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Biomedical subjects

M Fogel

Publications and source records attributed to M Fogel.

At least 19 recordsLinked to original sources

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

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

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

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

Alpha smooth muscle actin (alpha-SM actin) in normal human ovaries, in ovarian stromal hyperplasia and in ovarian neoplasms.

An immunohistochemical investigation of alpha-smooth muscle actin (alpha-SM actin) using the monoclonal anti-alpha-SM-1 antibody was carried out in 15 normal ovaries, in three ovaries with stromal hyperplasia and in 27 neoplastic ovaries. In selected cases the pattern of actin isoforms was examined by means of 2 D-gel electrophoresis. In addition, the tissues were stained for vimentin and desmin. In normal ovaries alpha-SM actin was found in the inner cortex and in the theca externa. In ovarian stromal hyperplasia expression of alpha-SM actin was minimal or absent. In primary and metastatic epithelial tumors there was positive stromal staining for alpha-SM actin, especially in the vicinity of epithelial elements. This tended to be more widespread in malignant neoplasms. Thecomas did not express alpha-SM-actin and could thus be differentiated from leiomyomas which stained intensely for alpha-SM actin. Only focal stromal staining of alpha-SM actin was observed in granulosa and germ cell tumors. In all the tissues studied blood vessels were strongly positive for alpha-SM actin. Desmin, although present in the stroma of most of the specimens, was less abundant than alpha-SM actin. We concluded that alpha-SM actin is a component of the normal human ovary where it may contribute to the contractility of its stroma. Its absence in the normal outer cortex and theca interna, and in stromal hyperplasia and thecoma implies that sex hormones do not constitute a stimulus for alpha-SM actin production in the ovary. Among neoplasms it is most widely represented in the stroma of epithelial tumors in which it may reflect stromal stimulation mediated by neoplastic epithelium.

Actins

Cytokeratin patterns in the epidermis of human ovarian mature cystic teratomas.

Using a battery of monoclonal antibodies, we investigated the cytokeratin pattern in the epidermides of 12 human ovarian mature cystic teratomas (MCTs) and compared them with those of infant, adult, and fetal skin. Histologically, two types of epidermal layers were identified in the MCTs, a mature layer and an immature layer. The mature layer was similar to the epidermis of infants and adults, while the immature layer resembled stratified nonkeratinizing and metaplastic squamous epithelium. The cytokeratin pattern of the histologically mature epidermis in MCT was either similar to that in infants and adults or was of the fetal type. The cytokeratin expression of the histologically immature epidermis in MCT also showed many similarities to the fetal cytokeratin pattern. We conclude that histologic maturity of the epidermis in MCT is not necessarily expressed by the cytokeratin pattern, which reflects the state of molecular rather than histologic differentiation. Since prognosis in germ cell tumors is usually related to the degree of tissue maturation, our observations raise the possibility that the cytokeratin profile may eventually prove to be a valuable prognostic tool in some of the neoplasms that contain epithelial elements.

Adult

Chorangioma. A cytoskeletal profile.

Cytoskeletal typing of five chorangiomas revealed diffuse staining of the blood vessels with antibodies to vimentin and to alpha smooth muscle (alpha-SM) actin, while cytokeratin 18 decorated the blood vessels focally. Focal staining for desmin was observed in two chorangiomas. Blood vessels of the placentas in which these chorangiomas arose stained for vimentin and alpha-SM actin. In addition, there was positive staining for cytokeratin polypeptide 18 in blood vessels within the chorionic plate and anchoring villi, and occasional staining for desmin. The vasculature of the terminal villi lacked cytokeratins. The stromal elements of the chorangiomas stained for vimentin and focally for alpha-SM actin and cytokeratin 18. A similar staining pattern was also found in the placental stroma, with most of the cytokeratin positivity encountered in the chorionic plate and anchoring villi. Blood vessels in extraplacental hemangiomas were devoid of cytokeratins. These results indicate that chorangiomas originate most likely from blood vessels of the chorionic plate and anchoring villi, which, as chorangiomas, are the site of vascular cytokeratin expression.

Actins

Comparison of lip function: surgery vs radiotherapy.

This work was undertaken to compare lip function after surgery and after radiotherapy. In all, 37 patients were studied, 19 post-surgery and 18 after radiotherapy. Both physical lip parameters, such as intercommissural distance and soft tissue gape, as well as sensation and functional outcome, were assessed. The cure rates were found to be comparable in both groups. Our study shows functional benefits when radiotherapy is used as opposed to extensive surgery. This is due primarily to the loss of sensation and elasticity which follows surgery.

Aged

Job satisfaction among academic coordinators of clinical education in physical therapy.

The Academic Coordinator of Clinical Education is the physical therapy faculty member who is responsible for the clinical component of the curriculum. The responsibilities involved in the ACCE's job are such that ACCEs seem to be at risk for job dissatisfaction and burnout. The purpose of this descriptive study was to investigate the levels and patterns of job satisfaction among ACCEs in physical therapy. A questionnaire, including a 32-item job satisfaction inventory, was sent to the ACCE at each accredited entry-level education program for physical therapists and physical therapist assistants (N = 169). One hundred twelve (66.3%) responses were received and analyzed. Demographic characteristics of the respondents are reported. The results of the study showed that ACCEs, in general, expressed low levels of occupational dissatisfaction and burnout. Satisfaction with the aspects of the job involving self-esteem, achievement, and creativity seems to outweight dissatisfaction with the time available, the work load, and organizational efficiency. Those ACCEs with doctoral degrees expressed the highest levels of dissatisfaction and burnout. Those ACCEs working in entry-level master's degree programs expressed the lowest level of dissatisfaction; those in tenure-track positions expressed the lowest level of burnout. Factors contributing to job satisfaction and dissatisfaction are discussed.

Achievement

Characterization of two rat globin cDNA clones.

The rat globin gene system is suitable for studying a coordinated regulation of seven genes from two gene families. A rat reticulocyte cDNA globin library has been constructed and two clones analyzed in detail. pBRrg 5 contains alpha while pBRrg X contains beta type sequence. These cloned cDNAs will be useful probes of structure and function of rat globin genes. The deduced amino acid sequences extend the information about the variability of rat globin chains.

Amino Acid Sequence

Metastatic potential severely altered by changes in tumor cell adhesiveness and cell-surface sialylation.

A plastic adherent variant line (ESb-M) of a highly invasive and metastatic murine T cell lymphoma (ESb) was found to have lost its metastatic potential while still being tumorigenic in normal syngeneic hosts. The variant retained most of its ESb-derived antigenic and biochemical characteristics but differed at binding sites for certain lectins with specificity for terminal N-acetylgalactosamine residues. Whereas such sites were masked by sialic acid on metastatic ESb cells, they became unmasked on the adherent variant line. Metastatic revertants of ESb-M cells did not express the respective lectin receptor sites because these were again masked by sialic acid. It is suggested that the masking of specific lectin receptors sites on the tumor cell surface is of crucial importance for metastatis. If freely exposed, these sites may change adherence characteristics of the cells possibly not only in vitro (to plastic) but also in vivo.

Animals

Phenotypic and genotypic differences between high- and low-metastatic related tumor lines and the problem of tumor progression and variant generation.

We have described a number of phenotypic and genotypic differences between defined tumor sublines from the Eb/ESb model system that differ greatly in metastatic capacity. Some of these differences are summarized in Figure 5. It can be seen that the differences are both structural and functional. They include differences in the glycosylation of membrane glycoproteins as well as differences in total membrane protein composition. The functional differences refer particularly to enzymatic activities, cell motility, and invasive capacity. In addition, a change in membrane fluidity and membrane dynamics was seen when we investigated membrane vesicles shed spontaneously from these tumor lines. ESb type cells were found to shed about three times as much membrane material as the low-metastatic, Eb cells. Since such vesicles carried degradative enzyme activity, they could play a role in the invasion process. The vesicles also carried TATA and thus could also play a role in preventing immunological attack against these tumor cells. Another immunological escape mechanism was found to be based on the ability of the high-metastatic cells to generate immunoresistant variants that no longer expressed the respective TATA. A cytogenetic comparison of such immunoresistant variants with the TATA+ line revealed several chromosomal changes. The contribution of chromosomal rearrangements to the ability of malignant cells to generate variants was discussed.

Animals

Different patterns of lectin binding and cell surface sialylation detected on related high- and low-metastatic tumor lines.

We have analyzed cell surface-bound carbohydrates in two different model systems for metastasis composed of closely related tumor cell lines with differing metastatic potential. The first system studied was that of the DBA/2-derived T-lymphoma lines (Eb/ESb) and some recently established sublines of ESb with altered metastatic behavior (ESb-M and ESb-MR). The second system consisted of the highly metastatic MDAY-D2 cells, a wheat germ agglutinin-resistant low metastatic subline MDW40, and two metastatic revertants from the latter. The cells were stained with fluorescein isothiocyanate-conjugated lectins and analyzed by flow cytofluorography. All low-metastatic tumor lines expressed receptor sites for the lectins soybean agglutinin (SBA) and Vicia villosa (VV). The metastatic lines had the respective lectin binding sites blocked by sialic acid (SA). A good correlation was found within the cell lineages Eb leads to ESb leads to ESb-M leads to ESb-MR and MDAY-D2 leads to MDW40 leads to MDW40M1 between reactivity of SBA and VV and metastatic potential. The amount of neuraminidase-accessible SA was similar for all cell types (except MDW40) indicating differences in the positioning of SA. For high-metastatic ESb cells, the sialylation of SBA and VV receptor sites was paralleled by a relative decrease of SA associated with receptor sites for peanut agglutinin. Low-metastatic Eb cells, in contrast, had their peanut agglutinin receptor sites sialylated but expressed asialylated SBA and VV receptor sites. Eb cells were also found to have 2-fold higher activities in galactose-specific sialyltransferases. It is proposed that the differences in positioning of SA on the cell surface leading to masking or unmasking of terminal sugars could influence the metastatic potential of tumor cells.

Animals

Antigenic variation in cancer metastasis: immune escape versus immune control.

Antigenic variation in cancer metastasis was observed in a syngeneic murine tumor system consisting of a low metastatic parental tumor line (derived from a methylcholanthrene-induced DBA/2 T lymphoma, Eb), a high metastatic spontaneous variant thereof (ESb), and a low metastatic 'revertant' from ESb (ESb-M). All three lines expressed tumor-associated transplantation antigens (TATA) which elicited specific T cell-mediated antitumor immune reactions in the host. The strongest host response was elicited upon intradermal inoculation. It could be followed by (a) the infiltration of the locally growing tumor by host cells, such as lymphocytes and macrophages, (b) the establishment of specific systemic antitumor immunity, (c) the generation of immune cells capable of transferring protective antitumor immunity into a normal syngeneic recipient, and (d) the generation of tumor specific cytotoxic T lymphocytes (CTL). Anti-TATA CTL were used as typing reagents to investigate the stability or variability in the TATA expression by cloned tumor cell lines. Antigenic variability in the TATA expression was seen under various conditions: (a) clone-dependent variation in the sensitivity to anti-TATA CTL lysis upon prolonged growth in tissue culture, (b) qualitative change in the TATA (TATA1 leads to TATA2) upon successive i.p. transplantation of the parental Eb tumor line and, (c) generation of TATA negative immune escape variants (TATA2 leads to TATA-) during metastasis formation from a s.c. site. The relative inefficiency of specific immunization procedures against ESb was found to be due to the effective generation of TATA negative variants by this highly metastatic tumor. The balance between immune control and immune escape could be influenced to the advantage of the host by some means, for instance optimizing the route of antitumor-immune sensitization or by infusion of allogeneic but H-2 identical antitumor-immune T cells. Such immune cells recognized the tumor via minor histocompatibility antigens and thus circumvented the need of TATA recognition. Finally, manipulations at the cell surface of the highly malignant ESb tumor such as those introduced in the ESb-M variant were found to dramatically effect its metastatic potential.

Animals

Hormonal variations during sleep in men with erectile dysfunction and normal controls.

Five physically healthy young males suffering from erectile impotence and five normal controls of similar age are the subjects of this preliminary report. All were studied in the sleep laboratory during 3 to 5 nights with the last two devoted to sequential hormonal sampling by means of an indwelling venous catheter. Electroencephalogram, eye movements, and penile tumescence were monitored continually through the night. Plasma LH, FSH, and testosterone were measured every 20 minutes by radioimmunoassay. There were no differences between the patients with erectile impotence and normal controls in all sleep parameters investigated, including mean tumescent time, time in simultaneous REM and tumescence, and number of full and partial tumescent episodes. Marked fluctuations in plasma LH, FSH, and testosterone were observed during sleep without differences noted between the two groups. Mean plasma LH, but not FSH or testosterone, was significantly lower in the impotent men. There were no significant differences in mean plasma gonadotrophins and testosterone between tumescent episodes and nontumescent periods in either group. A significant relation was found in normals, but not in the men with erectile dysfunction, between the occurrence of REM sleep and abrupt elevations in testosterone. Testosterone levels during REM sleep with tumescence were also consistently higher than during the condition of non-REM without tumescence in the normal, but not in the impotent, group.

Adult