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W Hancock

Publications and source records attributed to W Hancock.

27 records · Page 2Linked to original sources
PubMed1989

Progress in experimental porcine small-bowel transplantation.

Studies in large animals are needed to overcome technical complications, allograft rejection, and graft-vs-host disease, which are major problems that prevent clinical application of small-bowel transplantation. The small bowel was allografted heterotopically or orthotopically into 30 pigs with the use of cyclosporine, prednisone, and azathioprine. When cyclosporine was given orally to heterotopically transplantation recipients, rejection was frequent, and graft-vs-host disease caused one death. After 30 days of intravenous cyclosporine followed by oral administration, no rejection occurred. Graft-vs-host disease was mild or absent, and there were some long-term survivors. Technical failures were relatively infrequent, but death from sepsis, eg, intra-abdominal abscess, occurred in 17% (5/30). Anastomoses of donor superior mesenteric vein to recipient portal vein offered no advantages over systemic venous drainage. Although the high cyclosporine levels used would be intolerable in humans, these results indicate that successful small-bowel transplantation can be achieved with adequate immunosuppression in a large animal.

Administration, Oral↗
PubMed1988

Characterization of T helper 1 and 2 cell subsets in normal mice. Helper T cells responsible for IL-4 and IL-5 production are present as precursors that require priming before they develop into lymphokine-secreting cells.

We have shown that the requirements for the production of IL-4 and IL-5 by normal L3T4+T cells from murine spleen are very different from those for the production of IL-2. Secretion of detectable quantities of IL-4 and IL-5 and induction of the mRNA for each lymphokine occurs in vitro only after cells are primed and re-stimulated. This priming can be achieved by mitogens (Con A), by antibodies to the TCR (anti-T3) or by stimulation with alloantigen. In contrast, requirements for induction of lymphokine production after priming resemble those for initial production of IL-2. Thus the majority of T cells of helper phenotype that have the potential to become IL-4- and IL-5-secreting T cells, exist in the form of precursors requiring stimulation and several days of culture as well as re-stimulation with mitogen or Ag before they become detectable as lymphokine-secreting cells. In contrast, among fresh CD4+T cells, secretion of IL-2, IL-3, granulocyte/macrophage CSF, and IFN-gamma is easily detected within 24 h of stimulation with mitogen or Ag. These observations establish that distinct phenotypes of Th cells are found at different times after stimulation and support the concept that synthesis and secretion of different lymphokines or groups of lymphokines are regulated independently. Furthermore the patterns of lymphokines secreted by fresh vs primed Th cells, which largely correspond to the patterns that have been used to define the Th1 and Th2 subsets among Th cell lines, provides evidence that different subsets of normal T cells exist that may correspond to these designations. Secretion of different lymphokines by two subsets of Th cells at different times in an immune response, and perhaps in different places, suggests a model in which the ratio of the two T cell subsets (Th1 vs Th2) and state of differentiation of each (precursor vs effector), influence or determine the direction of the response, with variations in these parameters leading to differing responses.

Animals↗
PubMed1983

Immunologic dynamics in cryapheresis for rheumatoid arthritis.

Five patients with erosive rheumatoid arthritis (RA) who had previously experienced a favorable response to lymphoplasmapheresis were treated with cryapheresis. Cryapheresis was performed 9 times in 3 weeks using a membrane filtration device that selectively removes plasma proteins with molecular weights greater than 100,000 daltons. Four of the 5 patients so treated improved clinically. The membranes selectively removed more immunoglobulins and complement components that were part of circulating immune complexes than those that were not. Plasma or albumin replacement was not necessary in these patients. Cryapheresis might be a safe and effective technology in treating patients with refractory RA.

Adult↗
PubMedDate not supplied

Adenovirus-mediated p53 gene transfer inhibits growth of human tumor cells expressing mutant p53 protein.

Human malignancies are often characterized by mutations of the p53 tumor suppressor gene. In a large proportion of cases, the mutation results in production of an altered protein that can bind and inactivate the wild-type gene product. This "dominant-negative" activity of mutant p53 molecules may limit the utility of p53 gene therapy of cancer. Using replication-deficient recombinant adenoviruses (rAd-p53) as a p53 gene delivery system, we evaluated the effects of p53 reintroduction on a series of 45 human cell lines containing wild-type, mutated, or no p53 protein. Results indicate a p53-specific, dose-dependent, and promoter-specific growth inhibition of a majority of p53-altered cell lines that correlates with the degree of adenovirus transgene expression. Similar effects were not observed on cells containing wild-type p53. rAd-p53 inhibited the growth of cells expressing various mutant p53 proteins including those characterized as "dominant negative mutants", and the antiproliferative effects were not abrogated by high levels of endogenous mutated p53 protein. In vivo, rAd-p53 also suppressed tumor growth and increased survival of nude mice bearing tumors that express mutant p53. These results support a role for p53 gene therapy of cancer, including malignancies harboring mutations in this tumor suppressor gene.

Adenoviridae↗