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Biomedical subjects

E E Furth

Publications and source records attributed to E E Furth.

At least 73 records · Page 4Linked to original sources
PubMed1996

A program of cell death and extracellular matrix degradation is activated in the amnion before the onset of labor.

Fetal membranes usually rupture during the process of labor. Premature fetal membrane rupture occurs not infrequently and is associated with significant fetal and maternal morbidity. The mechanisms of normal and pathologic fetal membrane rupture are not well understood. We have examined structural and biochemical changes in the rat amnion as labor approaches in order to characterize this process in normal pregnancy. Here we report that before the onset of active labor the amnion epithelial cells undergo apoptotic cell death which encompasses degradation of 28S ribosomal subunit RNA and associated P proteins and fragmentation of nuclear DNA. Concurrent with these cellular changes, the amnion type I collagen matrix is degraded with the accumulation of three-quarter length type I collagen fragments in extraembryonic fluid, characteristic of the cleavage of fibrillar collagen by interstitial collagenase. Western blot and immunohistochemical analyses confirmed that interstitial collagenase protein appears in association with the loss of amnion type I collagen. We conclude that amnion epithelial cells undergo a process of programmed cell death associated with orchestrated extracellular matrix degradation which begins before the onset of active labor. Thus, fetal membrane rupture is likely to be the result of biochemical changes as well as physical forces.

Amnion↗
PubMed1996

Prolonged metabolic correction in adult ornithine transcarbamylase-deficient mice with adenoviral vectors.

A murine model of ornithine transcarbamylase (OTC) deficiency was used in this study to evaluate the efficacy of recombinant adenoviruses for correcting the metabolic defect in liver. Recombinant adenoviruses deleted in E1 and containing a human OTC cDNA expressed little functional OTC enzyme in vivo and had no observable impact on the underlying metabolic abnormalities of the OTC-deficient mouse (i.e. elevated urinary orotate and serum glutamine). E1-deleted vectors were improved through the use of the strong constitutive promoter from cytomegalovirus driving the normal murine homolog of OTC cDNA and the ablation of E2a with a temperature-sensitive mutation. Infusion of this improved vector into the mouse model was associated with a complete normalization of liver OTC enzyme activity that persisted for at least 2 months with complete but transient correction in serum glutamine and urine orotic acid. These studies illustrate the utility of improved adenoviral vectors in the treatment of liver metabolic disease.

Adenoviridae↗
PubMed1996

Regulated expression of cadherin-11 in human epithelial cells: a role for cadherin-11 in trophoblast-endometrium interactions?

Cadherin-11 is a novel member of the cadherin supergene family. Cadherin-11 expression is localized to mesenchymal tissue and specific regions of the neural tube during mouse embryogenesis. Here we report that cadherin-11 is spatiotemporally expressed in the epithelial cells of the human placenta. Cadherin-11 mRNA levels were low in freshly isolated cytotrophoblast cells but increased as the cytotrophoblast cells aggregated and fused to form syncytiotrophoblast cells in vitro. The increase in cadherin-11 mRNA levels was concomitant with a decrease in E-cadherin expression. Cadherin-11 was localized to the syncytial trophoblast and extravillous cytotrophoblasts, but not the villous cytotrophoblasts of the human placenta by immunohistochemistry. As both of the former cell types have intimate interactions with the endometrium, we examined cadherin-11 expression in the human endometrium. Cadherin-11 was detected in the glandular and surface epithelium of the endometrium at all stages of the menstrual cycle. However, cadherin-11 was abundant only in the stroma in the late secretory stage of the menstrual cycle. The accumulation of cadherin-11 in the stroma correlated with decidualization. Taken together, our observations demonstrate that cadherin-11 is expressed in certain epithelial cell lineages and suggest the possibility that cadherin-11 plays an important role in mediating trophoblast-endometrium interactions.

Blotting, Northern↗
PubMed1996

Histological predictors of active Helicobacter pylori infection.

Helicobacter pylori is a common cause of gastritis. No single test is 100% accurate for H. pylori diagnosis. In order to determine whether the presence of typical histological features of H. pylori gastritis may yield diagnostic information, we compared antral histology by H & E stain to the presence of organisms as detected on Thiazine stain of antral specimens, CLOtest, urea breath test and anti-H. pylori serology in 50 consecutive patients. Patients were diagnosed as having active H. pylori infection if at least two of these tests were positive. Patients with only one test positive (N = 5) were considered indeterminate for H. pylori and were excluded, resulting in 19 patients (42%) being classified as H. pylori positive. All slides were reviewed by a single blinded expert gastrointestinal pathologist and graded 0 (none) to 3 (severe) for the presence of acute (polymorphonuclear cells) or chronic (lymphocytes, monocytes, plasma cells) inflammation, lymphoid aggregates, and intestinal metaplasia. Active infection was associated with the presence of both acute and chronic inflammation (P < 0.0001) but not lymphoid aggregates (P = 0.09) or intestinal metaplasia (P = 0.10). The best positive predictors of infection were the presence of any acute inflammation (PPV = 86%) and the combination of any acute and chronic inflammation (PPV = 92%). The best negative predictor was absence of chronic inflammation (NPV = 100%). The presence of moderate to severe (grade 2 or 3) acute or chronic inflammation were each 100% predictive of infection. Moderate to severe chronic inflammation had both 100% sensitivity and specificity for active H. pylori infection, while moderate to severe acute inflammation was only 26% sensitive but 100% specific. The presence of any acute, or the combination of acute and chronic gastritis, is predictive of active H. pylori infection. Moreover, the predictive value correlates closely with the severity of the inflammation. The absence of chronic inflammatory cells rules out active H. pylori infection. These findings support the use of H & E histology-determined features in conjunction with other tests to diagnose H. pylori infection.

Antibodies, Bacterial↗
PubMed1996

New noninvasive tests for Helicobacter pylori gastritis. Comparison with tissue-based gold standard.

The current gold standard for diagnosing H. pylori gastritis requires antral biopsy for urease test (eg, CLOtest) and/or history. We compared this gold standard to a new low-dose capsule-based 1 microCi [4C]urea breath test (UBT) and a rapid serum test for anti-H. pylori antibodies (FlexSure HP) in 50 consecutive patients undergoing upper endoscopy. Antral biopsies within 3 cm of the pylorus were used for CLOtest and were stained with H&E and thiazine. Slides were reviewed by a single, blinded pathologist (Review) and compared to the pathology department report (Report). A true positive was defined as a positive CLOtest or Review. The prevalence of H. pylori infection by each test was: CLOtest 32%, Review 36%, gold standard 42%, UBT 38%, FlexSure HP 44%, Report 44%. UBT had sensitivity = 90%, specificity = 96%, positive predictive value = 95%, and negative predictive value = 93% and accurately determined H. pylori status in a subgroup of 10 patients who had completed treatment. The one false positive breath test occurred in a patient with 2+ chronic inflammation on biopsy and a positive antibody test. There were two false negative breath tests. Each had both negative CLOtests and negative antibody tests. FlexSure HP had sensitivity = 74%, specificity = 89%, positive predictive value = 88%, and negative predictive value = 77% in patients not previously treated, but had a high false-positive rate in the 10 patients after treatment. Pathology department Report and blinded pathologist Review had only 84% agreement, kappa = 0.67. Both CLOtest and UBT agreed better with Review (86%, 87%, kappa = 0.68, 0.73, respectively) than Report (78%, 77%, kappa = 0.53, 0.53, respectively) suggesting that Review is more accurate than Report. When biopsy is done, we recommend that a CLOtest be performed followed by histological examination if the CLOtest is negative to ensure adequate sensitivity. However, interpretation of histological slides has significant interobserver variability even in experienced hands and may be inaccurate at times. FlexSure HP has good PPV but inadequate sensitivity to rule out active infection and is not useful in patients after treatment. UBT is an excellent noninvasive test that should be considered in cases where EGD is otherwise not indicated.

Antibodies, Bacterial↗
PubMed1996

Quantitative evaluation of histological features in "time-zero" liver allograft biopsies as predictors of rejection or graft failure: receiver-operating characteristic analysis application.

Harvest injury in liver transplantation adversely affects both allograft function and subsequent acute rejection. The aim of this study was to use receiver-operating characteristic (ROC) analysis to determine the strength of histological features in time-zero liver allograft biopsies as predictors of subsequent acute rejection episodes or primary allograft failure. The study population consisted of 38 patients who underwent orthotopic liver transplantation between 1989 and 1992. Time-zero biopsies and all subsequent biopsies were retrospectively reviewed. The following time-zero histological features were graded: hepatocyte swelling, centrilobular necrosis, centrilobular hemorrhage, neutrophilic infiltrate, cholestasis, and number of apoptotic cells. Eleven transplants showed primary graft nonfunction; 15 experienced one or more episodes of moderate to severe acute rejection; 4 experienced only mild rejection episodes; and 8 showed no rejection over long follow-up periods. ROC analysis showed that the presence of hepatocyte swelling in the time-zero biopsy is a significant predictor of subsequent moderate to severe rejection. Apoptotic cells, centrilobular hemorrhage, hepatocyte swelling, and centrilobular necrosis were all significant predictors of primary graft failure. No histological feature was predictive of subsequent mild rejection. In conclusion, certain histological features serve as markers for adverse outcomes in the liver transplant population. Patients who show apoptotic cells, centrilobular hemorrhage and necrosis, or hepatocyte swelling in their time-zero biopsy should be monitored carefully for signs of graft failure and rejection.

Adult↗
PubMed1996

Role of eosinophils in uterine responses to estrogen.

Administration of estradiol (E2) to ovariectomized mice results in a dramatic increase in uterine growth and an influx of eosinophilic leukocytes. This influx is mediated by stimulation of an E2-dependent eosinophilic chemotactic factor in the uterus (ECF-U). The role of this eosinophil infiltration in uterus is presently unknown but could involve early growth and/or remodeling processes. In an attempt to better define eosinophil function in uterine tissue, we produced ovariectomized mice severely depleted of circulating eosinophils by administration of a purified rat IgG monoclonal antibody against interleukin-5 (IL-5). Seven days later, animals were submitted to estradiol treatment. Experimental groups included mice treated with saline alone, saline followed by E2, IgG followed by E2, and anti-IL-5 followed by E2. Pretreatment with IL-5 antibodies led to no significant alteration in E2-induced increase in uterine wet weight. However, histological evaluation demonstrated a clear and almost complete blockade of E2-stimulated influx of eosinophils in anti-IL-5 treated animals. In addition, IL-5 antibody administration significantly reduced E2-induced increase in peroxidase activity. Dramatic reduction of eosinophils did not affect E2 stimulation of ECF-U activity by stromal cells or complement C3 synthesis by the epithelial cells. Thus, it appears that differences in E2 responses in eosinophil-deficient mice are not directly associated with presence or absence of eosinophils. Taken together, these data suggest that eosinophils most likely do not contribute to early growth in the E2-stimulated uterus. A possible role in other events such as remodeling remains to be elucidated.

Animals↗
PubMed1996

Transduction of human trophoblast cells by recombinant adenoviruses is differentiation dependent.

To explore the feasibility of adenoviral (Ad)-mediated gene transfer to the human placenta, we examined the ability of two recombinant Ad vectors to transduce isolated human cytotrophoblast cells and two choriocarcinoma cell lines (BeWo and JEG-3, which have different potentials to undergo morphological differentiation in response to cAMP). Recombinant Ad efficiently transduced cytotrophoblast cells. However, there was a marked reduction in the transduction efficiency of these vectors after the terminal differentiation of the mononucleate cytotrophoblasts into multinucleate syncytial trophoblast. BeWo and JEG-3 cells were readily transduced with the recombinant Ad, but a striking reduction in transduction efficiency of the Ad vector was observed in BeWo cells following cAMP-stimulated cellular differentiation, which includes cell fusion to form syncytia. In contrast, JEG-3 cells, which are not induced to fuse in the presence of cAMP, did not show a reduced transduction efficiency when exposed to the cyclic nucleotide. Reporter gene copy number increased with Ad-mediated gene transfer into undifferentiated Bewo cells but was low in cells that had been previously exposed to cAMP. In contrast, both undifferentiated and cAMP-treated BeWo cells were capable of expressing a reporter gene when transfected with an Ad-based plasmid. Taken together, these results demonstrate that the reduction in transduction efficiency of the Ad vectors in cAMP-treated BeWo is the result of reduced infectivity rather than of a reduction in the transcription/translation efficiency of the exogenous genes. Our findings demonstrate that recombinant Ad vectors will not be useful for the transfer of genes into differentiated trophoblast cells because these cells are resistant to Ad infection. This may limit the utility of Ad-based vectors for placental gene therapy. However, we have documented that less-differentiated trophoblast cells are susceptible to Ad-mediated gene transfer. Our observations also suggest a mechanism by which differentiated human trophoblast cells resist Ad infection and prevent fetal infection by maternally derived Ad.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Expression of proliferating cell nuclear antigen in gastrointestinal tract lesions and its relationship to bcl-2 expression.

We report the relationship between proliferation as measured by the expression of proliferating cell nuclear antigen (PCNA) and the proto-oncogene bcl-2 in inflammatory and neoplastic lesions of the gastrointestinal tract and associated normal tissues. We found that (1) PCNA and bcl-2 are coexpressed in the stem cell-regenerative compartments of normal tissues but are not coexpressed in carcinomas or adjacent histologically normal epithelium, (2) there is marked heterogeneity of PCNA and bcl-2 expression in neoplastic lesions of the gastrointestinal tract, and (3) overexpression of PCNA is frequently seen in histologically inactive ulcerative colitis. We postulate (1) increased bcl-2 expression in epithelium adjacent to tumors represents an inherent change in the morphologically normal epithelium because it occurs without the corresponding high proliferative state seen in the normal crypt-regenerative compartment, (2) heterogeneity may provide a mechanistic explanation for chemotherapeutic resistance in tumors since cells having high bcl-2 but low proliferative activity would have prolonged survival and might show resistance to chemotherapeutic agents, and (3) the increased proliferative state in histologically inactive ulcerative colitis may provide a partial explanation for the increased risk of colon carcinomas in these patients.

Adenocarcinoma↗
PubMed1996

A rapid method for the detection of hepatitis C virus RNA by in situ hybridization.

The histologic detection of hepatitis C (Hep C) in paraffin-embedded tissue sections has been problematic. We describe the use of a rapid, i.e., less than 2 hours, in situ hybridization technique to detect Hep C by use of a manual capillary action system (MicroProbe Staining System) and a 24-base synthetic multibiotinylated oligonucleotide antisense probe from the prototype Hep C virus base sequence -16 to -13. This technique is rapid, i.e., it requires a 30-minute hybridization time and easily reproducible, and it uses a nonradioactive detection system, i.e., streptavidin-conjugated horseradish peroxidase. We tested formalin-fixed tissue from explanted human livers and found an overall sensitivity of 69%. Furthermore the technique is highly specific, with negative staining in normal liver tissue from four cases of partial hepatic resection for nontumoric diagnoses and in hepatic tissue obtained from cases of primary biliary cirrhosis, familial amyloidosis, and acute and chronic Budd-Chiari syndrome, for a total of seven confirmed Hep C-negative specimens. Staining with probes for Epstein-Barr virus NotI and EBER sequences was negative in Hep C-positive liver sections from both resected native livers at the time of transplantation and biopsy specimens from post-transplantation patients in whom Hep C has recurred. In those livers staining positively with probe against Hep C, the distribution was both patchy, i.e., staining only fairly well-preserved hepatocytes and not all hepatocytes, and intracytoplasmic, supporting the observations of previously published reports. Finally, the technique was employed on formalin-fixed liver biopsy specimens from four patients with recurrent Hep C; there was repeatedly positive staining in all cases. We think this technique could provide a clinically useful adjunct in the diagnosis of Hep C from formalin-fixed tissue from liver biopsy specimens and that it may be useful in the characterization of the pathophysiologic features of Hep C virus infection.

Base Sequence↗
PubMed1995

Receiver operating characteristic analysis of serum chemical parameters as tests of liver transplant rejection and correlation with histology.

Receiver operating characteristic (ROC) analysis was used to determine the strength of the serum chemical parameters alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase (GGT), total bilirubin, conjugated bilirubin, and the ratio of delta bilirubin to conjugated bilirubin as tests of acute cellular rejection in liver transplant patients. The study consisted of 70 liver biopsies performed between February 1989 and January 1992 on 37 transplant patients who were classified as showing either no rejection (35 biopsies) or moderate to severe rejection (35 biopsies); mild cellular rejection biopsies were not included in this study to highlight any differences between rejectors and nonrejectors. Corresponding serum values for liver enzymes, alkaline phosphatase, GGT, and bilirubin fractions were obtained on the morning of the biopsy. ROC analysis demonstrated that there is no single chemical parameter or combination thereof that can statistically or clinically distinguish patients with acute rejection from those with other etiologies of allograft dysfunction. We also assessed by regression analysis the correlation between histologic features in the biopsies and corresponding serum parameters. The degree of histologic cholestasis was compared with the same-day serum value for total bilirubin, alkaline phosphatase, and GGT. The degree of centrilobular necrosis and the number of apoptotic cells were compared with values for aspartate aminotransferase and alanine amino-transferase. There was no correlation between the serum values and histologic abnormalities. We conclude that serum chemistry values are not good tests for rejection or histologic abnormalities in the liver transplant population; liver biopsy should therefore be performed on a scheduled basis.

Alanine Transaminase↗
PubMed1995

Neonatal adenovirus infection: a case report with in situ hybridization confirmation of ascending intrauterine infection.

Adenovirus infection is a rare, but serious infection, during the neonatal period. The actual model of infection at birth is currently unknown, however, several mechanisms have been proposed. We describe a case of fatal neonatal adenovirus pneumonia in a 25-wk gestational age infant. Adenovirus was confirmed by electron microscopy and by in situ hybridization. The maternal cervical/endocervical smear taken prior to the delivery contained epithelial cells with changes suggestive of adenovirus, which was confirmed by in situ hybridization on the smear. These findings suggest that ascending viral infection is a factor in the pathogenesis of neonatal adenovirus infection. The identification and reporting of adenovirus may be important during pregnancy in order to avoid delay in delivery of the fetus once membranes have ruptured.

Adenoviridae↗
PubMed1995

Striking changes in the structure and organization of rat fetal membranes precede parturition.

Premature rupture of fetal membranes can harm infant and mother. It is unclear whether structural changes predispose these membranes to breaking. We thus assessed rat visceral yolk sac placenta (VYSP) and amnion by light and by transmission electron microscopy on Days 18-21 of gestation. Light microscope sections were stained for connective tissue (extracellular matrix) components: collagen, glycoprotein, and glycosaminoglycans/proteoglycans. Some tissue was incubated with chondroitinase ABC. We observed that fetal membranes became increasingly fragile, rupturing readily on Day 21. On Days 18-20, the two epithelial layers of the capsular VYSP were separated by a well-developed, well-vascularized connective tissue layer that stained intensely for all matrix components studied; on Day 21, the connective tissue layer was thinner, moderately stained, and less vascularized. On Days 18-20, the two cellular layers of the amnion were separated by a narrow, compact connective tissue layer that stained modestly for all matrix components; on Day 21, this area was widened and stained faintly. Transmission electron microscopy showed that collagen fibrils of the amnion were abundant, closely packed, and well organized on Days 18-20, whereas on Day 21 they were few in number, widely spaced, and disorganized. Similar changes were present after incubation with chondroitinase ABC. In addition, amniotic epithelial cells were moribund and delaminating, basal laminae were deteriorating or absent, and few cells were at the outer surface of the amnion. All changes preceded parturition. We conclude that the structural integrity of rat fetal membranes is impaired before birth through the loss of connective tissue components and cells, changes that presumably underlie membrane rupture. Lastly, the similarity of structural changes in rat and human fetal membranes point to the potential usefulness of the rat model.

Amnion↗
PubMed1995

Abdominal lymphangioma masquerading as a pancreatic cystic neoplasm.

Lymphangiomas are congenital abnormalities of the lymphatics that occur predominantly in the head and neck, most often in children. We present an unusual case of a middle-aged man who had a large septated cystic lesion adherent to the pancreas that could not be differentiated from a pancreatic cystic neoplasm despite analysis by ultrasound, computed tomography, magnetic resonance imaging, or percutaneous needle aspiration. The correct diagnosis was established only via laparotomy and subsequent pathologic interpretation. Although lymphangiomas are rare, they should be included in the differential diagnosis of pancreatic cystic neoplasms.

Biopsy↗
PubMed1995

Helicobacter pylori gastritis: radiographic findings.

PURPOSE: To determine whether there are useful radiographic criteria for diagnosing Helicobacter pylori. MATERIALS AND METHODS: Radiographs from double-contrast upper gastrointestinal examinations of 88 patients with H pylori and 41 control subjects were blindly reviewed. The results were analyzed by means of receiver operating characteristic (ROC) curves. RESULTS: Thickened gastric folds were detected in 39 patients with H pylori (44%) and nine control subjects (22%). The area under the ROC curve was 0.62 (standard deviation [SD] = 0.05, P < .01). Among the 48 subjects with thickened gastric folds, polypoid gastritis with thickened, lobulated folds was detected in 24 patients with H pylori (62%) and four control subjects (44%). The area under the ROC curve was 0.59 (SD = 0.05, P < .01). No substantial differences were observed in the frequencies of gastric ulcers, erosive gastritis, gastric narrowing, duodenal ulcers, duodenitis, and duodenal narrowing in patients with and without H pylori. CONCLUSION: The presence of thickened gastric folds was the best radiographic criterion for differentiating subjects with from those without H pylori.

Adult↗
PubMed1995

Colon cancer: morphology detected with barium enema examination versus histopathologic stage.

PURPOSE: To determine the relationship between the morphology of colon carcinomas detected with barium enema examination and the cancer stage. MATERIALS AND METHODS: Clinical, radiographic, endoscopic, surgical, and histopathologic findings were retrospectively reviewed in 152 patients with colon cancer detected with barium enema examination during a 2-year period. RESULTS: Eighty-six patients (57%) had lesions in the rectum and sigmoid and descending colon, and 66 (43%) patients had lesions more proximally in the colon. Lesions on the right side of the colon were less likely to cause symptoms than those on the left side. Eighty-one patients (53%) had annular or semiannular lesions, 57 (38%) had polypoid lesions, and 14 (9%) had plaquelike or carpet lesions. Six patients (4%) had Dukes stage A lesions; 84 (55%), Dukes stage B lesions; 42 (28%), Dukes stage C lesions; and 20 (13%), Dukes stage D lesions. CONCLUSION: Annular or semiannular carcinomas had higher rates of serosal invasion and lymph node metastasis than polypoid carcinomas, but the rates of liver metastases were comparable.

Adenocarcinoma↗