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Biomedical subjects

M Fogel

Publications and source records attributed to M Fogel.

At least 19 recordsLinked to original sources
PubMed2004

The role of L1 in the progression of ovarian carcinomas.

The L1 molecule has recently emerged as a promising new biomarker for the prognosis of human ovarian and endometrial tumors. It was initially described as an adhesion molecule for the development of the nervous system but its function in tumor cells is not well known. In this article we summarize recent data on the role of L1 in promoting tumor cell adhesion and migration and in gene regulation. We address the question how L1 determination in tumor tissue samples and in serum and ascites could potentially improve the disease management.

Biomarkers, Tumor↗
PubMed2003

[The relationship between osteoporosis, osteopenia and periodontitis].

A review of the literature on the reciprocal influence of osteoporosis and periodontitis. The imbalance in coupling of bone remodeling causes skeletal osteopenia and osteoporosis. Does the remodeling imbalance influence the oral bone? Both diseases are chronic, multifactorial and result at bone loss. In addition, the diseases share common risk factors such genetics, dietary, environmental and systemic factors. Different studies indicate that the skeletal bone loss in osteoporosis accelerate the decrease in bone density in oral bone. Although the differences in etiology between the two diseases some studies showed that treatment of osteoporosis improved the periodontal health. Further investigation of the mechanisms behind the relationship between osteoporosis and periodontitis may lead to common treatment strategies.

Alveolar Bone Loss↗
PubMed2001

Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins.

The L1 adhesion molecule plays an important role in axon guidance and cell migration in the nervous system. L1 is also expressed by many human carcinomas. In addition to cell surface expression, the L1 ectodomain can be released by a metalloproteinase, but the biological function of this process is unknown. Here we demonstrate that membrane-proximal cleavage of L1 can be detected in tumors and in the developing mouse brain. The shedding of L1 involved a disintegrin and metalloproteinase (ADAM)10, as transfection with dominant-negative ADAM10 completely abolishes L1 release. L1-transfected CHO cells (L1-CHO) showed enhanced haptotactic migration on fibronectin and laminin, which was blocked by antibodies to alpha v beta 5 and L1. Migration of L1-CHO cells, but not the basal migration of CHO cells, was blocked by a metalloproteinase inhibitor, indicating a role for L1 shedding in the migration process. CHO and metalloproteinase-inhibited L1-CHO cells were stimulated to migrate by soluble L1-Fc protein. The induction of migration was blocked by alpha v beta 5-specific antibodies and required Arg-Gly-Asp sites in L1. A 150-kD L1 fragment released by plasmin could also stimulate CHO cell migration. We propose that ectodomain-released L1 promotes migration by autocrine/paracrine stimulation via alpha v beta 5. This regulatory loop could be relevant for migratory processes under physiological and pathophysiological conditions.

Amyloid Precursor Protein Secretases↗
PubMed2000

Anticardiolipin autoantibodies in serum samples and cryoglobulins of patients with chronic hepatitis C infection.

OBJECTIVE: Chronic hepatitis C virus (HCV) has been linked to extrahepatic autoimmune phenomena. In addition, a variety of autoantibodies are found in patients with HCV. The prevalence, nature, and clinical significance of anticardiolipin (aCL) autoantibodies in serum samples of patients with HCV were therefore investigated. PATIENTS AND METHODS: A prospective study of 48 consecutive patients with chronic HCV with no evidence of previous hepatitis B virus (HBV) infection or any other autoimmune disorder. Thirty patients with HBV and 50 healthy volunteers matched for age and sex served as control groups. Anticardiolipin antibodies in the serum samples and cryoprecipitates were measured by a sensitive enzyme linked immunosorbent assay (ELISA). The beta(2) glycoprotein I (beta(2)-GPI) dependency was determined by carrying out aCL assays in the presence or absence of fetal calf serum samples. RESULTS: High levels of IgG aCL antibodies were detected in serum samples of 21/48 (44%) patients with HCV. These autoantibodies showed no beta(2)-GPI dependency. The control groups had much lower levels of aCL antibodies (20% in the patients with HBV and none in the normal volunteers). Cryoprecipitates from four patients with HCV (three aCL positive; one aCL negative) were further isolated. In two of the three aCL positive patients, specific cardiolipin reactivity was shown in the cryoprecipitates. The group of patients with HCV and aCL antibodies in their serum showed significantly higher total IgG levels, a higher incidence of antinuclear antibodies, and viraemia (HCV RNA) than the aCL negative patients. None of the patients with HCV and aCL antibodies showed any clinical manifestations related to those autoantibodies. CONCLUSIONS: This study clearly shows a high prevalence of IgG aCL antibodies in the serum of patients with HCV and the localisation of these antibodies in some cryoprecipitates. The role of these autoantibodies on the course of HCV infection and their clinical significance has not yet been determined.

Adult↗
PubMed1999

CD24 is a marker for human breast carcinoma.

CD24 is a small, mucin-type glycosylphosphatidylinositol-linked cell surface molecule expressed by neutrophils, pre B lymphocytes and certain human tumor cell lines. CD24 has been identified as a ligand for P-selectin in both mouse and human cells. We previously reported that the P-selectin-CD24 binding pathway is important for the binding of the breast carcinoma cell line KS to platelets and the rolling of these cells on endothelial P-selectin. In the present study we have analyzed the expression of CD24 on human breast carcinoma cell lines and on fresh breast carcinoma specimens using the CD24-specific antibody ML-5. Our study clearly demonstrates that CD24 is abundantly expressed on cell lines and fresh tissues of breast carcinomas. We find a differential expression of CD24 in breast carcinomas (cytoplasmic pattern) versus benign breast lesions (apical pattern). Moreover, the intensity of CD24 expression increases with the histological grade of the tumor. Thus, CD24 expression might be a useful marker for human breast carcinoma and play a role in facilitating metastasis by the interaction between tumor cells and platelets or endothelial cells.

Antibodies, Monoclonal↗
PubMed1998

A novel germ-line mutation in the noncoding region of the p53 gene in a Li-Fraumeni family.

We identified a novel germ-line p53 mutation in the noncoding, nonsplicing regions of a Li-Fraumeni family. Patients belonging to this family included pediatric medulloblastoma and rhabdomyosarcoma patients and a breast carcinoma patient. Three positions in the p53 gene were analyzed for loss of heterozygosity (LOH). One of the three loci retained heterozygosity, whereas the other two exhibited LOH. Sequence analysis of the third locus identified a change of 5'-CCGGGTGA-3' to 5'-CCAGGTTGGA-3', 63 bp downstream of exon 6. The mutation was identified in the germ line of the two pediatric patients and in each of the related parents. We excluded any additional mutation in the entire coding region of the p53 gene, including splice-site intronic sequences. Strong positive nuclear staining of the p53 protein was detected in both normal and tumor paraffin-embedded tissues. Eighty-five normal persons were negative for this alteration, which thus supports it as a mutation. These results may indicate that genetic changes within the noncoding region of the p53 gene may serve as an alternative mechanism of activating this gene. Mutations in the noncoding region of this gene should be further studied.

Adolescent↗
PubMed1998

Thyroid profile modifications during oral hormone replacement therapy in postmenopausal women.

There are few data available about changes in thyroid hormone profiles after hormone replacement therapy (HRT). We analyzed the effect of two different oral estrogens/progestins (E/P) associations on thyroid hormones and thyroxine-binding globulin (TBG) levels in 14 postmenopausal normal women distributed at random into two groups. Both groups received daily for a year 2 mg of estradiol valeriante per os. In Group A (n = 7), estrogen was associated with norethisterone acetate. In Group B, estrogen was associated with promegestone in a similar schedule to Group A. Blood samples were withdrawn to measure estradiol (E2), thyroxine (T4), triiodothyronine (T3), free T4 (fT4), thyroid-stimulating hormone (TSH) and TBG before and after 3, 6 and 12 months of treatment. Estradiol level increased significantly in both groups, being higher in Group A than in B. Under therapy, T4 and TBG levels were increased in both groups, but within the normal range. T4 mean level increased by 34% in Group A and 20% in Group B. TBG increment was slightly significant for Group A (p < 0.02); with only a trend in Group B (p = 0.08). T3, fT4 and TSH levels did not change significantly and remained within the normal range. Oral therapy with associated E/P produces moderate increases in T4 and TBG levels. Our results suggest that in postmenopausal women on oral HRT, fT4 and TSH levels are the most useful tools to evaluate the thyroid axis status.

Administration, Oral↗
PubMed1997

CD24, a mucin-type glycoprotein, is a ligand for P-selectin on human tumor cells.

P-selectin (CD62P) is a Ca2+-dependent endogenous lectin that can be expressed by vascular endothelium and platelets. The major ligand for P-selectin on leukocytes is P-selectin glycoprotein ligand-1 (PSGL-1). P-selectin can also bind to carcinoma cells, but the nature of the ligand(s) on these cells is unknown. Here we investigated the P-selectin binding to a breast and a small cell lung carcinoma cell line that are negative for PSGL-1. We report that CD24, a mucin-type glycosylphosphatidylinositol-linked cell surface molecule on human neutrophils, pre B lymphocytes, and many tumors can promote binding to P-selectin. Latex beads coated with purified CD24 from the two carcinoma cell lines but also neutrophils could bind specifically to P-selectin-IgG. The binding was dependent on divalent cations and was abolished by treatment with O-sialoglycoprotein endopeptidase but not endoglycosidase F or sialidase. The beads were stained with a monoclonal antibody (MoAb) to CD57 (HNK-1 carbohydrate epitope) but did not react with MoAbs against the sialylLe(x/a) epitope. The carcinoma cells and CD24-beads derived from these cells could bind to activated platelets or P-selectin transfected Chinese hamster ovary cells (P-CHO) in a P-selectin-dependent manner and this binding was blocked by soluble CD24. Transfection of human adenocarcinoma cells with CD24 enhanced the P-selectin-dependent binding to activated platelets. Treatment of the carcinoma cells or the CD24 transfectant with phosphatidylinositol-specific phospholipase C reduced CD24 expression and P-selectin-IgG binding concomitantly. These results establish a role of CD24 as a novel ligand for P-selectin on tumor cells. The CD24/P-selectin binding pathway could be important in the dissimination of tumor cells by facilitating the interaction with platelets or endothelial cells.

Amino Acid Sequence↗
PubMed1997

A novel germ line p53 mutation in intron 6 in diverse childhood malignancies.

Screening for p53 mutations in exons 5 to 8 in 124 pediatric malignancies identified 18 abnormal shifts using single strand conformation polymorphism: 12 were missense mutations and in 6, no mutation was detected in the exon or in the splice donor acceptor sequences. Sequencing was then performed in the adjacent introns, revealing a G to A base substitution at 39 base pairs upstream to exon 7. This mutation was identified in the germ line of five of the patients, and also in the father of one, whose parents were available. For comparison, of the 184 normal controls similarly screened, only one had this mutation (P=0.036). Positive staining of p53 protein was observed in three of the paraffin embedded tissues that were available: brain tumor, rhabdomyosarcoma, and lymphocytes from a normal lymph node from the rhabdomyosarcoma patient. All tumors with the identified intron mutation were Li-Fraumeni syndrome tumors. Sequencing of all exons including splice sites was performed and revealed no mutation. We suggest that this mutation in intron 6 of the p53 gene stabilizes the wild type p53 protein, resulting in its abnormal accumulation. Mutations in the noncoding region of p53 should be further studied.

Brain Neoplasms↗
PubMed1996

Anticardiolipin, but not the 16/6 Id anti-DNA antibody induces pregnancy failure.

The primary antiphospholipid syndrome or the antiphospholipid syndrome in systemic lupus erythematosus patients (defined as secondary antiphospholipid syndrome) are characterized by the presence of thrombosis, thrombocytopenia and recurrent fetal loss in association with anticardiolipin antibodies. To determine the causal role of these antibodies in the pathogenesis of pregnancy failure we studied the effects of immunization with monoclonal anti-DNA antibody (designated 16/6 Id; no cardiolipin reactivity) and anticardiolipin monoclonal antibody (designated 2C4C2; binds DNA as well) on the outcome of allogeneic pregnancies in BALB/c mice. Mating of BALB/c females 4 weeks after active immunization with the 16/6 Id, anti-DNA monoclonal antibody resulted in normal pregnancy outcome, similar to control mouse groups. In contrast to that, immunization with the 2C4C2 anticardiolipin antibodies resulted in severe gestational failure with low pregnancy rate, low numbers of fetuses and high rates of resorptions. The fertility index of those mice was extremely low as compared to the 16/6 Id-immunized mice or the control groups. Furthermore, a correlation was shown between the presence of anticardiolipin antibody levels in the sera of the mice at the time of gestation and the pregnancy fate. The 2C4C2-immunized mice which produced high levels of anticardiolipin antibodies demonstrated severe pregnancy failure, whereas normal gestations were observed in the 16/6 Id primed or the control mouse groups that did not produce measurable amounts of the latter antibodies. Thus, our studies demonstrate that anticardiolipin but not the 16/6 Id anti-DNA antibodies can induce severe gestational impairment.

Abortion, Spontaneous↗
PubMed1995

Three-dimensional reconstruction of MR images in congenital heart disease.

Commercially available software is now available for reconstructing three-dimensional (3D) tomographic slices. We have used these 3-D images for 8 years to enhance anatomic diagnosis and functional evaluation pre- and postoperatively in children with congenital cardiac and great vessel diseases. The advantages of 3-D imaging are reduced examination time, improved display of complex intracardiac relationships, better understanding of relationships between great vessels and adjacent major airways, and facilitated demonstration of cardiovascular anatomy for those unfamiliar with tomographic images.

Heart Defects, Congenital↗
PubMed1991

Congenital heart disease and fetal thoracoabdominal anomalies: associations in utero and the importance of cytogenetic analysis.

We examined the frequency with which congenital heart disease (CHD) and cytogenetic abnormalities were found associated with omphalocele, gastroschisis, duodenal atresia and posterior diaphragmatic hernias. We performed fetal echocardiograms on 80 patients with these diagnoses and found congenital heart disease in 13 of 37 with omphalocele (35%), 2 of 17 with gastroschisis (12%), 4 of 15 with duodenal atresia (27%), and 2 of 11 with posterior diaphragmatic hernia (18%). Karyotypes were obtained in 74 and were abnormal in 24 (32%). Although most fetuses with these extracardiac malformations and abnormal karyotypes had associated CHD, many did not. Normal karyotypes were found in 69% of fetuses with CHD and omphalocele, and 50% of fetuses with CHD and duodenal atresia. We conclude that CHD may be present in fetuses with extracardiac malformations whether or not the karyotype is normal and that the prenatal evaluation of fetuses with these lesions should include both karyotype and fetal echocardiography. Although karyotypes play an important role in prenatal diagnosis, they are not predictive of normal cardiac structure when normal in the abnormalities studied. Even when the karyotype is normal in the presence of these abnormalities, fetal echocardiography is indicated.

Abdominal Muscles↗
PubMed1991

Intermediate filament protein profiles of human testicular non-seminomatous germ cell tumors: correlation of cytokeratin synthesis to cell differentiation.

The patterns of cytoskeletal differentiation were studied in 20 testicular non-seminomatous germ cell tumors by immunohistochemistry, using diverse monoclonal antibodies specific for different intermediate filament (IF) proteins and for desmoplakin. Immunofluorescence and immunoperoxidase methods on both formalin-fixed and frozen tissues were applied, in some cases together with a gel electrophoretic analysis of IF proteins. The tumors examined included embryonal carcinoma (EC), endodermal sinus tumor (EST), choriocarcinoma and teratoma. Nine of the tumors were composed of only one histological type, the others showed mixed components. Cytokeratins 8 and 18 were identified in all these neoplasms, but their immunostaining was weak in ECs. Cytokeratin 19 was absent or very scarce in ECs, but strongly expressed in ESTs, choriocarcinomas and teratomas, thus allowing the identification of small EST and choriocarcinoma elements in ECs even when they were morphologically not obvious. Occasionally, some cells in ECs and ESTs also stained for cytokeratins 4 and/or 17, indicating potential for epithelial stratification. The majority of the germ cell tumors showed varied amounts of vimentin, often in co-existence with cytokeratins. Neurofilaments were demonstrated in scattered tumor cells in a single case of EST. In the teratomas studied, each type of tissue component present showed the expected IF protein. However, in many germ cell tumors some stromal cells and blood vessels contained, in addition to vimentin and desmin, also cytokeratins 8 and 18. This heterogeneity of the cytoskeletal profile of germ cell tumors is indicative of the varied differentiation potential inherent in these neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation↗
PubMed1990

Ovarian mucinous cystadenoma with leiomyomatous mural nodule.

A case of an ovarian mucinous cystadenoma with a leiomyomatous mural nodule is described. The diagnosis was confirmed by immunohistochemical methods. This is the first report of a mural nodule of leiomyomatous nature, thus widening the histologic spectrum that may be encountered in these lesions.

Cystadenoma↗
PubMed1990

Heterogeneity of intermediate filament expression in human testicular seminomas.

Testicular seminoma has in the past been considered to represent a germ cell tumor incapable of further differentiation. In recent years this view has been challenged on the basis of morphologic and chromosomal studies. Moreover, studies of intermediate filaments (IF) of seminoma cells have provided evidence of the capability of seminoma cells to differentiate in different directions. In the present study of the IF protein profile of 26 human testicular seminomas, using frozen as well as formalin-fixed, paraffin-embedded tissues, we report evidence of a heterogeneous differentiation potential inherent in these neoplasms. Thus, in 4 of the seminomas neither cytokeratins nor vimentin were detected; 3 showed vimentin positive cells but no cytokeratins; in 4 seminomas only cytokeratins were detected. In the remaining 15 cases both cytokeratins and vimentin were present, with occasional cells demonstrating coexpression of cytokeratin and vimentin. While the cytokeratins present were mostly of the "simple epithelial type", in 2 instances seminoma cells also contained cytokeratins 4 and 17, normally found in stratified and/or complex glandular epithelia. Furthermore, in 3 cases scattered tumor cells stained for desmin and in 2 other seminomas neurofilaments were identified. All of the cases showed variable positive staining for desmoplakins and desmoglein, indicative of the presence of desmosomes. It can therefore be concluded that, while some seminomas seem to be devoid of IFs, most of them show varied differentiation patterns usually with epithelial features but occasionally also with components commonly regarded as characteristic of myogenic or neurogenic differentiation. These observations may help to elucidate the relationship of seminomas to other germ cell tumors, and also contribute to our understanding of the histogenesis of these neoplasms.

Desmin↗