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Biomedical subjects

M Osborn

Publications and source records attributed to M Osborn.

At least 199 records · Page 11Linked to original sources

An F-actin- and calmodulin-binding protein from isolated intestinal brush borders has a morphology related to spectrin.

A high molecular weight protein from the brush border of chicken intestinal epithelial cells has been purified. This protein (TW 260/240), a complex of two polypeptides with apparent molecular weights of 260,000 and 240,000, accounts for a significant amount of the terminal web organization. TW 260/240 is an F-actin-binding protein that also interacts with calmodulin. Rotary shadowing reveals long flexible rods of double-stranded morphology tightly connected at each end. TW 260/240 is quite distinct from smooth muscle filamin and macrophage actin-binding protein (APB), but, in spite of its higher contour length (265 nm), seems to be related to erythrocyte spectrin (194 nm for the tetramer). Immunofluorescence microscopy with antibodies against TW 260/240 indicates the existence of a submembranous organization distinctly different from that of stress fibers. We have compared TW 260/240 with fodrin, a brain protein known to occur in submembranous organization but not previously characterized in molecular terms. TW 260/240 and fodrin are clearly distinct molecules but are similar in many aspects. Ultrastructural, biochemical and immunological results indicate three distinct classes of rod-like high molecular weight actin-binding proteins, possibly reflected by the prototypes filamin (ABP), spectrin and TW 260/240 (fodrin). The latter group may be responsible for calmodulin control of submembranous microfilament structures in various nonmuscle cells.

Actins↗

Expression of intermediate filaments in different human epithelial and mesenchymal tumors.

Fifty primary gastrointestinal and breast carcinomas, four embryonal rhabdomyosarcomas, six nonmuscular mesenchymal malignant tumors and one mesothelioma have been studied to determine what type of intermediate filaments they express, using affinity purified antibodies to prekeratin, vimentin and desmin and FITC or peroxidase labeled second antibodies. The tissues were alcohol fixed and paraffin embedded before use. In all carcinoma cases the tumor cells are stained by antibodies to prekeratin, while the vimentin antibody only decorates the stroma. Prekeratin positive tumor cells are not only seen in well differentiated tumors, but also in signet ring cell carcinomas. In the case of rhabdomyosarcoma the tumor cells clearly were decorated by antibodies to desmin, while the vimentin antibody only stained very few tumor cells. In cases of nonmuscular mesenchymal tumors, the tumor cells could only be labeled by antibodies to vimentin and not by antibodies to prekeratin or desmin. In biphasic tumors like mesothelioma, different parts of the tumor were separated by antibodies to prekeratin and vimentin.

Adenocarcinoma, Mucinous↗

The expression of different intermediate-sized filaments in human salivary glands and their tumours.

The intermediate-sized filaments can be divided into several groups which are characteristic of different types of tissues (e.g.: epithelial, mesenchymal, muscle, astrocytic and neural origin). Antibodies specific for some of these filament types have been used to analyse a group of salivary gland tumours. Prekeratin-positive cells were seen in the normal gland, cystadenolymphomas, mucoepidermoid tumours, and squamous cell carcinomas which are all tumours of epithelial origin. The pleomorphic adenomas showed the presence of some cells which appeared to contain both prekeratin and vimentin. The results are discussed with respect to their histogenetic implications.

Adenoma↗

Immunofluorescent localization of vimentin, prekeratin and actin during odontoblast and ameloblast differentiation.

The localization of constitutive proteins of different types of cytoskeletal components (prekeratin, vimentin, and actin) was examined in embryonic mouse molars using specific antibodies and immunofluorescence microscopy on frozen sections. Prekeratin and actin were found in the enamel organ. Preameloblasts demonstrated uniform staining, whereas ameloblasts demonstrated an apical accumulation of both prekeratin and actin. Vimentin and actin were observed in the dental papilla. A redistribution of vimentin accompanied the polarization of odontoblasts. A possible transmembranous control of cytoskeletal activities by the extracellular matrix is discussed.

Actins↗

In vitro differentiation of mouse teratocarcinoma cells monitored by intermediate filament expression.

Teratocarcinoma differentiation has been studied using sera specific for each of the five intermediate filament (IF) classes. These antibodies distinguish cells of epithelial, muscle, neural, astrocytic, and mesenchymal origin. In embryoid bodies, derived from embryo transplants and obtained in the ascitic fluid by transplantation of teratocarcinoma, the cells of the inner cellular mass did not express any of these intermediate filament types while the outer cells expressed cytokeratin. Intermediate filament expression in the embryoid body thus appears analogous to that in the blastocyst and differs from that in embryonal carcinoma (EC) lines. Twelve EC lines have now been shown to express vimentin although in some EC lines not all cells express vimentin. Other established permanent differentiated cell lines, derived from EC lines in vitro or from tumors in vivo, have been characterized with respect to the type of IF they contain. The distribution of different IF types has been examined in EC cells induced to differentiate by addition of retinoic acid. The proportion of cells expressing each type of intermediate filament appears to depend on the EC cell line used, on the inducing agent, and on the length of treatment. Thus, for instance, F9 cells express cytokeratin, PCC3 derivatives express vimentin, many 1009 derivatives express either glial fibrillar acidic protein (GFA) or neurofilament proteins. Overall the results obtained are in excellent agreement with emerging principles of intermediate filament expression during embryonic differentiation, thus emphasizing the potential use of the various EC lines to study differentiation in culture.

Animals↗

Adolescents who take overdoses: their characteristics, problems and contacts with helping agencies.

In a consecutive sample of 50 adolescents aged 13-18 admitted to hospital after taking overdoses, 90 per cent were girls. There were other clear differences between this sample and adolescents in general. Twenty-four per cent had visited their general practitioners in the previous week, and 50 per cent during the previous month. The most common difficulties preceding the overdoses were problems with parents, boys or girlfriends, and with school or work, including unemployment. A substantial proportion of the subjects had recent recurrent physical ill health. In the majority of cases the problems appeared to be transient so that one month later two-thirds of the adolescents had shown considerable general improvement. However, 14 per cent were referred to hospital for further self-poisoning or self-injury in the following year. The recent increase in the incidence of self-poisoning among adolescents suggests that more attention must be paid to this group in terms of both primary and secondary prevention.

Adolescent↗

Classification of adolescents who take overdoses.

A simple method of classifying adolescent self-poisoners into three sub-groups on the basis of the duration of their problems and the presence or absence of behavioural disturbance is described. The three groups differed markedly in terms of factors concerning their families, especially their relationships with their parents, and in their medical and psychiatric histories, the nature of their overdoses and the problems they were facing at the time. The treatment offered to members of the three groups also differed. The method of classification may offer a useful means of distinguishing between subjects in terms of outcome, including subsequent adjustment and repeat attempts.

Adolescent↗

Evaluation of a modified self-report measure of social adjustment.

A self-report Social Adjustment Scale (SAS-M) for use in British populations was devised by modifying the original North American version, its usefulness was evaluated among 331 women drawn from two local populations. In a group of mothers of one year old babies (n = 130), high levels of agreement were found between the subjects' self-ratings on the SAS-M and (i) a psychiatrist's ratings of their social adjustment made at interview; (ii) ratings of the subjects' social adjustment made by their husbands on the SAS-M; (iii) measures of concurrent mental state. In a group of women undergoing elective sterilization (n = 201), the SAS-M was found to be sensitive to changes in mental state over time. Possible application of the SAS-M in psychiatric research, particularly when an interview is not feasible, are discussed.

Age Factors↗

Motivational aspects of deliberate self-poisoning in adolescents.

A systematic study of 50 adolescent self-poisoners aged from 13 to 18 demonstrated considerable discrepancies between the reasons chosen by the subjects to explain the overdoses and those chosen by clinical assessors. Most adolescents indicated that they had been feeling lonely or unwanted, or angry with someone, and had taken the overdose to alleviate or demonstrate this distress. A third said they had wanted to die. In contrast, clinical assessors tended to attribute the overdose to punitive or manipulative reasons and suggested that only seven out of the 50 had wished to die. The adolescents rarely indicated that they had taken the overdose to get help; this may explain the resistance that may be shown to psychiatric intervention, that casts doubt on the possible effectiveness of preventive agencies. Modification of attitudes to both self-poisoning and early help-seeking may be a more effective means of prevention.

Adolescent↗

Antibodies to intermediate filaments as diagnostic tools: human gastrointestinal carcinomas express prekeratin.

Twenty-five primary gastrointestinal carcinomas have been studied using immunofluorescence microscopy with affinity-purified antibodies to prekeratin and to vimentin. The tissues were alcohol fixed and paraffin embedded before use. In all cases (i.e., one case of esophagal carcinoma, seven stomach carcinomas, and 17 large bowel carcinomas) the tumor cells are stained by antibodies to prekeratin. In cases in which only very few tumor cells are present, such as signet ring carcinoma, immunofluorescence with prekeratin antibody provides an easy way to visualize single tumor cells. When the same specimens were tested with antibodies to vimentin, the tumor cells were unstained, and only the fibroblasts and vessels of the stroma were decorated. Four of the tumors were also negative when tested with antibodies specific for either desmin, or glial fibrillary acidic protein or neurofilaments. Three metastases to the abdominal region from tumors originating in the ovary, stomach, and large bowel were like the primary tumors in that the tumor cells were positive when stained with antibodies to prekeratin and negative when tested with the antibodies to vimentin.

Adenocarcinoma↗

Centriole number and process formation in established neuroblastoma cells and primary dorsal root ganglion neurones.

Electron microscopy on serial sections has been used to compare the number and position of centrioles and processes in four neuroblastoma clones and in primary dorsal root ganglion neurones. Studies of Neuro-2a and NB41, as well as further experiments on N18 and N115 confirm that a sizeable percentage of the cells in all four neuroblastoma clones have multiple centrioles (2-12 per cell). No significant differences were seen between the number and arrangement of centrioles in the undifferentiated or differentiated states. In contrast primary dorsal root ganglion neurones, although characterized by multiple processes, exhibit only two centrioles per cell, usually located as a pair on one side of the nucleus. The observation that both dorsal root ganglion neurones, as well as neuroblastoma cells with only two centrioles were capable of multiple process formation suggests that multiple centrioles are not obligatory for multiple process formation. In addition no consistent relationship was seen between the location of the centrioles and the position of the processes casting further doubts on models which assume a direct relation between these characteristics.

Animals↗

Centrioles, microtubules and microfilaments in activated mononuclear and multinucleate macrophages from rat peritoneum: electron-microscopic and immunofluorescence microscopic studies.

In male Wistar rats of the BD I strain, mononuclear macrophages and multinucleate giant cells obtained from the peritoneum 1 day to 5 weeks after implantation of coverslips coated with dermoid cyst sebum, were examined by light microscopy and immunofluorescence microscopy, using antibodies specific for actin and tubulin and also by scanning and transmission electron microscopy. In activated mononuclear macrophages, microtubules radiate from the centrioles, situated in the perinuclear area, into the cytoplasm and the major cell processes. Microfilaments form a dense meshwork beneath the plasmalemma. When mononuclear macrophages fuse to form multinucleate giant cells, the initially unordered ("Foreign body") syncytia still reveal the original distribution patterns of centrioles, microtubules and microfilaments similar to those seen in the individual cells. In the ordered (Langhans) multinucleate giant cell all centrioles are accumulated in a main pluricorpuscular central group. Centrioles are the initiating and organising centres in the formation of microtubules. From the centrioles microtubules extend into the entire cytoplasm of the syncytium as a uniformly organised, stellate, radial system. The centrosphere, which is characteristic for ordered multinucleate giant cells, seems free from microfilaments, which form a ring-shaped woven network encircling the nuclei. Depolymerisation and inhibition of microtubules upon exposure to colchicine, indicates that both the organisation of the cytoplasm and the cellular movements depend on the undisturbed coordination of centrioles, microtubules and microfilaments. This applies also to the fusion of mononuclear macrophages to form syncytia, the ordering processes within multinucleate giant cells, and the function of ordered giant cells.

Animals↗