Biomedical subjects

F Fogt

Publications and source records attributed to F Fogt.

At least 55 records · Page 3Linked to original sources

PubMed1998

bcl-2 expression in normal adrenal glands and in adrenal neoplasms.

Archival paraffin-embedded tissue from 5 normal adrenal glands (including 1 from a fetus of 28 weeks' gestation), 6 cases of adrenal cortical hyperplasia, 9 cortical adenomas, 14 cortical carcinomas, and 11 pheochromocytomas were immunostained with monoclonal antibody against bcl-2. Ultrastructural localization of bcl-2 protein was also performed on selected cases. Positive immunostaining for bcl-2 was seen in all of the layers of the normal adrenal cortex, with different staining characteristics. bcl-2 expression was never observed in the normal adrenal medulla. Electron microscopic studies revealed bcl-2 to be localized predominantly to mitochondria, with a small number of labels along the nuclear envelope. Analysis of adrenal neoplasms showed expression of bcl-2 in cortical tumors, but only one positive case in pheochromocytomas. Restriction of bcl-2 expression to adrenal cortex-derived tissue versus adrenal medulla-derived tissue might prove to be helpful for the differential diagnosis between cortical and medullary tumors.

Adolescent↗

PubMed1998

Loss of heterozygosity and microsatellite instability in non-neoplastic mucosa from patients with chronic ulcerative colitis.

Microsatellite instability and allelic deletions of tumor suppressor genes have been observed frequently in tumors. Molecular pathogenesis of the development of dysplasia and carcinoma in ulcerative colitis is still unclear. In order to detect microsatellite alterations in ulcerative colitis, we analyzed loss of heterozygosity (LOH) and microsatellite instability (MI) on chromosomes 3, 6, 7, 12, and tumor suppressor gene loci, including p53, APC, and p16, of chronically inflamed, non-dysplastic epithelium after microdissection. Twelve of 13 (92%) cases showed LOH and/or MI at one or more loci. LOH at chromosome 3 and MI at chromosome 12 were observed in 50% and 62%, respectively. However, LOH at p53 and p16 was detected in only one case each. These results suggest that chronic inflammation may initiate microsatellite alteration, which subsequently transform ulcerative colitis to dysplasia or cancer. This finding provides information for the evaluation and treatment of patients with ulcerative colitis.

Journal Article↗

PubMed1997

A prospective analysis of the frequency, location, and curability of ectopic (nonpancreaticoduodenal, nonnodal) gastrinoma.

BACKGROUND: Extrapancreatic, extraduodenal and extralymphatic (ectopic) gastrinomas have been reported only rarely. The frequency, locations, and surgical outcome of these lesions are unknown. METHODS: From 1982 to 1997, 215 patients with Zollinger-Ellison syndrome were evaluated prospectively at the National Institutes of Health and 142 patients (66%) underwent standardized surgical exploration and resection. Eight patients (5.6%) (six men and two women; mean age, 41 years) had primary gastrinoma located in ectopic sites. Long-term follow-up was derived from a prospective database. RESULTS: Ectopic gastrinoma tissue was identified and resected in the liver (three patients), common bile duct (one patient), jejunum (one patient), omentum (one patient), pylorus (one patient), and ovary (one patient). Seven patients (88%) were cured biochemically after resection and five patients (63%) have sustained cures, with a mean follow-up of 7.5 years (range, 0.4 to 11.7 years). One patient with a jejunal primary gastrinoma had a biochemical recurrence at 2 years, and another with a primary hepatic gastrinoma had a recurrence 6 years after resection. A patient with a pyloric primary gastrinoma was not cured. CONCLUSIONS: Extraduodenal, extrapancreatic, and extranodal gastrinomas are encountered in 5.6% of patients who undergo exploration with curative intent. If no gastrinoma is found in the usual locations, other ectopic sites should be examined carefully. Resection of these primary ectopic tumors can lead to durable biochemical cures.

Adult↗

PubMed1997

Topoisomerase II alpha expression in normal, inflammatory, and neoplastic conditions of the gastric and colonic mucosa.

Topoisomerase II alpha (TP) excises and reconnects double-stranded super-coiled DNA during the replicative cell cycle. We studied the localization of TP and Ki-67 in inflammatory and neoplastic mucosal lesions of the stomach and of TP in similar conditions of the colon. TP expression was correlated with tumor stage, grade, and survival time in the colonic tumors to evaluate its potential utility as a predictive marker for clinical outcome. Forty-three sections of chronic gastritis, lesions indefinite for dysplasia, low- and high-grade dysplasia, and gastric adenocarcinomas were immunostained with antibody against TP and Ki-67. For the colon, 71 sections of normal mucosa, chronic colitis, hyperplastic polyps, adenomas, and carcinomas were examined; fresh tissue was analyzed by flow cytometry. Expression of TP in non-neoplastic gastric mucosa was maximal in neck/foveolar cells and focal in surface and deep gland cells. Increased surface and deep gland positivity was found in low-grade dysplasia and a diffuse distribution of positive cells in high-grade dysplasia and carcinoma. The Ki-67 staining pattern was similar. TP in non-neoplastic colon was restricted to the lower crypt zone; it was greatly expanded in the surface/upper crypt region in adenomas and was diffuse in carcinomas. Flow cytometric analysis revealed TP expression mainly in the S and G2/M phase, with higher labeling index in tumors. There was no correlation of TP with stage, grade, or survival times in the colonic tumors. Staining for TP and Ki-67 might help in the distinction of inflammatory and neoplastic lesions of the stomach and colon.

Antigens, Neoplasm↗

PubMed1997

Comparison of topoisomerase II alpha and MIB-1 expression in uterine cervical squamous lesions.

The aim of this study was to assess the role of MIB-1 in the classification of cervical squamous lesions and to compare it with a novel proliferation marker, topoisomerase II alpha (TP II alpha). We classified 46 archival uterine cervical cases into 6 groups: normal (n = 3); human papillomavirus (n = 15); mild (n = 10), moderate (n = 7), and severe (n = 6) cervical intra-epithelial neoplasia; and invasive carcinoma (n = 5). The formalin-fixed, paraffin-embedded tissue sections were stained with monoclonal antibodies to Ki-67 (MIB-1) and TP II alpha with a standard streptavidin immunohistochemical technique, with antigen retrieval to assess enzyme presence. The results were based on nuclear staining and percentage of positivity. We found that the mean percentage of positive nuclei increased from normal through increasing grades of dysplasia to its maximal level in invasive carcinoma. The level of positive nuclei in the epithelium also generally increased from basal to full thickness with progression of the lesions. The correlation between the percentage of nuclei positive for both antibodies with the use of linear regression was close, with an r value of 0.85. Our conclusions were that MIB-1 is an adjunct in the classification of squamous lesions of the uterine cervix and that TP II alpha is a useful proliferation marker in this setting.

Antigens, Neoplasm↗

PubMed1997

Allelic deletion and mutation of the von Hippel-Lindau (VHL) tumor suppressor gene in pancreatic microcystic adenomas.

An association between pancreatic microcystic (serous) adenomas (MCAs) and von Hippel-Lindau (VHL) disease has been suggested. However, genetic alterations of the VHL gene in MCAs of the pancreas have never been reported. In this study, we performed genetic analysis of 12 pancreatic MCAs. In 2 cases, VHL disease was documented clinically, and 10 cases were sporadic. For LOH analysis, tumor and normal pancreatic cells were procured from formalin-fixed, paraffin-embedded material using tissue microdissection. After DNA extraction, the samples were amplified by polymerase chain reaction using the polymorphic markers D3S2452, D3S1110, D3S192, and D3S656. In addition, the sporadic tumors were analyzed for VHL gene mutations using probes 3b/10b and K55/K56. Both MCAs associated with VHL disease showed LOH with at least one of the microsatellite markers tested. Among the 10 sporadic cases, 7 tumors showed LOH at the VHL gene locus. A somatic VHL gene mutation on exon 2 was documented in one sporadic case. The study provides the first direct genetic evidence for the role of the VHL gene in MCA tumorigenesis. Furthermore, VHL gene alterations may be detected in both VHL-associated and sporadic pancreatic MCAs.

Adenoma↗

PubMed1996

Alterations in nuclear ploidy and cell phase distribution of rat liver cells in experimental alcoholic liver disease: relationship to antioxidant enzyme gene expression.

The ability of a cell to withstand oxidative stress has been hypothesized to be related to its ploidy status. We used the intragastric feeding rat model for alcoholic liver disease to evaluate the relationship between severity of liver injury, antioxidant mRNA levels, and DNA ploidy of liver cells. Rats were fed ethanol with different dietary fats (saturated fat, corn oil, and fish oil); pair-fed control animals received isocaloric amounts of dextrose. All animals were euthanized at 1 month and had evaluation of pathologic changes in the liver, DNA content by flow cytometry, and mRNA levels for catalase and glutathione peroxidase. The fish oil-ethanol group exhibited the most severe pathology, the corn oil-ethanol group had intermediate pathologic changes, and no pathologic changes were seen in the saturated fat-ethanol and dextrose-fed controls. Flow cytometric analysis of propidium iodide-stained nuclei revealed that saturated fat-dextrose and corn oil-dextrose groups had about 65% of cells with (diploid) G1 DNA content and about 30% of cells with tetraploid (4C) nuclei. The fish oil-dextrose had a significantly higher (p < 0.001) number of 4C cells (67.4 +/- 2.1%) compared to the other two dextrose-fed groups. In the animals showing pathologic liver injury, there was a higher percentage of cells with hypertetraploid nuclei. The highest percentage of these hypertetraploid cells was seen in the fish oil-ethanol group. Catalase and glutathione peroxidase mRNA levels correlated significantly with polyploidy. A significant correlation was seen between the number of cells in the greater than G2 + M phase and glutathione peroxidase mRNA levels (r = 0.91, p < 0.01) and catalase mRNA. The different slopes of correlation analysis between catalase mRNA and dietary fats show that the degree of saturation of fatty acids may influence catalase mRNA expression in cells with different ploidy states. We propose that polyploidization of liver cell nuclei may serve as a defense mechanism against ethanol-induced hepatotoxicity. This defense mechanism may also, in part, account for the antiregenerative effect of ethanol on hepatocytes.

Animals↗

PubMed1996

Medium chain triglycerides and vitamin E reduce the severity of established experimental alcoholic liver disease.

Lipid peroxidation may be important in the pathogenesis of alcoholic liver injury. We investigated the potential of medium chain triglycerides and vitamin E to decrease lipid peroxidation and reverse established alcoholic liver injury. Four groups (five rats/group) of male Wistar rats were studied. Rats in group 1 were fed a fish oil-ethanol diet for 6 weeks. Rats in groups 2, 3 and 4 were fed the fish oil-ethanol diet for 6 weeks before being switched to fish oil-dextrose (group 2), fish oil-dextrose plus vitamin E (group 3) or medium chain triglycerides-dextrose (group 4) diets for 2 weeks. Liver samples were analyzed for histopathology, lipid peroxidation, fatty acid composition and cytochrome P450 2E1 activity. By 6 weeks, all rats developed fatty liver, inflammation and necrosis. After switching to the dextrose-containing diets, there was minimal histologic improvement in group 2, moderate improvement in group 3 and near normalization of the histology in group 4. Histologic improvement was associated with decreased lipid peroxidation and cytochrome P450 2E1 activity. Higher levels of polyunsaturated fatty acids were seen in groups 2 and 3 than in group 4. Our results indicate that a diet enriched in saturated (group 4) but not polyunsaturated (group 2) fatty acids effectively reverses alcoholic liver injury. Treatment with vitamin E also led to histologic improvement. These effects may be explained, at least in part, by down-regulation of lipid peroxidation. Other effects of medium chain triglycerides, such as their propensity for oxidation rather than esterification, may also be important.

Animals↗

PubMed1995

Intercellular adhesion molecule-1 expression in experimental alcoholic liver disease: relationship to endotoxemia and TNF alpha messenger RNA.

We used the intragastric feeding rat model for alcoholic liver disease to evaluate the relationship among intercellular adhesion molecule-1 (ICAM-1) expression, tumor necrosis factor-alpha (TNF-alpha), plasma endotoxin, and inflammatory changes in the liver. Rats were fed different dietary fats (saturated fat, corn oil, and fish oil) with ethanol; control rats were fed isocaloric amounts of dextrose instead of ethanol. At sacrifice the following were evaluated: liver pathologic changes, TNF-alpha mRNA by reverse transcription-PCR, plasma endotoxin, and ICAM-1 by immunohistochemistry and immunoblot analysis. Upregulation of ICAM-1 in endothelial lining cells in central and portal veins was observed in rats showing evidence of pathologic changes. Rats fed fish oil and ethanol, which exhibited the most severe inflammation, also showed hepatocyte ICAM-1 staining. The presence of ICAM-1 staining, in general, correlated with the level of TNF-alpha mRNA expression and plasma endotoxin levels. Upregulation of ICAM-1 in rats fed ethanol may contribute to the inflammatory changes seen in this model. The association between ICAM-1 upregulation and endotoxin and TNF-alpha mRNA suggests a role for these mediators in the inflammatory process in alcoholic liver injury.

Animal Feed↗

PubMed1995

Dietary saturated fatty acids: a novel treatment for alcoholic liver disease.

BACKGROUND & AIMS: Lipid peroxidation may be important in the pathogenesis of alcoholic liver injury. The purpose of this study was to determine whether a saturated fatty acid-based therapy (palm oil) could decrease lipid peroxidation and alcoholic liver injury during ethanol withdrawal. METHODS: Three groups of male Wistar rats (5 rats/group) were studied. Rats in group 1 were fed a fish oil-ethanol diet for 6 weeks; rats in groups 2 and 3 were fed a fish oil-ethanol diet for 6 weeks before treatment with fish oil-dextrose (group 2) or palm oil-dextrose (group 3) for 2 weeks. Liver samples were analyzed for histopathology, lipid peroxidation, fatty acid composition, cytochrome P450 2E1 activity, and tocopherol levels. RESULTS: By 6 weeks, all rats had developed fatty liver, inflammation, and necrosis. Group 2 showed minimal histological improvement, whereas group 3 showed near normalization of the histology. The improvement in group 3 was associated with decreased lipid peroxidation and P450 2E1 activity. Higher levels of omega-3 fatty acids were detected in group 2 than group 3. Tocopherol levels were similar among the groups. CONCLUSIONS: A diet enriched in saturated but not unsaturated fatty acids reversed alcoholic liver injury. This effect may be explained by down-regulation of lipid peroxidation.

Animals↗

PubMed1995

Nitric oxide production in experimental alcoholic liver disease in the rat: role in protection from injury.

BACKGROUND & AIMS: Regulation of blood flow and oxygen supply are important pathogenetic factors in alcoholic liver disease. Because nitric oxide may have an important role, its effects on alcoholic liver injury were investigated. METHODS: Rats were fed ethanol intragastrically with either saturated fat or corn oil. Spontaneous production of NO by liver nonparenchymal cells was compared in the two dietary groups. Two additional groups of rats fed corn oil and ethanol were treated with either an NO inhibitor (L-NAME) or supplemented with L-arginine. Liver pathology and plasma NO production were evaluated. RESULTS: In the corn oil and ethanol group, a progressive decrease in liver nonparenchymal cell NO production and increased plasma NO levels were associated with liver injury. Reduced nicotinamide adenine dinucleotide phosphate diaphorase staining showed increased centrilobular staining of hepatocytes in the corn oil and ethanol group and L-NAME-treated group. Moreover, L-NAME increased the severity, whereas L-arginine supplementation completely prevented liver injury. In the saturated fat and ethanol group, in which there was no liver injury, the levels of NO2- in nonparenchymal supernatant were 5-10-fold higher than in the corn oil and ethanol group. CONCLUSIONS: Decreased NO production by nonparenchymal cells may contribute to liver injury in ethanol-fed rats, and the compensatory increase in hepatocyte NO production may contribute to centrilobular liver injury.

Analysis of Variance↗

PubMed1995

Nucleolar organizer regions (AgNOR) and Ki-67 immunoreactivity in cutaneous melanocytic lesions.

A stepwise schema for the developmental biology of malignant melanomas has been proposed. In this study, two properties associated with malignant transformation--AgNOR production and Ki-67 immunoreactivity--were tested on a series of lesions representative of this model. Fourteen ordinary nevi (N), seven dysplastic nevi (DN), 12 radial growth phase melanomas (RGPM), and eight vertical growth phase melanomas (VGPM) were stained for AgNORs; Ki-67 immunoreactivity was determined in paraffin sections after antigen retrieval. AgNORs averaged 2.1 in N, 3.8 in DN, 5.4 in RGPM, and 7.3 in VGPM (p < 0.001 between all groups). Ki-67 immunoreactivity averaged < 1 in nevi, 1.6 in dysplastic nevi, 23.3 in RGPM, and 20.1 in VGPM. No difference was observed between N and DN, and RGPM/VGPM had higher Ki-67 indices than N/DN (p < 0.01). Stepwise increases in cellular AgNORs parallel the melanocytic progression model and thereby corroborate the intermediate nature of the dysplastic nevus. The order of magnitude increase in Ki-67 immunoreactivity observed in RGP and VGP melanomas compared with N and DN likely reflects the onset of loss of cell cycle control in these lesions.

Cell Cycle↗

PubMed1995

Apoptosis and bcl-2 protein expression in experimental alcoholic liver disease in the rat.

We used the intragastric feeding rat model to investigate the relationship between severity of alcoholic liver injury, apoptosis, bcl-2 protein expression, and lipid peroxidation. Rats were fed ethanol with different dietary fats (saturated fat, corn oil, and fish oil) for a 1-month period. Apoptosis was evaluated using an immunohistochemical method, and flow cytometry. Bcl-2 protein concentrations in liver were evaluated by Western blot analysis and lipid peroxidation by measurement of conjugated dienes. Pathological changes (fatty liver, necrosis, and inflammation) were present in corn oil-ethanol and fish oil-ethanol groups only. The highest number of apoptotic cells were seen in the group of rats exhibiting liver injury. The fish oil-ethanol-fed group had the highest concentrations of bcl-2 protein; this protein was localized in the bile duct epithelial and inflammatory cells. A significant correlation was seen between bcl-2 protein assessed densitometrically and the number of inflammatory cells/mm2 (r = 0.78, p < 0.02) and conjugated diene levels (r = 0.82, p < 0.01). Increased numbers of apoptotic cells were seen in rats developing ethanol-induced pathological liver injury. Increased bcl-2 protein concentration are associated with the presence of inflammatory cells and lipid peroxidation.

Animals↗

PubMed1995

Alterations in glucose transporter proteins in alcoholic liver disease in the rat.

We used the intragastric feeding rat model for alcoholic liver disease to investigate alterations in glucose transporter isoforms GLUT 1 and GLUT 2 in response to different dietary fats and ethanol. Six groups of rats (three rats/group) were fed ethanol or dextrose with either saturated fat, corn oil, or fish (menhaden) oil. All control animals were pair fed the same diets as ethanol-fed rats except that ethanol was isocalorically replaced by dextrose. In all animals, the following were assessed: pathological changes in the liver, immunohistochemical and Western blot analysis of GLUT 1 and GLUT 2 isoforms, and glycogen distribution. The most severe pathological changes were seen in fish oil/ethanol fed rats, moderate changes were seen in the corn oil/ethanol group and no changes were observed in the dextrose-fed or saturated fat/ethanol groups. In the groups of rats showing pathological liver injury (corn oil/ethanol and fish oil/ethanol), the depletion in liver glycogen was accompanied by decreased GLUT 2 expression and increased GLUT 1 expression. A decrease in glycogen and GLUT 2 expression was also seen in the fish oil/dextrose-fed rats. We hypothesize that the shift in glucose transporters from GLUT 2 to GLUT 1 probably reflects a compensatory response to attenuated gluconeogenic activity and to meet the increased intracellular demand for glucose. This demand for glucose in the presence of depleted glycogen may serve to provide a source for ATP synthesis in the centrilobular zone where hypoxia occurs secondary to ethanol metabolism.

Animals↗

PubMed1994

Neural cyst of the ovary with central nervous system microvasculature.

A case of a monodermal teratoma of the ovary composed solely of mature neuroglial elements is described. The cyst lining comprised ependymal cells surrounded by white matter which itself was resting on mesothelial cells. Astrocytes, oligodendrocytes, microglia and neurofilament-positive fibres were seen, but no neuron cell bodies were present. Immunohistochemical stains showed positivity for glial fibrillary acidic protein in ependymal, subependymal and the white matter regions while S-100 protein positivity was restricted to the white matter. Vessels within neuroectodermal tissue, but not those within the mesodermal tissue, stained positively for anti-glucose transporter protein, a marker shown to be present in vessels with barrier functions. We conclude that this is a rare case of monodermal teratoma consisting of purely mature brain tissue with a microvasculature exhibiting blood-brain barrier characteristics.

Adult↗

PubMed1994

Clival marrow changes in AIDS: findings at MR imaging.

PURPOSE: To determine the prevalence and clinical significance of marrow changes in the clivus identified at magnetic resonance (MR) imaging in patients with the acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: MR images of the head of 119 patients with AIDS and 119 control subjects were retrospectively reviewed. Marrow signal intensity patterns in the clivus of each patient were evaluated and scored as type 1 (homogeneous high signal intensity on T1-weighted images [normal]), type 2 (heterogeneous low signal intensity on T1-weighted images [abnormal]), or type 3 (homogeneous low signal intensity on T1-weighted images [abnormal]) and correlated with clinical parameters including CD4 counts, evidence of previous systemic disease, and presence of coexistent disease on corresponding MR head images. RESULTS: Abnormal clival signal intensity (type 2 and 3) was observed in 64 (54%) patients with AIDS and nine (7.5%) control subjects (P < .001), correlating with both a marked decrease in CD4 count (P < .001) and the presence of systemic disease (P < .001). CONCLUSION: Clival marrow signal abnormality is commonly identified in patients with AIDS and may be a marker of advanced disease.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Androgen receptor immunohistochemistry on paraffin-embedded tissue.

Androgen deprivation remains the primary therapy for patients with metastatic prostate cancer. Response to hormonal manipulation, however, has been quite variable. Androgen receptor (AR) expression has been used to predict clinical response to antiandrogenic treatment. However, methods of detection of AR expression have been limited to receptor biochemical assays in cytosolic or nuclear fractions of frozen tissue homogenates with obvious contamination problems by nonmalignant epithelial and stromal cells. As a result, studies correlating AR expression with response to hormonal therapy have been limited and controversial. More recently, immunohistochemical methods of analysis have become available, but only on frozen tissue. We describe a simple method to evaluate ARs on formalin-fixed, paraffin-embedded tissue sections using antigen retrieval methods. Primary, as well as metastatic, prostate carcinomas showed nuclear staining for ARs. Secretory cells stained uniformly in hyperplastic and normal prostatic glands. The majority of stromal cells had strong nuclear positivity. All other cancers tested (colon, breast, lung, skin, kidney) were negative. This immunohistochemical technique allows evaluation of prostate cancer AR status in routinely processed tissues. Thus, application of this technology to archival material should permit assessment of whether AR expression is predictive of response to endocrine therapy in advanced prostate cancer.

Adenocarcinoma↗

PubMed1994

Multiple large hyperplastic polyps of the colon coincident with adenocarcinoma.

Diminutive hyperplastic polyps are the most common non-neoplastic lesions of the colon. Typically, they are small (< 0.5 cm) sessile lesions, lack cellular atypia, and are found predominantly in the rectosigmoid region of the colon. Multiple large hyperplastic polyps (> 1 cm) are rare. Although the relationship between diminutive hyperplastic polyps and adenomatous polyps or carcinoma is controversial, even less data are available on the significance of large hyperplastic polyps. We report the case of a 56-yr-old man who was seen because of fatigue, anemia, and Hemoccult-positive stool. On air contrast barium enema study and colonoscopy, multiple polyps that were similar in appearance were found distributed symmetrically throughout the colon. However, histologic examination revealed 16 hyperplastic polyps 1-2 cm in size, multiple diminutive hyperplastic polyps, one adenomatous polyp, and one adenomatous polyp containing well-differentiated adenocarcinoma. Because multiple large hyperplastic polyps are rare, we suspect this entity may be distinct from diminutive hyperplastic polyps. In our patient, large hyperplastic polyps were distributed symmetrically throughout the colon and were associated with a synchronous carcinoma. Because large hyperplastic polyps may be coincident with adenomatous polyps and carcinoma of the colon, we recommend that patients found to have large hyperplastic polyps undergo removal of all polyps for histologic study.

Adenocarcinoma↗