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Biomedical subjects

M A Hall

Publications and source records attributed to M A Hall.

At least 37 records · Page 2Linked to original sources
PubMed2000

Genetic polymorphism of IL-12 p40 gene in immune-mediated disease.

Understanding of the genetic basis of autoimmune diseases is currently incomplete. Cytokine gene polymorphisms warrant consideration as factors explaining variation in the human immune and inflammatory responses and as candidate susceptibility genes for related pathological states. Interleukin 12 (IL-12) is a key regulator of the polarisation of immune responses to T helper 1 or 2 categories and plays a role in autoimmune and infectious diseases. Using a bioinformatic strategy, we aligned cDNA and expressed sequence tag sequences to identify putative polymorphic regions of the IL-12 p40 gene. Position 1188 in the 3' untranslated region (UTR) was polymorphic with the frequency of the common allele around 80% in healthy UK Caucasoids. PCR genotyping of multiple Caucasoid groups and an African group showed significant population variation. In a case-control design, the polymorphism was not associated with rheumatoid arthritis, Felty's syndrome or large granular lymphocyte syndrome with arthritis or multiple sclerosis. A nonsignificant increase in the B allele frequency was observed in the rare large granular lymphocyte syndrome without arthritis (odds ratio 2.02 95% CI 0.95-4.3). This new genetic marker could be useful in anthropological studies and should be investigated in other autoimmune, allergic, inflammatory and infectious diseases.

Alleles↗
PubMed2000

Genetic influence on peripheral blood T lymphocyte levels.

T lymphocytes are a major component of the adaptive immune system. CD4 positive T cell subpopulations regulate B cell and macrophage effector function while CD8 positive T cells are largely responsible for anti-viral cytotoxic activity. The degree of natural variation in the levels and ratios of the various T cell subpopulations is a possible risk factor for the development of autoimmune disease, infectious disease and cancer. There is some evidence from studies of inbred strains of mice and humans which suggests that variation in T cell subpopulations is genetically influenced. However, family studies alone cannot distinguish between common environmental and shared genetic influences and provide less robust estimates of the heritability than twin studies. To comprehensively examine genetic influences on a selection of important T cell phenotypes, we investigated variation in levels of total lymphocytes, CD3+, CD4+, CD8+, CD3+CD4+, CD3+CD8+ lymphocytes and in CD4:CD8 ratio as a proportion of lymphocytes and of T cells using the classical twin model approach. Healthy female twin pairs were sampled from the St. Thomas' UK Adult Twin Registry. A maximum of 103 monozygotic (MZ) and 186 dizygotic (DZ) twins aged 18-80 years participated in the study. Whole blood samples were analysed for T cell subsets by flow cytometry. The relative genetic contribution to these phenotypes was estimated using a variance components model-fitting approach. Heritability estimates were calculated of 65% for CD4:CD8 T cell and lymphocyte ratios, around 50% for absolute lymphocyte, CD3+ and CD4+ counts, and 56% for CD8+ numbers. Unique (rather than shared) familial environment explains the remainder of the variance. Genetic factors have a major influence on the variation in peripheral T cell subset numbers. Polymorphism dictating such variation should be taken into account when assessing risk factors for T cell immune-mediated disease with a genetic background.

Adolescent↗
PubMed2000

Laws restricting health insurers' use of genetic information: impact on genetic discrimination.

Since 1991, 28 states have enacted laws that prohibit insurers' use of genetic information in pricing, issuing, or structuring health insurance. This article evaluates whether these laws reduce the extent of genetic discrimination by health insurers. From the data collected at multiple sites, we find that there are almost no well-documented cases of health insurers either asking for or using presymptomatic genetic test results in their underwriting decisions, either (a) before or after these laws have been enacted or (b) in states with or without these laws. By using both in-person interviews with insurers and a direct market test, we found that a person with a serious genetic condition who is presymptomatic faces little or no difficulty in obtaining health insurance. Furthermore, there are few indications that the degree of difficulty varies according to whether a state regulates the use of genetic information. Nevertheless, these laws have made it less likely that insurers will use genetic information in the future. Although insurers and agents are only vaguely aware of these laws, the laws have shaped industry norms and attitudes about the legitimacy of using this information.

Genetic Counseling↗
PubMed2000

Audit of rheumatology services for adolescents and young adults in the UK. British Paediatric Rheumatology Group.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is associated with significant morbidity in adulthood with at least one third of children continuing to have active inflammatory disease into their adult years and up to 60% of all patients continuing to have some limitation of their activities of daily living. A survey of service provision for these young people in the transition from paediatric to adult rheumatology care was therefore undertaken. METHODS: A postal questionnaire was sent to all 92 members of the British Paediatric Rheumatology Group, representing 61 units providing a paediatric rheumatology service in the UK and Eire. RESULTS: Fifty-five replies were received representing a 60% completion rate of doctors and 84% of units on the mailing list. The majority of respondents were adult rheumatologists (n = 36, 65%) with 42% of respondents based in teaching hospitals. A median of 24 patients (new and follow-up, range 1-225) were seen in a median of two paediatric rheumatology clinics (range 0-15) per month. Eighteen per cent of units had a dedicated adolescent clinic (n = 9) with a median of one clinic per month and a median number of new patients per month of two (range 0-24) and 10 review patients (4-32). All the adolescent clinics involved an adult rheumatologist with five having a paediatrician in clinic and four having access to a paediatrician. The majority of clinics involved a specialist registrar (n = 6), a nurse specialist (n = 6), an occupational therapist (n = 6) and a physiotherapist (n = 5). The majority of clinics had flexible entry and exit criteria. In seven clinics there was a standardized process of transfer, first discussed at a median age of 13 yr (range 12-16) but no unit provided literature or organized pre-visits for this process. A demand for patient information resources (e.g. disease and drug information, careers) specifically aimed at adolescents with rheumatic diseases was identified. Generic health issues were only addressed by two clinics. Obstacles to current service provision and ideas for future developments were identified. CONCLUSIONS: This survey identifies a heterogeneity of provision of healthcare for adolescents with rheumatic disease and highlights the potential for further research and development.

Adolescent↗
PubMed2000

The role of independent agents in the success of health insurance market reforms.

The impact of reforms on the health insurance markets cannot be understood without more information about the role played by insurance agents and a closer analysis of their contribution. An in-depth, qualitative study of insurance-market reforms in seven illustrative states forms the basis for this report on how agents help to shape the efficiency and fairness of insurance markets. Different types of agents relate to insurers in their own ways and are compensated differently. This study shows agents to be almost uniformly enthusiastic about guaranteed-issue requirements and other components of market reforms. Although insurers devise strategies for manipulating agents in order to avoid undesirable business, these opportunities are limited and do not appear to be seriously undermining the effectiveness of market reforms. Despite the layer of cost that agents add to the system, they play an important role in making market reforms work, and they fill essential information and service functions for which many purchasers have no ready substitute.

Health Care Reform↗
PubMed2000

Purchasing cooperatives for small employers: performance and prospects.

Health insurance purchasing cooperatives were established in the early to mid-1990s for the purpose of making health insurance more affordable and accessible for small employers. Extensive interviews at six cooperatives reveal that while some cooperatives enrolled large numbers of small employers, most have won only small market shares and a number have struggled for survival, not always successfully. They have allowed small employers to offer individual employees choice of health plans, but none has been able to sustain lower prices than are available in the conventional market. Among the important impediments to their success are limited support from health plans and conflicts over the role of insurance agents.

Group Purchasing↗
PubMed2000

The impact of health insurance market reforms on market competition.

OBJECTIVES: To assess the impact of state and federal health insurance market reforms on the nature and extent of market competition. STUDY DESIGN: Qualitative, comparative case studies in 7 states. METHODS: Two rounds of in-depth interviews were conducted with over 100 key informants from the insurance industry. In each state, these sources included 2 to 4 regulators, 5 to 6 independent agents, and several sources at each of 4 to 5 of the top insurers. Extensive documentary data relating to market activity were also collected. These multiple sources of information and data were analyzed with both qualitative and quantitative techniques. RESULTS: (1) Small-group health insurance markets are highly competitive, both in price and in product innovation and diversity. (2) In some of the more heavily regulated states, there is very little competition in less-populated areas, especially for indemnity insurance. (3) The rapid growth of managed care in the small-group market may have been precipitated by these reforms. (4) Standardized benefit plans have not achieved their objectives. (5) Competitive forces still focus to a considerable extent on risk selection techniques. CONCLUSION: Small-group market reforms have not harmed market competition and may have improved competition in several respects. However, these reforms do not alter the fundamental orientation of competitive insurance markets, which is to focus on risk selection factors and techniques to the extent feasible.

Economic Competition↗
PubMed1999

The effect of ethylene and cytokinin on guanosine 5'-triphosphate binding and protein phosphorylation in leaves of Arabidopsis thaliana.

Binding of [alpha-32P]guanosine 5'-triphosphate ([alpha-32P]GTP) has been demonstrated in a Triton X-100-solubilised membrane fraction from leaves of Arabidopsis thaliana (L.) Heynh. Binding was stimulated by 1 h pre-treatment of leaves with ethylene and this effect was antagonised by the inclusion of N6-benzyladenine in the medium used for homogenisation. The ethylene-insensitive mutants eti 5 and etr showed contrasting responses. In eti 5 the constitutive level of GTP binding was higher than in the wild type whereas in etr the level was much lower. Neither ethylene nor cytokinin affected GTP binding in the mutants. The GTP-binding activity was localised in two bands at 22 and 25 kDa, both of which were immunoprecipitated by anti-pan-Ras antibodies, indicating that the activity is due to small GTP-binding proteins. In a similar membrane fraction, ethylene was shown to increase protein phosphorylation and benzyladenine antagonised this effect. In eti 5 the constitutive level of protein phosphorylation was higher than in the wild type, but benzyladenine increased activity substantially while ethylene was without effect. In etr, protein phosphorylation was lower than in the wild type, ethylene was without effect, but cytokinin increased activity. A protein of M(r) 17 kDa was detected on gels using antibodies to nucleoside diphosphate kinase. Phosphorylation of this protein was upregulated by ethylene but nucleoside diphosphate kinase activity was unaffected. The results are compared with the effect of the two hormones on the senescence of detached leaves and discussed in relation to pathways proposed for ethylene signal transduction.

Adenine↗
PubMed1999

Legal rules and industry norms: the impact of laws restricting health insurers' use of genetic information.

Since 1991, twenty-eight states have enacted laws that prohibit insurers' use of genetic information in pricing, issuing, or structuring health insurance. This article evaluates whether these laws reduce the extent of genetic discrimination by health insurers. Using multiple data sources, it concludes that there are almost no well-documented cases of health insurers asking for or using pre-symptomatic genetic test results in their underwriting decisions either before or after these laws, or in states with or without these laws. At present, health insurers are not thinking about or interested in using genetic information of this sort. Using this information is not cost effective and is not seen as contributing significantly to underwriting accuracy. However, if genetic testing information were easily available, some health insurers would consider using it in some fashion if that were legal. In the future, such information could become much more relevant to health insurers than it is now. Therefore, the major effect of these laws is to make it less likely that insurers will use genetic information in the future. Although insurers and agents are only vaguely aware of these laws, the laws have helped to convince the industry that it is not appropriate or socially legitimate to use this information. Thus, these laws have caused the insurance industry to embrace more socially oriented norms and attitudes.

Evaluation Studies as Topic↗
PubMed1998

Ethical practice in managed care: a dose of realism.

This article examines the ethics of medical practice under managed care from a pragmatic perspective that gives physicians more useful guidance than do existing ethical statements. The article begins with a framework for constructing a realistic set of ethical principles, namely, that medical ethics derives from physicians' role as healers; that ethical statements are primarily aspirational, not regulatory; and that preserving patient trust is the primary objective. The following concrete ethical guidelines are presented: Financial incentives should influence physicians to maximize the health of the group of patients under their care; physicians should not enter into incentive arrangements that they are embarrassed to describe accurately to their patients; physicians should treat each patient impartially without regard to source of payment, consistent with the physician's own treatment style; if physicians depart from this ideal, they should inform their patients honestly; and it is desirable, although not mandatory, to differentiate medical treatment recommendations from insurance coverage decisions by clearly assigning authority over these different roles and by physicians advocating for recommended treatment that is not covered.

Disclosure↗
PubMed1998

Important immunoregulatory role of interleukin-11 in the inflammatory process in rheumatoid arthritis.

OBJECTIVE: To investigate the possible immunoregulatory role of interleukin-11 (IL-11) in rheumatoid arthritis (RA). METHODS: IL-11 protein was assayed in RA tissue, and the effect of exogenous IL-11 on neutralization of endogenous IL-11 was investigated with respect to tumor necrosis factor alpha (TNFalpha), matrix metalloproteinase (MMP), and tissue inhibitor of metalloproteinases (TIMP) production. RESULTS: IL-11 was found in RA synovial membranes, synovial fluids, and blood sera. Blockade of endogenous IL-11 resulted in a 2-fold increase in TNFalpha levels, which increased to 22-fold if endogenous IL-10 was also blocked. Addition of exogenous IL-11 inhibited spontaneous TNFalpha production in RA synovium only in the presence of soluble IL-11 receptor. However, exogenous IL-11 directly inhibited spontaneous MMP-1 and MMP-3 production, and up-regulated TIMP-1 in RA synovial tissue. CONCLUSION: IL-11 has important endogenous immunoregulatory effects in RA synovium, which suggests that exogenous IL-11 may have therapeutic activity in RA.

Adjuvants, Immunologic↗
PubMed1998

Ulnar lengthening in juvenile chronic arthritis.

Ten wrists in eight children with severe destructive changes in the wrist due to juvenile chronic arthritis underwent distraction lengthening of the ulna between 1983 and 1996 in an attempt to restore wrist alignment, which had not been preserved by previous splinting. Eight wrists in six patients (four female and two male) were evaluated. The average age at the time of operation was 13.8 years (range, 12-15.5). The average follow-up period was 70 months (range, 12-152). The average ulna minus deformity was between 8 and 9 mm. It was found that ulnar lengthening can be done safely and the procedure seems to stabilize the carpus, is likely to improve appearance, may improve function and in the majority of cases does eliminate the use of an external splint. Results seem to be stable for at least 3 to 5 years.

Adolescent↗
PubMed1998

The distribution of human TCR junctional region lengths shifts with age in both CD4 and CD8 T cells.

Several normal and pathological antigen-driven immune responses are associated with limited TCR usage. CDR3 sequence and to some extent length represent clonal markers which can be used to follow the course of an immune response. We investigated whether differences exist in the CDR3 length distribution in the CD4 versus CD8 populations which might reflect the HLA class restriction of the T cell subpopulation. We showed that the range is similar in both the CD4 and CD8 populations for most BV families. Differences exist between CDR3 length distributions of adult versus cord blood CD4 and CD8 T cells. The percentage expressing CDR3 of 10 amino acids or more across all BV families was significantly lower in the cord blood T cells compared to the adults for both CD4 and CD8 populations. This is likely to reflect either differences in the development of the T cell population such as increased N region length post-partum or may be the result of foreign antigen exposure. To address this issue, samples of TCRBV sequences from cord and adult T cell populations were compared. No significant differences were found in either exonucleolytic removal or N region addition between the adult and cord blood samples suggesting that the population shift is the result of antigen exposure. No spectratype distortions existed for any BV family in the adult or cord blood CD4 populations; however, distortions were seen in CD8 populations from all the adults and much less frequently in the cord blood T cells. We investigated the ability to detect clonality at frequencies that one would expect to find antigen-specific T cells in the peripheral repertoire. It was possible to identify a clone at a frequency of 0.1% in a polyclonal CD4 population. This frequency corresponds to that of some individual clones after antigen-driven T cell expansion and establishes parameters within which T cell immune responses may be tracked ex vivo.

Adult↗