Combination of Anti-CD4 with Anti-LFA-1 and Anti-CD154 Monoclonal Antibodies Promotes Long-Term Survival and Function of Neonatal Porcine Islet Xenografts in Spontaneously Diabetic NOD Mice

2007 ◽  
Vol 16 (8) ◽  
pp. 787-798 ◽  
Author(s):  
Hossein Arefanian ◽  
Eric B. Tredget ◽  
Ray V. Rajotte ◽  
Gregory S. Korbutt ◽  
Ron G. Gill ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Nod Mice ◽  
Β Cells ◽  
Short Term ◽  
Term Survival ◽  
Long Term Survival ◽  
Porcine Islet ◽  
Term Administration ◽  
And Function

Type 1 diabetes mellitus (T1DM) is caused by the autoimmune destruction of pancreatic islet β-cells, which are required for the production of insulin. Islet transplantation has been shown to be an effective treatment option for T1DM; however, the current shortage of human islet donors limits the application of this treatment to patients with brittle T1DM. Xenotransplantation of pig islets is a potential solution to the shortage of human donor islets provided xenograft rejection is prevented. We demonstrated that a short-term administration of a combination of anti-LFA-1 and anti-CD154 monoclonal antibodies (mAbs) was highly effective in preventing rejection of neonatal porcine islet (NPI) xenografts in non-autoimmune-prone B6 mice. However, the efficacy of this therapy in preventing rejection of NPI xenografts in autoimmune-prone nonobese diabetic (NOD) mice is not known. Given that the current application of islet transplantation is for the treatment of T1DM, we set out to determine whether a combination of anti-LFA-1 and anti-CD154 mAbs could promote long-term survival of NPI xenografts in NOD mice. Short-term administration of a combination of anti-LFA-1 and anti-CD154 mAbs, which we found highly effective in preventing rejection of NPI xenografts in B6 mice, failed to promote long-term survival of NPI xenografts in NOD mice. However, addition of anti-CD4 mAb to short-term treatment of a combination of anti-LFA-1 and anti-CD154 mAbs resulted in xenograft function in 9/12 animals and long-term graft (>100 days) survival in 2/12 mice. Immunohistochemical analysis of islet grafts from these mice identified numerous insulin-producing β-cells. Moreover, the anti-porcine antibody as well as autoreactive antibody responses in these mice was reduced similar to those observed in naive nontransplanted mice. These data demonstrate that simultaneous targeting of LFA-1, CD154, and CD4 molecules can be effective in inducing long-term islet xenograft survival and function in autoimmune-prone NOD mice.

Short-term weight loss after hospitalization predicts long-term survival in patients with chronic heart failure

2006 ◽  
Vol 31 (03) ◽  
Author(s):  
M Lainscak ◽  
S von Haehling ◽  
A Sandek ◽  
I Keber ◽  
M Kerbev ◽  
...  
Keyword(s):  
Heart Failure ◽  
Weight Loss ◽  
Chronic Heart Failure ◽  
Short Term ◽  
Term Survival ◽  
Long Term Survival

An oncology clinical trial design with randomization adaptive to both short- and long-term responses

2017 ◽  
Vol 28 (7) ◽  
pp. 2015-2031 ◽  
Author(s):  
Hao Liu ◽  
Xiao Lin ◽  
Xuelin Huang
Keyword(s):  
Trial Design ◽  
Clinical Trial Design ◽  
Therapeutic Benefit ◽  
Survival Outcome ◽  
Operating Characteristics ◽  
Short Term ◽  
Term Survival ◽  
Long Term Survival ◽  
Term Response

In oncology clinical trials, both short-term response and long-term survival are important. We propose an urn-based adaptive randomization design to incorporate both of these two outcomes. While short-term response can update the randomization probability quickly to benefit the trial participants, long-term survival outcome can also change the randomization to favor the treatment arm with definitive therapeutic benefit. Using generalized Friedman’s urn, we derive an explicit formula for the limiting distribution of the number of subjects assigned to each arm. With prior or hypothetical knowledge on treatment effects, this formula can be used to guide the selection of parameters for the proposed design to achieve desirable patient number ratios between different treatment arms, and thus optimize the operating characteristics of the trial design. Simulation studies show that the proposed design successfully assign more patients to the treatment arms with either better short-term tumor response or long-term survival outcome or both.

High long-term survival and function of cryopreserved primary hepatocytes in two different culture systems

2003 ◽  
Vol 124 (4) ◽  
pp. A736
Author(s):  
Meindert Sosef ◽  
Keishi Sugimachi ◽  
John Baust ◽  
Mehmet Toner
Keyword(s):  
Primary Hepatocytes ◽  
Term Survival ◽  
Long Term Survival ◽  
Culture Systems ◽  
And Function

Analysis of the Intrahospital and Long-Term Survival of Heart Transplant Patients With a Short-Term Mechanical Assistance Device

2021 ◽  
Author(s):  
Raquel López-Vilella ◽  
Ignacio Sánchez-Lázaro ◽  
Azucena Pajares Moncho ◽  
Mónica Talavera Peregrina ◽  
Manuel Pérez Guillén ◽  
...  
Keyword(s):  
Heart Transplant ◽  
Short Term ◽  
Term Survival ◽  
Long Term Survival ◽  
Transplant Patients ◽  
Mechanical Assistance

Impact of body mass index on short-term and long-term survival in prevalent hemodialysis patients

2019 ◽  
Vol 23 (3) ◽  
pp. 375-383
Author(s):  
Muhittin Ertilav ◽  
W. Nathan Levin ◽  
Aygul Celtik ◽  
Fatih Kircelli ◽  
Stefano Stuard ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Hemodialysis Patients ◽  
Short Term ◽  
Term Survival ◽  
Long Term Survival

Short-Term Immunosuppression Enhances Long-Term Survival of Bovine Chromaffin Cell Xenografts in Rat Cns

1992 ◽  
Vol 1 (1) ◽  
pp. 33-41 ◽  
Author(s):  
John D. Ortega ◽  
Jacqueline Sagen ◽  
George D. Pappas
Keyword(s):  
Blood Brain Barrier ◽  
Chromaffin Cells ◽  
Chromaffin Cell ◽  
Short Term ◽  
Term Survival ◽  
Long Term Survival ◽  
Bovine Chromaffin Cell ◽  
Bovine Chromaffin Cells ◽  
Rat Cns

Xenogeneic donors, a largely untapped resource, would solve many of the problems associated with the limited availability of human donor tissue for neural transplantation. Previous work in our laboratory has revealed that xenografts of isolated bovine chromaffin cells survive transplantation into the periaqueductal gray (PAG) of immunosuppressed adult rats. Electron microscopic analysis reveals that graft sites contain healthy chromaffin cells, but do not contain host immune cells typical of graft rejection. The aim of the current study was to assess the necessary conditions for long-term survival of bovine chromaffin cell xenografts in the central nervous system (CNS). In particular, the need for short-course vs. permanent immunosuppressive therapy with cyclosporine A (CsA) for the long-term survival of grafted bovine chromaffin cells was addressed. Grafts from animals receiving continuous CsA treatment for either 3, 6, or 12 wk contained large clumps of dopamines-β-hydroxylase (DBH) positive cells in contrast to the few surviving cells observed in nonimmunosuppressed animals. In addition, grafts from animals that had CsA treatment terminated at 3 or 6 wk contained similarly large clumps of DBH-positive cells. Furthermore, short-term immunosuppression (3 wk) appeared to enhance the long-term survival of grafted cells, since clumps of DBH staining cells could still be positively identified in the host PAG at least 1 yr after transplantation. Complete rejection of graft tissue depends on several factors, such as blood–brain barrier integrity, the presence of major histocompatability complex (MHC) antigens in either the host or graft, and the status of the host immune system. By using a suspension of isolated bovine chromaffin cells, potential MHC antigen presenting cells, such as endothelial cells, are eliminated. In addition, CsA treatment may negate the immunologic consequences of increased blood–brain barrier permeability following surgical trauma by attenuating the host cell mediated response. In summary, long-term survival of isolated chromaffin cell xenografts in the rat CNS may be attained by a short-term course of CsA.

scholarly journals Negative Attitudes Among Short-Term Stroke Survivors Predict Worse Long-Term Survival

Stroke ◽  
2001 ◽  
Vol 32 (7) ◽  
pp. 1640-1645 ◽  
Author(s):  
S.C. Lewis ◽  
M.S. Dennis ◽  
S.J. O’Rourke ◽  
M. Sharpe
Keyword(s):  
Stroke Survivors ◽  
Short Term ◽  
Negative Attitudes ◽  
Term Survival ◽  
Long Term Survival

scholarly journals Impact of weekend treatment on short-term and long-term survival after urgent repair of ruptured aortic aneurysms in Germany

2019 ◽  
Vol 69 (3) ◽  
pp. 792-799.e2 ◽  
Author(s):  
Christian-Alexander Behrendt ◽  
Art Sedrakyan ◽  
Thea Schwaneberg ◽  
Tilo Kölbel ◽  
Konstantinos Spanos ◽  
...  
Keyword(s):  
Aortic Aneurysms ◽  
Short Term ◽  
Term Survival ◽  
Long Term Survival
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