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S Fligiel

Publications and source records attributed to S Fligiel.

At least 19 recordsLinked to original sources
PubMed2001

Prognostic significance of the labeling of Adnab-9 in pancreatic intraductal papillary mucinous neoplasms.

BACKGROUND: Pancreatic intraductal papillary mucinous neoplasms (IPMN), morphologically resembling colonic adenomas, often have an indefinable malignant potential. We used a monoclonal antibody (MAb) raised against colonic adenomas, Adnab-9, to identify patients with a better prognosis. METHODS: We assessed Adnab-9-labeled sections of these neoplasms from 50 patients, 13 pancreatic adenocarcinomas, and 32 colonic adenomas using standard immunohistochemical techniques. RESULTS: 26% of the IPMNs labeled with Adnab-9 as compared to 0% of pancreatic ductal cancers or surrounding benign tissues, (p < 0.001) and 53% of adenomas (p < 0.025). Labeling in IPMNs was usually seen in the noninvasive epithelium suggesting that Adnab-9 is a premalignant marker in these lesions. Labeling of invasive IPMN's identified a group of patients with a superior overall survival (p = 0.027). CONCLUSION: Adnab-9 labeling-characteristics appear similar for both IPMNs and adenomatous polyps, suggesting that they are analogous lesions. Adnab-9 labeling may also be a useful prognostic marker for invasive intraductal papillary mucinous neoplasms.

Adenocarcinoma, Mucinous↗
PubMed2000

Pulmonary-specific expression of SP-D corrects pulmonary lipid accumulation in SP-D gene-targeted mice.

Targeted disruption of the surfactant protein (SP) D (SP-D) gene caused a marked pulmonary lipoidosis characterized by increased alveolar lung phospholipids, demonstrating a previously unexpected role for SP-D in surfactant homeostasis. In the present study, we tested whether the local production of SP-D in the lung influenced surfactant content in SP-D-deficient [SP-D(-/-)] and SP-D wild-type [SP-D(+/+)] mice. Rat SP-D (rSP-D) was expressed under control of the human SP-C promoter, producing rSP-D, SP-D(+/+) transgenic mice. SP-D content in bronchoalveolar lavage fluid was increased 30- to 50-fold in the rSP-D, SP-D(+/+) mice compared with the SP-D(+/+) parental strain. Lung morphology, phospholipid content, and surfactant protein mRNAs were unaltered by the increased concentration of SP-D. Likewise, the production of endogenous mouse SP-D mRNA was not perturbed by the SP-D transgene. rSP-D, SP-D(+/+) mice were bred to SP-D(-/-) mice to assess whether lung-selective expression of SP-D might correct lipid homeostasis abnormalities in the SP-D(-/-) mice. Selective expression of SP-D in the respiratory epithelium had no adverse effects on lung function, correcting surfactant phospholipid content and decreasing phosphatidylcholine incorporation significantly. SP-D regulates surfactant lipid homeostasis, functioning locally to inhibit surfactant phospholipid incorporation in the lung parenchyma and maintaining alveolar phospholipid content in the alveolus. Marked increases in biologically active tissue and alveolar SP-D do not alter lung morphology, macrophage abundance or structure, or surfactant accumulation.

Animals↗
PubMed1999

Monoclonal antibody Adnab-9 defines a preneoplastic marker in epithelium at risk for adenocarcinoma of the small intestine.

Unlike colorectal cancer, risk markers for adenocarcinoma of the small intestine (ASI) have not been identified. Because the demographic and pathological features of both of these diseases are similar, immunohistochemistry was performed using monoclonal antibodies for three colonic premalignant markers, Adnab-9 (recognizes a colonic adenoma epitope), CaCo3/61, and FBB2/29 (small intestine proteoglycans expressed ectopically in colonic neoplasms), in normal and neoplastic small intestinal epithelium, and the results were compared with normal controls. Adnab-9 was also examined in 20 familial adenomatous polyposis (FAP) patients, a population known to be at an increased risk for ASI. Immunohistochemistry in normal and neoplastic tissue (adenoma, adenocarcinoma) from 18 patients with primary adenocarcinoma of the small intestine was compared with normal small intestine from 10 nonneoplastic controls. Four of 10 (40%) cases of normal small intestinal epithelium from controls were mildly positive in less than 10% of crypts, versus strong staining (>50% of crypts) in 16 of 18 (89%) patients with adenocarcinoma, and in 17 of 20 (85%) patients with FAP (P<.05). Adnab-9 predominantly stained Paneth cells as well as rare crypt and basal villous goblet cells. Adenomatous epithelium from the adenocarcinoma cases and adenomas from the FAP patients showed staining of Adnab-9 in 63% and 78% of cases, respectively. Only 17% of adenocarcinomas were positive for Adnab-9. In contrast, neither CaCo3/61 nor FBB2/29 showed any significant differences in the degree of staining in normal small intestinal epithelium in patients with adenocarcinoma compared with controls. Enhanced Adnab-9 staining in normal small intestinal epithelium from patients who harbor adenocarcinoma, and in FAP patients, supports its role as a risk marker of small intestinal neoplasia.

Adenocarcinoma↗
PubMed1992

Cellular distribution of a colonic adenoma-associated antigen as defined by monoclonal antibody Adnab-9.

Adenomatous colonic polyps constitute a precursor for colorectal cancer. Antibodies to these precancerous lesions might identify specific early tumor antigens. Adnab-9 is a murine monoclonal antibody raised against membranes of colonic adenomas. Adnab-9 binding in colonic washings (effluent) correlates with the presence of colorectal cancer. Immunohistochemical staining with Adnab-9 shows cytoplasmic reactivity in scattered cells in 4 of 31 adenomatous tissue sections, 0 of 14 sections of colorectal cancer cells, and 1 of 8 normal-appearing colonic mucosa specimens examined. Adnab-9 recognized a dominant M(r) 87,000 protein species in tissue extracts in the membrane-bound fraction of effluent by Western blotting. Adnab-9 binding by enzyme-linked immunosorbent assay in adenomatous extracts is higher than cancer or normal tissue, is membrane-bound, and is absent from established colorectal cancer cell lines. This distribution and nature of immunostaining suggest that Adnab-9 recognizes a determinant associated with the membrane component of a subpopulation of adenoma cells which may have a role in early colorectal neoplasia.

Adenoma↗
PubMed1991

Antisense-mediated reduction in thrombospondin reverses the malignant phenotype of a human squamous carcinoma.

Thrombospondin (TSP) is a trimeric glycoprotein which is synthesized and incorporated into the extracellular matrix by a wide variety of cells. TSP is involved in a number of cellular processes which govern tumor cell behavior including mitogenesis, attachment, migration, and differentiation. To directly assess the role of TSP in tumor cell growth and spread, a human squamous carcinoma cell line, with high TSP production and an invasive phenotype, was transfected with a TSP cDNA antisense expression vector. Five unique transfected clones were obtained with reduced TSP production. Expression of the transfected antisense sequence in these clones was verified by a ribonuclease protection assay. These clones demonstrated reduced growth rates in vitro when compared with a vector transfected control. After subcutaneous inoculation into athymic mice, the antisense clones formed either no tumors or tumors that were slow growing and highly differentiated. This contrasted with the vector-transfected clone which produced poorly differentiated, rapidly growing, invasive tumors. Our results argue in favor of a direct role for TSP in determining the malignant phenotype of certain human tumors.

Animals↗
PubMed1989

Attachment of neuroblastoma cells to extracellular matrix: correlation with metastatic capacity.

Extracellular matrix (ECM) serves important attachment functions during organogenesis in mammalian species. When layered on a plastic surface, ECM extracted from the rat lung, liver, or kidney enhances the attachment of C1300 murine neuroblastoma cells to that surface. Enhanced attachment to ECM by these cells correlates with their potential to form metastatic deposits in vivo. Conversely, neuroblastoma cells selected for increased metastatic potential by in vivo passaging demonstrate enhanced attachment to organ-derived ECM. However, although ECM provides attachment sites for these murine neuroblastoma cells, the attachment is not preferential for any of the organ ECMs tested (lung, liver, kidney). Histopathologic examination of the murine liver, lungs, and kidneys performed 20 to 22 days after intravenous inoculation of C1300 cells reveals notable metastatic seeding in each of these organs, but the liver clearly exhibits a greater degree of replacement by tumor metastases than the lungs or the kidneys. Therefore, the data from the attachment assays, coupled with the histopathologic findings obtained after tumor inoculation, suggest that although the ability to attach to ECM correlates with metastatic potential, additional factors are important in determining the preferential pattern of metastatic disease observed in murine neuroblastoma.

Animals↗
PubMed1987

Tracheobronchial changes in habitual, heavy smokers of marijuana with and without tobacco.

We performed flexible fiberoptic bronchoscopy in 29 habitual, heavy marijuana smokers 25 to 45 yr of age, with and without concomitant tobacco smoking, to inspect and biopsy their proximal tracheobronchial tree for the evaluation of histopathologic changes. Control tobacco smokers (TS) and nonsmokers (NS) residing in the same metropolitan area were similarly studied and compared with the marijuana smokers (MS) and marijuana-tobacco smokers (MTS). Respiratory and drug histories, physical examination, and pulmonary function tests were obtained prior to bronchoscopy. The prevalence of respiratory symptoms and pulmonary function abnormalities was generally higher in the 3 smoking groups than in the NS group but was not statistically different across all groups. However, bronchoscopic inspection revealed airway hyperemia and other visible abnormalities in 32 (91%) subjects in the 3 smoking groups, unlike the unremarkable findings in the NS group. Light microscopy showed 2 or more histopathologic changes in the bronchial epithelium of all MS, MTS, and TS. Squamous metaplasia was observed in all MTS, a prevalence that was significantly different from that in MS, TS, and NS. Hyperplasia of basal and goblet cells was more prevalent in the MS than in the NS, whereas cellular disorganization was more prevalent in the MS than in the TS. A direct relationship between cumulative marijuana use (joint-years) and bronchoscopic and histopathologic changes was not apparent in this study sample. These results indicate that relatively young, habitual, heavy marijuana smokers have a high prevalence of abnormal airway appearance and histologic findings, irrespective of concomitant tobacco smoking.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake.

We sought to clarify the impact of dietary restriction (undernutrition without malnutrition) on aging. Female mice from a long-lived strain were fed after weaning in one of six ways: group 1) a nonpurified diet ad libitum; 2) 85 kcal/wk of a purified diet (approximately 25% restriction); 3) 50 kcal/wk of a restricted purified diet enriched in protein, vitamin and mineral content to provide nearly equal intakes of these essentials as in group 2 (approximately 55% restriction); 4) as per group 3, but also restricted before weaning; 5) 50 kcal/wk of a vitamin- and mineral-enriched diet but with protein intake gradually reduced over the life span; 6) 40 kcal/wk of the diet fed to groups 3 and 4 (approximately 65% restriction). Mice from groups 3-6 exhibited mean and maximal life spans 35-65% greater than for group 1 and 20-40% greater than for group 2. Mice from group 6 lived longest of all. The longest lived 10% of mice from group 6 averaged 53.0 mo which, to our knowledge, exceeds reported values for any mice of any strain. Beneficial influences on tumor patterns and on declines with age in T-lymphocyte proliferation were most striking in group 6. Significant positive correlations between adult body weight and longevity occurred in groups 3-5 suggesting that increased metabolic efficiency may be related to longevity in restricted mice. Mice from groups 3-6 ate approximately 30% more calories per gram of mouse over the life span than did mice from group 2. These findings show the profound anti-aging effects of dietary restriction and provide new information for optimizing restriction regimes.

Aging↗
PubMed1985

Thymus involution in the acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome (AIDS) is a severe disorder of unknown etiology and pathogenesis, predominantly affecting homosexual males and other high-risk groups and characterized by profound alterations in T-lymphocyte function. The authors have examined thymus tissue from 14 patients who died of AIDS and compared the results with findings in five control groups: healthy age-matched controls, elderly individuals, patients with chronic or debilitating illnesses other than AIDS, infants with conditions causing "stress atrophy," and patients with myasthenia gravis. The AIDS group included 11 homosexual males, 1 Haitian, 1 homosexual who was also a drug abuser, and a 10-month-old infant believed to have contracted AIDS following blood transfusion. All the AIDS cases showed marked thymus involution with severe depletion of both lymphocytes and epithelial elements. The latter component consisted primarily of thin cords and nests of primitive-appearing epithelial cells that could be defined by positive immunohistochemical staining for keratin. Many cases showed a variable plasma cell infiltration, and the majority exhibited distinct vascular changes in the form of hyalinization and/or onion-skin patterns, primarily in the adventitia. Most striking of all was the marked paucity of Hassall's corpuscles; four patients had none at all, while in the other ten patients all the Hassall's corpuscles were calcified. These changes were far more extensive than those seen in any of the control groups, which retained most of their complement of Hassall's corpuscles even in the face of marked overall involution. The physiologic function of Hassall's corpuscles is not known, but recent immunohistochemical studies have implicated them in the synthesis of "facteur thymique serique" (FTS, thymulin) and other thymic hormones known to play a role in regulating T-helper and suppressor cell activity. It is conceivable that the extensive destruction of Hassall's corpuscles observed in AIDS may be a crucial element in the pathogenesis of this syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Mesangial fenestrations, sieving, filtration, and flow.

Small tracers in the circulation enter the rat mesangium rapidly and in large amounts that indicate a sizable plasma flow into the mesangium. Entrance is effected through mesangial fenestrations with a mean width in scanning electron microscopy of 376 A, a size similar to fenestrations in peripheral glomerular capillary walls. This is considerably smaller than the mean size of 678 A found with transmission electron microscopy, but the difference is probably due largely to the anionic surface coat on endothelial cells. Measurements of asymmetric thorium dioxide particles show that smaller ones with a mean length of 315 A enter the mesangium preferentially and that larger particles with a mean length of 405 A are partially restricted, supporting the idea that the measured width in scanning electron microscopy is close to the actual width in vivo. Fluid flow into the mesangium requires fluid flow out. The appearance time and accumulation of tracers suggest the following exit paths of flow from the mesangium: through the overlying epithelium into the urinary space contributing to glomerular filtration and concentrating large tracers beneath the basement membrane in the paramesangial region, into the efferent glomerular capillaries after tracers have been filtered out by the fibrillar matrix, and through the hilus into the juxtaglomerular apparatus (quantitatively small).

Animals↗
PubMed1984

Kaposi's sarcoma presenting as pulmonary disease in the acquired immunodeficiency syndrome: diagnosis by lung biopsy.

Kaposi's sarcoma frequently develops in patients with the acquired immunodeficiency syndrome (AIDS), and in most cases cutaneous lesions herald the disease. Although the lungs are often involved when the neoplasm becomes disseminated, it is rare for the initial diagnosis to be made by lung biopsy. This report describes two patients with AIDS in whom Kaposi's sarcoma was present in lung biopsy specimens and in whom there was no other systemic evidence of the neoplasm. Both patients experienced hemoptysis, and pulmonary hemorrhage accompanied the neoplasm in each case. Only five microscopic foci of tumor were found in a total of 44 sections of lung examined. The focal distribution of the lesions in the pulmonary interstitium and the presence of coexisting lung disease posed problems in the evaluation of the biopsies. Awareness of the appearances of Kaposi's sarcoma in lung tissue is important because the neoplasm will probably be encountered in lung biopsies with increasing frequency as more cases of AIDS are discovered.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Pathologic features of the lung in the acquired immune deficiency syndrome (AIDS): an autopsy study of seventeen homosexual males.

The lungs of 17 homosexual males who died of the acquired immune deficiency syndrome were studied to determine the type and extent of pulmonary disease present at autopsy. All patients had two or more pathologic processes, including one or more infections in their lungs. Cytomegalovirus pneumonia was the most common pulmonary infection identified at autopsy (15 patients) but was documented morphologically rarely during life (two patients). Most patients with Pneumocystis pneumonia had recurrent or persistent pneumocystosis. Although some of these individuals had evidence of early interstitial fibrosis, others showed complete resolution of the pulmonary changes. Diffuse alveolar damage was observed in 12 patients, and cytomegalovirus and/or Pneumocystis carinii was a likely etiologic agent in each instance. Mycobacterium avium-intracellulare infection was identified in four patients but was not associated with significant pulmonary alterations. Kaposi's sarcoma was found in the lungs of six patients. Early pulmonary involvement appeared as interstitial infiltrates with progression to nodular tumor masses obliterating the underlying lung. Pulmonary hemorrhage was an important complication of Kaposi's sarcoma involving the lung.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Acute megakaryocytic leukemia following chemotherapy for a malignant teratoma.

A 20-year-old man underwent systemic chemotherapy (four cycles of vinblastine sulfate, bleomycin sulfate, and cisplatin) following full resection of a malignant mediastinal teratoma without evidence of metastatic spread. Five months following this resection, pancytopenia, circulating blast cells, and bone marrow necrosis developed. An autopsy disclosed a disseminated megakaryocytic neoplasm. Although a cause-effect relationship is suggested, the duration between the institution of therapy and the appearance of this megakaryocytic malignant neoplasm is less than the latent periods previously reported for cases of therapy-related leukemias. This case is also compared with other reports of therapy-related hematopoietic disorders with prominent megakaryocytic proliferations.

Adult↗
PubMed1983

Multilocular cyst of renal hilum.

A case of a multilocular cyst in a sixty-three-year-old woman is reported. The cyst was located in the hilum of a kidney and was distorted but did not involve the renal pelvis or parenchyma. Although unique in location, it fulfilled all the criteria for a multilocular renal cyst.

Female↗
PubMed1983

Bronchopulmonary dysplasia in the adult.

We describe 3 patients with adult respiratory distress syndrome that eventuated in a pathologic picture of honeycomb lung and a radiographic picture of variably cystic lung super-imposed on a background of diffuse alveolar infiltrates. All 3 patients had been treated with unusually high pressures of PEEP as well as high concentrations of oxygen for long periods of time (3 to 7 wk). Microscopically, the cystic structures in our patients appeared to be derived from collapse and fibrosis of the alveolar parenchyma with dilatation of the alveolar ducts. We suggest that this process is morphologically and radiographically similar to bronchopulmonary dysplasia as seen in the newborn.

Adolescent↗