Hypertriglyceridemia and the apolipoprotein CIII gene locus: lack of association with the variant insulin response element in Italian school children.

Hypertriglyceridemia is a common metabolic disorder with a major inherited component. In some individuals the condition is suspected to occur as a result of overproduction of apolipoprotein (apo)CIII, a major constituent of triglyceride-rich lipoproteins. Population studies have established an association with the apoCIII gene but the identify of the causal mutation remains unknown. In the present study we have examined a series of six 5' polymorphic nucleotides (G-935 to A, C-641 to A, G-630 to A, deletion of T-625, C-482 to T, and T-455 to C) that lie within the promoter region of the apoCIII gene for evidence of possible involvement in disease susceptibility. The polymorphic nucleotides at positions -455 and -482 reside within a negative insulin-response element. We show, in a community-based sample of 503 school children, that a DNA polymorphism (S2 allele) within the 3'-noncoding region of the apoCIII gene was associated with elevated apoCIII and triglyceride levels, but that the polymorphic nucleotides of the promoter were not. In addition, no obvious effect of any extended apoCIII promoter haplotype on plasma apoCIII or triglyceride levels, over and above that conferred by the presence of the S2 polymorphic nucleotide, was detected. These results demonstrate that none of the 5' apoCIII polymorphisms can account for the association of the apoCIII gene locus with hypertriglyceridemia and, moreover, owing to linkage disequilibrium, raise the possibility that the region conferring susceptibility maps downstream, rather than upstream, of the apoCIII gene promoter sequences.

Variation at the apo AI/CIII/AIV gene complex is associated with elevated plasma levels of apo CIII.

A number of studies have reported that a variant allele (S2) of the apo AI/CIII/AIV complex is associated with high plasma lipid levels in some populations and furthermore that the frequency of this allele is 2-5-fold higher in patient groups with premature coronary heart disease compared to control groups. This study shows in the healthy "English" population that the S2 allele is associated with elevated plasma apo CIII levels but not with low apo AI levels. In addition, it shows that the allele is associated with elevated plasma levels of apo B in men. Regression analysis shows in both men and women that apo CIII levels are positively correlated with plasma triglyceride levels and moreover that they are a stronger predictor of this parameter than apo AI, B or AIV. Apo CIII levels are also an independent predictor of total plasma cholesterol and HDL-cholesterol levels in males and females, respectively. Together these data suggest that a genetic predisposition to develop elevated plasma levels of apo CIII, alone or in combination with elevated plasma apo AIV levels, is the primary defect responsible for the association of the S2 allele with hyperlipidemia and/or premature CHD.

The apolipoprotein B gene is constitutively expressed in HepG2 cells: regulation of secretion by oleic acid, albumin, and insulin, and measurement of the mRNA half-life.

The objective of this study was to establish conditions whereby apoB secreted from HepG2 cells could be regulated over a wide range, and to determine whether changes of output were correlated with the level of apoB mRNA. The presence of oleate (complexed to 3% albumin at a molar ratio of 1.7:1) resulted in a 3.5-fold stimulation of apoB secretion that was apparent after only 3 h. Insulin halved the rate of apoB output and the inhibition was detectable within the physiological insulin range, but was not apparent until 12-16 h. Albumin in the culture medium had a dose-dependent inhibitory effect on apoB production. Overall, apoB secretion from HepG2 cells was modulated over a 7-fold range. However, when apoB mRNA was assayed by slot-blot hybridization, no change was detectable under any of the conditions that modulated apoB output. Quantitative solution hybridization was used to confirm that oleate did not affect the level of apoB mRNA. Kinetic analysis of the decay of [3H]uridine-labeled apoB mRNA showed that the half-life of apoB mRNA was 16 h. We conclude from these studies that the apoB gene is constitutively expressed in HepG2 cells and that the mechanism of acute regulation of apoB production by these cells must involve co- or post-translational processes.

Streptococcus suis bacteraemia.

Streptococcus suis is a zoonotic pathogen which causes meningitis, arthritis and septicaemia in pigs, and rarely meningitis or septicaemia in humans. This organism has recently been isolated from pigs in New Zealand, where it appears to be widely distributed in pig herds. This case is the first report of human infection in New Zealand.

The pattern of management after stroke.

A large population-based study of stroke is used to describe the pattern of management and the relative contribution of hospital care and community care in the year following an acute stroke episode. Two thirds of the 680 patients registered in the study were admitted to a public hospital during the acute stage of their illness, while almost one quarter of all patients were managed entirely at home. One month after the initial episode the majority of patients admitted to hospital had either died or had been discharged. Overall, four-fifths of the care during the first year after the onset of the stroke took place out of hospital, either at home or in private long-term institutions.

Event, incidence and case fatality rates of cerebrovascular disease in Auckland, New Zealand.

Death rates for cerebrovascular disease (stroke) in New Zealand are declining. To investigate the reasons for this decline and to measure the impact of stroke on a defined population, a register of new episodes of stroke was kept in the Auckland region for the year ending March 1982. All cases were followed for one year, with in-depth interviews at onset, one month and six months and a telephone follow-up at one year to establish dead or alive status. A total of 703 episodes were registered for 680 patients, 331 men and 349 women. The crude event rate for all those over 15 years was 228 and 220 per 100,000 for men and women, respectively. Age-adjusted event rates for all strokes were 28% higher for men than women and the age-adjusted event rates for Maoris were 44% higher than for non-Maoris. The case fatality rates were 23.1% at one week, 33.5% at one month, 43.5% at six months and 48.5% at one year. In comparison with other studies, case fatality rates are similar but the incidence rates appear to be lower.

Subarachnoid hemorrhage in New Zealand: an epidemiological study.

To examine long-term trends in subarachnoid hemorrhage (SAH) mortality and morbidity, an analysis of routinely available information is presented for the 20 year period from 1959. To document the current incidence and case fatality of SAH, the results of a large scale community-based study in the Auckland region are presented. SAH mortality rates for both men and women, especially women, have declined since the mid-1970's. The decline appears to be real, and is most striking in the 45-64 year age groups. A corresponding decline in discharge rates from hospital has also occurred in these age groups. In contrast, cases fatality rates have remained stable at about 42% for the 20 year period under review. The community-based study identified 92 cases in a total population of 829,464 in a twelve month period. The age standardised incidence rates were 13.4 and 15.8 per 100,000 for men and women respectively. In the age group 25-35 years, the incidence rate was particularly high at 8.5/100,000. Case fatality at 28 days was 52%. A decline in incidence appears the most likely explanation for the overall decline in national mortality.

Blood pressure measurements in hospital.

Blood pressure on admission to hospital is a "stressed blood pressure" that will tend to exaggerate the prevalence of hypertension. Twelve per cent of patients admitted to Auckland Hospital did not have their blood pressure recorded. The number of blood pressure recordings was excessive in many untreated hypertensive patients admitted to Auckland Hospital. The physician tends to examine patients with high blood pressure in a predictable manner without regard to the severity of pressure recorded. The diagnosis of hypertension or kidney disease was recorded in the medical case summaries sent to the general practitioners in only 11% of patients whose admission blood pressure was raised. The blood pressure of many hypertensive patients was not communicated to the general practitioner; this information was given in 60% of treated and 39% of untreated hypertensive patients.

Immunological enhancement in the pathogenesis of pyelonephritis.

The role of the immune response in pyelonephritis was investigated by manipulation of the host's immune capacity using the immunosuppressive drugs 6-mercaptopurine, cyclophosphamide and thiamphenicol. Treatment with 6-mercaptopurine depressed the humoral immune response but did not have an adverse effect on the course of renal infection. Thiamphenicol administration prevented the development of pathological lesions but this was due to the anti-bacterial activity of thiamphenicol and not to its immunosuppressive activity. Pyelonephritic animals treated with cyclophosphamide did not produce anti-bacterial antibody. Despite this, cyclophosphamide-treated animals were able to eliminate organisms more readily from the infected kidney than untreated animals with a normal humoral immune response. We believe that blocking of the phenomenon of immunological enhancement explains these unexpected results and that the immune response to renal infection may have an immunoenhancing role protecting the bacterial cell from otherwise effective host defence mechanisms.