Martin R. Weiser
Brigham and Women's Hospital
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Featured researches published by Martin R. Weiser.
American Journal of Physiology-gastrointestinal and Liver Physiology | 1997
Julian P. Williams; Martin R. Weiser; Taine T. V. Pechet; Les Kobzik; Francis D. Moore; Herbert B. Hechtman
The aim of this study was to look at the role of α1-acid glycoprotein as a natural anti-inflammatory agent with particular respect to its antineutrophil and anticomplement activity. A recombinantly engineered form of sialyl Lewisx(sLex)-bearing α1-acid glycoprotein (sAGP) was administered intravenously to pentobarbital-anesthetized rats after 50 min of intestinal ischemia just before 4 h of reperfusion. A non-sLex-bearing form of AGP (nsAGP) was used as control. sAGP-treated animals had a 62% reduction ( P < 0.05) in remote lung injury, assessed by 125I-albumin permeability, compared with those treated with nsAGP (permeability index of 3.61 ± 0.15 × 10-3 and 5.18 ± 0.67 × 10-3, respectively). There was a reduction in pulmonary myeloperoxidase levels in sAGP-treated rats compared with nsAGP-treated rats. Complement-dependent intestinal injury, assessed by 125I-albumin permeability was reduced by 28% ( P < 0.05) in animals treated with sAGP (7.58 ± 0.63) compared with those treated with nsAGP (10.4 ± 0.54). We conclude that sAGP ameliorates both complement- and neutrophil-mediated injuries.
Shock | 1996
Martin R. Weiser; S Gibbs; C. R. Valeri; David Shepro; Herbert B. Hechtman
Restoration of blood flow to ischemic skeletal muscle results in a reperfusion injury characterized by permeability edema in part mediated by neutrophils that adhere via the selectin family of adhesion molecules. Rats underwent 4 h of hindlimb tourniquet ischemia followed by 4 h reperfusion. The role of neutrophils was determined by rendering one group of animals neutropenic before ischemia. In additional experimental groups, selectins were blocked with either a soluble form of the selectin counter-receptor, sialyl-Lewis X (SLX) or a monoclonal antibody directed against P-selectin (PB1.3). Neutrophil depletion resulted in a 36.1% reduction in hindlimb permeability (p < .05). SLX reduced hindlimb permeability index (PI) 23.9% at 1 mg/kg and 36.1% at 10 mg/kg compared to a nonfucosylated oligosaccharide, sialyl-N-acetylactosamine (p < .05). SLX also reduced neutrophil sequestration by 48.6% (p < .05). PB1.3 reduced hindlimb injury by 26.5% (p < .05) but did not reduce leukosequestration. We interpret these data to indicate that ischemia and reperfusion lead to selectin-mediated neutrophil sequestration. The oligosaccharide SLX, while moderately effective in limiting neutrophil sequestration was as effective as neutrophil depletion in reducing hindlimb permeability. The lack of concordance between the ability of SLX and PB1.3 in limiting neutrophil sequestration and permeability indicate mechanisms of action of these two agents that are in addition to the blocking of adhesion.
Surgery | 1996
S Gibbs; Martin R. Weiser; Lester Kobzik; C. Robert Valeri; David Shepro; Herbert B. Hechtman
BACKGROUND Ischemia and reperfusion injury of rodent intestine is complement mediated. P-selectin antagonism reduces local injury, yet neutrophil depletion does not. This study tests the thesis that the protective mechanism of P-selectin antagonists involves complement inhibition. METHODS We subjected rats (n = 86) to 50 minutes of complete mesenteric ischemia and 4 hours of reperfusion. Treatment with a monoclonal antibody (PB1.3) against P-selectin reduced intestinal injury as judged by 125I-albumin permeability index (7.33 +/- 0.40) compared with saline solution treatment (11.4 +/- 0.49) (p < 0.05). RESULTS However, intestinal neutrophil sequestration assessed by myeloperoxidase assay was unchanged. Immunohistochemistry revealed that mucosal C5b-9 was deposited in animals treated with saline solution and was absent in the sham group. PB1.3 treatment reduced C5b-9 deposition in the intestinal mucosa compared with that in animals treated with saline solution (p < 0.05). Neutrophil-dependent remote lung injury assessed by 125I-albumin permeability and pulmonary myeloperoxidase assay were not significantly reduced by PB1.3. Treatment with a soluble form of P-selectin ligand, sialyl Lewisx (sLex), reduced intestinal myeloperoxidase (0.065 +/- 0.006) compared with saline solution treatment (0.136 +/- 0.02) (p < 0.05), but it did not reduce permeability. Remote lung permeability was reduced (4.52 +/- 0.65 x 10(-3)) by sLex compared with saline solution treatment (6.11 +/- 0.41 x 10(-3)) (p < 0.05). CONCLUSIONS Antagonizing the lectin domain of P-selectin and thereby neutrophil adhesion was without local benefit in this model. In contrast, PB1.3 exerted a novel antagonism of P-selectin and reduced complement deposition.
International Journal of Pancreatology | 1996
Martin R. Weiser; S Gibbs; Francis D. Moore; Herbert B. Hechtman
SummaryConclusionCerulein-induced pancreatitis in rats associated with remote liver and lung dysfunction. Soluble complement receptor 1 (sCR1) does not reduce the local or remote injury. Thus complement activation does not moderate cerulein-induced pancreatitis or the associated liver and lung injury.BackgroundThe local and remote injury of pancreatitis resembles other inflammatory events that are mediated by complement. This study examines the effect of complement inhibition with sCR1 in cerulein-induced pancreatitis in rats.MethodsThirteen Sprague-Dawley rats received five hourly subcutaneous doses of cerulein (100 μg initially, then 50 μg/kg). Six of these animals received hourly iv sCR1 (15 mg/kg, a proven complement-inhibiting dose in rats) and the other seven received iv saline. In parallel, 12 additional rats received hourly sc and iv saline.ResultsCompared to saline controls, rats receiving cerulein showed increased pancreatic wet-to-dry ratio (3.25∶8.52) hematocrit (40 to 47%), ascites volume (2.1 to 6.1 mL), serum amylase (1680 to 10,700 U/L), and ascites amylase (32,200 to 167,000 U/L) (allp<0.05). None of these parameters were modified by treatment with sCR1. Serum SGPT, which increased from 33.4 to 46.6 U/L in cerulein-infused rats, showed a trend toward reduction to 38.8 U/L in rats treated with sCR1. Cerulein-treated rats also had increased lung myeloperoxidase (0.069 to 0.097 U/g) and lung permeability, as assessed by alveolar lavage to serum ratio of labeled albumen (0.041∶0.121) (bothp<0.05). Neither were changed by sCR1 treatment.
Journal of Experimental Medicine | 1996
Martin R. Weiser; J P Williams; Francis D. Moore; Lester Kobzik; M Ma; Herbert B. Hechtman; Michael C. Carroll
Journal of Applied Physiology | 1999
Julian P. Williams; Taine T. V. Pechet; Martin R. Weiser; Russell Reid; Les Kobzik; Francis D. Moore; Michael C. Carroll; Herbert B. Hechtman
Journal of Applied Physiology | 1997
Martin R. Weiser; Taine T. V. Pechet; Julian P. Williams; Minghe Ma; Paul S. Frenette; Francis D. Moore; Lester Kobzik; Richard O. Hines; Denisa D. Wagner; Michael C. Carroll; Herbert B. Hechtman
Shock | 1995
Herbert B. Hechtman; S Gibbs; Martin R. Weiser
Shock | 1997
Herbert B. Hechtman; Martin R. Weiser; T Pechet; David Shepro; Francis D. Moore; M C Carroll
Shock | 1995
Herbert B. Hechtman; Martin R. Weiser; S Gibbs