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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

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

Enhancement of host cell reactivation of ultraviolet-irradiated Herpes simplex virus by caffeine, hydroxyurea and 5-bromodeoxyuridine.

Enhancement of host cell reactivation (HCR) of ultraviolet (UV)-irradiated herpes simplex virus (HSV) was demonstrated in cell cultures pretreated with caffeine, hydroxyurea, or 5-bromodeoxyuridine (BrdUrd). The effect of caffeine on HCR was shown to depend on the time of drug treatment with respect to infection. In cultures treated with caffeine during the course of virus replication, the infectivity of irradiated HSV was reduced about nine-fold, while cultures pretreated with the drug before infection showed an increase in infectivity. The extent of HCR enhancement depended on the time interval between treatment with caffeine and infection, drug concentration, and the UV irradiation dose to which HSV was exposed. Magnitude of enhancement of HCR by caffeine differed in various cell species. The results suggest that enhanced HCR of UV-irradiated HSV by DNA antimetabolities is associated with DNA repair activated in consequence of cell DNA damage.

Animals

Tumor-associated antigenic differences between the primary and the descendant metastatic tumor cell populations.

The existence of antigenic differences between cell populations in the local growth of the 3LL tumor (L-3LL) and its lung metastases (M-3LL) was studied. Normal C57BL/6 spleen cells sensitized in vitro for 5 days against L-3LL monolayers lysed preferentially L-3LL targets but not M-3LL tumor cell targets. Conversely, anti-M-366-sensitized lymphocytes killed M-3LL targets more efficiently than they killed L-3LL targets. Furthermore, spleen cells from mice bearing subcutaneous L-3LL tumors were significantly more cytotoxic to L-3LL targets than to M-3LL targets and vice versa. M-3LL cells were found also to be more resistant in vitro and in vivo to natural killer cells than were L-3LL tumor cells. M-3LL cells were more resistant than L-3LL cells to hybrid resistant mechanisms when they were inoculated into F1 (C3Heb x C57BL/6) or F1 (BALB/c x C57BL/6) mice. Anti-M-3LL lymphocytes generated both in vitro and in vivo, but not anti-L-3LL lymphocytes, admixed with L-3LL or M-3LL tumor cells and inoculated into footpads of syngeneic recipients suppressed the development of lung metastases. These results suggest that metastatic cells are indeed phenotypic variants of the local growing tumor cell populations. Presumably, these variants are selected for their capacity to home to and grow in the lungs, and for their resistance to specific immune effects initially evoked against the local tumor and to nonspecific natural killer cells. These data may prove to be of importance with respect to any rational approach to the problem of immunotherapy.

Animals

Differences in cell surface antigens of tumor metastases and those of the local tumor.

Tests were made to determine whether cell surface tumor antigens of metastases differed from the tumor antigens of the cell population of the local tumor growth. C57BL/6 mouse spleen lymphocytes sensitized against monolayers of the local growth of the 3LL Lewis lung carcinoma (L-3LL) in the presence of syngeneic serum generated lymphocytes that were cytotoxic to L-3LL but significantly less cytotoxic to target cells derived from lung metastases (M-3LL). Lymphocytes sensitized against M-3LL were significantly more cytotoxic against M-3LL than against L-3LL cells. Anti-M-3LL cytotoxic lymphocytes but not anti-L-3LL, admixed with either L-3LL cells or M-3LL tumor cells, when injected into syngeneic recipients reduced lung metastasis significantly. Results indicated that cells with high metastatic capacity and distinct antigenic properties exist within the tumor cell population and that immunoselection might be involved in the production of lung metastases.

Animals

Differences in resistance of metastatic tumor cells and cells from local tumor growth to cytotoxicity of natural killer cells.

Cells from local tumor growth (L-3LL) were compared to metastatic tumor cells (M-3LL) for their susceptibility to the cytotoxicity of natural killer (NK) cells. M-3LL cells were more resistant in vitro to NK cells from normal spleens than were L-3LL cells. A similar phenomenon of relative resistance of metastatic cells to NK activity was found when L-3LL and M-3LL cells were admixed with normal spleen cells and then inoculated into syngeneic mice. Because hybrid resistance was shown to be based on mechanisms that in principle are similar to mechanisms involved in NK activity, we tested the growth of M-3LL and L-3LL cells in semiallogeneic F1 mice. The in vitro effect of NK cells from semiallogeneic mice on M-3LL and L-3LL cells was tested in parallel. In vitro tests showed that irrespective of the haplotype of the spleen cell donors, L-3LL cells were more susceptible to NK activity than were M-3LL cells. In vivo experiments indicated that whereas M-3LL and L-3LL cells grew similarly in syngeneic recipients, M-3LL cells grew far more in F1 mice than did L-3LL cells. Thus metastatic cells are more resistant to NK activity than are cells of the local tumor growth. This relative resistance may determine, among other factors, the metastatic spread and progression of tumor cells.

Animals

Specific cytotoxic lymphocytes against syngeneic tumors are generated in culture in the presence of syngeneic, but not xenogeneic, serum.

Experiments were performed to test the effect of xenogeneic (fetal calf) serum (FCS) , as compared to syngeneic mouse serum (SMS) on the generation in culture of specific cytotoxic lymphocytes (CL) against syngeneic tumors. Sensitization in FCS against 3LL tumor cells resulted in CL cross-reacting with B-16 tumor cells and vice versa. Anti-syngeneic fibroblast CL also cross-reacted with 3LL. Such cross-reactivities were shown to be derived from CL directed against FCS determinants. In contrast, sensitization in the presence of SMS resulted in CL directed against tumor-specific antigens. Anti-3LL generated in SMS lysed 3LL targets but not B-16, and anti-B-16 lysed B-16 but not 3LL. The two types of CL had two distinct reactivities in vivo. Anti-3LL CL generated in FCS enhanced tumor growth in vivo, whereas anti-3LL CL generated in SMS had an inhibiting effect on the growth of tumor cells. These results indicate that the application of syngeneic serum during in vitro sensitization against syngeneic tumors may open up new possibilities for the analysis of tumor-specific antigens and for eliciting specific immune reactions against such antigens.

Animals

Pituitary-gonadal function in XYY and XXY men identified in a population survey.

Evidence on pituitary-gonadal function in XYY subjects has been inconclusive and based, for the most part, on selected samples such as institutionalized individuals or subjects examined for particular behavioural or medical characteristics. We report the results of a double-blind hormonal study of a sample from an entire well-defined birth cohort of men. The starting population included all males born in Copenhagen during the period 1944-1947 comprising 31,436 individuals. Chromosome determinations conducted on 4139 men representing the top 15.9% of the height distribution of the sample identified 12 XYY and 16 XXY men. All the XYY subjects and 14 XXYs consented to participate in an individual case study and were individually matched to XY controls selected from the total sample. The XYY men had significantly higher plasma concentrations of LH, FSH and testosterone than matched XY controls. There were no differences in testicular size and in the reported number of children between the XYYs and control group. XXY men from the same population showed significantly higher LH and FSH, lower concentrations of testosterone, had smaller testes and reported fewer children than their matched controls.

Adult

Effect of caffeine on the replication of nonirradiated and ultraviolet-irradiated cytomegalovirus.

The effect of caffeine on cytomegalovirus (CMV) replication in human embryo lung (HEL) and human embryo kidney (HEK) cells was studied. In HEL cultures, nonirradiated CMV yielded up to 6.7 times more plaques in caffeine-treated cultures than in control cultures. Virus growth curves exhibited different profiles, depending on the time of treatment of the cultures with the drug. Incorporation of [3H]TdR into virus DNA was enhanced and began about 24 h earlier in the caffeine-treated cultures than in the untreated cultures. A relationship between decreased incorporation of [3D]TdR into cellular DNA caused by caffeine and increased virus replication was observed in the HEL cells. In caffeine-treated HEK cultures, CMV replicated better than in untreated cultures in which virus growth was transitory and decreased after 10 days of incubation. The infectivity of CMV irradiated with UV light doses of 3,120-12,480 erg/mm2 decreased as a function of the UV dose. The extent of multiplicity reactivation of the irradiated virus increased when irradiated with higher UV doses. The effect of caffeine on the infectivity of UV-irradiated CMV depended on the dose with which the virus was irradiated. Caffeine increased the infectivity of CMV irradiated with lowest UV dose (3,120 erg/mm2) but did not increase the infectivity of virus irradiated with 12,480 erg/mm2. Multiplicity reactivation of the UV-irradiated CMV was inhibited by caffeine regardless of the UV dose with which the virus was irradiated.

Caffeine