Biomedical subjects

E E Furth

Publications and source records attributed to E E Furth.

113 records · Page 7Linked to original sources

PubMedDate not supplied

Glutamine enhancement of structure and function in transplanted small intestine in the rat.

Total parenteral nutrition is required by all patients in need of small bowel transplantation. Untoward side effects of total parenteral nutrition include atrophy and hypofunction of the small intestine. Glutamine, the preferred fuel for the enterocyte, is presumably present in insufficient amounts in diets given to patients with intestinal dysfunction. In a rat model of total parenteral nutrition and small bowel transplantation, this study investigated the following: (1) whether glutamine improves graft structure and function, (2) the optimal route of glutamine delivery (intravenous vs direct infusion into the graft), and (3) the effect of glutamine on ultrastructure of the graft enterocyte. Lewis rats underwent small bowel transplantation as a Thiry-Vella graft and received total parenteral nutrition for 14 days while assigned to one of four infusion groups: 2% intravenous glutamine; 2% intravenous isonitrogenous mixture, nonessential amino acids (control); 2% glutamine into the graft; or 2% nonessential amino acids into the graft (control). Graft mucosal villous height, villous surface area, crypt depth, weight, protein, deoxyribonucleic acid content, glucose absorption, and enterocyte ultrastructure were then evaluated. Infusion of glutamine directly into the graft significantly increased mucosal villous height (p = .045), surface area (p = .029), and glucose absorption (p = .004) when compared with controls. Intravenous glutamine infusion significantly increased mucosal villous height (p = .002), surface area (p = .001), weight (p = .005), and glucose absorption (p = .04) when compared with controls. Most enterotrophic and functional benefits of glutamine were not significantly different between intravenous infusions and direct administration into the graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Differentiation-dependent expression of the BCL-2 proto-oncogene in the human trophoblast lineage.

OBJECTIVE: We explored the role of the BCL-2 proto-oncogene in the life cycle of trophoblast cells by examining: 1) the patterns of BCL-2 expression in normal placenta at various gestational ages and in specimens of hydatidiform moles and choriocarcinomas, and 2) the effects of cyclic adenosine monophosphate (cAMP) treatment of JEG-3 choriocarcinoma cells, which induces differentiated functions, on BCL-2. METHODS: BCL-2 protein was localized by indirect immunofluorescence and immunoperoxidase staining of tissue sections and cells using monoclonal and polyclonal antibodies. Western and Northern blotting were used to assess BCL-2 and p53 protein and mRNA levels, respectively. JEG-3 cells were transfected with a BCL-2 expression plasmid to establish that BCL-2 protein could be expressed at high levels in this cell type. RESULTS: BCL-2 immunostaining was most prominent in the syncytiotrophoblast of normal placenta. It was found in syncytiotrophoblast of complete and partial hydatidiform moles, whereas cytotrophoblast staining was weak. BCL-2 immunostaining was also barely detectable in choriocarcinoma cells (JEG-3 cells) and a primary choriocarcinoma. However, BCL-2 protein could be transiently overexpressed in JEG-3 cells by transfection with an expression plasmid. Western blot analysis revealed low levels of BCL-2 in JEG-3 cells and a rise in BCL-2 protein in placental extracts from 10 weeks' gestation to term. In contrast, p53 protein was abundant in JEG-3 cells and normal placenta at 10 weeks' gestation, but low at term, BCL-2 transcripts were substantially more abundant in term placenta than in JEG-3 cells. Treatment of JEG-3 cells with 8-Br-cAMP, which induces genes characteristic of the syncytiotrophoblast, raised BCL-2 protein approximately twofold, whereas p53 mRNA declined. CONCLUSIONS: We conclude that: 1) There is a differentiation-dependent pattern of BCL-2 expression in the placenta, with the protein being most abundant in terminally differentiated trophoblast cells; 2) there appears to be an inverse relation between BCL-2 and p53 expression in trophoblast; and 3) cAMP regulates BCL-2 protein in trophoblast cells. We speculate that the expression of BCL-2 in terminally differentiated trophoblast cells, and hence resistance to apoptotic cell death, may be one mechanism by which trophoblast mass is preserved during pregnancy. Conversely, the relatively low expression of BCL-2 in choriocarcinoma cells may render them more susceptible to apoptosis.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMedDate not supplied

Apoptosis and p53 in inverting papilloma of the sinonasal tract.

The objective of this study was to identify apoptotic bodies and p53 positivity in inverting papilloma lesions to study these two as biomarkers in premalignant lesions. Archival specimens of 15 patients with inverting papilloma between the years 1992 and 1995 were retrieved. In situ end labeling technique was used to identify apoptotic bodies. Immunohistochemistry was used to detect p53 in the same specimens. The clinical course was evaluated conducting a retrospective chart review in these patients. Compared to normal epithelium, inverting papilloma lesions had a greater proportion of apoptotic bodies, which was nearly statistically significant (average 0.506/100 cells for inverting papilloma compared with 0.1/100 cells for the normal surrounding tissue). Four cases of inverting papilloma were p53 positive. There was, however, no association between p53 positive staining and the apoptotic rate. The minimum follow-up for patients was 2 years. All had a uniformly good clinical outcome with only one patient who was p53 positive showing concurrent squamous cell carcinoma. We concluded that inverting papilloma contained a higher average number of apoptotic bodies compared with normal surrounding sinonasal tissue. This showed a trend toward a positive between the apoptotic rate and premalignancy, suggesting both increased cellular proliferation and increased cell death may occur in such lesions. In this study p53 did not show a positive association with the apoptotic rate, suggesting that p53 may not be directly involved in the apoptotic regulatory pathway in inverting papillomas.

Apoptosis↗

PubMedDate not supplied

Sporadic Zollinger-Ellison syndrome with ectopic production of corticotropin: surgical management.

OBJECTIVE: To describe two patients with concurrent Zollinger-Ellison syndrome and ectopic production of corticotropin in whom Cushing's syndrome was managed surgically. METHODS: Two case vignettes are presented, and a general approach is discussed for determining a management strategy for optimal potential for survival. RESULTS: The prognosis associated with medical management of patients with sporadic Zollinger-Ellison syndrome and Cushing's syndrome attributable to ectopic production of adrenocorticotropic hormone (corticotropin) is dismal. Two surgical options may yield improved outcomes. The first approach is bilateral adrenalectomy followed by replacement therapy with corticosteroids and mineralocorticoids. The second surgical approach consists of removal of the organ producing the corticotropin (the liver) and performance of hepatic transplantation. These two treatment strategies were used in our two patients, both of whom had widely metastatic disease at the time of initial assessment. The patient who underwent bilateral adrenalectomy continued to do well 4 years postoperatively. CONCLUSION: Treatment of patients with Zollinger-Ellison syndrome and ectopic production of corticotropin presents a challenge. Because results with medical therapy have been suboptimal, aggressive surgical intervention seems warranted.

Journal Article↗

PubMedDate not supplied

Realities of diagnosing Helicobacter pylori infection in clinical practice: a case for non-invasive indirect methodologies.

BACKGROUND: The current, arbitrarily defined gold standard for the diagnosis of H. pylori infection requires histologic examination of two specially stained antral biopsy specimens. However, routine histology is potentially limited in general clinical practice by both sampling and observer error. The current study was designed to examine the diagnostic performance of invasive and non-invasive H. pylori detection methods that would likely be available in general clinical practice. METHODS: The diagnostic performance of rotating clinical pathology faculty using thiazine staining was compared with that of an expert gastrointestinal pathologist in 38 patients. In situ hybridization stains of adjacent biopsy cuts were also examined by the expert pathologist for further comparison. Receiver operator characteristic (ROC) analysis was performed to evaluate whether the diagnostic performance of the expert pathologist differed depending upon the histologic method employed. A similar analysis was made to evaluate the diagnostic performance of pathology trainees relative to the expert. In the absence of an established invasive gold standard, non-invasive testing methods (rapid serum antibodies, formal Elisa antibodies and carbon-14 urea breath testing) were evaluated in 74 patients by comparison with a gold standard defined using a combination of diagnostic tests. RESULTS: Using either rapid urease testing of biopsy specimens or urea breath testing as the gold standard for comparison, the diagnostic performance of the rotating clinical pathology faculty was inferior to that of the expert gastrointestinal pathologist especially with regard to specificity (e.g., 69 percent for the former versus 88 percent, with the latter relative to rapid urease testing). Although interpretation of in situ hybridization staining by the expert appeared to have an even higher specificity, ROC analysis failed to show a difference. The mean ROC areas for thiazine and in situ hybridization staining for trainee pathologists relative to the expert were 0.88 and 0.94, respectively. In untreated patients, urea breath testing had a sensitivity and specificity of 100 percent as compared with thiazine staining with a sensitivity of 83 percent and a specificity of 97 percent. Post-therapy, breath testing had a sensitivity of 100 percent but a specificity of only 86 percent as compared with invasive testing with a sensitivity and specificity of 100 percent. Rapid serum antibody testing and formal Elisa antibody testing agreed in 93 percent of cases (Kappa 0.78) with the rapid test being correct in three of the four disagreements. CONCLUSIONS: The current study illustrates a number of realities regarding H. pylori diagnosis. There is no diagnostic gold standard in general clinical practice. Accurate interpretation of specially stained slides is a learned activity with a tendency towards overdiagnosis early on. Urea breath testing is likely to be the diagnostic method of choice for untreated patients in general clinical practice although antibody testing is almost as accurate. Rapid antibody tests are at least as accurate as formal Elisa antibody tests. Urea breath testing is useful for confirming cure after therapy, but false-positive results may occur in some patients.

Biopsy↗