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Victor E Pricolo

Publications and source records attributed to Victor E Pricolo.

11 recordsLinked to original sources
PubMed2006

NK2 receptor-mediated spontaneous phasic contractions in normal and ulcerative colitis human sigmoid colon.

Human colonic circular muscle produces spontaneous phasic contractions that are reduced in ulcerative colitis. How the spontaneous phasic contractions develop and why they decrease in ulcerative colitis are not known. We found that spontaneous phasic contractions of normal sigmoid circular muscle strips were significantly reduced by 90-min incubation with tetrodotoxin (10(-5) M), which blocked neurokinin A release in basal conditions and in response to electrical stimulation. In addition, spontaneous contraction of human sigmoid colon was significantly decreased by the NK2 receptor antagonists MEN10376 (Asp-Tyr-D-Trp-Val-D-Trp-D-Trp-Lys-NH2) and NK2ra (Bz-Ala-Ala-D-Trp-Phe-D-pro-Pro-Nle-NH2) but not by atropine or by the NK1 antagonist FK888 (N2-[(4R)-4-hydroxyl-1-(1-methyl-1H-indol-3-yl)carbonyl-l-prolyl]-N-methyl-N-phenylmethyl-3-(2-naphthyl)-l-alaninamide), suggesting that NK2 receptors are involved in their development. The spontaneous phasic contractions were abolished by thapsigargin and cyclopiazonic acid and significantly decreased by the protein kinase C inhibitor chelerythrine and by the calmodulin inhibitor CGS9343B (1,3-dihydro-1-[1-[(4-methyl-4H,6H-pyrrolo[1,2-a]-[4,1]-benzoxazepin-4-yl)methyl]-4-piperidinyl]-2H-benzimidazol-2-one (1:1) maleate), suggesting that spontaneous phasic contractions may be mediated by Ca2+ release from intracellular stores and by a protein kinase C- and calmodulin-dependent pathway. In strips from patients with ulcerative colitis, spontaneous contractions were significantly reduced, and this reduction was partially restored by the hydrogen peroxide scavenger catalase. Neurokinin A release, however, was not affected. We conclude that spontaneous phasic contractions of human sigmoid circular smooth muscle may be mediated by activation of NK2 receptors, calcium release from intracellular stores, and activation of calmodulin and protein kinase C. In ulcerative colitis patients, spontaneous phasic contractions are decreased, and this decrease may be in part due to overproduction of hydrogen peroxide affecting sigmoid circular muscle.

Colitis, Ulcerative↗
PubMed2005

Production of IL-1beta, hydrogen peroxide, and nitric oxide by colonic mucosa decreases sigmoid smooth muscle contractility in ulcerative colitis.

We have previously shown that sigmoid circular muscle cells from patients with ulcerative colitis (UC) exhibit reduced contraction and Ca2+ signaling in response to the neurotransmitter neurokinin A (NKA) and that IL-1beta and H2O2 may contribute to these reduced responses in UC. In addition, we have found that nitric oxide (NO) levels were significantly increased in UC circular muscle. To establish the site of origin for IL-1beta, H2O2, and NO, we assembled an in vitro system in which normal or UC mucosa were sealed between two chambers filled with oxygenated Krebs solution. Because the mucosa consists of full-thickness mucosa and submucosa, it is expected that whatever is released into the undernatant from the submucosal side may diffuse to the circular muscle layer in the intact colon. Treatment of normal sigmoid circular muscle cells for 2 h with undernatants collected from the UC submucosal side (UCS) significantly decreased contraction induced by NKA and thapsigargin and the NKA- and caffeine-induced Ca2+ signal in Ca2+-free medium. In addition, UC mucosa released into the undernatant on its submucosal side significantly more H2O2, IL-1beta, and NO than normal mucosa. The reduction in contraction and Ca2+ signal induced by UCS was partially reversed by pretreatment with an IL-1beta antibody or with catalase. The NO scavenger hemoglobin partially prevented UCS-induced reduction in contraction and Ca2+ signaling in response to NKA but not the reduced response to thapsigargin or caffeine. Sodium nitroprusside inhibited NKA but not the caffeine-induced Ca2+ signal. We conclude that in UC the mucosa releases IL-1beta, H2O2, and NO, which may contribute to the impaired Ca2+ release and altered sigmoid muscle contractility.

Caffeine↗
PubMed2005

Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study.

Tight junction associated proteins are key molecular components governing cellular adhesion, polarity and glandular differentiation. Tight junction proteins also play critical roles in cellular proliferation and neoplastic pathways via their functions as couplers of the extracellular milieu to intracellular signaling pathways and the cytoskeleton. Neoplastic cells frequently exhibit structural and functional deficiencies in the tight junction. The purpose of this study was to determine the pattern of expression and prognostic value of four tight junction associated proteins, claudin-1, claudin-4, occludin and ZO-1 in a cohort of TNM stage II colon cancer using tissue microarray technology. In this study, we retrospectively analyzed, resected and otherwise untreated paraffin embedded specimens from 129 consecutive patients with TNM stage II colonic carcinomas for claudin-1, claudin-4, occludin and ZO-1 protein expression by immunohistochemistry. Seventy-five, 58, 56 and 44% of the tumors exhibited normal to elevated expression levels (+2 and +3 immunopositivity) of claudin-1, claudin-4, occludin and ZO-1 respectively. Low expression levels of claudin-1 and ZO-1 were directly associated with higher tumor grade (P=0.05 and 0.03 respectively). Multivariate analysis indicated that lymphovascular invasion (P=0.01) and low levels of claudin-1 (P=0.0001) expression were independent predictors of recurrence and that reduced claudin-1 expression (P=0.0001) was associated with poor survival. This study is the first to comprehensively examine the expression of several tight junction associated proteins in colonic neoplasms and to correlate their expression with disease progression. Loss of claudin-1 expression proved to be a strong predictor of disease recurrence and poor patient survival in stage II colon cancer.

Adult↗
PubMed2004

Interleukin 1beta-induced production of H2O2 contributes to reduced sigmoid colonic circular smooth muscle contractility in ulcerative colitis.

We have shown that neurokinin A-induced contraction of human sigmoid circular muscle (HSCM) is reduced in patients with ulcerative colitis and that interleukin (IL)-1beta may play a role in this change. We now examine changes in the signal transduction pathway mediating neurokinin A-induced contraction of HSCM and explore the role of IL-1beta and of H(2)O(2) in these changes. In Fura 2-AM-loaded ulcerative colitis HSCM cells, neurokinin A- and caffeine-induced peak Ca(2+) increase and cell shortening were significantly reduced. In normal cells, neurokinin A-induced contraction was decreased by protein kinase C inhibitor chelerythrine and by calmodulin inhibitor CGS9343B [1,3-dihydro-1-[1-[(4-methyl-4H,6H-pyrrolo[1,2-a][4,1]-benzoxazepin-4-yl)methyl]-4-piperidinyl]-2H-benzimidazol-2-one (1:1) maleate]. In ulcerative colitis muscle cells, contraction was inhibited only by chelerythrine but not by CGS9343B. IL-1beta treatment of normal HSCM strips and cells reproduced the changes observed in ulcerative colitis. IL-1beta-induced reduction in caffeine-induced peak Ca(2+) increase and contraction was reversed by catalase, suggesting a role of H(2)O(2). IL-1beta-induced H(2)O(2) production was inhibited by mitogen-activated protein kinase (MAPK) kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone) and by cytosolic phospholipase A2 (cPLA(2)) inhibitor AACOCF3 (arachidonyltrifluoromethyl ketone), but neither by p38 MAPK inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole] nor by nuclear factor-kappaB (NF-kappaB) inhibitory peptide NF-kappaB SN50 (H-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Val-Gln-Arg-Lys-Arg-Gln-Lys-Leu-Met-Pro-OH). IL-1beta significantly increased the phosphorylation of extracellular signal-regulated kinase 1 (ERK1)/ERK2 MAPKs and cPLA(2) and IL-1beta-induced cPLA(2) phosphorylation was blocked by PD98059. We conclude that Ca(2+) stores of HSCM cells may be reduced in ulcerative colitis and that the signal transduction pathway of neurokinin A-induced contraction switches from calmodulin- and protein kinase C-dependent in normal cells to protein kinase C-dependent in ulcerative colitis cells. IL-1beta reproduces these changes, possibly by production of H(2)O(2) via sequential activation of MAPKs (ERK1/ERK2) and cPLA(2).

Calcium↗
PubMed2004

Epidermal growth factor receptor, c-MET, beta-catenin, and p53 expression as prognostic indicators in stage II colon cancer: a tissue microarray study.

PURPOSE: Through the use of molecular markers, it may be possible to identify aggressive tumor phenotypes and tailor therapies to treat them. This approach would be particularly useful for stage II colon cancer. The purpose of this study was to define the prognostic value of epidermal growth factor receptor (EGFR), c-MET, beta-catenin, and p53 protein expression in TNM stage II colon cancer using tissue microarray technology. EXPERIMENTAL DESIGN: In this study, we retrospectively analyzed, resected, and otherwise untreated paraffin-embedded specimens from 134 consecutive patients with Tumor-Node-Metastasis stage II colonic carcinomas for EGFR, c-MET, beta-catenin, and p53 protein expression by immunohistochemistry. RESULTS: Thirty-five percent, 77, and 65% of tumors exhibited strong (+2 and +3 immunopositivity) expression of EGFR, c-MET, and beta-catenin, respectively. Fifty-four percent exhibited nuclear staining for p53 in >10% of the tumor cells. Univariate analysis revealed that increased nuclear p53 expression (P = 0.001), strong membranous EGFR expression (P = 0.04), and lymphovascular invasion (P = 0.01) were significantly related to disease recurrence and that p53 (P = 0.02) and EGFR (P = 0.05) expression were associated with decreased survival. Increased nuclear p53 expression also correlated with the presence of distal metastasis (P = 0.027). No significant association was seen between c-MET expression and prognosis, whereas a strong trend was detected between loss of beta-catenin (P = 0.065) expression and poor outcome. Multivariate analysis indicated that p53 (P = 0.04), EGFR (P = 0.05), and lymphovascular invasion (P = 0.03) were independent predictors of recurrence and that p53 (P = 0.02) and EGFR (P = 0.01) expression were both associated with poor survival. CONCLUSIONS: This retrospective tumor microarray study, restricted to Tumor-Node-Metastasis stage II colon cancer patients who did not undergo adjuvant therapy, supports the use of EGFR and p53 as biological markers, which may assist in predicting disease recurrence and survival.

Adult↗
PubMed2003

Hydrogen peroxide contributes to motor dysfunction in ulcerative colitis.

Ulcerative colitis (UC) affects colonic motor function, but the mechanism responsible for this motor dysfunction is not well understood. We have shown that neurokinin A (NKA) may be an endogenous neurotransmitter mediating contraction of human sigmoid colonic circular muscle (HSCCM). To elucidate factors responsible for UC motor dysfunction, we examined the role of hydrogen peroxide (H(2)O(2)) in the decrease of NKA-induced response of HSCCM. As previously demonstrated, NKA-induced contraction or Ca(2+) increase of normal muscle cells is mediated by release of Ca(2+) from intracellular stores, because it was not affected by incubation in Ca(2+)-free medium (CFM) containing 200 microM BAPTA. In UC, however, CFM reduced both cell contraction and NKA-induced Ca(2+) increase, suggesting reduced Ca(2+) release from intracellular stores. In normal Ca(2+) medium, NKA and KCl caused normal Ca(2+) signal in UC cells but reduced cell shortening. The decreased Ca(2+) signal and contraction in response to NKA or thapsigargin were partly recovered in the presence of H(2)O(2) scavenger catalase, suggesting involvement of H(2)O(2) in UC-induced dysmotility. H(2)O(2) levels were higher in UC than in normal HSCCM, and enzymatically isolated UC muscle cells contained much higher levels of H(2)O(2) than normal cells, which were significantly reduced by catalase. H(2)O(2) treatment of normal cells in CFM reproduced the reduction of NKA-induced Ca(2+) release observed in UC cells. In addition, H(2)O(2) caused a measurable, direct release of Ca(2+) from intracellular stores. We conclude that H(2)O(2) may contribute to reduction of NKA-induced Ca(2+) release from intracellular Ca(2+) stores in UC and contribute to the observed colonic motor dysfunction.

Calcium↗
PubMed2003

Portal venous gas detected by computed tomography: is surgery imperative?

BACKGROUND: Portal vein gas (PVG) has historically been associated with mortality rates of 75% or higher and mandatory abdominal exploration. The following study reassesses the clinical significance of gas in the portal venous system detected by computed tomography (CT) and reevaluates the need for surgical intervention in that setting. METHODS: We performed a retrospective chart review of 26 patients presenting with gas in the portal venous system as imaged by CT between August 1, 1993 and April 8, 2001. Characteristics assessed included age, sex, clinical presentation and course, additional CT findings, diagnosis, surgical versus non-surgical management, surgical findings, pathologic correlation, and mortality. RESULTS: Of the 26 patients who had gas in the portal venous system by CT, 11 underwent surgery to determine underlying pathology. Of those who underwent surgery, 8 survived to be discharged while 3 died (73% surgical survival). The survivors presented with gastrointestinal related signs/symptoms and were found at the time of surgery to have adhesions, non-surgically treated inflammation, unclear pathology, or resectable lesions. Those who died all demonstrated marked bowel ischemia intraoperatively. Among patients who did not undergo surgery, 9 survived and 6 died (60% nonsurgical survival). Those who survived presented either asymptomatically or with pathology including acute pancreatitis, recent hypotensive episode, uncomplicated diverticulitis, unresectable colon cancer, or infectious etiology. Those who died were poor surgical candidates or status postvascular procedure. The overall survival in patients with portal venous gas by CT was 65%. CONCLUSION: Portal venous gas on CT is associated with a wide range of pathologies that do not necessarily warrant surgical management. Clinical presentation should be correlated with the presence of PVG and other associated CT findings prior to deciding whether surgery should be performed.

Adult↗
PubMed2003

Gracilis muscle transposition for iatrogenic rectourethral fistula.

OBJECTIVE: To assess the utility of gracilis muscle transposition in the treatment of iatrogenic rectourethral fistula. SUMMARY BACKGROUND DATA: Iatrogenic rectourethral fistula poses a rare but challenging complication of treatment for prostate cancer. A variety of procedures have been described to treat this condition, none of which has gained acceptance as the procedure of choice. The aim of this study was to review the authors' experience with gracilis muscle transposition in the treatment of iatrogenic rectourethral fistula. METHODS: A retrospective chart review of all patients who underwent gracilis muscle transposition for iatrogenic rectourethral fistula was performed, and follow-up was established by telephone interview. Successful repair was defined as absence of a fistula after reversal of fecal and urinary diversions. RESULTS: Eleven men, mean age of 62 years, underwent 12 gracilis muscle transpositions for rectourethral fistula between 1996 and 2001. Six patients had a history of pelvic radiotherapy, and five patients had previous failed attempts to repair the fistula. In nine patients, the fistula healed following gracilis muscle transposition. One patient developed a rectocutaneous fistula that healed with fibrin glue injection, and one developed perineal sepsis requiring debridement of the transposed gracilis. This patient underwent a second gracilis transposition, which uneventfully healed. Overall, all of the patients had closure of their diverting stomas and maintained healed rectourethral fistulas. There were no intraoperative complications, and the only long-term complication of this procedure was mild medial thigh numbness in two patients. CONCLUSIONS: Gracilis muscle transposition is an effective surgical treatment for iatrogenic rectourethral fistula. It is associated with low morbidity and a high success rate.

Aged↗
PubMed2002

Abnormal motility in patients with ulcerative colitis: the role of inflammatory cytokines.

HYPOTHESIS: Interleukin 1 beta (IL-1 beta) levels are elevated in the colonic mucosa of patients with ulcerative colitis (UC). We propose that IL-1 beta may also be elevated in the circular muscle layer of the colon and may be partially responsible for the motility dysfunction observed in patients with UC. DESIGN: Cohort analytic study. SETTING: Research laboratory in a tertiary academic medical center. PARTICIPANTS: Normal smooth muscle was obtained from the disease-free margins of human sigmoid colon specimens resected from patients with cancer and compared with specimens from patients with UC. INTERVENTIONS: An enzyme-linked immunosorbent assay was used to measure IL-l beta. Standard muscle chambers were used to measure force changes. Single muscle cells were isolated by enzymatic digestion, and cell shortening in response to neurokinin A (NKA) and thapsigargin was measured under a microscope. Cytosolic Ca(2+) (calcium) concentrations were measured by standard techniques. MAIN OUTCOME MEASURE: Effects of IL-1 beta on smooth muscle function in normal and UC colons. RESULTS: In patients with UC, IL-1 beta was elevated in the muscularis propria, and sigmoid circular smooth muscle contractions in response to NKA and thapsigargin were significantly reduced. In fura-2-loaded cells from patients with UC, the NKA-induced Ca(2+) signal was also significantly reduced in Ca(2+)-free medium, indicating the reduced intracellular Ca(2+) stores after UC. Exposure of normal cells to IL-1 beta mimicked the changes observed in patients with UC. An IL-1 beta-induced reduction in contraction and release of intracellular Ca(2+) in response to NKA was partially restored by the hydrogen peroxide scavenger catalase. CONCLUSION: In patients with UC, IL-1 beta was increased in colonic circular muscles and may contribute to motor dysfunction after UC through production of hydrogen peroxide.

Adenosine Triphosphate↗
PubMedDate not supplied

Factors affecting the professional image of physicians.

OBJECTIVE: The purpose of this study was to use an experimental design to determine the effect of selected aspects of dress on the professional image of physicians in an adult outpatient setting by those who use the health care services the most (55+), the least (18 to 22), and other physicians on whom we depend for referrals. METHODS: Ten slides of physicians representing a variety of ages; ethnic and religious affiliations were shown to 3 populations across the United States and Canada. Set 1 (N = 216) was shown to undergraduates and rated on 10 attributes of professional image. Two slides were altered and retested in a rotated order (Set 2). Set 1 was then tested with groups of elderly and surgeons (N = 277). RESULTS: Significant differences were found between Set 1 and Set 2 for the altered physician slides. There was high correlation of professionalism with the identified attributes for all 3 rater populations. The nonverbal attributes chosen for this study did accurately assess "professionalism." Gender of the rater or physician did not have any effect. Although the most "professional" surgeon was the oldest in the study, the second most "professional" was the youngest. CONCLUSIONS: It is clear that a surgeon's image is a mirror of competence, trust, expertise, and compassion. The variables described in this study may easily be implemented to reflect a more positive professional image with our peers and patients than simply adding a white coat. No one goes to see a surgeon to establish a casual relationship, and because it is difficult to counteract initial impressions, attention to these variables is important.

Adult↗