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  • 1
    ISSN: 1433-8580
    Keywords: Endotoxin ; LPS ; Rat PMN ; LTC4/D4 and TxB2 synthesis ; PMN functions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect ofSalmonella enteritidis endotoxin on in vitro rat neutrophil cyclo-oxygenase and lipoxygenase metabolism, phagocytic activity, superoxide (O 2 - ) generation, and microbicidal activity was investigated. Incubation of polymorphonuclear leukocytes (PMN) with 5, 25, and 50 µg of endotoxin significantly enhanced synthesis of immunoreactive (i) leukotriene (LT)C4/D4 and thromboxane (Tx)B2 (P 〈 0.001) as compared to control cells. Endotoxin 5 µg/ml produced optimal stimulation of the arachidonic acid metabolites. Calcium ionophore, A23187, significantly enhanced iLTC4/D4 and iTxB2 synthesis more than that elicited with endotoxin. Although phagocytic function was not significantly altered by endotoxin, intracellular killing ofC. albicans demonstrated enhanced microbicidal activity at 5 µg/ml of endotoxin. Superoxide generation was significantly enhanced in neutrophils stimulated with phorbol myristate acetate (PMA). Endotoxin (5 µg/ml) further potentiated superoxide generation by these cells when stimulated by PMA. These findings demonstrate that endotoxin directly enhances neutrophil iLTC4/D4 and iTxB2 synthesis. The enhanced arachidonic acid metabolism elicited by endotoxin in these cells parallels increased microbicidal activity and superoxide generation.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes mellitus ; genetic epidemiology ; genetic linkage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Non-insulin-dependent diabetes mellitus (NIDDM) has a substantial genetic component, but the mode of inheritance and the molecular basis are unknown. We have undertaken segregation analysis of NIDDM after studying 247 subjects in 59 Caucasian nuclear pedigrees ascertained without regard to family history of the disorder. The analyses were performed using POINTER and COMDS, which are computer programs which apply statistical models to the data. POINTER analysis was performed defining the phenotype as a presence or absence of hyperglycaemia. Among single locus hypotheses, the analyses rejected a recessive model and favoured a dominant model, but could not statistically show that this fitted better than a mixed model (a single locus against a polygenic background) or a polygenic model. COMDS analysis assumed a continuum of hyperglycaemia from normality to NIDDM, classified family members into a series of diathesis classes with increasing plasma glucose levels and compared the distribution with that found by screening the normal population. This analysis improved the likelihood of a dominant single locus model and suggested a gene frequency of 7.4%. It raised the possibility of a second locus, but cannot identify or exclude a polygenic model. In conclusion, two types of segregation analyses rejected a recessive model and favoured a dominant model of inheritance, although they could not statistically show that this fitted better than the polygenic model. The results raised the possibility of a common dominant gene with incomplete penetrance, but genetic analysis of NIDDM needs to take into account the likelihood of polygenic inheritance with genetic heterogeneity.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Key words Non-insulin-dependent diabetes mellitus ; genetic epidemiology ; genetic linkage.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Non-insulin-dependent diabetes mellitus (NIDDM) has a substantial genetic component, but the mode of inheritance and the molecular basis are unknown. We have undertaken segregation analysis of NIDDM after studying 247 subjects in 59 Caucasian nuclear pedigrees ascertained without regard to family history of the disorder. The analyses were performed using POINTER and COMDS, which are computer programs which apply statistical models to the data. POINTER analysis was performed defining the phenotype as a presence or absence of hyperglycaemia. Among single locus hypotheses, the analyses rejected a recessive model and favoured a dominant model, but could not statistically show that this fitted better than a mixed model (a single locus against a polygenic background) or a polygenic model. COMDS analysis assumed a continuum of hyperglycaemia from normality to NIDDM, classified family members into a series of diathesis classes with increasing plasma glucose levels and compared the distribution with that found by screening the normal population. This analysis improved the likelihood of a dominant single locus model and suggested a gene frequency of 7.4 %. It raised the possibility of a second locus, but cannot identify or exclude a polygenic model. In conclusion, two types of segregation analyses rejected a recessive model and favoured a dominant model of inheritance, although they could not statistically show that this fitted better than the polygenic model. The results raised the possibility of a common dominant gene with incomplete penetrance, but genetic analysis of NIDDM needs to take into account the likelihood of polygenic inheritance with genetic heterogeneity. [Diabetologia (1994) 37: 1231–1240]
    Type of Medium: Electronic Resource
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