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Biomedical subjects

Carl E Haisch

Publications and source records attributed to Carl E Haisch.

9 recordsLinked to original sources
PubMed2005

Repair of damaged organs in vitro.

Treatments that can be performed ex vivo following ischemia to accelerate cellular recovery and ameliorate reperfusion injury could have major impact. An acellular, near-normothermic perfusion was employed to deliver growth factors to ischemically damaged kidneys. During the treatment oxidative metabolism was sufficiently restored to support up-regulation of cellular processes with the potential to modulate both injury and repair proteins in damaged kidneys. The results suggest that growth factor administration, without concomitant inflammation, triggers pathways for new synthesis leading to cellular recovery rather than cell death.

Animals↗
PubMed2004

Characterization of Lewis lung clonal variants in a model of syngeneic pulmonary murine metastases.

Lung cancer is the leading cause of cancer-related mortality world-wide. Since the majority of cancer deaths result from metastatic complications, understanding cellular alterations contributing to organ specific metastases is a continuing cancer research goal. Desirable models involve easy, efficient methodologies for development of pulmonary metastases utilizing genetically related syngeneic tumor cell lines varying in clonogenic frequency and growth rate for comparative studies. This work focused on development and characterization of primary and metastatic Lewis lung subclones (LLCC3, LLC1, LLCab) in a histocompatible C57B1/6 model. Surgical resection of primary tumors utilizing these cell lines resulted in reliable development of pulmonary metastases (> 90% of injected mice), while tail-vein injection proved sporadic (20% of injected mice). The preliminary analysis of selected cell-surface molecules indicates potential genetic differences that may underlie phenotypic variations. The combination of subcutaneous resection methodology and variant cell lines results in robust metastatic lung cancer for testing potential therapeutic interventions.

Animals↗
PubMed2002

HLA matching and the United Network for Organ Sharing Allocation System: impact of HLA matching on African-American recipients of cadaveric kidney transplants.

BACKGROUND: A recent proposal supports the elimination of allocation points for human leukocyte antigen (HLA) mismatches (MM) in cadaveric kidney transplantation. The intent is to increase access for some racial groups that might be disadvantaged by the representation of race-specific HLA in a largely white donor pool. We report our experience from two transplant centers that serve a large African American (AA) patient population. METHODS: All cadaveric transplants into AA recipients from 1994 to 2000 (n=162) were included in a retrospective review. RESULTS: Superior graft survival was observed in AA recipients of 0 MM transplants. When induction therapy was used, the graft survival at 3 years for the human leukocyte antigen (HLA)-BDR MM grades given allocation points (0,1,2 MM) was 82% versus only 49% for BDR MM grades not given points (3,4 MM: =0.0022). CONCLUSIONS: Our collective experience demonstrates that AA patients having HLA-BDR MM grades given allocation points had better graft survival. Removing points for HLA from the national allocation system may result in significantly poorer outcome in AA kidney recipients.

Adolescent↗
PubMed2002

Overcoming severe renal ischemia: the role of ex vivo warm perfusion.

BACKGROUND: The ability to effectively utilize kidneys damaged by severe (2 hr) warm ischemia (WI) could provide increased numbers of kidneys for transplantation. The present study was designed to examine the effect of restoring renal metabolism after severe WI insult during ex vivo warm perfusion using an acellular technology. After warm perfusion for 18 hr, kidneys were reimplanted and evaluated for graft function. METHODS: Using a canine autotransplant model, kidneys were exposed to 120 min of WI. They were then either reimplanted immediately, hypothermically machine perfused (4 degrees C) for 18 hr with Belzer's solution, or transitioned to 18 hr of warm perfusion (32 degrees C) with an acellular perfusate before implantation. RESULTS: Warm perfused kidneys with 120 min of WI provided life-sustaining function after transplantation, whereas the control kidneys immediately reimplanted or with hypothermic machine perfusion did not. The mean peak serum creatinine in the warm perfused kidneys was 3.7 mg/dl, with the mean peak occurring on day 2 and normalizing on day 9 posttransplant. CONCLUSIONS: These results indicate that 18 hr of ex vivo warm perfusion of kidneys is feasible. Furthermore, recovery of renal function during warm perfusion is demonstrated, resulting in immediate function after transplantation. The use of ex vivo warm perfusion to recover function in severe ischemically damaged kidneys could provide the basis for increasing the number of transplantable kidneys.

Animals↗
PubMed2002

Induction of cytolytic anti-Gal antibodies in alpha-1,3-galactosyltransferase gene knockout mice by oral inoculation with Escherichia coli O86:B7 bacteria.

Naturally occurring antibodies against [Gal alpha-1,3-Gal] structures (anti-Gal antibodies) are the primary effectors of human hyperacute rejection (HAR) of nonhuman tissue. Unlike most mammals, humans lack a functional alpha-1,3-galactosyltransferase (GalT) gene and produce abundant anti-Gal antibodies, putatively in response to GalT(+) enteric bacteria. GalT knockout (KO) mice have been generated as a small animal model of HAR but inconsistently express anti-Gal antibodies. We hypothesized that enteric exposure of GalT KO mice to live GalT(+) bacteria would produce cytolytic anti-Gal antibodies. Naive mice lacking anti-Gal antibodies were orally immunized with 10(10) live GalT(+) Escherichia coli O86:B7 bacteria and assayed for anti-Gal antibody titer, isotype, and cytolytic activity. Fecal samples were tested for E. coli O86:B7 prior to and after inoculation. In two separate experiments, 77 to 100% (n = 31) of mice developed serum anti-Gal immunoglobulin G (IgG; titer, 1:5 to 1:80) and/or anti-Gal IgM antibodies (titer, 1:5 to 1:1,280) 14 days postinoculation. Induced anti-Gal antibodies caused complement-mediated cytolysis of GalT(+) target cells, with extensive cytolysis observed consistently at serum IgM titers of >/=1:320. Absorption with synthetic [Gal alpha-1,3-Gal] inhibited both antibody binding and cytolysis. E. coli O86:B7 was recovered from stool samples from 83 to 94% of inoculated mice but not from naive mice, thus confirming enteric exposure. These findings demonstrate that oral inoculation with E. coli O86:B7 is a novel and effective method to induce cytolytic anti-Gal antibodies in GalT KO mice and support the premise that enteric exposure to GalT(+) bacteria induces anti-Gal antibodies in humans. These studies also suggest a role for GalT KO mice in elucidating anti-Gal responses in microbial immunity.

Animals↗
PubMedDate not supplied

Performance standards improve American Board of Surgery In-Training Examination scores.

PURPOSE: Although several studies have evaluated factors affecting American Board of Surgery In-Training Examination (ABSITE) performance, none has examined the impact of setting a minimally acceptable standard. It was hypothesized that establishing such a criterion would improve ABSITE scores. METHODS: An expectation for residents to score at the 35th percentile or higher was established in 1996. The proportion of test scores above or below the 35th and 50th percentiles for the time periods before and after institution of the standard were compared using Fisher's exact test. The subsequent performance of residents scoring below the 35th percentile was analyzed for the 2 time periods. RESULTS: After the institution of the standard, the proportion of scores below the 35th percentile decreased from 46.7% to 21.9% (p = 0.0005). Similarly, the proportion of scores at or above the national average increased from 42.1% to 65.6% (p = 0.0005). After establishing the standard, fewer residents continued to have scores below the criterion in subsequent years. CONCLUSIONS: Establishing a performance criterion improved ABSITE scores. The decision to institute a standard must be individualized for each program. The rationale for the standard and a plan to assist residents failing to achieve the benchmark must be communicated.

Journal Article↗
PubMedDate not supplied

Suppression of Lewis lung tumor development in alpha 1,3 galactosyltransferase knock-out mice.

BACKGROUND: Humans lack the gene alpha 1,3 galactosyltransferase (GalT) and instead produce abundant cytolytic antibodies against cells bearing the antigen [gal alpha1,3 gal] (alphaGal). We have previously studied humoral anti-alphaGal responses in GalT knock-out (GalT KO) mice and shown that murine anti-alphaGal IgM, like human anti-alphaGal IgM, causes extensive complement-mediated cytolysis of GalT+ murine Lewis Lung carcinoma cells (LLCa) in vitro. Here we test the hypothesis that anti-alphaGal immune responses can inhibit the in vivo development of GalT+ tumors. MATERIALS AND METHODS: GalT KO mice orally immunized to produce anti-alphaGal antibodies (n =52) and naïve non-immunized KO mice (n=37) were challenged s.c. with 10(5) LLCa tumor cells. Anti-alphaGal antibody titers were measured before and after LLCa challenge. RESULTS: Anti-alphaGal IgM titers present at challenge correlated with protection from tumor development (p<0.04). Seventy-five percent of mice with titers > or = 1:1280 remained tumor-free versus 43% of naïve mice. Tumor onset was delayed in mice with circulating anti-alphaGal IgM versus naïve animals (p=0.02). LLCa challenge itself induced and augmented anti-alphaGal IgM and post-challenge titers correlated highly with protection from tumor development (p<0.001). No mice with post-challenge anti-alphaGal IgM titers > or = 1:1280 developed tumors, compared to 83% of mice lacking antibody. Inhibition studies showed that 30% of post-challenge IgM recognized LLCa antigens distinct from alphaGal. Anti-alphaGal IgG was low or undetectable both pre- and post challenge and did not affect tumor formation. CONCLUSION: The finding that anti-alphaGal IgM suppresses GaIT+ tumor development in vivo supports the premise that immunotherapy using GalT expression can utilize human anti-alphaGal responses and induce significant anti-tumor effects.

Animals↗