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Biomedical subjects

C Pellecchia

Publications and source records attributed to C Pellecchia.

At least 19 recordsLinked to original sources

Pseudomyxoma peritonei manifesting as intestinal obstruction.

Pseudomyxoma peritonei is an appendiceal tumor with distinct clinical and pathologic features. It frequently presents a problem in diagnosis and management. We report a case of pseudomyxoma peritonei, which initially appeared with intestinal obstruction. This is a rare initial manifestation in patients who have not had multiple surgical procedures. We review the literature and discuss the unique clinical features and misconceptions surrounding pseudomyxoma peritonei.

Adenocarcinoma↗

Comparison of nuclear matrix protein composition in colon cancer and dysplasia.

BACKGROUND: Abnormal nuclear morphology associated with cancer may reflect changes in the proteins of the nuclear matrix. METHODS: Nuclear matrix (NM) proteins were isolated from colonic tissue and analyzed by two-dimensional gel electrophoresis. RESULTS: Several matrix proteins that were found in ulcerative colitis (UC) dysplasia (n = 5) and/or UC cancer (n = 4) were not identified in normal colonic tissue. UC dysplasia tissue showed three specific NM proteins with molecular masses of 49.2 kDa, 20.0 kDa, and 19.0 kDa, whereas 29.0-kDa and 32.0-kDa proteins were specific to UC cancer. Three proteins with 59.5-kDa (pI 6.3 and 6.6) and 33.75-kDa (pI 7.5) masses were common to both dysplasia and cancer tissue. CONCLUSIONS: These data suggest that NM proteins may have a role in the transition of tissue towards the malignant phenotype.

Antigens, Nuclear↗

Combination of cisplatin-procaine complex DPR with anticancer drugs increases cytotoxicity against ovarian cancer cell lines.

DPR, cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate, is a newly developed water-soluble platinum compound which possess minimal cross-resistance to cisplatin and shows relatively less side effects. In an attempt to establish whether the combination of DPR with other conventional anticancer drugs would be of any benefit we assessed in vitro the cytotoxic effects of combinations of DPR with the antimetabolites 5-fluorouracil (5-FU) and methotrexate (MTX), the alkylating agents mitomycin C (MMC) and cisplatin, the antimicrotubule agent taxol (TAX), and the intercalating agent of the anthracycline group doxorubicin (DOX) on murine M5076 ovarian reticulosarcoma and human A2780 ovarian carcinoma cells. These agents were selected because of their common use in the clinic and because they represent four distinct categories of antineoplastic mechanisms. Cells were incubated for 72 h in the presence of single or combined drugs, and the cytotoxic effect was determined by the MTT assay. The analysis of combination treatment was made by the isobole method. In human A2780 cells, an overall synergy was found for DPR combined with 5-FU, DOX and cisplatin. Synergistic effects were also observed for most combinations with MTX or MMC. A DPR concentration-dependent additivity and antagonism was seen at the highest MTX concentration (1 microM), while additive effects were observed for the combined treatments of DPR and low concentrations of MMC (0.008 and 0.0016 microM). Additive effects were also observed for the association of DPR and TAX over most combinations tested. In murine M5076 cells, synergism was the prevailing result observed when DPR was combined with 5-FU, DOX, MMC or cisplatin. When administered together with MTX we observed additivity over most combinations tested. These findings suggest that DPR, when simultaneously administered with standard anticancer agents, may be advantagious for cytokilling.

Antibiotics, Antineoplastic↗

Clostridium difficile colitis associated with treatment of Helicobacter pylori infection.

Helicobacter pylori infection of the stomach is being detected and treated more often now than ever before. This is likely to result in an increase in complications such as antibiotic-associated diarrhea. However, there is no literature on the incidence of such diarrhea, particularly Clostridium difficile colitis, in patients treated for Helicobacter pylori infection. We report the case of a patient who developed Clostridium difficile colitis after treatment for Helicobacter pylori infection with metronidazole, amoxicillin, H2 blockers, and bismuth subsalicylate. This patient presented with severe diarrhea that responded to a course of metronidazole with rapid disappearance of symptoms. The incidence of Clostridium difficile colitis in patients treated for Helicobacter pylori infection has not been studied. This unique association, although not unexpected, has not yet been reported in the literature. The increasing number of patients being diagnosed and treated for this infection requires a heightened awareness on the part of physicians, to assure early diagnosis and treatment of this treatable, yet potentially dangerous, complication.

Aged↗

Dysplasia expresses altered nuclear matrix protein composition in human ulcerative colitis.

We compared nuclear matrix protein compositions (NMPS) in colonic tissue from three different patient groups: 1) normal controls; 2) ulcerative colitis (UC); and 3) ulcerative colitis with dysplasia (UC-dysplasia). NMPS were separated by two-dimensional electrophoresis using isoelectrofocusing and SDS-PAGE. Six specific NMPS (59,500 Kd, pI 6.6 and 6.3; 49,250 Kd, pI 7.4; 33,750 Kd, pI 7.5; 20,000 Kd, pI 7.5; and 19,000 Kd, pI 6.3) were identified in UC-dysplasia that were not found in normal controls nor in UC colonic tissue. These observations suggest that NMPS may serve as important biochemical markers of dysplasia in UC.

Colitis, Ulcerative↗

Neutrophil-activating peptide (interleukin-8) in colonic mucosa from patients with Crohn's disease.

We considered the role of two neutrophil chemotactic agents (interleukin-8 and leukotriene B4) and of myeloperoxidase (a neutrophil-associated enzyme) in the pathologic condition of Crohn's disease (CD). Serial biopsy samples were taken at different sites in the colon, washed in 0.02 M phosphate-saline buffer, homogenized, and then sonicated. Interleukin-8 levels were significantly increased throughout the colonic mucosa (> 300 pg/mg protein) in patients with CD compared with control groups (< 40 pg/mg protein) (p < or = 0.01). A two- to six-fold increase in leukotriene B4 was also found in CD, whereas mucosal levels of myeloperoxidase were unchanged compared with control subjects. This study demonstrates that interleukin-8 and leukotriene B4 may have an immunologic role in the pathologic condition of CD.

Adult↗

Interleukin-8 and neutrophil markers in colonic mucosa from patients with ulcerative colitis.

In this study, mediators of inflammation were characterized in colonic and terminal ileum mucosa from subjects with ulcerative colitis. We considered the role of two different chemotactic factors (interleukin-8 and leukotriene B4) and of myeloperoxidase in the pathology of inflammatory bowel disease. Serial biopsy specimens were taken at different sites, washed in 0.02 M phosphate/saline buffer, homogenized, and then sonically disrupted. In both the proximal and distal regions of the colonic mucosa of ulcerative colitis patients, there was a more than 10-fold increase in interleukin-8 levels over that in control subjects (> 300 pg/mg protein vs. 30 pg/mg protein in controls, p < or = 0.01). However, terminal ileum levels of interleukin-8 were the same in ulcerative colitis and control groups (150 pg/mg protein). There was also a 3- to 5-fold increase in leukotriene B4 levels and a several-fold increase in myeloperoxidase levels throughout the colonic mucosa in patients with ulcerative colitis. This study demonstrates that 1) interleukin-8 may have an immunoregulatory role in the pathogenesis of inflammatory bowel disease, and 2) interleukin-8, myeloperoxidase, and leukotriene B4 may be useful markers for the biochemical identification of inflammatory bowel disease.

Adult↗

Binding and internalization of VIP in rat intestinal epithelial cells.

We have prepared villous cells from the jejunum of the rat small intestine and studied the effects of divalent cations and bacitracin on the binding and internalization of VIP. Villous epithelial cells (4 x 10(6) cells/ml) were suspended in a Hepes-NaCl buffer with 1.0% BSA, (pH 7.4) and the cells were incubated for varying periods of time with 125I-VIP at 24 degrees C. Specific binding of radiolabeled VIP was maximal within 10 min (10%) and slowly declined to 9.0 percent after 30 min. In the presence of 1.0 mg/ml bacitracin, however, maximal specific binding of VIP was only 2.7 percent (P less than or equal to 0.001). The addition of CA2+ or Mg2+ to the buffer significantly decreased binding of VIP in a concentration dependent manner. At 8.0, 4.0, 2.0 and 1.0 mM Ca2+, binding of 125I-VIP decreased by 70, 60, 40 and 25 percent, whereas in the presence of the same concentrations of Mg2+ binding was decreased to 50, 38, 25 and 10 percent (P less than or equal to 0.01). To determine if epithelial cells internalize VIP, we bound 125I-VIP to villous cells and then differentiated surface-bound and internalized radioactivity by treating with trypsin (150 micrograms/ml). Surface bound radioligand was the same at both 24 and 4 degrees C (5.3%), while internalized 125I-VIP was 4.0% at 24 degrees C compared to only 1.0% at 4 degrees C (P less than or equal to 0.001). At 24 and 4 degrees C, both Ca2+ (4.0 mM) and Mg2+ (8.0 mM) decreased surface bound radioligand by 60 percent (P less than or equal to 0.01) and lowered internalized radioactivity. These data demonstrate that (1) bacitracin decreases the binding of VIP to small intestinal epithelial cells, (2) both Ca2+ and Mg2+ affect the binding of VIP to its surface receptor and (3) VIP is internalized into epithelial cells.

Animals↗

Kaposi's sarcoma presenting as linitis plastica.

A 31-yr-old woman presenting with abdominal complaints and fever was found to have linitis plastica on upper gastrointestinal series. Endoscopic studies confirmed these findings; however, pathology revealed the diagnosis to be Kaposi's sarcoma. We believe this to be the first case report of linitis plastica presenting as Kaposi's sarcoma.

Adult↗

Chloroquine alters the processing of secretin in isolated rat pancreatic acinar cells.

In this study we considered the effect of chloroquine on the processing and intracellular distribution of internalized secretin radioligand in acinar cells. Chloroquine (100 microM) had no effect on the total amount of 125I-secretin bound but had marked effects on the processing of this radioligand in acinar cells. After an initial 60 min of radioligand binding in the presence and absence of chloroquine, cells were washed free of unbound radioligand, resuspended and then processed for different times at 37 degrees C. During 60, 120 and 180 min of processing, the amount of internalized radioligand in the presence of 100 microM chloroquine was increased by 116, 194 and 273%, respectively, compared to untreated control samples. Chloroquine also increased the amount of intact 125I-secretin radioligand within the cell as measured by rebinding to pancreatic plasma membranes. After 120 and 180 min of processing, intact peptide within the acinar cell was 25 and 66% greater in the presence of this agent than in control samples (P less than or equal to 0.01). To determine if chloroquine affected intracellular localization of the secretin radioligand, we measured the amount of radioactivity in soluble and particulate fractions of cell homogenates. Chloroquine decreased radioactivity entering particulate fractions of the cell by greater than 35% after 120 and 180 min of processing (P less than or equal to 0.01). This study demonstrates that (1) chloroquine inhibits the intracellular degradation of secretin in acinar cells and (2) chloroquine alters intracellular localization of this peptide during processing.

Animals↗

Preparation and characterization of a fully active biotinylated probe of cholecystokinin.

In this study we describe the synthesis and purification of biotinylated cholecystokinin-8 (Bio-CCK-8) and characterize its use as a probe for the pancreatic cholecystokinin receptor. CCK-8 (0.1 umoles) was reacted with either radiolabeled d-[8,9(-3)H]biotin succinimide ester (0.5 umoles) or N-hydroxysuccinimidyl-biotin in dimethylformamide and triethylamine, and purified by anion exchange chromatography. Concentrations of Bio-CCK-8 and CCK-8 needed for half-maximal inhibition of [125]I-CCK-8 binding to pancreatic membranes were the same (1.0 and 1.3 nM). Bio-CCK-8 retained full biological activity as determined by stimulation of pancreatic protein secretion from rats, and the biotin group bound to CCK-8 retained its high sensitivity for avidin.

Animals↗

Secretin internalization and adenosine 3',5'-monophosphate levels in pancreatic acinar cells.

The internalization of [125I]secretin in pancreatic acinar cells was evaluated by differentiation of surface-bound and internalized radioligand with an acidified glycine buffer. The amount of surface-bound radioligand was 2-fold higher at 37 C than at 4 C between 15 and 60 min; internalized radioactivity was more than 10-fold greater at 37 C than at 4 C during the same time period. The effects of chloroquine, dithiothreitol (DTT), carbonyl cyanide m-chlorophenyl-hydrazone (CCCP), and dansylcadaverine on the binding and internalization of secretin were then evaluated. Chloroquine (0.1 mM), a lysosomotropic agent, did not affect secretin radioligand binding to its pancreatic receptor, while DTT, a sulfhydryl reducing agent, significantly lowered binding by more than 90% from 15-60 min. The metabolic inhibitor CCCP, however, significantly enhanced binding of the secretin radioligand in both the surface and the internalized pools. Surface binding was 1.6- to 3.3-fold greater from 15-60 min (P less than or equal to 0.01) in acinar cells exposed to CCCP than in untreated controls, while internalized radioactivity increased from 2.8- to 1.4-fold above the control value (P less than or equal to 0.01) at the same times. Dansylcadaverine, an inhibitor of receptor recycling, reduced internalized radioligand by 40% after 30 min of binding. The effects of these chemical agents on cAMP production were also considered. cAMP production was significantly reduced by DTT, CCCP, and dansylcadaverine at secretin concentrations of 0.1, 3.0, and 10 nM, respectively. This study demonstrates that 1) pancreatic acinar cells rapidly internalize [125I]secretin; 2) internalization of secretin does not enhance cAMP production; and 3) disulfide linkages are important for secretin receptor activity.

Adenosine Monophosphate↗

Internalization and cellular processing of cholecystokinin in rat pancreatic acinar cells.

To evaluate the internalization of cholecystokinin, monoiodinated imidoester of cholecystokinin octapeptide [125I-(IE)-CCK-8] was bound to dispersed pancreatic acinar cells, and surface-bound and internalized radioligand were differentiated by treating with an acidified glycine buffer. The amount of internalized radioligand was four- and sevenfold greater at 24 and 37 degrees C than at 4 degrees C between 5 and 60 min of association. Specific binding of radioligand to cell surface receptors was not significantly different at these temperatures. Chloroquine, a lysosomotropic agent that blocks intracellular proteolysis, significantly increased the amount of CCK-8 internalized by 18 and 16% at 30 and 60 min of binding, respectively, compared with control. Dithiothreitol (DTT), a sulfhydryl reducing agent, also augmented the amount of CCK-8 radioligand internalized by 25 and 29% at 30 and 60 min, respectively. The effect of chloroquine and DTT on the processing of internalized radioligand was also considered after an initial 60 min of binding of radioligand to acinar cells. After 180 min of processing, the amount of radioligand internalized was significantly greater in the presence of chloroquine compared with controls, whereas the amount of radioligand declined in acinar cells treated with DTT. Internalized and released radioactivity from acinar cells was rebound to pancreatic membrane homogenates to determine the amount of intact radioligand during intracellular processing. Chloroquine significantly increased the amount of intact 125I-(IE)-CCK-8 radioligand in released and internalized radioactivity while DTT increased the amount of intact radioligand only in internalized samples. This study shows that pancreatic acinar cells rapidly internalize large amounts of CCK-8 and that chloroquine and DTT inhibit intracellular degradation.

Animals↗

Large-scale procedure for the purification of fibronectin domains.

Human plasma fibronectin is composed of at least seven distinct domains, with affinities for different macromolecules and cell surfaces. Here we describe in detail a simple high-yield procedure for the purification of large amounts of fibronectin domains. This involves thermolysin digestion of the fibronectin molecule followed by the purification of the domain using mainly hydroxyapatite chromatography columns. This procedure represents a great simplification over those previously reported.

Amino Acids↗

Jaundice secondary to hepatic artery aneurysm: radiological appearance and clinical features.

Hepatic artery aneurysm comprises only 20% of all visceral aneurysms. The classical triad of abdominal pain, hemobilia, and jaundice is seen in less than one-third of cases. Up to 60% of patients present with an abdominal catastrophe. In our case of hepatic artery aneurysm, the diagnosis was suggested by CT scan and confirmed by angiography. Its appearance is also demonstrated on sonogram and cholangiogram. To our knowledge, this is the first case to be reported where the aneurysm was demonstrated on multiple radiographic images.

Aged↗