Spiegel, J R

2001-06-01

Vocal fold scar disrupts the mucosal wave and interferes with glottic closure. Treatment involves a multidisciplinary approach that includes voice therapy, medical management, and sometimes surgery. We reviewed the records of the first eight patients who underwent autologous fat implantation for vocal fold scar. Information on the etiology of scar, physical findings, and prior interventions were collected. Videotapes of videostroboscopic findings and perceptual voice ratings [Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS)] were randomized and analyzed independently by four blinded observers. Etiology of scar included mass excision (7), vocal fold stripping (3), congenital sulcus (2), and hemorrhage (1). Prior surgical procedures performed included thyroplasty (1), autologous fat injection (9), excision of scar (2), and lysis of adhesions (2). Strobovideolaryngoscopy: Statistically significant improvement was found in glottic closure, mucosal wave, and stiffness (P = 0.05). Perceptual ratings (GRBAS): Statistically significant improvement was found in all five parameters, including overall Grade, Roughness, Breathiness, Asthenia, and Strain (P = 0.05). Patients appear to have improved vocal fold function and quality of voice after autologous fat implantation in the vocal fold. Autologous fat implantation is an important adjunctive procedure in the management of vocal fold scar, and a useful addition to the armamentarium of the experienced phonomicrosurgeon.

Autologous osteoblast transplantation, an innovative method of bone defect treatment: role of a tissue and cell bank in the process.

PubMed

Olender, E; Brubaker, S; Uhrynowska-Tyszkiewicz, I; Wojtowicz, A; Kaminski, A

2014-10-01

The idea of cell treatment of various diseases and medical conditions has become very popular. Some procedures are well established, as is autologous chondrocyte implantation, whereas others are still in the process of early development, laboratory experiments, and some clinical trials. This report is devoted to an example of an emerging cell treatment: bone augmentation with the use of autologous cells and its legal and technical background. Various requirements set by law must be met by tissue banks performing cell seeding of grafts. In Europe, the requirements are described in directives 2004/23/EC, 2006/17/EC, 2006/86/EC, and in the regulation 2007/1394/EC. Revitalization of biostatic allografts gives new, promising tools for creation of functional parts of organs; brings the methodology used in tissue banks closer to tissue engineering; places the enterprise in the mainstream of advanced biotechnology; allows the full potential of tissue allografts; and opens a new, large area for clinical and laboratory research. Cell and tissue processing also have a financial impact on the treatment: it produces additional expenditures. Clinical effectiveness will be the most decisive factor of whether this innovative treatment will be applied in a particular type of medical condition. From a tissue establishment perspective, the most important issue is to develop a procedure that ensures safety for the patient in graft quality terms.

Adoptive Cell Transfer Therapy Following Non-Myeloablative but Lymphodepleting Chemotherapy for the Treatment of Patients With Refractory Metastatic Melanoma

PubMed Central

Dudley, Mark E.; Wunderlich, John R.; Yang, James C.; Sherry, Richard M.; Topalian, Suzanne L.; Restifo, Nicholas P.; Royal, Richard E.; Kammula, Udai; White, Don E.; Mavroukakis, Sharon A.; Rogers, Linda J.; Gracia, Gerald J.; Jones, Stephanie A.; Mangiameli, David P.; Pelletier, Michelle M.; Gea-Banacloche, Juan; Robinson, Michael R.; Berman, David M.; Filie, Armando C.; Abati, Andrea; Rosenberg, Steven A.

2006-01-01

Purpose We investigated the combination of lymphodepleting chemotherapy followed by the adoptive transfer of autologous tumor reactive lymphocytes for the treatment of patients with refractory metastatic melanoma. Patients and Methods Thirty-five patients with metastatic melanoma, all but one with disease refractory to treatment with high-dose interleukin (IL)-2 and many with progressive disease after chemotherapy, underwent lymphodepleting conditioning with two days of cyclophosphamide (60 mg/kg) followed by five days of fludarabine (25 mg/m2). On the day following the final dose of fludarabine, all patients received cell infusion with autologous tumor-reactive, rapidly expanded tumor infiltrating lymphocyte cultures and high-dose IL-2 therapy. Results Eighteen (51%) of 35 treated patients experienced objective clinical responses including three ongoing complete responses and 15 partial responses with a mean duration of 11.5 ± 2.2 months. Sites of regression included metastases to lung, liver, lymph nodes, brain, and cutaneous and subcutaneous tissues. Toxicities of treatment included the expected hematologic toxicities of chemotherapy including neutropenia, thrombocytopenia, and lymphopenia, the transient toxicities of high-dose IL-2 therapy, two patients who developed Pneumocystis pneumonia and one patient who developed an Epstein-Barr virus-related lymphoproliferation. Conclusion Lymphodepleting chemotherapy followed by the transfer of highly avid antitumor lymphocytes can mediate significant tumor regression in heavily pretreated patients with IL-2 refractory metastatic melanoma. PMID:15800326

Assessment of bone marrow lymphocytic status during tyrosine kinase inhibitor therapy and its relation to therapy response in chronic myeloid leukaemia.

PubMed

El Missiry, Mohamed; Adnan Awad, Shady; Rajala, Hanna L; Al-Samadi, Ahmed; Ekblom, Marja; Markevän, Berit; Åstrand-Grundström, Ingbritt; Wold, Maren; Svedahl, Ellen Rabben; Juhl, Birgitte Ravn; Bjerrum, Ole Weis; Haulin, Inger; Porkka, Kimmo; Olsson-Strömberg, Ulla; Hjorth-Hansen, Henrik; Mustjoki, Satu

2016-05-01

Tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukaemia have been reported to induce immunomodulatory effects. We aimed to assess peripheral blood (PB) and bone marrow (BM) lymphocyte status at the diagnosis and during different TKI therapies and correlate it with treatment responses. BM and PB samples were acquired from 105 first-line TKI-treated patients. Relative number of BM lymphocytes was evaluated from MGG-stained BM aspirates, and immunophenotypic analyses were performed with multicolour flow cytometry. Early 3-month expansion of BM lymphocytes was found during all different TKIs (imatinib n = 71, 20 %; dasatinib n = 25, 21 %; nilotinib n = 9, 22 %; healthy controls n = 14, 12 %, p < 0.0001). Increased PB lymphocyte count was only observed during dasatinib therapy. The BM lymphocyte expansion was associated with early molecular response; patients with 3-month BCR-ABL1 <10 % showed higher lymphocyte counts than patients with BCR-ABL1 >10 % (23 vs. 17 %, p < 0.05). Detailed phenotypic analysis showed that BM lymphocyte expansion consisted of various lymphocyte subclasses, but especially the proportion of CD19+ B cells and CD3negCD16/56+ NK cells increased from diagnostic values. During dasatinib treatment, the lymphocyte balance in both BM and PB was shifted more to cytotoxic direction (increased CD8+CD57+ and CD8+HLA-DR+ cells, and low T regulatory cells), whereas no major immunophenotypic differences were observed between imatinib and nilotinib patients. Early BM lymphocytosis occurs with all current first-line TKIs and is associated with better treatment responses. PB and BM immunoprofile during dasatinib treatment markedly differs from both imatinib- and nilotinib-treated patients.

The impact of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio among patients with intrahepatic cholangiocarcinoma.

PubMed

Buettner, Stefan; Spolverato, Gaya; Kimbrough, Charles W; Alexandrescu, Sorin; Marques, Hugo P; Lamelas, Jorge; Aldrighetti, Luca; Gamblin, T Clark; Maithel, Shishir K; Pulitano, Carlo; Weiss, Matthew; Bauer, Todd W; Shen, Feng; Poultsides, George A; Marsh, J Wallis; IJzermans, Jan N M; Koerkamp, Bas Groot; Pawlik, Timothy M

2018-06-11

Neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio may be host factors associated with prognosis. We sought to determine whether neutrophil-to-lymphocyte and platelets-to-lymphocyte ratio were associated with overall survival among patients undergoing surgery for intrahepatic cholangiocarcinoma. Patients who underwent resection for intrahepatic cholangiocarcinoma between 1990 and 2015 were identified from 12 major centers. Clinicopathologic factors and overall survival were compared among patients stratified by neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio. Risk factors identified on multivariable analysis were included in a prognostic model and the discrimination was assessed using Harrell's concordance index (C index). A total of 991 patients were identified. Median neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio were 2.7 (interquartile range [IQR]: 2.0-4.0) and 109.6 (IQR: 72.4-158.8), respectively. Preoperative neutrophil-to-lymphocyte ratio was elevated (≥5) in 100 patients (10.0%) and preoperative platelets-to-lymphocyte ratio (≥190) in 94 patients (15.2%). Patients with low and high neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio generally had similar baseline characteristics with regard to tumor characteristics. Overall survival was 37.7 months (95% confidence interval [CI]: 32.7-42.6); 1-, 3-, and 5-year overall survival was 78.8%, 51.6%, and 39.3%, respectively. Patients with an neutrophil-to-lymphocyte ratio <5 had a median survival of 47.1 months (95% CI: 37.9-53.3) compared with a median survival of 21.9 months (95% CI: 4.8-39.1) among patients with an neutrophil-to-lymphocyte ratio ≥5 (P = .001). In contrast, patients who had a platelets-to-lymphocyte ratio <190 vs platelets-to-lymphocyte ratio ≥190 had comparable long-term survival (P > .05). On multivariable analysis, an elevated neutrophil-to-lymphocyte ratio was independently associated with decreased overall survival

Stabilization of the Chest Wall: Autologous and Alloplastic Reconstructions

PubMed Central

Mahabir, Raman Chaos; Butler, Charles E.

2011-01-01

The goals of chest wall stabilization include maintenance of a rigid airtight cavity, protection of the thoracic and abdominal contents, optimization of respiration, and, whenever possible, an aesthetic reconstruction. Evidence suggests that bony fixation results in reduced ventilator dependence, a shorter overall hospital stay, and improved upper extremity function. We prefer to accomplish this with autologous tissue alone (such as the pectoralis major, latissimus dorsi, or rectus abdominus muscle flaps) for small to moderate defects. En bloc resection of defects larger than 5 cm or containing four or more ribs will likely benefit from chest wall stabilization. For patients previously treated with radiation, even larger defects may be tolerated owing to fibrosis. For these larger defects, methyl methacrylate composite meshes are used and covered with vascularized tissue. Contaminated wounds are generally reconstructed with bioprosthetic mesh rather than synthetic mesh. Using these principles, the reconstructive plastic surgeon can devise a comprehensive and safe plan to repair tremendous defects of the chest wall. PMID:22294941

Zoledronic acid increases the circulating soluble RANKL level in mice, with a further increase in lymphocyte-derived soluble RANKL in zoledronic acid- and glucocorticoid-treated mice stimulated with bacterial lipopolysaccharide.

PubMed

Abe, Takahiro; Sato, Tsuyoshi; Kokabu, Shoichiro; Hori, Naoko; Shimamura, Yumiko; Sato, Tomoya; Yoda, Tetsuya

2016-07-01

The nitrogen-containing bisphosphonate (BP) zoledronic acid (ZA) is a potent antiresorptive drug used in conjunction with standard cancer therapy to treat osteolysis or hypercalcemia due to malignancy. However, it is unclear how ZA influences the circulating levels of bone remodeling factors. The aim of this study was to evaluate the effects of ZA on the serum levels of soluble receptor activator of NF-kB ligand (sRANKL) and osteoprotegerin (OPG). The following four groups of C57BL/6 mice were used (five mice per group): (1) the placebo+phosphate-buffered saline (PBS) group, in which placebo-treated mice were injected once weekly with PBS for 4weeks; (2) the placebo+ZA group, in which placebo-treated mice were injected once weekly with ZA for 4weeks; (3) the prednisolone (PSL)+PBS group, in which PSL-treated mice were injected once weekly with PBS for 4weeks; and (4) the PSL+ZA group, in which PSL-treated mice were injected once weekly with ZA for 4weeks. At the 3-week time point, all mice were subjected to oral inflammatory stimulation with bacterial lipopolysaccharide (LPS). The sera of these mice were obtained every week and the levels of sRANKL and OPG were measured using enzyme-linked immunosorbent assay. At the time of sacrifice, femurs were prepared for micro-computed tomography (micro-CT), histological, and histomorphometric analyses. Our data indicated that ZA administration remarkably reduced bone turnover and significantly increased the basal level of sRANKL. Interestingly, the PSL+ZA group showed a dramatically elevated sRANKL level after LPS stimulation. In contrast, the PSL+ZA group in nonobese diabetic mice with severe combined immunodeficiency disease (NOD-SCID mice), which are characterized by the absence of functional T- and B-lymphocytes, showed no increase in the sRANKL level. Our data suggest that, particularly with combination treatment of ZA and glucocorticoids, surviving lymphocytes might be the source of inflammation-induced sRANKL. Thus

[Breast reconstruction: autologous tissue versus implant].

PubMed

Plogmeier, K; Handstein, S; Schneider, W

1998-01-01

Modified radical mastectomy remains the standard for treatment of breast cancer. Women faced with the diagnosis of breast cancer often find it difficult to cope with the arousing emotions. Fear of death or cancer recurrence and a perceived loss of femininity often coexists with the desire for a return to normality and wholeness. For women seeking breast reconstruction various techniques have been developed. Two different ways for breast reconstruction have become a standard. One way is the reconstruction by tissue expansion or transposing locally available tissue with the use of implants. The other way is the reconstruction of the breast without using any implants with the Latissimus dorsi flap or the TRAM flap. We performed 291 breast reconstructions. In 125 women available tissue and an implant was used. The Latissimus dorsi flap was used in 57 cases and 109 TRAM flaps either pedicled or as a microvascular flap were performed. Using expanders we found a perforation of the device in 2 cases. After using implants there were capsular contracture in 2 cases and in 1 case we had an infection. Using autologous tissue we had 2 partial flap necrosis, 4 hematomas, and 4 prolonged healings. There was no complete flap necrosis. Breast reconstruction using autologous tissue i.e. the TRAM flap is supposed to be a standard technique. Microsurgical transplantation of the TRAM flap shows almost no morbidity of the donor site area. Autologous tissue follows the changes of the body like weight gain or reduction to a certain extend and shows neither capsular contracture nor other implant associated side effects. Women get the impression that the TRAM flap is like soft tissue to the touch and not like a foreign body. The aesthetic results were in all cases superior sometimes needing minor secondary correction and mostly shaping of the nippel-areola complex. All patients were pleased with the result.

A phase II trial of vaccination with autologous, tumor-derived heat-shock protein peptide complexes Gp96, in combination with GM-CSF and interferon-alpha in metastatic melanoma patients.

PubMed

Pilla, Lorenzo; Patuzzo, Roberto; Rivoltini, Licia; Maio, Michele; Pennacchioli, Elisabetta; Lamaj, Elda; Maurichi, Andrea; Massarut, Samuele; Marchianò, Alfonso; Santantonio, Cristina; Tosi, Diego; Arienti, Flavio; Cova, Agata; Sovena, Gloria; Piris, Adriano; Nonaka, Daisuke; Bersani, Ilaria; Di Florio, Annabella; Luigi, Mariani; Srivastava, Pramod K; Hoos, Axel; Santinami, Mario; Parmiani, Giorgio

2006-08-01

The aim of this study was to determine the immunogenicity and antitumor activity of autologous, tumor-derived heat shock protein gp96-peptide complex vaccine (HSPPC-96; Oncophage given with GM-CSF and IFN-alpha in pre-treated metastatic (AJCC stage IV) melanoma patients. Patients underwent surgical resection of metastatic lesions for HSPPC-96 production. HSPPC-96 was administered subcutaneously (s.c.) in four weekly intervals (first cycle). Patients with more available vaccine and absence of progressive disease received four additional injections in 2-week intervals (second cycle) or more. GM-CSF was given s.c. at the same site at days -1, 0 and +1, while IFN-alpha (3 MU) was administered s.c. at a different site at days +4 and +6. Antigen-specific anti-melanoma T and NK lymphocyte response was assessed by enzyme-linked immunospot assay on peripheral blood mononuclear cells obtained before and after vaccination. Thirty-eight patients were enrolled, 20 received at least four injections (one cycle) of HSPPC-96 and were considered assessable. Toxicity was mild and most treatment-related adverse events were local erythema and induration at the injection site. Patients receiving at least four injections of HSPPC-96 were considered evaluable for clinical response: of the 18 patients with measurable disease post surgery, 11 showed stable disease (SD). The ELISPOT assay revealed an increased class I HLA-restricted T and NK cell-mediated post-vaccination response in 5 out of 17 and 12 out of the 18 patients tested, respectively. Four of the five class I HLA-restricted T cell responses fall in the group of SD patients. Vaccination with autologous HSPPC-96 together with GM-CSF and IFN-alpha is feasible and accompanied by mild local and systemic toxicity. Both tumor-specific T cell-mediated and NK cell responses were generated in a proportion of patients. Clinical activity was limited to SD. However, both immunological and clinical responses were not improved as compared with

Autologous neurosensory retinal free patch transplantation for persistent full-thickness macular hole.

PubMed

De Giacinto, Chiara; D'Aloisio, Rossella; Cirigliano, Gabriella; Pastore, Marco Rocco; Tognetto, Daniele

2018-03-27

To evaluate anatomical and functional outcomes after autologous neurosensory retinal free patch (ANRFP) transplantation for persistent idiopathic full-thickness macular hole (iFTMH). A 65-year-old woman with persistent macular hole in her right eye after previous 27-gauge pars plana vitrectomy with internal limiting membrane peeling and long-acting gas tamponade underwent ANRFP transplantation. Before surgery, best corrected visual acuity in her right eye was 20/800. Optical coherence tomography (OCT) showed a 715-micron-diameter FTMH. To treat the persistent FTMH, a small autologous neurosensory retinal patch was transplanted and placed inside the macular hole under perfluorocarbon liquids (PFCL). PFCL-air exchange was performed, and long-acting gas tamponade was carried out. Clinical features of the macular area, visual acuity (VA), fundus autofluorescence, microperimetry and OCT were recorded during the 10-month follow-up. The macular hole appeared successfully closed with retinal patch stable and well plugged into the hole during the whole follow-up. VA improved to 20/100 and microperimetry revealed an increase in mean retinal sensitivity from 14.7 dB at 1 month to 15.6 dB at 10 months postoperatively. OCT showed a well-distinguishable retinal patch into the hole 1 month after surgery and a completely integrated retinal patch between the retinal layers 10 months postoperatively. No intra- and postoperative complications were noticed. ANRFP transplantation may represent an innovative technique for persistent iFTMH treatment.

Tissue-Engineered Autologous Grafts for Facial Bone Reconstruction

PubMed Central

Bhumiratana, Sarindr; Bernhard, Jonathan C.; Alfi, David M.; Yeager, Keith; Eton, Ryan E.; Bova, Jonathan; Shah, Forum; Gimble, Jeffrey M.; Lopez, Mandi J.; Eisig, Sidney B.; Vunjak-Novakovic, Gordana

2016-01-01

Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care—the use of bone harvested from another region in the body—has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, without bone morphogenic proteins, using native bovine bone matrix and a perfusion bioreactor for the growth and transport of living grafts. The ramus-condyle unit (RCU), the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatan minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material, and crafted it into an anatomically correct shape using image-guided micromilling, to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either non-seeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering. PMID:27306665

Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing

PubMed Central

Neves, Paulo César Fagundes; de Campos Vieira Abib, Simone; Neves, Rogério Fagundes; Pircchio, Oronzo; Saad, Karen Ruggeri; Saad, Paulo Fernandes; Simões, Ricardo Santos; Moreira, Marcia Bento; de Souza Laurino, Cristiano Frota

2013-01-01

OBJECTIVES: The purpose is to study the effects of hyperbaric oxygen therapy and autologous platelet concentrates in healing the fibula bone of rabbits after induced fractures. METHODS: A total of 128 male New Zealand albino rabbits, between 6–8 months old, were subjected to a total osteotomy of the proximal portion of the right fibula. After surgery, the animals were divided into four groups (n = 32 each): control group, in which animals were subjected to osteotomy; autologous platelet concentrate group, in which animals were subjected to osteotomy and autologous platelet concentrate applied at the fracture site; hyperbaric oxygen group, in which animals were subjected to osteotomy and 9 consecutive daily hyperbaric oxygen therapy sessions; and autologous platelet concentrate and hyperbaric oxygen group, in which animals were subjected to osteotomy, autologous platelet concentrate applied at the fracture site, and 9 consecutive daily hyperbaric oxygen therapy sessions. Each group was divided into 4 subgroups according to a pre-determined euthanasia time points: 2, 4, 6, and 8 weeks postoperative. After euthanasia at a specific time point, the fibula containing the osseous callus was prepared histologically and stained with hematoxylin and eosin or picrosirius red. RESULTS: Autologous platelet concentrates and hyperbaric oxygen therapy, applied together or separately, increased the rate of bone healing compared with the control group. CONCLUSION: Hyperbaric oxygen therapy and autologous platelet concentrate combined increased the rate of bone healing in this experimental model. PMID:24141841

Adoptive Immunotherapy with T Lymphocytes Engineered for Enhanced Survival | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed a method of genetically engineering lymphocytes to expressed elevated levels of cytokine proteins. This technology is useful for improving cellular adoptive immunotherapies to treat a range of infectious diseases and cancers.

Immunophenotype of infiltrating cells in protocol renal allograft biopsies from tacrolimus-versus cyclosporine-treated patients.

PubMed

Serón, Daniel; O'Valle, Francisco; Moreso, Francesc; Gomà, Montse; Hueso, Miguel; Grinyó, Josep M; Garcia del Moral, Raimundo

2007-03-15

The prevalence of subclinical rejection is lower in patients receiving tacrolimus than in patients treated with cyclosporine. However, it is not known whether this difference is related to the modulation of a specific cell immunophenotype. We perform a two case-one control study in patients treated with tacrolimus (n=44) or cyclosporine (n=22) with a protocol biopsy performed at 4 to 6 months. Immunophenotype of infiltrating cells was evaluated with monoclonal antibodies directed against CD45 (all leukocytes), CD3 (T lymphocytes), CD68 (monocytes/macrophages), and CD20 (B lymphocytes) and expressed as interstitial positive cells/mm(2). The number of interstitial CD45 (290+/-209 vs. 696+/-560; P<0.01), CD3 (121+/-84 vs. 208+/-104; P<0.01), and CD68 (155+/-232 vs. 242+/-280; P<0.05) but not CD20 (137+/-119 vs. 197+/-154) positive cells was lower in tacrolimus-treated patients. T lymphocytes and macrophages interstitial infiltration was reduced in tacrolimus treated patients evaluated with protocol biopsies in comparison to cyclosporine-treated patients.

[Post-anesthetic autologous blood donation used in knee and hip arthroplasty].

PubMed

Wei, Wei; Kou, Bolong; Ju, Rongseng

2006-06-01

To explore the clinical application of the postanesthetic autologous donation and the postoperative transfusion during the knee and hip replacement surgeries. Thirty-three patients (17 males, 16 females) admitted for the elective joint replacement surgeries from September 2004 to January 2005 were included in this study. Of the 33 patients, 5 were diagnosed with rheumatoid arthritis, 23 with femoral head necrosis, and 5 with knee osteoarthritis. Immediately after anesthesia, 400 ml of the blood was drawn and transfused after the surgery. The blood pressure was monitored during the blood drawing, postoperative blood parameters were recorded, surgical site drainage and signs of infections were observed, and the other clinical data were collected. Of the 33 patients, 27 only received autologous transfusion, including 21 patients who underwent the unilateral hip replacement and 6 patients who underwent the unilateral knee replacement. All these 6 patients with the unilateral knee replacement received the blood drained from the surgical sites in addition to the blood obtained from the post-anesthetic autologous donation. Another 6 cases with the bilateral hip and knee replacement received the blood drained from the surgical sites, the blood obtained from the post-anesthetic autologous donation and 400 ml of the allogeneic blood transfusion. The blood received postoperatively averaged 650 ml (range, 200-1 150 ml), haemoglobin (Hb) was averaged 88 g/L (68-102 g/L), and Hct was averaged 24.6% (20.5%-31.5%). Hb and Hct were lower after operation than before operation (P < 0.01). Postoperative blood transfusion following the postanesthetic and preoperative autologous donation can be successfully applied to most of the patients undergoing the knee or hip replacement so as to reduce complications of the allogeneic blood transfusion.

Effects of (-)-epigallocatechin gallate (EGCG) on DNA strand breaks as evaluated by single-cell gel electrophoresis (SCG) in human lymphocytes.

PubMed

Yuquan, L; Takeshita, T; Morimoto, K

2001-01-01

(-)-Epigallocatechin gallate (EGCG), a catechin polyphenol component, is the main ingredient of green tea extract. Although the anti-carcinogenic and cancer inhibitory effects of EGCG have been widely reported, its genotoxicity is not clear and seldom reported. In this study, we examined the effects of EGCG on DNA strand breaks in the isolated lymphocytes and whole blood lymphocytes obtained from two smoking subjects and a nonsmoking healthy subject using a single cell gel electrophoresis (SCG) assay. The results showed that after 2 hrs of treating the isolated lymphocytes from the smokers, EGCG induced a significant, increase in DNA strand breaks at concentrations from 2.5×10(-5) M to 2.0×10(-4) M, while after 2 hrs of treating the whole blood obtained from the same smokers, EGCG suppressed the DNA strand breaks in the lymphocytes at concentrations of 1.0×10(-4) M and 2.0×10(-4) M. A similar suppressive result was also shown in the whole blood lymphocytes from the nonsmoker at nearly the same concentrations, while at concentrations of 1.0×10(-3) M or 2.0×10(-3) M, EGCG induced a significant increase in DNA strand breaks in the whole blood lymphocytes from the nonsmoker. This result suggests that EGCG is not only inhibitory against DNA strand breaks in whole blood, but also genotoxic to the isolated or whole blood lymphocytes at high concentrations. Thus, more research is needed to comprehensively assess the effects of EGCG on genetic materials.

Long-Term Hematopoietic Engraftment of Congenic Amniotic Fluid Stem Cells After in Utero Intraperitoneal Transplantation to Immune Competent Mice

PubMed Central

Shangaris, Panicos; Loukogeorgakis, Stavros P.; Blundell, Michael P.; Petra, Eleni; Shaw, Steven W.; Ramachandra, Durrgah L.; Maghsoudlou, Panagiotis; Urbani, Luca; Thrasher, Adrian J.

2018-01-01

Clinical success of in utero transplantation (IUT) using allogeneic hematopoietic stem cells (HSCs) has been limited to fetuses that lack an immune response to allogeneic cells due to severe immunological defects, and where transplanted genetically normal cells have a proliferative or survival advantage. Amniotic fluid (AF) is an autologous source of stem cells with hematopoietic potential that could be used to treat congenital blood disorders. We compared the ability of congenic and allogeneic mouse AF stem cells (AFSC) to engraft the hematopoietic system of time-mated C57BL/6J mice (E13.5). At 4 and 16 weeks of age, multilineage donor engraftment was higher in congenic versus allogeneic animals. In vitro mixed lymphocyte reaction confirmed an immune response in the allogeneic group with higher CD4 and CD8 cell counts and increased proliferation of stimulated lymphocytes. IUT with congenic cells resulted in 100% of donor animals having chimerism of around 8% and successful hematopoietic long-term engraftment in immune-competent mice when compared with IUT with allogeneic cells. AFSCs may be useful for autologous cell/gene therapy approaches in fetuses diagnosed with congenital hematopoietic disorders. PMID:29482456

[Autologous fat grafting in children].

PubMed

Baptista, C; Bertrand, B; Philandrianos, C; Degardin, N; Casanova, D

2016-10-01

Lipofilling or fat grafting transfer is defined as a technique of filling soft tissue by autologous fat grafting. The basic principle of lipofilling is based on a harvest of adipose tissue, followed by a reinjection after treatment. Lipofilling main objective is a volume defect filling, but also improving cutaneous trophicity. Lipofilling specificities among children is mainly based on these indications. Complications of autologous fat grafting among children are the same as those in adults: we distinguish short-term complications (intraoperative and perioperative) and the medium and long-term complications. The harvesting of fat tissue is the main limiting factor of the technique, due to low percentage of body fat of children. Indications of lipofilling among children may be specific or similar to those in adults. There are two types of indications: cosmetic, in which the aim of lipofilling is correcting a defect density, acquired (iatrogenic, post-traumatic scar) or malformation (otomandibular dysplasia, craniosynostosis, Parry Romberg syndrom, Poland syndrom, pectus excavatum…). The aim of functional indications is correcting a velar insufficiency or lagophthalmos. In the paediatric sector, lipofilling has become an alternative to the conventional techniques, by its reliability, safety, reproducibility, and good results. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Cartilage Repair With Autologous Bone Marrow Mesenchymal Stem Cell Transplantation: Review of Preclinical and Clinical Studies.

PubMed

Yamasaki, Shinya; Mera, Hisashi; Itokazu, Maki; Hashimoto, Yusuke; Wakitani, Shigeyuki

2014-10-01

Clinical trials of various procedures, including bone marrow stimulation, mosaicplasty, and autologous chondrocyte implantation, have been explored to treat articular cartilage defects. However, all of them have some demerits. We focused on autologous culture-expanded bone marrow mesenchymal stem cells (BMSC), which can proliferate without losing their capacity for differentiation. First, we transplanted BMSC into the defective articular cartilage of rabbit and succeeded in regenerating osteochondral tissue. We then applied this transplantation in humans. Our previous reports showed that treatment with BMSC relieves the clinical symptoms of chondral defects in the knee and elbow joint. We investigated the efficacy of BMSC for osteoarthritic knee treated with high tibial osteotomy, by comparing 12 BMSC-transplanted patients with 12 cell-free patients. At 16-month follow-up, although the difference in clinical improvement between both groups was not significant, the arthroscopic and histological grading score was better in the cell-transplanted group. At the over 10-year follow-up, Hospital for Special Surgery knee scores improved to 76 and 73 in the BMSC-transplanted and cell-free groups, respectively, which were better than preoperative scores. Additionally, neither tumors nor infections were observed in all patients, and in the clinical study, we have never observed hypertrophy of repaired tissue, thereby guaranteeing the clinical safety of this therapy. Although we have never observed calcification above the tidemark in rabbit model and human histologically, the repair cartilage was not completely hyaline cartilage. To elucidate the optimum conditions for cell therapy, other stem cells, culture conditions, growth factors, and gene transfection methods should be explored.

Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia.

PubMed

Tissino, Erika; Benedetti, Dania; Herman, Sarah E M; Ten Hacken, Elisa; Ahn, Inhye E; Chaffee, Kari G; Rossi, Francesca Maria; Dal Bo, Michele; Bulian, Pietro; Bomben, Riccardo; Bayer, Elisabeth; Härzschel, Andrea; Gutjahr, Julia Christine; Postorino, Massimiliano; Santinelli, Enrico; Ayed, Ayed; Zaja, Francesco; Chiarenza, Annalisa; Pozzato, Gabriele; Chigaev, Alexandre; Sklar, Larry A; Burger, Jan A; Ferrajoli, Alessandra; Shanafelt, Tait D; Wiestner, Adrian; Del Poeta, Giovanni; Hartmann, Tanja Nicole; Gattei, Valter; Zucchetto, Antonella

2018-02-05

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL). The lymphocytosis experienced by most patients under ibrutinib has previously been attributed to inhibition of BTK-dependent integrin and chemokine cues operating to retain the tumor cells in nodal compartments. Here, we show that the VLA-4 integrin, as expressed by CD49d-positive CLL, can be inside-out activated upon BCR triggering, thus reinforcing the adhesive capacities of CLL cells. In vitro and in vivo ibrutinib treatment, although reducing the constitutive VLA-4 activation and cell adhesion, can be overcome by exogenous BCR triggering in a BTK-independent manner involving PI3K. Clinically, in three independent ibrutinib-treated CLL cohorts, CD49d expression identifies cases with reduced lymphocytosis and inferior nodal response and behaves as independent predictor of shorter progression-free survival, suggesting the retention of CD49d-expressing CLL cells in tissue sites via activated VLA-4. Evaluation of CD49d expression should be incorporated in the characterization of CLL undergoing therapy with BCR inhibitors. © 2018 Tissino et al.

Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia

PubMed Central

Tissino, Erika; Benedetti, Dania; Herman, Sarah E.M.; ten Hacken, Elisa; Rossi, Francesca Maria; Dal Bo, Michele; Bulian, Pietro; Bomben, Riccardo; Bayer, Elisabeth; Härzschel, Andrea; Gutjahr, Julia Christine; Postorino, Massimiliano; Santinelli, Enrico; Zaja, Francesco; Pozzato, Gabriele; Chigaev, Alexandre; Sklar, Larry A.; Burger, Jan A.; Ferrajoli, Alessandra; Shanafelt, Tait D.; Wiestner, Adrian; Del Poeta, Giovanni; Hartmann, Tanja Nicole

2018-01-01

The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL). The lymphocytosis experienced by most patients under ibrutinib has previously been attributed to inhibition of BTK-dependent integrin and chemokine cues operating to retain the tumor cells in nodal compartments. Here, we show that the VLA-4 integrin, as expressed by CD49d-positive CLL, can be inside-out activated upon BCR triggering, thus reinforcing the adhesive capacities of CLL cells. In vitro and in vivo ibrutinib treatment, although reducing the constitutive VLA-4 activation and cell adhesion, can be overcome by exogenous BCR triggering in a BTK-independent manner involving PI3K. Clinically, in three independent ibrutinib-treated CLL cohorts, CD49d expression identifies cases with reduced lymphocytosis and inferior nodal response and behaves as independent predictor of shorter progression-free survival, suggesting the retention of CD49d-expressing CLL cells in tissue sites via activated VLA-4. Evaluation of CD49d expression should be incorporated in the characterization of CLL undergoing therapy with BCR inhibitors. PMID:29301866

Office-based Autologous Fat Injection Laryngoplasty for Vocal Process Granuloma.

PubMed

Hu, Hao-Chun; Hung, Yi-Ting; Lin, Shu-Yi; Chang, Shyue-Yih

2016-11-01

To present the outcomes of office-based autologous fat injection laryngoplasty for the treatment of vocal process granuloma in conjunction with glottic insufficiency. Retrospective chart review. This study included nine patients with vocal process granuloma in conjunction with glottic insufficiency who received autologous fat injection laryngoplasty. Videolaryngostroboscopic data, objective voice assessment, perceptual measurements of vocal quality, and subjective ratings of voice quality were examined before and after treatment. Of the nine patients, seven (78%) exhibited complete remission. The other two patients (22%) exhibited a partial response following the injection. In a subgroup of five patients who were refractory to antireflux and voice therapies, the resolution rate was 60%. Phonatory function presented significant improvements in jitter, noise-to-harmonic ratio, maximal phonation time, and asthenia. Videolaryngostroboscopic rating revealed significant improvements in closure phase ratio in the vibratory cycle. Autologous fat injection laryngoplasty can ameliorate glottic insufficiency and the resulting hyperfunctional behavior of the larynx. This therapy also encourages remission of vocal process granuloma and may represent an alternative treatment strategy. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Role of IL-17-producing lymphocytes in severity of multiple sclerosis upon natalizumab treatment.

PubMed

Bühler, Ulrike; Fleischer, Vinzenz; Luessi, Felix; Rezk, Ayman; Belikan, Patrick; Graetz, Christiane; Gollan, René; Wolf, Christina; Lutz, Jens; Bar-Or, Amit; Siffrin, Volker; Zipp, Frauke

2017-04-01

Natalizumab is known to prevent T-helper cells entering the central nervous system (CNS). We hypothesize that more pathogenic T-helper cells are present outside the CNS and a possible relationship to disease severity. Characterization and enrichment of human CD4+IL-17+ cells were performed ex vivo using peripheral blood mononuclear cells from natalizumab-treated relapsing-remitting multiple sclerosis (RRMS) patients ( n = 33), untreated RRMS patients ( n = 13), and healthy controls ( n = 33). Magnetic resonance imaging (MRI) scans were performed routinely for patients. Lymphocytes were elevated in peripheral blood of natalizumab-treated patients compared to untreated patients and healthy controls. Whereas group comparison for CD4+IL-17+ numbers also differed, CD4+IFN-γ+ and CD4+IL-22+ counts were not increased. CD4+IL-17+ cells not only expressed but also secreted IL-17. In natalizumab-treated patients, IL-17+ cell frequency was found to correlate with T1-hypointense lesions, but was not an indicator for rebound activity after treatment discontinuation, except in one patient who experienced a fulminant rebound, and interestingly, in whom the highest IL-17+ cell levels were observed. Increased lymphocytes and CD4+IL-17+ cells in the blood of RRMS patients receiving natalizumab corroborate the drug's mechanism of action, that is, blocking transmigration to CNS. Correlation between IL-17-expressing lymphocytes and T1-hypointense lesions underlines the important role of these cells in the disease pathology.

Comparative quantitative analysis of cluster of differentiation 45 antigen expression on lymphocyte subsets.

PubMed

Im, Mijeong; Chae, Hyojin; Kim, Taehoon; Park, Hun-Hee; Lim, Jihyang; Oh, Eun-Jee; Kim, Yonggoo; Park, Yeon-Joon; Han, Kyungja

2011-07-01

Since the recent introduction of radioimmunotherapy (RIT) using antibodies against cluster of differentiation (CD) 45 for the treatment of lymphoma, the clinical significance of the CD45 antigen has been increasing steadily. Here, we analyzed CD45 expression on lymphocyte subsets using flow cytometry in order to predict the susceptibility of normal lymphocytes to RIT. Peripheral blood specimens were collected from 14 healthy individuals aged 25-54 yr. The mean fluorescence intensity (MFI) of the cell surface antigens was measured using a FACSCanto II system (Becton Dickinson Bioscience, USA). MFI values were converted into antibody binding capacity values using a Quantum Simply Cellular microbead kit (Bangs Laboratories, Inc., USA). Among the lymphocyte subsets, the expression of CD45 was the highest (725,368±42,763) on natural killer T (NKT) cells, 674,030±48,187 on cytotoxic/suppressor T cells, 588,750±48,090 on natural killer (NK) cells, 580,211±29,168 on helper T (Th) cells, and 499,436±21,737 on B cells. The Th cells and NK cells expressed a similar level of CD45 (P=0.502). Forward scatter was the highest in NKT cells (P<0.05), whereas side scatter differed significantly between each of the lymphocyte subsets (P<0.05). CD3 expression was highest in the Th and NKT cells. NKT cells express the highest levels of CD45 antigen. Therefore, this lymphocyte subset would be most profoundly affected by RIT or pretargeted RIT. The monitoring of this lymphocyte subset during and after RIT should prove helpful.

Autologous mesenchymal stem cell treatment increased T regulatory cells with no effect on disease activity in two systemic lupus erythematosus patients.

PubMed

Carrion, F; Nova, E; Ruiz, C; Diaz, F; Inostroza, C; Rojo, D; Mönckeberg, G; Figueroa, F E

2010-03-01

Mesenchymal stem cells (MSCs) exert suppressive effects in several disease models including lupus prone mice. However, autologous MSC therapy has not been tested in human systemic lupus erythematosus (SLE). We evaluate the safety and efficacy of bone marrow (BM)-derived MSCs in two SLE patients; the suppressor effect of these cells in-vitro and the change in CD4+CD25+FoxP3+ T regulatory (Treg) cells in response to treatment. Two females (JQ and SA) of 19 and 25 years of age, fulfilling the 1997 American College of Rheumatology (ACR) criteria for SLE were infused with autologous BM-derived MSCs. Disease activity indexes and immunological parameters were assessed at baseline, 1, 2, 7 and 14 weeks. Peripheral blood lymphocyte (PBL) subsets and Treg cells were quantitated by flow cytometry, and MSCs tested for in-vitro suppression of activation and proliferation of normal PBLs. No adverse effects or change in disease activity indexes were noted during 14 weeks of follow-up, although circulating Treg cells increased markedly. Patient MSCs effectively suppressed in-vitro PBL function. However, JQ developed overt renal disease 4 months after infusion. MSC infusion was without adverse effects, but did not modify initial disease activity in spite of increasing CD4+CD25+FoxP3+ cell counts. One patient subsequently had a renal flare. We speculate that the suppressive effects of MSC-induced Treg cells might be dependent on a more inflammatory milieu, becoming clinically evident in patients with higher degrees of disease activity.

The relation of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mean platelet volume with the presence and severity of Behçet's syndrome.

PubMed

Alan, Sevil; Tuna, Serpil; Türkoğlu, Elif Betül

2015-12-01

Behçet's syndrome (BS) is associated with chronic inflammation and endothelial dysfunction. Although there have been extensive investigations on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) in many diseases, their roles in BS is unclear. The purpose of the present study was to evaluate NLR, PLR, and MPV levels in BS patients and explore their clinical significance. The study included 254 patients with BS and 173 healthy individuals. Age, sex, age of onset, duration of disease, smoking, Behçet activity score, total white blood counts, neutrophil, platelet, and T lymphocyte counts of the patients were recorded. White blood cell (WBC), neutrophil, platelet, NLR, and PLR were significantly higher in patients with BS when compared with healthy controls (all p < 0.001). Lymphocyte counts and MPVs of the BS group were not statistically different from healthy controls (all p > 0.05). In the BS group, PLR and MPV were significantly different among the three severity groups (p = 0.037 and p = 0.016, respectively). We showed that any laboratory markers were not associated with joint, eye, central nervous system, large vessel, or gastrointestinal involvement in BS. NLR was shown to be an independent factor for BS by multivariate analysis. We suggest that NLR can be considered to be a diagnostic criterion of BS given the support of the findings from larger prospective studies. Copyright © 2015. Published by Elsevier Taiwan.

The role of autologous blood stem cells in support of high-dose therapy for multiple myeloma.

PubMed

Fermand, J P; Chevret, S; Levy, Y; Miclea, J M; Tsapis, A; Gerota, J; Benbunan, M; Brouet, J C

1992-04-01

During the last few years, high-dose therapy with hemopoietic stem cell support has become a well-admitted therapeutic option for young patients with MM. The role of allogeneic or autologous graft and of blood rather than bone marrow as the source of hemopoietic stem cells must be further investigated. Autologous PBSC transplantation has, however, both practical and theoretic advantages over allogeneic and autologous BMT: (1) It can be applied to most patients, especially if blood stem cells are collected early in the course of therapy. (2) It usually induces relatively rapid hematologic reconstitution. (3) In comparison with autologous BMT, it appears to minimize the hazard of the reinfusion of malignant cells.

Lymphocyte ceruloplasmin and Behçet's disease.

PubMed

Oliveira, Rita; Banha, João; Martins, Fátima; Paixão, Eleonora; Pereira, Dina; Barcelos, Filipe; Teixeira, Ana; Patto, José Vaz; Costa, Luciana

2006-01-01

Behçet's disease (BD) is a rare chronic inflammatory disorder of unknown aetiology. However, it has been postulated that a dysregulation of the prooxidant/antioxidant balance may be important to its pathogenesis. Ceruloplasmin (CP) is an acute phase protein expressed at the surface of peripheral blood lymphocytes (PBL) with antioxidant properties and with a relevant role in iron (Fe) metabolism. To study CP expression at the surface of PBL (PBLCP) in patients with BD. We measured serum CP and PBLCP obtained from BD patients (n=10) and respective controls (n=10) using nephelometry and flow cytometry techniques, respectively. Additionally, haematological parameters, biochemical Fe metabolism markers [serum Fe, serum ferritin, serum transferrin, total Fe binding capacity (TIBC), transferrin saturation] and non-specific markers of inflammation [serum C reactive protein (CRP), beta2-microglobulin] were measured in all individuals. Despite the absence of significant differences between the two study groups when comparing serum CP, a significant difference in PBLCP was found in BD patients mainly due to a significant decrease of CP expression at the surface of CD3-CD56+ lymphocytes. Also, a significant decrease of PBLCP was observed in patients treated with azathioprine compared to patients that were not being treated with this drug. According to this study, we suggest that the significant decrease of PBLCP observed in BD patients might be due to azathioprine treatment and not directly related to the pathophysiology of BD.

Autologous Adipose-Derived Tissue Matrix Part I: Biologic Characteristics.

PubMed

Schendel, Stephen A

2017-10-01

Autologous collagen is an ideal soft tissue filler and may serve as a matrix for stem cell implantation and growth. Procurement of autologous collagen has been limited, though, secondary to a sufficient source. Liposuction is a widely performed and could be a source of autologous collagen. The amount of collagen and its composition in liposuctioned fat remains unknown. The purpose of this research was to characterize an adipose-derived tissue-based product created using ultrasonic cavitation and cryo-grinding. This study evaluated the cellular and protein composition of the final product. Fat was obtained from individuals undergoing routine liposuction and was processed by a 2 step process to obtain only the connective tissue. The tissue was then evaluated by scanning electronic microscope, Western blot analysis, and flow cytometry. Liposuctioned fat was obtained from 10 individuals with an average of 298 mL per subject. After processing an average of 1 mL of collagen matrix was obtained from each 100 mL of fat. Significant viable cell markers were present in descending order for adipocytes > CD90+ > CD105+ > CD45+ > CD19+ > CD144+ > CD34+. Western blot analysis showed collagen type II, III, IV, and other proteins. Scanning electronic microscope study showed a regular pattern of cross-linked, helical collagen. Additionally, vital staing demonstrated that the cells were still viable after processing. Collagen and cells can be easily obtained from liposuctioned fat by ultrasonic separation without alteration of the overall cellular composition of the tissue. Implantation results in new collagen and cellular growth. Collagen matrix with viable cells for autologous use can be obtained from liposuctioned fat and may provide long term results. 5. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

Effect of activated autologous platelet-rich plasma on proliferation and osteogenic differentiation of human adipose-derived stem cells in vitro

PubMed Central

Xu, Fang-Tian; Li, Hong-Mian; Yin, Qing-Shui; Liang, Zhi-Jie; Huang, Min-Hong; Chi, Guang-Yi; Huang, Lu; Liu, Da-Lie; Nan, Hua

2015-01-01

To investigate whether activated autologous platelet-rich plasma (PRP) can promote proliferation and osteogenic differentiation of human adipose-derived stem cells (hASCs) in vitro. hASCs were isolated from lipo-aspirates, and characterized by specific cell markers and multilineage differentiation capacity after culturing to the 3rd passage. PRP was collected and activated from human peripheral blood of the same patient. Cultured hASCs were treated with normal osteogenic inductive media alone (group A, control) or osteogenic inductive media plus 5%, 10%, 20%, 40%PRP (group B, C, D, E, respectively). Cell proliferation was assessed by CCK-8 assay. mRNA expression of osteogenic marker genes including alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN) and core binding factor alpha 1 (Cbfa1) were determined by Real-Time Quantitative PCR Analysis (qPCR). Data revealed that different concentrations of activated autologous PRP significantly promoted hASCs growth in the proliferation phase compared to the without PRP group and resulted in a dose-response relationship. At 7-d and 14-d time point of the osteogenic induced stage, ALP activity in PRP groups gradually increased with the increasing of concentrations of PRP and showed that dose-response relationship. At 21-d time point of the osteogenic induced stage, PRP groups make much more mineralization and mRNA relative expression of ALP, OPN, OCN and Cbfa1 than that without PRP groups and show that dose-response relationship. This study indicated that different concentrations of activated autologous PRP can promote cell proliferation at earlier stage and promote osteogenic differentiation at later stage of hASCs in vitro. Moreover, it displayed a dose-dependent effect of activated autologous PRP on cell proliferation and osteogenic differentiation of hASCs in vitro. PMID:25901195

Post-treatment neutrophil-to-lymphocyte ratio predicts for overall survival in brain metastases treated with stereotactic radiosurgery.

PubMed

Chowdhary, Mudit; Switchenko, Jeffrey M; Press, Robert H; Jhaveri, Jaymin; Buchwald, Zachary S; Blumenfeld, Philip A; Marwaha, Gaurav; Diaz, Aidnag; Wang, Dian; Abrams, Ross A; Olson, Jeffrey J; Shu, Hui-Kuo G; Curran, Walter J; Patel, Kirtesh R

2018-05-30

Neutrophil-to-lymphocyte ratio (NLR) is a surrogate for systemic inflammatory response and its elevation has been shown to be a poor prognostic factor in various malignancies. Stereotactic radiosurgery (SRS) can induce a leukocyte-predominant inflammatory response. This study investigates the prognostic impact of post-SRS NLR in patients with brain metastases (BM). BM patients treated with SRS from 2003 to 2015 were retrospectively identified. NLR was calculated from the most recent full blood counts post-SRS. Overall survival (OS) and intracranial outcomes were calculated using the Kaplan-Meier method and cumulative incidence with competing risk for death, respectively. 188 patients with 328 BM treated with SRS had calculable post-treatment NLR values. Of these, 51 (27.1%) had a NLR > 6. The overall median imaging follow-up was 13.2 (14.0 vs. 8.7 for NLR ≤ 6.0 vs. > 6.0) months. Baseline patient and treatment characteristics were well balanced, except for lower rate of ECOG performance status 0 in the NLR > 6 cohort (33.3 vs. 44.2%, p = 0.026). NLR > 6 was associated with worse 1- and 2-year OS: 59.9 vs. 72.9% and 24.6 vs. 43.8%, (p = 0.028). On multivariable analysis, NLR > 6 (HR: 1.53; 95% CI 1.03-2.26, p = 0.036) and presence of extracranial metastases (HR: 1.90; 95% CI 1.30-2.78; p < 0.001) were significant predictors for worse OS. No association was seen with NLR and intracranial outcomes. Post-treatment NLR, a potential marker for post-SRS inflammatory response, is inversely associated with OS in patients with BM. If prospectively validated, NLR is a simple, systemic marker that can be easily used to guide subsequent management.

Evaluation of cytogenetic and DNA damage in human lymphocytes treated with adrenaline in vitro.

PubMed

Djelić, Ninoslav; Radaković, Milena; Spremo-Potparević, Biljana; Zivković, Lada; Bajić, Vladan; Stevanović, Jevrosima; Stanimirović, Zoran

2015-02-01

Catechol groups can be involved in redox cycling accompanied by generation of reactive oxygen species (ROS) which may lead to oxidative damage of cellular macromolecules including DNA. The objective of this investigation was to evaluate possible genotoxic effects of a natural catecholamine adrenaline in cultured human lymphocytes using cytogenetic (sister chromatid exchange and micronuclei) and the single cell gel electrophoresis (Comet) assay. In cytogenetic tests, six experimental concentrations of adrenaline were used in a range from 0.01-500 μM. There were no indications of genotoxic effects of adrenaline in sister chromatid exchange and micronucleus tests. However, at four highest concentrations of adrenaline (5 μM, 50 μM, 150 μM and 300 μM) we observed a decreased mitotic index and cell-cycle delay. In addition, in the Comet assay we used adrenaline in a range from 0.0005-500 μM, at two treatment times: 15 min or 60 min. In contrast to cytogenetic analysis, there was a dose-dependent increase of DNA damage detected in the Comet assay. These effects were significantly reduced by concomitant treatment with quercetin or catalase. Therefore, the obtained results indicate that adrenaline may exhibit genotoxic effects in cultured human lymphocytes, most likely due to production of reactive oxygen species. Copyright © 2014 Elsevier Ltd. All rights reserved.

Vivostat®: an autologous fibrin sealant as useful adjunct in endoscopic transnasal CSF-leak repair.

PubMed

Tomazic, Peter Valentin; Edlinger, Stefan; Gellner, Verena; Koele, Wolfgang; Gerstenberger, Claus; Braun, Hannes; Mokry, Michael; Stammberger, Heinz

2015-06-01

The benefit of fibrin glue for reduction of postoperative CSF-leaks after endoscopic skull base surgery is not clearly evident in literature. However, its use is supposed to be beneficial in fixing grafting material. As of today there is no specific data available for otolaryngological procedures. A retrospective data analysis at a tertiary care referral center on 73 patients treated endoscopically transnasally for CSF-leaks at the ENT-department Graz between 2009 and 2012 was performed. Primary closure rate between conventional fibrin glue and autologous fibrin glue were analyzed. The Vivostat(®) system was used in 33 CSF-leak closures and in 40 cases conventional fibrin glue was used. Comparing the two methods the primary closure rate using the autologous Vivostat(®) system was 75.8 and 85.0 % with conventional fibrin glue. The secondary closure the rates were 90.9 % with Vivostat(®) 92.5 % with conventional fibrin glue. The Vivosat(®) system is a useful adjunct in endoscopic CSF-leak closure. Its advantages over conventional fibrin glue are its application system for fixation of grafting material particularly in underlay techniques. Despite this advantage it cannot replace grafting material or is a substitute for proper endoscopic closure which is reflected by the closure rates.

Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes.

PubMed

Tsai, Wei-Jern; Chang, Chu-Ting; Wang, Guei-Jane; Lee, Tzong-Huei; Chang, Shwu-Fen; Lu, Shao-Chun; Kuo, Yuh-Chi

2011-03-25

Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT.

The effect of supportive E. coli mastitis treatment on PMN chemiluminescence and subpopulations of T lymphocytes.

PubMed

Markiewicz, H; Krumrych, W; Gehrke, M

2013-01-01

The aim of this field study was to assess the impact of a single i.m. injection of lysozyme dimer and flunixin meglumine in combination with intramammary and systemic antibiotic on chemiluminescence of PMN (polymorphonuclear leucocytes) and subpopulations of lymphocyte T in blood of cows with E. coli mastitis. Examinations were performed on 30 dairy cows affected with naturally occurring acute form of E. coli mastitis. Cows were randomly divided into three groups according to the method of treatment. The first group was treated with approved intramammary antibiotic product, the same antibiotic in i.m. injection and one injection of flunixin meglumine on the first day of therapy. Next group was treated with the same antibiotic and additionally one injection of lysozyme dimer on the first day of therapy. The third one was treated only with an antibiotic and served as a control group. Blood samples were taken before treatment and on days 3 and 7. In samples haematology indices were determined, spontaneous and opsonised zymosan stimulated CL and PMA measurements were performed and the subpopulations of T lymphocyte (CD2(+), CD4(+), CD8(+)) were assayed in whole blood. There was no effect of the applied supportive treatment on the value of morphological blood indices. A significant influence of the time of sample collection on the level of CL and dynamics of lymphocytes T subpopulation was demonstrated. A single injection of flunixin meglumine or lysozyme dimer on the day of the beginning of treatment of E. coli mastitis, does not affect the level of neutrophil chemiluminescence and the percentage of T lymphocytes in the blood of mastitic cows in the analysed period of time.

Angiogenesis in rat uterine cicatrix after injection of autologous bone marrow mesenchymal stem cells.

PubMed

Maiborodin, I V; Yakimova, N V; Matveyeva, V A; Pekarev, O G; Maiborodina, E I; Pekareva, E O

2011-04-01

Results of injection of autologous bone marrow mesenchymal stem cells with transfected GFP gene into the rat uterine horn cicatrix were studied by light microscopy. Large groups of blood vessels with blood cells inside were seen after injection of autologous bone marrow cells into the cicatrix on the right horn, formed 2 months after its ligation; no groups of vessels of this kind were found in the cicatrix in the contralateral horn. Examination of unstained sections in reflected UV light showed sufficiently bright fluorescence in the endothelium and outer vascular membrane in the uterine horn cicatrix only on the side of injection. Hence, autologous mesenchymal stem cells injected into the cicatrix formed the blood vessels due to differentiation into endotheliocytes and pericytes. The expression of GFP gene not only in the vascular endothelium, but also in vascular outer membranes indicated that autologous mesenchymal stem cells differentiated in the endothelial and pericytic directions.

Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy.

PubMed

Hollyman, Daniel; Stefanski, Jolanta; Przybylowski, Mark; Bartido, Shirley; Borquez-Ojeda, Oriana; Taylor, Clare; Yeh, Raymond; Capacio, Vanessa; Olszewska, Malgorzata; Hosey, James; Sadelain, Michel; Brentjens, Renier J; Rivière, Isabelle

2009-01-01

On the basis of promising preclinical data demonstrating the eradication of systemic B-cell malignancies by CD19-targeted T lymphocytes in vivo in severe combined immunodeficient-beige mouse models, we are launching phase I clinical trials in patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia. We present here the validation of the bioprocess which we developed for the production and expansion of clinical grade autologous T cells derived from patients with CLL. We demonstrate that T cells genetically modified with a replication-defective gammaretroviral vector derived from the Moloney murine leukemia virus encoding a chimeric antigen receptor (CAR) targeted to CD19 (1928z) can be expanded with Dynabeads CD3/CD28. This bioprocess allows us to generate clinical doses of 1928z+ T cells in approximately 2 to 3 weeks in a large-scale semiclosed culture system using the Wave Bioreactor. These 1928z+ T cells remain biologically functional not only in vitro but also in severe combined immunodeficient-beige mice bearing disseminated tumors. The validation requirements in terms of T-cell expansion, T-cell transduction with the 1928z CAR, biologic activity, quality control testing, and release criteria were met for all 4 validation runs using apheresis products from patients with CLL. Additionally, after expansion of the T cells, the diversity of the skewed Vbeta T-cell receptor repertoire was significantly restored. This validated process will be used in phase I clinical trials in patients with chemorefractory CLL and in patients with relapsed acute lymphoblastic leukemia. It can also be adapted for other clinical trials involving the expansion and transduction of patient or donor T cells using any CAR or T-cell receptor.

The Effects of Aloe vera Cream on the Expression of CD4+ and CD8+ Lymphocytes in Skin Wound Healing.

PubMed

Prakoso, Yos Adi; Kurniasih

2018-01-01

The aim of this study is to explore the effect of topical application of Aloe vera on skin wound healing. Thirty-six male Sprague-Dawley rats weighing 150-200 grams were divided into four groups. All groups were anesthetized, shaved, and exposed to round full-thickness punch biopsy on the back: group I (control); group II (treated with 1% Aloe vera cream); group III (treated with 2% Aloe vera cream); and group IV (treated with madecassol®). The treatments were given once a day. Macroscopic and microscopic examination were observed at 5, 10, and 15 days after skin biopsy. Skin specimens were prepared for histopathological study using H&E stain and IHC stain against CD4 + and CD8 + lymphocytes. All the data were analyzed using SPSS16. The result showed that topical application of 1% and 2% Aloe vera cream significantly reduced the percentage of the wound, leucocytes infiltration, angiogenesis, and expression of CD8 + lymphocytes and increased the epidermal thickness and the expression of CD4 + lymphocytes ( p ≤ 0,05). There was no significant difference in the number of fibroblasts in all groups. Topical application of 1% and 2% Aloe vera cream has wound healing potential via their ability to increase the ratio of CD4 + /CD8 + lymphocytes in the wound area.

Pretreatment lymphocyte-to-monocyte ratio as an independent prognostic factor for head and neck cancer.

PubMed

Kano, Satoshi; Homma, Akihiro; Hatakeyama, Hiromitsu; Mizumachi, Takatsugu; Sakashita, Tomohiro; Kakizaki, Tomohiko; Fukuda, Satoshi

2017-02-01

The purpose of this study was to analyze the relationship between pretreatment inflammatory markers and the prognosis of patients with oropharyngeal, hypopharyngeal, and laryngeal cancers. The data for 285 patients treated with curative intent by concurrent chemoradiotherapy (CRT) were obtained and their pretreatment inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. Significant relationships were observed between a high NLR and oropharyngeal or hypopharyngeal cancer, T3 to T4, N2b to N3, and clinical stage III to IV, whereas significant relationships were observed between a high LMR and laryngeal cancer, T1 to T2, and clinical stage I to II. With regard to survival outcomes, a high NLR, a high PLR, and a low LMR were all significantly associated with decreases in overall survival (OS) and disease-free survival (DFS). Furthermore, multivariate analysis showed that LMR was an independent prognostic factor. Pretreatment LMR was found to be an independent prognostic factor for patients with head and neck cancers treated by concurrent CRT. © 2016 Wiley Periodicals, Inc. Head Neck 39: 247-253, 2017. © 2016 Wiley Periodicals, Inc.

Amifostine reduces gastro-intestinal toxicity after autologous transplantation for multiple myeloma.

PubMed

Malek, Ehsan; Gupta, Vinita; Creger, Richard; Caimi, Paolo; Vatsayan, Anant; Covut, Fahrettin; Bashir, Qaiser; Champlin, Richard; Delgado, Ruby; Rondon, Gabriela; Cooper, Brenda; de Lima, Marcos; Lazarus, Hillard M; Qazilbash, Muzaffar

2018-01-02

High-dose melphalan (HDM) followed by autologous hematopoietic cell transplantation (auto-HCT) remains the standard-of-care therapy for multiple myeloma (MM) even with the availability of proteasome inhibitors and immunomodulatory drugs. Gastrointestinal (GI) toxicity is the main cause of morbidity after HDM. Amifostine, a cytoprotective agent, may reduce HDM-associated GI toxicity. We conducted a case control study comparing HDM + auto-HCT with or without amifostine for MM patients. One hundred and seven patients treated at University Hospitals Cleveland Medical Center who received pre-transplant amifostine were compared to 114 patients treated at MD Anderson Cancer Center without use of this agent. Amifostine 740 mg/m 2 was administered as a bolus infusion at 24 h and 15 min before HDM. Patients' characteristics were similar in both the groups. Amifostine therapy was well tolerated without any significant adverse effects. Grade II or greater oral mucositis (27.1% vs 47.4%; p = .002), nausea (31.8% vs. 86.0%; p = .0001), vomiting (18.7% vs. 52.6%; p = .0001) and diarrhea (56.1% vs. 72.7%; p = .006) occurred less frequently in the amifostine-treated group. There was no discernable effect of amifostine on engraftment, progression-free or overall survival. Our results indicate that amifostine decreases GI toxicity while preserving anti-myeloma efficacy of HDM and auto-HCT.

Immune Modulation in Normal Human Peripheral Blood Mononuclear Cells (PBMCs) (Lymphocytes) in Response to Benzofuran-2-Carboxylic Acid Derivative KMEG during Spaceflight

NASA Astrophysics Data System (ADS)

Okoro, Elvis; Mann, Vivek; Ellis, Ivory; Mansoor, Elvedina; Olamigoke, Loretta; Marriott, Karla Sue; Denkins, Pamela; Williams, Willie; Sundaresan, Alamelu

2017-08-01

Microgravity and radiation exposure during space flight have been widely reported to induce the suppression of normal immune system function, and increase the risk of cancer development in humans. These findings pose a serious risk to manned space missions. Interestingly, recent studies have shown that benzofuran-2-carboxylic acid derivatives can inhibit the progression of some of these devastating effects on earth and in modeled microgravity. However, these studies had not assessed the impacts of benzofuran-2- carboxylic acid and its derivatives on global gene expression under spaceflight conditions. In this study, the ability of a specific benzofuran-2-carboxylic acid derivative (KMEG) to confer protection from radiation and restore normal immune function was investigated following exposure to space flight conditions on the ISS. Normal human peripheral blood mononuclear cells (lymphocytes) treated with 10 µ g/ml of KMEG together with untreated control samples were flown on Nanoracks hardware on Spacex-3 flight. The Samples were returned one month later and gene expression was analyzed. A 1g-ground control experiment was performed in parallel at the Kennedy spaceflight center. The first overall subtractive unrestricted analysis revealed 78 genes, which were differentially expressed in space flight KMEG, untreated lymphocytes as compared to the corresponding ground controls. However, in KMEG-treated space flight lymphocytes, there was an increased expression of a group of genes that mediate increased transcription, translation and innate immune system mediating functions of lymphocytes as compared to KMEG-untreated samples. Analysis of genes related to T cell proliferation in spaceflight KMEG-treated lymphocytes compared to 1g-ground KMEG- treated lymphocytes revealed six T cell proliferation and signaling genes to be significantly upregulated (p < 0.001) and five related genes were found to be significantly down-regulated. These genes play a significant role in

Induced Autologous Stem Cell Transplantation for Treatment of Rabbit Renal Interstitial Fibrosis

PubMed Central

Ruan, Guang-Ping; Xu, Fan; Li, Zi-An; Zhu, Guang-Xu; Pang, Rong-Qing; Wang, Jin-Xiang; Cai, Xue-Min; He, Jie; Yao, Xiang; Ruan, Guang-Hong; Xu, Xin-Ming; Pan, Xing-Hua

2013-01-01

Introduction Renal interstitial fibrosis (RIF) is a significant cause of end-stage renal failure. The goal of this study was to characterize the distribution of transplanted induced autologous stem cells in a rabbit model of renal interstitial fibrosis and evaluate its therapeutic efficacy for treatment of renal interstitial fibrosis. Methods A rabbit model of renal interstitial fibrosis was established. Autologous fibroblasts were cultured, induced and labeled with green fluorescent protein (GFP). These labeled stem cells were transplanted into the renal artery of model animals at 8 weeks. Results Eight weeks following transplantation of induced autologous stem cells, significant reductions (P < 0.05) were observed in serum creatinine (SCr) (14.8 ± 1.9 mmol/L to 10.1 ± 2.1 mmol/L) and blood urea nitrogen (BUN) (119 ± 22 µmol/L to 97 ± 13 µmol/L), indicating improvement in renal function. Conclusions We successfully established a rabbit model of renal interstitial fibrosis and demonstrated that transplantation of induced autologous stem cells can repair kidney damage within 8 weeks. The repair occurred by both inhibition of further development of renal interstitial fibrosis and partial reversal of pre-existing renal interstitial fibrosis. These beneficial effects lead to the development of normal tissue structure and improved renal function. PMID:24367598

Chronic lymphocytic thyroiditis (CLT) has a positive prognostic value in papillary thyroid cancer (PTC) patients: the potential key role of Foxp3+ T lymphocytes.

PubMed

Pilli, T; Toti, P; Occhini, R; Castagna, M G; Cantara, S; Caselli, M; Cardinale, S; Barbagli, L; Pacini, F

2018-06-01

An impact of chronic lymphocytic thyroiditis (CLT) on papillary thyroid cancer (PTC) outcome has long been advocated but it is still controversial. The aim of this study was to evaluate the prognostic value of CLT in a retrospective cohort of PTC patients and to characterize the lymphocytic subpopulations and infiltrate (LI). We assessed 375 PTC patients, aged 45.2 ± 16.4 years, and treated with thyroidectomy and radioiodine remnant ablation, with a mean follow-up of 6.28 ± 3.86 years. In a subgroup of patients (n = 81) tissue sections were reviewed for the presence of CLT or lymphocytes associated with tumor in absence of background thyroiditis (TAL); cytotoxic CD8+/regulatory Foxp3+ T lymphocyte (CD8+/Foxp3+) ratio was characterized by immunohistochemistry: a low ratio is suggestive of a less effective anti tumor immune response. Seventy-five/375 patients (20%) had a histological diagnosis of CLT and showed at the last follow-up a significantly better outcome compared to those with no CLT (cure rate: 91.8 versus 76.3%, p = 0.003). LI was characterized in 81 PTC patients (24 with CLT and 57 with TAL): the peri-tumoral CD8+/Foxp3+ ratio was lower in patients not cured at the final evaluation. Our data suggest that concurrent CLT has a protective effect on PTC outcome and that the imbalance between cytotoxic and regulatory T lymphocytes in the peri-tumoral TAL may affect the tumor-specific immune response favoring a more aggressive behavior of cancer.

Comparison of clinical outcomes of patients with relapsed acute promyelocytic leukemia induced with arsenic trioxide and consolidated with either an autologous stem cell transplant or an arsenic trioxide-based regimen.

PubMed

Thirugnanam, Rajasekar; George, Biju; Chendamarai, Ezhil; Lakshmi, Kavitha M; Balasubramanian, Poonkuzhali; Viswabandya, Auro; Srivastava, Alok; Chandy, Mammen; Mathews, Vikram

2009-11-01

In patients with relapsed acute promyelocytic leukemia (APL), the best consolidation regimen following induction of remission with arsenic trioxide (ATO) remains to be defined. Since January 2000, 37 patients with relapsed APL were treated at our center. The median age was 34 years (range, 6-57 years), and there were 20 males (54.1%). The median duration of first remission was 20.3 months (range, 2.9-81.2 months). Relapse was treated with single-agent ATO in 22 patients (59.5%), ATO+ATRA in 5 patients (13.5%), and ATO+ATRA + anthracycline in 10 patients (27%). Thirty-three patients (89%) achieved molecular remission after induction and a consolidation course. Fourteen patients opted to undergo autologous stem cell transplantation (SCT), and the remaining 19 patients received monthly cycles of ATO as a single agent (n=13) or ATO+ATRA (n=6) for 6 months. At a median follow-up of 32 months, the 5-year Kaplan-Meier estimate of event-free survival (EFS) was 83.33% +/- 15.21% in those who underwent autologous SCT versus 34.45% +/- 11.24% in those who did not (P=.001; log-rank test). Following remission induction with ATO-based regimens in patients with relapsed APL, consolidation with autologous SCT is associated with a significantly superior clinical outcome compared with ATO- and ATO+ATRA-based maintenance regimens.

Nodular lymphocyte-predominant Hodgkin lymphoma: a unique disease deserving unique management.

PubMed

Eichenauer, Dennis A; Engert, Andreas

2017-12-08

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity with an incidence of 0.1 to 0.2/100 000/y. Compared with the more common subtypes of classical Hodgkin lymphoma, NLPHL is characterized by distinct pathological and clinical features. Histologically, the disease-defining lymphocyte predominant cells consistently express CD20 but lack CD30. Clinically, NLPHL mostly has a rather indolent course, and patients usually are diagnosed in early stages. The prognosis of early-stage NLPHL is excellent, with progression-free survival and overall survival rates exceeding 90% after involved-field radiotherapy (IF-RT) alone (stage IA) or combined modality treatment consisting of a brief chemotherapy with 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy followed by IF-RT (early stages other than stage IA). In contrast, patients with advanced disease at diagnosis tend to relapse either with NLPHL histology or with histological transformation into aggressive B-cell non-Hodgkin lymphoma despite more aggressive first-line treatment with 6 to 8 cycles of multiagent chemotherapy. However, even NLPHL patients with multiple relapses successfully respond to salvage therapy in many cases. Salvage therapies range from single-agent anti-CD20 antibody treatment to high-dose chemotherapy followed by autologous stem cell transplantation. Treatment at disease recurrence should be chosen on the basis of various factors, including histology at relapse, time to relapse, extent of disease at relapse, and prior treatment. Because death among NLPHL patients is more often caused by therapy-related late effects than lymphoma-related complications, optimizing the risk-benefit ratio of treatment by decreasing toxicity whenever possible is the major goal of clinical research in this disease. © 2016 by The American Society of Hematology. All rights reserved.

Lymphocyte responses to phytohaemagglutinin: age-related effects.

PubMed Central

Fernandez, L A; MacSween, J M; Langley, G R

1976-01-01

Cell-mediated immunity is depressed in elderly individuals compared to young individuals, and lymphocytes from elderly individuals have been reported to have impaired lymphocyte responsiveness to stimulation by PHA after 4 days of culture. We have confirmed this observation. However, after 8 days of culture, the lymphocyte responses were greater in elderly normal individuals than in young normal individuals. Responses of lymphocytes from young individuals decreased with time from 4 to 8 days in culture, while there were increased responses with time when lymphocytes from elderly individuals were studied. When adherent cells from lymphocytes of young individuals were removed by passage through protein-coated Degalan-bead columns, the lymphocyte responses to PHA were significantly increased at 8 days. Passage of lymphocytes from elderly individuals through coated Degalan bead columns did not alter the lymphocyte responses. Removal of macrophages from the mononuclear cells obtained from young individuals did not result in increased lymphocyte responses to PHA after 8 days in culture. Removal of adherent cells appeared to have the same effect regardless of the efficiency of removing B cells. The adherent cells removed by the protein coated columns, therefore, appear to be nonphagocytic mononuclear cells which are not B lymphocytes. PMID:1086285

Lymphocyte-platelet crosstalk in Graves' disease.

PubMed

Kuznik, Boris I; Vitkovsky, Yuri A; Gvozdeva, Olga V; Solpov, Alexey V; Magen, Eli

2014-03-01

Platelets can modulate lymphocytes' role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves' disease (GD). One hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation. The group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3, HLA-DR+ lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10 cells/µL) than TMG group (251 ± 97 × 10 cells/µL; P < 0.05) and control group (262 ± 95 × 10 cells/µL; P < 0.05). In GD group, more platelet-bound lymphocytes (332 ± 91 /µL) were found than that in TMG group (116 ± 67/µL, P < 0.005) and control group (104 ± 58 /µL; P < 0.001). GD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.

Mobiloization of intracellular calcium ions in chicken and rat lymphocytes induced by T cell mitogens.

PubMed

Gerilechaogetu; Narahara, Kiyoaki; Abe, Asaki; Kondo, Yasuhiro

2009-04-01

Cytosolic Ca(2+) is known to be an important factor in intracellular signaling pathways that regulate several cellular functions. The present study was designed to measure the intracellular concentrations of Ca(2+) ([Ca(2+)](i)) in T cell mitogen-stimulated chicken lymphocytes, and to compare the results with those in rat lymphocytes. [Ca(2+)](i) was increased in the thymocytes, splenocytes and bursacytes of chickens, and in the thymocytes and splenocytes of rats following exposure to the mitogens phytohaemagglutinin (PHA) and concanavalin A (ConA). Increases were greatest in the thymocytes followed by the splenocytes and bursacytes. The PHA-induced changes in the thymocytes and splenocytes were similar in chickens and rats, but the ConA-induced increases were significantly lower in the chickens than rats. Pretreatment with EGTA before the application of PHA and ConA completely suppressed the rise in [Ca(2+)](i) in all the chicken lymphocytes, indicating that the increases that occurred in PHA- and ConA-treated chicken lymphocytes could be entirely attributed to the influx of extracellular Ca(2+). On the other hand, the PHA- and ConA-induced increase in [Ca(2+)](i) in rat lymphocytes was not completely suppressed by EGTA, indicating the recruitment of Ca(2+) from the intracellular Ca(2+) pool. The results suggest species differences in the Ca(2+)-based responses to T cell mitogens between chicken lymphocytes and rat lymphocytes.

Elevated Expression of Immunoreceptor Tyrosine-Based Inhibitory Motif (TIGIT) on T Lymphocytes is Correlated with Disease Activity in Rheumatoid Arthritis.

PubMed

Luo, Qing; Deng, Zhen; Xu, Chuxin; Zeng, Lulu; Ye, Jianqing; Li, Xue; Guo, Yang; Huang, Zikun; Li, Junming

2017-03-10

BACKGROUND It is well known that lymphocytes play an important role in rheumatoid arthritis (RA). T cell immunoreceptors with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (TIGIT) have immunosuppressive co-stimulatory molecules that mediate inhibitory effects, but their roles in RA are poorly understood. MATERIAL AND METHODS Were recruited 76 patients with RA and 33 healthy controls (HC). Clinical manifestations, laboratory measurements, physical examination, and medical history of RA patients were recorded. The expression of TIGIT on CD3+ T lymphocytes, B lymphocytes, monocytes, neutrophils, CD3+CD4+ T lymphocytes, and CD3+CD8+ T lymphocytes was determined using flow cytometry. The expression of TIGIT on T lymphocytes in patients with RA was further analyzed to investigate its correlations with markers of autoimmune response, inflammation, and disease activity in RA. RESULTS Compared with HC, the expression levels of TIGIT on CD3+CD4+ T lymphocytes and CD3+CD8+ T lymphocytes were significantly increased in patients with RA (P < 0.01). The frequency of TIGIT-expressing CD3+CD4+ T lymphocytes was positively correlated with RF, increased ACPA, ESR, and CRP levels. The frequency of TIGIT-expressing CD3+CD8+ T lymphocytes was positively correlated with RF and ESR levels. Furthermore, the expression level of TIGIT on CD3+CD4+ T lymphocytes was positively correlated with the DAS28 score in RA. CONCLUSIONS The expression levels of TIGIT on T lymphocytes were elevated and correlated with disease activity in RA.

Noni (Morinda citrifolia L.) fruit juice delays immunosenescence in the lymphocytes in lymph nodes of old F344 rats.

PubMed

Pratap, Uday P; Priyanka, Hannah P; Ramanathan, Karthik R; Raman, Vishak; Hima, Lalgi; Thyagarajan, Srinivasan

2018-05-01

Aging is associated with the development of diseases because of immunosuppression and altered functioning of the neuroendocrine system. The medicinal properties of Morinda citrifolia L. have been widely exploited for the treatment of age-associated diseases. This study aims to investigate the in vitro and in vivo effects of noni (M. citrifolia) fruit juice (NFJ) on neuro-immunomodulation in the lymph node lymphocytes of F344 rats. Lymphocytes isolated from axillary and inguinal lymph nodes of young (3-4 months) and old (18-21 months) rats were treated in vitro with different concentrations (0.0001%, 0.01%, and 1%) of NFJ for a period of 24 h. In the in vivo study, old (16-17 months) male F344 rats were treated with 5 mL/kg body weight of 5%, 10% and 20% of NFJ, twice a day, by oral gavage, and lymph node lymphocytes were isolated after 60 d. Concanavalin A (Con A)-induced lymphocyte proliferation, interleukin-2 (IL-2) and interferon-γ (IFN-γ) production and expression of intracellular markers, such as phospho-extracellular signal-regulated kinase (p-ERK1/2), phospho-cAMP response element-binding protein, phospho-protein kinase B (p-Akt), phospho-tyrosine hydroxylase (p-TH), phospho-nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor-α (p-IκB-α) and phospho-nuclear factor-κB (p-NF-κB p65 and p50) were examined in the lymphocytes of lymph nodes. NFJ increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and p-ERK1/2 expression both in vitro and in vivo. In in vivo NFJ-treated old rats, lymph node lymphocytes showed increased expression of p-TH and Akt, nitric oxide production and decreased expression of p-NF-κB p65 and p50. These results suggest that the immunostimulatory properties of NFJ are facilitated through intracellular signaling pathways involving ERK1/2, Akt and NF-κB. Copyright © 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Acetabular fractures in the elderly treated with a primary Burch-Schneider reinforcement ring, autologous bone graft, and a total hip arthroplasty: a prospective study with a 4-year follow-up.

PubMed

Enocson, Anders; Blomfeldt, Richard

2014-06-01

To investigate the clinical and radiologic outcomes in elderly patients suffering from an acetabular fracture operated with an acute primary acetabular reinforcement ring, autologous bone graft, and a total hip arthroplasty (THA). Prospective cohort study. Tertiary care university hospital. Fifteen elderly patients (7 women) with a mean age of 76 years and a displaced acetabular fracture after a low-energy trauma were included. The fractures involved the anterior column, but no patients with associated both column fractures were included. All the patients were able to walk independently before the fracture occurred. Primary operation with a Burch-Schneider reinforcement ring, autologous bone graft, and a THA. The patients were reviewed at 4, 12, 24, and 48 months after the fracture occurred. The outcome assessments included complications, reoperations, activity of daily living function, functional scores (Harris hip score and short musculoskeletal function assessment), health-related quality of life [EuroQol (EQ-5D) index score], and radiologic evaluation. There were no prosthetic dislocations, periprosthetic fractures, deep infections, or other adverse events. There were no radiologic signs of loosening of the reinforcement ring or the prosthesis components at any of the follow up sessions, and the autologous bone graft was well incorporated in all the patients at the final follow-up. At 48 months, the mean Harris hip score was 88, the mean short musculoskeletal function assessment dysfunction score was 30, the bother score was 25, and the mean EQ-5D index score was 0.65. All the patients were able to walk independently at the final follow-up. Treatment of displaced anterior column, anterior column posterior hemitransverse and transverse acetabular fractures in elderly patients using a primary reinforcement ring, autologous bone graft, and a THA seems to be a safe option with good functional and radiologic outcomes. Therapeutic Level IV. See Instructions for

Long-term outcomes in patients with early stage nodular lymphocyte-predominant Hodgkin's lymphoma treated with radiotherapy.

PubMed

Solanki, Abhishek A; LeMieux, Melissa Horoschak; Chiu, Brian C-H; Mahmood, Usama; Hasan, Yasmin; Koshy, Matthew

2013-01-01

Radiation therapy (RT) is commonly used as definitive treatment for early-stage nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL). We evaluated the cause-specific survival (CSS), overall survival (OS), and second malignancy (SM) rates in patients with early-stage NLPHL treated with RT. Patients with stage I-II NLPHL between 1988 and 2009 who underwent RT were selected from the Surveillance, Epidemiology and End Results database. Univariate analysis (UVA) for CSS and Os was performed using the Kaplan-Meier method and included age, gender, involved site, year of diagnosis, presence of B-symptoms, and extranodal involvement (ENI). Multivariable analysis (MVA) was performed using Cox Proportional Hazards modeling and included the above clinical variables. SM were classified as RT-related or non-RT-related. Freedom from SM and freedom from RT-related SM were determined using the Kaplan-Meier method. The study cohort included 469 patients. Median age was 37 years. The most common involved sites were the head and neck (36%), axilla/arm (26%), and multiple lymph node regions (18%). Sixty-eight percent had stage I disease, 70% were male, 4% had ENI, and 7% had B-symptoms. Median follow-up was 6 years. Ten-year CSS and Os were 98% and 88%, respectively. On UVA, none of the covariates was associated with CSS. Increasing age (p<0.01) and female gender (p<0.01) were associated with worse Os. On MVA, older age (p<0.01), female gender (p=0.04), multiple regions of involvement (p=0.03), stage I disease (p=0.02), and presence of B-symptoms (p=0.02) were associated with worse Os. Ten-year freedom from SM and freedom from RT-related SM were 89% and 99%, respectively. This is the largest series to evaluate the outcomes of stage I-II NLPHL patients treated with RT and found that this patient population has an excellent long-term prognosis and a low rate of RT-related second malignancies.

[Application and usefulness of flowcytometry in the haematology laboratory].

PubMed

Kubota, K; Makino, M

1991-02-01

Recent technological advances, in both hardware and software, and availability of various monoclonal antibodies (MoAb) for membrane antigens of blood cells have expanded the application of flow cytometry (FCM) in medicine. In the haematology laboratory, FCM has been used mainly for assessment of leukemia and lymphoma and for determination of lymphocyte subsets. In acute leukemia, FCM is useful to classify ALL accurately, particularly for bi phenotypic or mixed lineage leukemia. In lymphocyte subset determination, we found that the use of magnetic beads to remove contaminating monocytes and some granulocytes to purify the lymphocyte-population is helpful in clarify the subsets. We present data describing the age dependent variation in lymphocyte subsets in the pediatric population. In early life (up to 2 years old), CD4 (+) 2H4 (+) lymphocyte overwhelmed CD4 (+) 2H4 (-) cells, implying predominance of suppressor-inducer activity. We also presented some cases of markedly increased double negative T cells (gamma/delta TCR) and a rare case of double positive (CD4+, CD8+) T cells.

[Clinical significance of autologous transplantation with hematopoietic stem cells in leukemia and solid tumors].

PubMed

Hinterberger, W; Adler, V; Bauer, K; Haberhauer, G; Habertheuer, K H; Höniger, S; Huber, K; Kier, P; Kittel, E; Ruckser, R

1995-01-01

Autologous Transplantation of hematopoietic tissue with frozen hematopoietic stem cells is increasingly used for leukemias and lymphomas, but also for some solid tumors. In the past, autotransplants have been performed with bone marrow as the source of hematopoietic stem cells. Circulating, blood derived hematopoietic stem cells, however, allow safe engraftment of all cell lines after supralethal chemo-radiotherapy. This survey describes the role of autologous stem cell transplantation in disorders that are currently in the center of clinical and scientific interest. This estimation is based on the proportion of protocols dealing with, and centering on, autologous stem cell transplantation in the context of treatment for leukemias and solid tumors ("Oncodisc", "PDQ").

Efficacy and Safety of a Novel Autologous Wound Matrix in the Management of Complicated, Chronic Wounds: A Pilot Study.

PubMed

Kushnir, Igal; Kushnir, Alon; Serena, Thomas E; Garfinkel, Doron

2016-09-01

The objective of this pilot study was to evaluate the efficacy and safety of a novel method using an autologous whole blood clot formed with the RedDress Wound Care System (RD1, RedDress Ltd, Israel), a provisional whole blood clot matrix used in the treatment of chronic wounds of various etiologies. Patients were treated at the bedside with the whole blood clot matrix. Blood was withdrawn from each patient using citrate, mixed with a calcium gluconate/kaolin suspension, and injected into an RD1 clotting tray. Within 10 minutes, a clot was formed, placed upon the wound, and fixed with primary and secondary dressings. Wounds were redressed weekly with a whole blood clot matrix. Treatment was terminated when complete healing was achieved, or when the clinician determined that the wound could not further improve without additional invasive procedures. Seven patients with multiple and serious comorbidities and 9 chronic wounds were treated with 35 clot matrices. Complete healing was achieved in 7 of 9 wounds (78%). In 1 venous ulcer with a nonhealing fistula, 77% healing was achieved. Treatment was terminated in 1 pressure ulcer at 82% closure, because an unexpected mechanical trauma resulted in deterioration; this was the only adverse event reported, unrelated to the product. No systemic adverse events occurred. This pilot study demonstrates the in vitro autologous whole blood clot matrix is effective and safe for treating patients with chronic wounds of different etiologies. A larger clinical trial is needed to assess the relative success rate of the matrix in different types of wounds in a diverse population with comorbidities.

Autologous transplantation of the internal limiting membrane for refractory macular holes.

PubMed

Morizane, Yuki; Shiraga, Fumio; Kimura, Shuhei; Hosokawa, Mio; Shiode, Yusuke; Kawata, Tetsuhiro; Hosogi, Mika; Shirakata, Yukari; Okanouchi, Toshio

2014-04-01

To determine the effectiveness of autologous transplantation of the internal limiting membrane (ILM) for refractory macular holes. Prospective, interventional case series. Ten eyes of 10 consecutive patients who underwent autologous transplantation of the ILM for the treatment of refractory macular holes were studied. The primary diseases in these patients were large idiopathic macular holes that had existed for more than 1 year (4 eyes), a traumatic macular hole (1 eye), myopic foveoschisis (2 eyes), foveoschisis resulting from pit-macular syndrome (2 eyes), and proliferative diabetic retinopathy (1 eye). Apart from the 5 eyes with idiopathic or traumatic macular holes, macular holes developed in the other 5 eyes after initial vitrectomies with ILM removal. In all eyes, regular macular hole surgery failed to achieve closure. The main outcome measures used in this study were macular hole closure and best-corrected visual acuity (BCVA). Macular holes were closed successfully in 9 eyes (90%) after autologous transplantation of the ILM. The postoperative BCVAs were significantly better than the preoperative BCVAs (P = .007, paired t test). Postoperative BCVAs improved by more than 0.2 logarithm of the minimal angle of resolution units in 8 eyes (80%) and were unchanged in 2 eyes (20%). Although this is a pilot study, the results suggest that autologous transplantation of the ILM may contribute to improved anatomic and visual outcomes in the treatment of refractory macular holes and may warrant further investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

Circulating microRNAs as Biomarkers for Detection of Autologous Blood Transfusion

PubMed Central

Leuenberger, Nicolas; Schumacher, Yorck Olaf; Pradervand, Sylvain; Sander, Thomas; Saugy, Martial; Pottgiesser, Torben

2013-01-01

MicroRNAs (miRNAs) are small non-coding RNAs that regulate various biological processes. Cell-free miRNAs measured in blood plasma have emerged as specific and sensitive markers of physiological processes and disease. In this study, we investigated whether circulating miRNAs can serve as biomarkers for the detection of autologous blood transfusion, a major doping technique that is still undetectable. Plasma miRNA levels were analyzed using high-throughput quantitative real-time PCR. Plasma samples were obtained before and at several time points after autologous blood transfusion (blood bag storage time 42 days) in 10 healthy subjects and 10 controls without transfusion. Other serum markers of erythropoiesis were determined in the same samples. Our results revealed a distinct change in the pattern of circulating miRNAs. Ten miRNAs were upregulated in transfusion samples compared with control samples. Among these, miR-30b, miR-30c, and miR-26b increased significantly and showed a 3.9-, 4.0-, and 3.0-fold change, respectively. The origin of these miRNAs was related to pulmonary and liver tissues. Erythropoietin (EPO) concentration decreased after blood reinfusion. A combination of miRNAs and EPO measurement in a mathematical model enhanced the efficiency of autologous transfusion detection through miRNA analysis. Therefore, our results lay the foundation for the development of miRNAs as novel blood-based biomarkers to detect autologous transfusion. PMID:23840438

Sulforaphane mitigates cadmium-induced toxicity pattern in human peripheral blood lymphocytes and monocytes.

PubMed

Alkharashi, Nouf Abdulkareem Omer; Periasamy, Vaiyapuri Subbarayan; Athinarayanan, Jegan; Alshatwi, Ali A

2017-10-01

Cadmium (Cd) is a highly toxic and widely distributed heavy metal that induces various diseases in humans through environmental exposure. Therefore, alleviation of Cd-induced toxicity in living organisms is necessary. In this study, we investigated the protective role of sulforaphane on Cd-induced toxicity in human peripheral blood lymphocytes and monocytes. Sulforaphane did not show any major reduction in the viability of lymphocytes and monocytes. However, Cd treatment at a concentration of 50μM induced around 69% cell death. Treatment of IC 10 -Cd and 100μM sulforaphane combination for 24 and 48h increased viability by 2 and 9% in cells subjected to Cd toxicity, respectively. In addition, IC 25 of Cd and 100μM sulforaphane combination recovered 17-20% of cell viability. Cd induced apoptotic and necrotic cell death. Sulforaphane treatment reduced Cd-induced cell death in lymphocytes and monocytes. Our results clearly indicate that when the cells were treated with Cd+sulforaphane combination, sulforaphane decreased the Cd-induced cytotoxic effect in lymphocytes and monocytes. In addition, sulforaphane concentration plays a major role in the alleviation of Cd-induced toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.