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S Arber

Publications and source records attributed to S Arber.

At least 19 recordsLinked to original sources
PubMed1996

Specificity of single LIM motifs in targeting and LIM/LIM interactions in situ.

The LIM motif defines a double zinc finger structure found in proteins involved in cell fate determination and growth control. LIM proteins, which include LIM homeo domain, LIM kinase, focal adhesion, and LIM-only proteins, usually contain two or more LIM motifs clustered at their amino- or carboxy-terminal end. At present, the mode of action of the LIM domain is not clear. In this study we have analyzed the binding properties of LIM motifs in the cellular environment. We show that MLP, CRP, and betaCRP define a subclass of LIM-only proteins with unique dual subcellular localization in the nucleus and along actin-based filaments in the cytosol. A double MLP construct that accumulated nearly exclusively along actin filaments promoted myogenic differentiation efficiently, arguing for a functional role of cytoskeleton-associated MLP. Binding of MLP to the actin cytoskeleton is specifically attributable to its second LIM motif. An additional LIM motif potentiates binding. Potentiating LIM motifs can be interchanged, resulting in differential targeting of interacting proteins. To analyze LIM-LIM interactions in situ, this property was exploited to develop a hybrid interaction approach based on the relocalization of LIM-containing constructs to the actin cytoskeleton. These experiments revealed the existence of marked selectivity in the interactions of single LIM motifs, and among LIM domains from different LIM-homeo domain and LIM-only proteins. Furthermore, the analysis suggested that the LIM motif has two interacting interfaces. On the basis of these findings, we propose that LIM motifs function as specific adapter elements to promote the assembly and targeting of multiprotein complexes.

3T3 Cells↗
PubMed1996

Integrating nonemployment into research on health inequalities.

An increasing proportion of the population is not currently employed; health inequalities research should include these people in analyses. Labor market position is the key determinant of health in Western societies; it is essential to clarify the independent effects of the three main components of labor market position: educational qualifications, occupational class, and employment status. These issues are addressed using national data from the British General Household Survey for 1991-1992 and two measures of ill-health: limiting long-standing illness and self-reported health. Occupational class is a stronger predictor than educational qualifications of measures of ill-health for men and long-term illness for women. When employment status is included in the models, the class gradient is weakened, suggesting that omitting the nonemployed from class analyses will produce a seeming weakening of class inequalities in health. The analyses show that class inequalities in health are somewhat greater for nonemployed than employed men, but weaker for nonemployed than employed women. In spite of older people having left the labor market many years earlier, class based on their previous occupation continues to have a major effect on their health. Class should be the primary variable in analyses of inequalities in health, and all groups of the nonemployed should be analyzed using their last main occupation.

Adult↗
PubMed1995

Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice.

Regulation of neurite outgrowth and structural plasticity may involve the expression of intrinsic determinants controlling growth competence. We have tested this concept by targeting constitutive expression of the growth-associated protein GAP-43 to the neurons of adult transgenic mice. Such mice showed striking spontaneous nerve sprouting at the neuromuscular junction and in the terminal field of hippocampal mossy fibers. In control mice, these nerve fibers did not express GAP-43, and did not sprout spontaneously. Lesion-induced nerve sprouting and terminal arborization during reinnervation were greatly potentiated in GAP-43-overexpressing mice. A mutant GAP-43 that cannot be phosphorylated by PKC had reduced sprout-promoting activity. The results establish GAP-43 as an intrinsic presynaptic determinant for neurite outgrowth and plasticity.

Animals↗
PubMed1995

Health inequalities in early adulthood: a comparison of young men and women in Britain and Finland.

Several studies have recently reported that social class differences in ill-health during adolescence are almost non-existent or invisible. The aims of this comparative study of two different welfare states are first, to compare whether the relationship between social class and health is similar among young men and women at different age groups in these two welfare states; second, to examine at what age social class differences in self-reported health and illness among young adults emerge in these two countries; and third, to find out whether class of origin (i.e. parental social class) or class of destination (i.e. individual's achieved social class) have greater explanatory power in studies of health among young adults. We used comparable nationally representative interview surveys from Britain and Finland. The British data is derived from the General Household Survey for 1988 and 1989, and the Finnish data from the 1986 Level of Living Survey. We analysed five year age groups between 16 and 39 years in Britain (N = 16,626) and 15 and 39 years in Finland (N = 5950). Two health indicators (limiting long-standing illness and self-assessed health), and several indicators for social class were compared. The best discriminator of differences in ill-health among young adults both in Finland and Britain was education. Social class differences by own occupation (achieved class) emerged soon after the age of 20 among men and women in both countries and strengthened with increasing age. There was a weaker but consistent association with class of origin in both countries. Housing tenure is strongly associated with young adults' health in Britain but not Finland.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Thrombospondin-4, an extracellular matrix protein expressed in the developing and adult nervous system promotes neurite outgrowth.

Extracellular matrix (ECM) molecules are involved in multiple aspects of cell-to-cell signaling during development and in the adult. In nervous system development, specific recognition processes, e.g., during axonal pathfinding and synaptogenesis involve modulation and signaling by ECM components. Much less is known about their presence and possible roles in the adult nervous system. We now report that thrombospondin-4 (TSP-4), a recently discovered member of the TSP gene family is expressed by neurons, promotes neurite outgrowth, and accumulates at the neuromuscular junction and at certain synapse-rich structures in the adult. To search for muscle genes that may be involved in neuromuscular signaling, we isolated cDNAs induced in adult skeletal muscle by denervation. One of these cDNAs coded for the rat homologue of TSP-4. In skeletal muscle, it was expressed by muscle interstitial cells. The transcript was further detected in heart and in the developing and adult nervous system, where it was expressed by a wide range of neurons. An antiserum to the unique carboxyl-terminal end of the protein allowed to specifically detect TSP-4 in transfected cells in vitro and on cryostat sections in situ. TSP-4 associated with ECM structures in vitro and in vivo. In the adult, it accumulated at the neuromuscular junction and at synapse-rich structures in the cerebellum and retina. To analyze possible activities of TSP-4 towards neurons, we carried out coculture experiments with stably transfected COS cells and motor, sensory, or retina neurons. These experiments revealed that TSP-4 was a preferred substrate for these neurons, and promoted neurite outgrowth. The results establish TSP-4 as a neuronal ECM protein associated with certain synapse-rich structures in the adult. Its activity towards embryonic neurons in vitro and its distribution in vivo suggest that it may be involved in local signaling in the developing and adult nervous system.

3T3 Cells↗
PubMed1994

Muscle LIM protein, a novel essential regulator of myogenesis, promotes myogenic differentiation.

Muscle LIM protein (MLP) is a novel positive regulator of myogenesis. Its expression and that of its Drosophila homolog DMLP1 are enriched in striated muscle and coincide with myogenic differentiation. In the absence of MLP, induced C2 cells express myogenin but fail to exit from the cell cycle and to differentiate. Over-expression of MLP in C2 myoblasts potentiates myogenic differentiation and reduces its sensitivity to TGF beta. Like MLP, single LIM domain deletion mutants of MLP and nonmuscle LIM-only proteins promote myogenic differentiation. In 3T3 fibroblasts, the same LIM proteins prevent phorbol ester-induced inhibition of DNA replication. These results establish MLP as an essential promoter of myogenesis and suggest that LIM-only proteins act via similar mechanisms to regulate aspects of cell differentiation.

Amino Acid Sequence↗
PubMed1993

Gender and inequalities in health in later life.

Little research attention has been given to examining inequalities in the health of elderly women and men, in spite of their high use of health services and the importance of health to maintaining independence in later life. This paper uses data from the British General Household Survey to analyse the variation in health of elderly women and men by class and material circumstances. Two measures of health are used; self-assessed health and functional disability. Elderly women assess their own health less positively than men, and are seriously disadvantaged compared to men in terms of functional disability. Class based on the individual's own previous main occupation is strongly associated with the two measures of health for elderly women and men at all ages. For elderly women, an 'individualistic' approach, using the woman's own last occupation, is compared with the 'conventional' approach of measuring class, which for married women uses their husband's last occupation and for other women their own last occupation. Using the two approaches makes little difference to the strength of association between class and health. Elderly women and men who live in advantaged material circumstances, in terms of income, car ownership and housing tenure, report significantly better health, after controlling for age and class. Level of functional disability is influenced by previous position in the labour market but not current material circumstances. Although elderly women suffer greater morbidity than elderly men, structural inequalities in health are equally pronounced for women and men in later life.

Aged↗
PubMed1993

Inequalities in women's and men's ill-health: Britain and Finland compared.

This paper examines inequalities in ill-health among men and women in Britain and Finland, using national survey data from the mid-1980s. Age-standardised illness ratios are compared followed by multivariate logistic regression analyses. The degree of social inequality in ill-health for women and men is greater in Finland than in Britain. British employed women in each class report less limiting long-standing illness than their Finnish counterparts. A major difference between the two countries is the poor health of British housewives. We relate these differences to societal variations in the participation of women in paid employment. In Finland women participate fully in paid work, whereas in Britain women are more likely to be full-time housewives or part-time employees. Unlike Finland, state provisions do not support the economic independence of British women. Structural variables, encapsulated by occupational class and employment status' are the primary factors associated with men's ill-health in Britain and Finland and also with Finnish women's ill-health. The difference between British and Finnish women is striking: class is associated with ill-health amongst women in both countries, but housing tenure and family roles are additional factors only among British women. In Britain, previously married women have particularly poor health. Our findings suggest that in a society such as Britain where paid employment is not universal for women, women's family roles and housing quality are associated with ill-health, but this is not the case in Finland, where women's participation in the labour market is near universal.

Adult↗
PubMed1992

s-cyclophilin is retained intracellularly via a unique COOH-terminal sequence and colocalizes with the calcium storage protein calreticulin.

Cyclophilins (cyclosporin A-binding proteins) are conserved, ubiquitous, and abundant proteins that accelerate the isomerization of XaaPro peptide bonds and the refolding of proteins in vitro. s-Cyclophilin is a member of the cyclophilin family with unique NH2- and COOH-terminal extensions, and with a signal sequence. We now report that s-cyclophilin is retained in the cell, and that the conserved s-cyclophilin-specific COOH-terminal extension VEKPFAIAKE is sufficient to direct a secretory protein to s-cyclophilin containing structures. Antibodies to s-cyclophilin-specific peptides were produced and the location of the protein was determined by an immunocytochemical study at the light microscopic level. s-Cyclophilin colocalized with the Ca(2+)-binding protein calreticulin and, to a lesser extent, with the microsomal Ca(2+)-ATPase in the myogenic cell line L6, and with the Ca(2+)-binding protein calsequestrin in skeletal muscle. In activated platelets, s-cyclophilin immunoreactivity was detected in a ring-like structure that might correspond to the Ca(2+)-storing and -releasing dense tubular network. In spreading cells, s-cyclophilin containing vesicular structures accumulated at actin-rich protrusion sites. While s-cyclophilin consistently codistributed with Ca2+ storage site markers, the distribution of s-cyclophilin immunoreactivity was not identical to that of ER markers. To determine whether the COOH-terminal extension of s-cyclophilin was involved in its intracellular transport we added this sequence to the COOH-terminus of the secretory protein glia-derived nexin. Appropriate constructs were expressed transiently in cultured cells and proteins were detected with specific antibodies. We found that glia-derived nexin with the COOH-terminal sequence VEKPFAIAKE (but not with the control sequence GLVVMNIT) colocalized with endogenous s-cyclophilin, indicating that the sequence contained retention information. These results indicate that s-cyclophilin is a retained component of an intracellular organelle and that it may accumulate in specialized portions of the ER, and possibly in calciosomes. Because of its conserved structure, widespread distribution, and abundance s-cyclophilin may be a useful marker to study the biogenesis and distribution of ER subcompartments.

Amino Acid Isomerases↗
PubMed1991

Women's lung cancer mortality, socio-economic status and changing smoking patterns.

Mortality data from the OPCS Longitudinal Study were used to determine whether the conventional classification of married women by their husband's occupation under-estimates the extent of social differences in lung cancer among this group. Differences existed for social class measures but alternatives based on housing tenure and car access defined socio-economic differences wider than any other previously recorded for England and Wales: married women living in rented housing and without a car were two and a half times as likely to die from lung cancer than those in owner occupied housing with access to a car. In 1957 and 1974 mothers of children included in the 1958 cohort study showed parallel socio-economic differences in smoking patterns as well as in uptake and cessation rates. Data from the General Household Survey for 1982 similarly suggest that cigarette smoking is more sharply differentiated using household rather than occupational measures of class. This suggests that wide differences in mortality are likely to persist through the eighties and beyond.

Adult↗
PubMed1991

Class, paid employment and family roles: making sense of structural disadvantage, gender and health status.

The British tradition of analysing differences in health has been dominated by class, with women belatedly entering this debate. The American tradition has been dominated by role analysis, with women's health considered primarily in terms of their marital, parental and employment roles, with recent research coming to contradictory conclusions. Research in both traditions has reached an impasse. This paper uses a sample of over 25,000 men and women from the 1985 and 1986 British General Household Survey to show how both traditions need to be reformulated and integrated. The ways in which family roles are associated with women's health status is determined by material circumstances, but the material circumstances cannot be captured by occupational class alone. Participation in the labour market and consumption divisions, in the form of housing tenure, are crucial additional indicators of structural disadvantage. Standardised limiting long-standing illness ratios and multivariate logit analysis confirm that occupational class and paid employment are the most important attributes associated with health status for women and men. Family roles are important for women; women without children and previously married women have particularly poor health status especially those not in paid employment and living in local authority housing.

Age Factors↗
PubMed1987

Social class, non-employment, and chronic illness: continuing the inequalities in health debate.

The 1981-2 General Household Survey showed steep class gradients in limiting longstanding illness for men and women aged 20-59 that were very similar to the class gradients in mortality in the 1979-83 decennial supplement. The class gradient for women classified by their husband's occupation was stronger than that when they were classified by their own occupation. Men and women who lacked paid employment reported poorer health than the employed and were concentrated in the lower social classes. Inequalities in ill health due to class were partly caused by the higher proportion in the lower social classes who were without work. Class differences in ill health still existed, however, among the currently employed, with unskilled men reporting particularly poor health and women manual workers reporting poorer health than women in non-manual jobs. Class differences were greater for the occupationless than for the currently employed. Thus class remains an important indicator of health inequalities despite the current high level of unemployment.

Chronic Disease↗
PubMed1987

What is a good GP?

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Appointments and Schedules↗
PubMed1985

The role of the receptionist in general practice: a 'dragon behind the desk'?

The power and influence of receptionists in general practice has been the subject of little research. We argue that the structural position of receptionists and the nature of primary medical care give receptionists a potential discretionary role in determining access to the general practitioner. A major criterion for access is the imputed urgency of the patient's condition, which frequently involves the receptionist making a medical assessment based on only a brief verbal exchange. The paper draws on interviews with a sample of over 1000 adults about their experiences of the reception process in general practice. The receptionist's role in the following areas is examined; delay in obtaining appointments, asking the reason for surgery consultations and home visits, reducing the number of home visits by suggesting patients attend the surgery, putting patients through to speak to the doctor on the telephone and giving health advice. Patients who have experienced receptionists as an active intermediary are more likely to report interaction difficulties with receptionists. The survey data lend support to two major findings: (1) that as practices become larger and more complex receptionists operate with more rigid rules, leading to greater hostility expressed by patients towards reception staff; and (2) parents with dependent children and young adults express more antagonism, because they are more likely to experience the receptionist as a 'gatekeeper' with whom they need to negotiate to see a doctor for acute care for themselves or for their children.

Adolescent↗