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Biomedical subjects

B W Warner

Publications and source records attributed to B W Warner.

At least 37 records · Page 2Linked to original sources
PubMed2000

Salivary epidermal growth factor and intestinal adaptation in male and female mice.

Salivary epidermal growth factor (sEGF) levels are increased in male mice after small bowel resection (SBR) and may be important during intestinal adaptation. Since males have greater sEGF than females, the influence of sex on postresection adaptation was tested. Females had lower sEGF; however, sEGF substantially increased in both sexes after a massive (50%) SBR. Adaptive increases in DNA and protein content, villus height, and crypt depth, as well as crypt cell proliferation rates in the remnant ileum, were not different between males and females. Although significant postresection increases in sEGF were identified, EGF mRNA and protein did not change within the submandibular gland. Glandular kallikrein-13 and ileal EGF receptor expression were greater after SBR in female mice. Intestinal adaptation is equivalent in female and male mice after SBR. Despite lower sEGF, females demonstrated increased expression of a kallikrein responsible for sEGF precursor cleavage as well as amplified ileal EGF receptor expression. These results endorse an important differential response between sexes regarding sEGF mobilization and intestinal receptor availability during adaptation.

Adaptation, Physiological↗
PubMed1999

Apoptosis and the pattern of DNase I expression following massive small bowel resection.

INTRODUCTION: Following massive small bowel resection (SBR), histologic evidence of increased enterocyte apoptosis has been demonstrated in several animal models. Deoxyribonuclease I (DNase I) is requisite for intranuclear cleavage of DNA during apoptosis; we therefore hypothesized that the expression of this gene would be increased following SBR. METHODS: Male ICR mice underwent either 50% proximal SBR or sham surgery (bowel transection/reanastomosis). After 12 h and 1, 3, and 7 days, rates of enterocyte proliferation and apoptosis were recorded as well as DNase I mRNA expression and activity. RESULTS: Adaptation after SBR was confirmed at each time point by increased proliferation. Enterocyte proliferation was increased by 12 h and apoptosis was increased by 24 h and remained elevated through Day 7. When compared with sham-operated mice, SBR resulted in a twofold increase in both DNase I expression and activity at 24 h postoperatively, which returned to baseline by Postoperative Day 3. CONCLUSIONS: DNase I expression and activity are increased early following massive SBR but return to baseline despite persistent increased rates of enterocyte apoptosis and proliferation. This enzyme may be important in the early induction of apoptosis following massive SBR, but not once a new set point has been established in the balance between the rate of enterocyte production and enterocyte loss.

Adaptation, Physiological↗
PubMed1999

Differential expression of ileal Na(+)/H(+) exchanger isoforms after enterectomy.

BACKGROUND: Na(+)/H(+) exchangers (NHE) are transporters involved in the absorption of NaCl along the gastrointestinal tract. The aim of this study was to determine the expression pattern of the intestinal brush border NHE isoforms 2 and 3 following massive small bowel resection (SBR). Additionally, the effect of epidermal growth factor (EGF) and salivarectomy (removal of the primary source of EGF) on the expression pattern was studied. MATERIALS AND METHODS: ICR mice underwent a proximal SBR or sham surgery and then received either orogastric saline or EGF (50 microg/kg/day). In separate experiments mice underwent salivarectomy followed by SBR or sham. Postoperatively the remaining ileum was isolated and levels of NHE-2 and NHE-3 mRNA and protein were resolved. RESULTS: Following SBR, the expression of both mRNA and protein for NHE-3 increased by approximately 2.5-fold. Treatment with EGF enhanced NHE-3 mRNA in sham animals with further elevation following SBR. The expression of NHE-2 mRNA demonstrated minimal change while protein marginally increased (40%) following SBR. EGF did not affect the expression of NHE-2 mRNA. Salivarectomy did not influence NHE-2 protein expression and inhibited the increased NHE-3 protein expression following SBR. CONCLUSIONS: Following SBR, the expression pattern for brush border NHE isoforms is distinctive. Increased expression of NHE-3 secondary to SBR and/or EGF treatment with loss of this increase following salivarectomy implies a common mechanism to enhance enterocyte proliferation and luminal absorption of NaCl and water. These results suggest that NHE-3 is an important ileal exchanger following SBR.

Animals↗
PubMed1999

The distribution of endogenous epidermal growth factor after small bowel resection suggests increased intestinal utilization during adaptation.

BACKGROUND/PURPOSE: Although exogenous epidermal growth factor (EGF) amplifies adaptation after massive small bowel resection (SBR), the role for endogenous EGF is unclear. The authors sought to determine whether SBR was associated with changes in the levels of EGF in the serum, saliva, or urine and EGF receptor (EGF-R) signaling in the ileum. METHODS: Male ICR mice underwent 50% proximal SBR or sham surgery bowel transection/reanastomosis). After 3 days, levels of EGF were measured by enzyme-linked immunosorbent assay (ELISA) in the serum, saliva, and urine. EGF-R activation was measured in isolated ileal enterocytes by probing an EGF-R immunoprecipitate with an antibody to phosphotyrosine. RESULTS: When compared with sham, SBR resulted in no change in serum, increased salivary (2209+/-266 nmol SBR v 1183+/-119 nmol sham, P<.05) and decreased urinary (417+/-58 nmol SBR v 940+/-143 nmol sham; P<.05) EGF levels. EGF-R activation increased 2.5-fold after SBR. CONCLUSIONS: Increased salivary and reduced urinary EGF linked with enhanced EGF-R activation suggests increased ileal utilization of EGF during adaptation. This observation, along with the known beneficial effects of exogenous EGF, infers a crucial role for endogenous EGF in the pathogenesis of intestinal adaptation after SBR.

Adaptation, Physiological↗
PubMed1999

The effect of epidermal growth factor on differentiation of isolated enterocytes after small bowel resection.

BACKGROUND/PURPOSE: In previous studies using mucosal scrapings or whole-bowel homogenates, epidermal growth factor (EGF) augments adaptation after massive small bowel resection (SBR). The purpose of this study was to determine directly the effect of adaptation and EGF on enterocyte differentiation using an explicit enterocyte cell population. METHODS: Male ICR mice underwent 50% proximal SBR or sham (bowel transection-reanastomosis) and were selected randomly to either orogastric saline or EGF (50 microg/kg/d). After 3 days, enterocytes were isolated from the remnant ileum by mechanical vibration and assayed for DNA and protein content as well as sucrase and alkaline phosphatase (AlkP) activity. RESULTS: Ileal wet weight, enterocyte protein, and DNA content were increased significantly after SBR and boosted even further with EGF. When normalized for protein, SBR caused an increase in AlkP and sucrase activity, and EGF treatment caused AlkP and sucrase activity to return to baseline. CONCLUSIONS: EGF enhances adaptation; however, when normalized for protein, the activity of two enterocyte-specific enzymes was not significantly altered by EGF. This analysis of an explicit enterocyte population supports the notion that the beneficial effects of EGF are more likely caused by increased numbers of enterocytes rather than an increase in the functional activity of each individual cell.

Adaptation, Physiological↗
PubMed1999

The expression and activation of EGF and c-NEU receptors are increased in enterocytes during intestinal adaptation.

BACKGROUND/PURPOSE: After massive small bowel resection (SBR), epidermal growth factor (EGF) and its intestinal receptor (EGF-R) play major roles during adaptation. The expression of a homologous enterocyte receptor termed c-neu (c-neu-R) is capable of forming heterodimers with EGF-R to facilitate cellular signaling. The purpose of this study was to determine the expression and activation of EGF-R and c-neu-R during the adaptive intestinal response to SBR. METHODS: Male ICR mice underwent either SBR or sham surgery. After 1, 3, and 7 days, enterocytes were isolated and protein immunoprecipitated with antibody to either EGF-R or c-neu-R. Receptor protein expression and activation status were determined. RESULTS: When compared with sham operation, the expression and activation status of both EGF-R (six- and twofold, respectively) and c-neu-R (nine- and twofold, respectively) were increased substantially in enterocytes from the adapting ileum after SBR by postoperative day 3. Minimal changes were appreciated for either EGF-R or c-neu-R expression or activation in the remnant bowel after enterocyte removal, liver, or kidney. CONCLUSIONS: Both the expression and activation status of EGF-R and c-neu-R are increased substantially in enterocytes from the adapting ileum by postoperative day 3 after massive SBR. These changes provide a unique mechanism for the enterocyte to enhance cellular signaling in response to EGF during intestinal adaptation.

Adaptation, Physiological↗
PubMed1999

The adaptive intestinal response to massive enterectomy is preserved in c-SRC-deficient mice.

BACKGROUND/PURPOSE: The Src family of protein tyrosine kinases has been implicated in the downstream mitogenic signaling of several ligands including epidermal growth factor (EGF). Because EGF likely plays a role in adaptation after massive small bowel resection (SBR), we tested the hypothesis that c-src is required for this important response. METHODS: A 50% proximal SBR or sham operation (bowel transection or reanastomosis alone) was performed on c-src-deficient (n = 14) or wild-type (C57bl/6) mice (n = 20). The ileum was harvested on postoperative day 3 and adaptive parameters determined as changes in ileal wet weight, protein and DNA content, proliferation index, villus height, and crypt depth. Comparisons were done using analysis of variance (ANOVA), and a Pvalue less than .05 was considered significant. Values are presented as mean +/- SEM. RESULTS: The activity of c-src was increased in the ileum of wild-type mice after SBR but remained unchanged in c-src-deficient mice. Despite this lack of increase, adaptation occurred after SBR in the c-src-deficient mice as demonstrated by increased ileal wet weight, protein and DNA content, proliferation index, villus height, and crypt depth similar to wild-type mice. CONCLUSIONS: The adaptive response of the intestine to massive SBR is preserved despite reduced activity of the c-src protein. The mitogenic signaling that characterizes intestinal adaptation and is associated with receptor activation by EGF or other growth factors probably occurs by mechanisms independent of c-src protein tyrosine kinase.

Adaptation, Physiological↗
PubMed1999

Imaging and radiological interventional techniques for gastrointestinal bleeding in children.

Causes of pediatric gastrointestinal (GI) bleeding in children are numerous. The role of radiology in defining associated pathology, pinpointing the bleeding site, and intervening to control hemorrhage is discussed here. Barium studies, computed tomography (CT), and magnetic resonance imaging (MRI) each may play a role in identifying the underlying pathology associated with the bleeding. The exact source of bleeding may be localized by means of nuclear scintigraphy as well as selective angiography. In cases of life-threatening or persistent hemorrhage, once a bleeding source is identified, the interventional radiologist may offer percutaneous transcatheter therapy with selective intraarterial vasopressin infusion or embolotherapy.

Adolescent↗
PubMed1999

Intestinal overexpression of EGF in transgenic mice enhances adaptation after small bowel resection.

The effect of direct intestinal overexpression of epidermal growth factor (EGF) on postresection adaptation has been investigated by the production of transgenic mouse lines. A murine pro-EGF cDNA construct was produced, and expression of the EGF construct was targeted to the small intestine with the use of the rat intestinal fatty acid-binding protein promoter. An approximately twofold increase in intestinal EGF mRNA and protein was detected in heterozygous mice. No changes in serum EGF levels were noted. Except for a slightly shortened small intestine, no other abnormal phenotype was observed. Intestinal adaptation (increases in body weight, DNA, protein content, villus height, and crypt depth) was markedly enhanced after a 50% proximal small bowel resection in transgenic mice compared with nontransgenic littermates. This transgenic mouse model permits the study of intestinal adaptation and other effects of EGF in the small intestine in a more physiological and directed manner than has been previously possible. These results endorse a direct autocrine/paracrine mechanism for EGF on enterocytes as a means to enhance adaptation.

Adaptation, Physiological↗
PubMed1999

Intestinal adaptation and enterocyte apoptosis following small bowel resection is p53 independent.

Adaptation following small bowel resection (SBR) signals enterocyte proliferation and apoptosis. Because p53-induced p21(waf1/cip1) may be important for apoptosis in many cells, we hypothesized that these genes are required for increased enterocyte apoptosis during adaptation. Male C57BL/6 (wild-type) or p53-null mice underwent 50% proximal SBR or sham operation (bowel transection-reanastomosis). Adaptation (DNA-protein content, villus height-crypt depth, enterocyte proliferation), appearance of apoptotic bodies, and p53 and p21(waf1/cip1) protein expression were measured in the ileum after 5 days. Adaptation was equivalent after SBR in both wild-type and p53-null mice as monitored by significantly increased ileal DNA-protein content, villus height, and enterocyte proliferation. The number of crypt apoptotic bodies increased significantly after SBR evenly in both wild-type and p53-null mice. In the p53-null mice, SBR substantially induced the expression of p21(waf1/cip1) protein in villus enterocytes. The p53-independent induction of p21(waf1/cip1) may account for the similar intestinal response to SBR between wild-type and p53-null mice. Intestinal adaptation and increased enterocyte apoptosis following intestinal resection occur via a p53-independent mechanism.

Adaptation, Physiological↗
PubMed1998

Epidermal growth factor augments adaptation following small bowel resection: optimal dosage, route, and timing of administration.

BACKGROUND: In assorted animal models of small bowel resection (SBR), exogenous epidermal growth factor (EGF) has been shown to augment intestinal adaptation. This study was designed to elucidate the optimal dose, route, and timing of exogenous EGF to boost adaptation in our murine model of SBR. METHODS: Male ICR mice underwent either 50% proximal SBR or sham surgery (bowel transection with reanastomosis) and then randomized to receive either saline or human recombinant EGF (5, 50, 150, or 300 microg/kg/day) by twice daily intraperitoneal (i.p.) injection or orogastric gavage (o.g.). At 7 days, protein and DNA content, crypt depth, and villus height were determined in the ileum. The premium dose and route was then given for 1 week either during (1 week after SBR) or after the adaptive phase (1 month after SBR). Differences between group means were analyzed using ANOVA. A P < 0.05 was considered significant. RESULTS: EGF enhanced DNA and protein content, crypt depth, and villus height to the greatest extent at a dosage of 50 microg/kg/day by the o.g. route. EGF had no significant effect on enhancing adaptation when given after the adaptive response had already occurred. CONCLUSIONS: Intestinal adaptation is optimally enhanced by a specific dose and route of EGF. Exogenous EGF enhances adaptation only during the adaptive response to SBR and not after it has already taken place. Determination of the best circumstances for EGF administration will permit a systematic approach toward understanding a mechanism for the beneficial effect of EGF during intestinal adaptation.

Adaptation, Physiological↗
PubMed1998

The EGF\EGF-receptor axis modulates enterocyte apoptosis during intestinal adaptation.

BACKGROUND: Adaptation after small bowel resection (SBR) is characterized by a new set point in the balance of enterocyte proliferation and apoptosis. Since epidermal growth factor (EGF) augments both proliferation and adaptation, we sought to determine the effect of EGF receptor manipulation on apoptosis following SBR. MATERIALS AND METHODS: Male ICR mice underwent 50% SBR or sham operation (bowel transection with reanastomosis) and then were given EGF (50 microg/kg/day) or saline by orogastric gavage. At 1 week, a proliferation index (PI) was measured in the ileum by BrdU uptake and an apoptosis index in crypts (cAI) and villi (vAI) scored by counting apoptotic bodies in enterocytes. In other experiments, AI was scored after SBR in mice with defective receptors (waved-2). Results are expressed as means +/- SE and evaluated statistically using ANOVA. # denotes P < 0.001. RESULTS: Following SBR, EGF increased PI (40 +/- 2% vs 50 +/- 1% BrdU + cells; #), villus height (252 +/- 4 micro(m) vs 401 +/- 15 micro(m); #), and crypt depth (77.3 +/- 1.5 micro(m) vs 120.8 +/- 5 micro(m); #). When compared with sham, SBR resulted in increased cAI (0.3 +/- 0.02 vs 2.0 +/- 0.1; #) and vAI (0.4 +/- 0.05 vs 1.1 +/- 0.1; #). EGF attenuated both cAI (0.5 +/- 0. 04) and vAI (0.5 +/- 0.03) following SBR. In the waved-2 mice, the highest levels of cAI (3.1 +/- 0.2) and vAI (3.6 +/- 0.3) were noted after SBR. CONCLUSIONS: Enterocyte apoptosis during adaptation is attenuated by EGF and exaggerated when the EGF receptor is defective. In addition to enhancing proliferation, suppression of apoptosis may provide a previously unrecognized mechanism for the beneficial effect of EGF during intestinal adaptation.

Adaptation, Physiological↗
PubMed1998

Alveolar capillary dysplasia with misalignment of the pulmonary veins: a rare but fatal cause of neonatal respiratory failure.

Respiratory failure in the neonate that is refractory to maximal medical management is a frequent indication for extracorporeal life support (ECLS). Alveolar capillary dysplasia with misalignment of the pulmonary veins is an irreversible cause of respiratory failure that cannot be diagnosed on clinical grounds alone and would not be expected to respond to ECLS therapy. A recent experience with a patient prompted us to review the literature regarding this condition for the purpose of identifying factors suggestive of this diagnosis. This condition should be considered in neonates with presumed pulmonary hypertension who cannot be weaned from ECLS. If the diagnosis is made by antemortem open-lung biopsy, a costly, protracted, and unnecessary continued course of ECLS may be avoided.

Capillaries↗
PubMed1998

An evidenced-based clinical pathway for acute appendicitis decreases hospital duration and cost.

BACKGROUND/PURPOSE: In the pediatric population, appendicitis remains the most common surgical emergency encountered. The purpose of this study was to determine the impact of an evidence-based clinical pathway for acute appendicitis on patient care as well as hospital and home care costs at the authors' pediatric institution. METHODS: A prospective evaluation was conducted of an appendicitis clinical pathway (June 1996 through November 1996) compared with historical control patients (June 1994 through November 1994) not cared for by the pathway. RESULTS: Data (average +/- SD) for 120 pathway (P) patients were compared with 122 control (C) patients. Age (11.5 +/- 3.6 years for C v 11.2 +/- 3.9 years for P), rates of negative appendectomy (12.3% for C v 9.2% for P) and perforation (26.2% for C v 18.3% for P) were similar. Pathway patients with nonperforated appendicitis were more often discharged from the hospital within 24 hours (48% for C v 67% for P; P = .014) with lower hospital costs ($4,095 +/- $1,280 for C v $3,638 +/- $1,633 for P; P = .001). Pathway patients with perforated appendicitis had shorter hospitalization (185.2 +/- 59 hours for C v 113 +/- 44 hours for P; P = .0001) and lower hospital costs ($11,175 +/- $3,893 for C v $7,823 +/- $2,366 for P; P = .0001). CONCLUSION: An evidence-based appendicitis pathway decreased duration of hospitalization and cost without adversely affecting diagnosis or therapy. Clinical pathways for surgical diagnoses may prove useful as a means to minimize costs without compromising patient care.

Acute Disease↗
PubMed1998

Utility of daily head ultrasonography for infants on extracorporeal membrane oxygenation.

BACKGROUND/PURPOSE: Intracranial hemorrhage (ICH) is a major concern during extracorporeal membrane oxygenation (ECMO). Daily cranial ultrasonography has been used by many ECMO centers as a diagnostic tool for both detecting and following ICH while infants are on bypass. The purpose of this patient review was to look at the usefulness of performing daily cranial ultrasonography (HUS) in infants on ECMO in detecting intraventricular hemorrhage of a magnitude sufficient to alter patient treatment. METHODS: The authors reviewed retrospectively all of the records of all neonates treated with ECMO at the Hermann Children's Hospital, Wilford Hall USAF Medical Center, Cincinnati Children's Hospital, The University of Texas Medical Branch at Galveston, and Texas Children's Hospital between February 1986 to March 1995. Two hundred ninety-eight patients were placed on ECMO during this period. All patients had HUS before, and daily while on ECMO, and all were reviewed by the staff radiologists. A total of 2,518 HUS examinations were performed. RESULTS: Fifty-two of 298 patients (17.5%) had an intraventricular hemorrhage seen on ultrasound scan. Nine of 52 patients (17.3%) had an ICH seen on the initial HUS examination before ECMO, all of which were grade I, and 43 of 52 patients (82.7%) had ICH while on ECMO. Of these ICH, 15 were grade I, 10 were grade II, 10 were grade III, and eight were grade IV. Forty of these ICH (93%) were diagnosed by HUS during the first 5 days of the ECMO course. Seven hundred eighty-six HUS were performed after day 5, at an estimated cost of $300,000 to $450,000 (charges), demonstrating three new intraventricular hemorrhages, one grade I, and one grade IV on day 7 and one grade I on day 8. Eight patients were taken off ECMO because of ICH diagnosed within the first 5 days. One patient was taken off ECMO because of ICH diagnosed after 5 days. This patient had clinical symptoms suggestive of ICH. CONCLUSIONS: Almost all ICH occur during the first 5 days of an ECMO course. Unless there is a clinical suspicion, it is not cost effective to perform HUS after the fifth day on ECMO, because subsequent HUS examinations are unlikely to yield information significant enough to alter management.

Cerebral Hemorrhage↗
PubMed1998

Epidermal growth factor upregulates the expression of its own intestinal receptor after small bowel resection.

BACKGROUND/PURPOSE: Epidermal growth factor (EGF) binds to its enterocyte receptor and enhances intestinal adaptation after massive small bowel resection (SBR). To ascertain the mechanism for enhanced adaptation by EGF, we sought to determine the effect of EGF administration on in vivo expression of the intestinal EGF receptor after SBR. METHODS: Male ICR mice underwent a 50% proximal SBR and then were assigned randomly to EGF (150 microg/kg/d) or saline by twice daily intraperitoneal injection. After 3 days, the ileum was harvested and total protein and DNA content were measured. Northern hybridization and a ribonuclease protection assay were used to detect qualitative and quantitative expression of EGF receptor mRNA. The remaining ileum was pooled for each group and Western blotting used to determine expression of EGF receptor protein. RESULTS: EGF augmented adaptation after SBR as monitored by significant increases in ileal protein (2.7+/-0.08 saline versus 3.9+/-0.17 mg/cm EGF; P<.001) and DNA (55.8+/-1.6 saline versus 104+/-8.4 microg/cm EGF; P<.001) content. Northern blotting results showed a marked (>fivefold) increase in ileal EGF receptor mRNA, which was confirmed with the ribonuclease protection assay. Administration of EGF after SBR induced a similar expression of EGF receptor protein. CONCLUSIONS: EGF enhanced intestinal adaptation after SBR. This augmented response is associated with increased ileal expression of EGF receptor mRNA and protein. Increased EGF receptor expression and subsequent enhanced ligand/ receptor activity may be one important mechanism for the beneficial effect of EGF administration during intestinal adaptation.

Adaptation, Physiological↗