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Biomedical subjects

S Arber

Publications and source records attributed to S Arber.

15 recordsLinked to original sources
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↗
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?

Explore the source record for details and available documents.

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↗