Familial dyslipidemic hypertension. Evidence from 58 Utah families for a syndrome present in approximately 12% of patients with essential hypertension

Population-based sibships with essential hypertension diagnosed before the age of 60 years are being screened in Utah to find two or more hypertensive siblings with the same biochemical abnormality as a clue to an inherited cause for their specific type of hypertension. Among 131 hypertensive subjects in 58 sibships, concordant abnormalities in fasting serum lipid concentrations were observed in two or more siblings in 48% of the sibships. After adjusting for effects of antihypertensive medications, abnormal values reported in only 10% of the Lipid Research Clinics data were observed in 30% of patients for serum triglycerides, 19% for serum low-density lipoprotein cholesterol, and 39% for high-density lipoprotein cholesterol. More than one lipid level was abnormal in almost all concordant sibships, suggesting an association between hypertension and a syndrome of mixed lipid abnormalities, probably familial combined hyperlipidemia (renamed "familial combined dyslipidemia" because of common low high-density lipoprotein cholesterol levels). We conclude that familial dyslipidemic hypertension may be a specific syndrome with lipid abnormalities more severe than blood pressure elevations.     

The meaning of “physical fitness”

The understanding of the term "physical fitness" was determined for a randomly selected sample (n = 94) of a population using a self-administered mailed questionnaire. Subjects were asked to state and give a reason for their perceived level of physical fitness, to state their perceived performance level in a number of physical fitness tests (muscular strength, daily physical work capacity, fatness, level of regular physical exercise, exercise speed, and body flexibility), and to rate how well these tests measure physical fitness. The reason most frequently stated for perceived level of physical fitness was the level of habitual physical activity (43%); significantly less frequently (P less than 0.01-0.0001) cited were reasons related to health (23%), physical performance (12%), and obesity (3%). The variation in perceived level of physical fitness was best explained by the variation in imagined regular exercise and fatness (r2 = 0.66, P less than 0.0001) with no significant additional contribution from imagined performance in remaining fitness tests. The measurement of regular exercise was most favored as a test of physical fitness. These results, taken together with evidence of the physical and psychological health benefits of regular exercise, imply that the most appropriate measure of physical fitness for the average person is an assessment of the habitual physical activity level.     

Architecture of secondary lymphoid tissue in sheep experimentally challenged with scrapie

Scrapie is a transmissible spongiform encephalopathy in which there is an accumulation of the abnormal form of the prion protein, PrPsc, in the lymphoreticular system and nervous system. There is a particular accumulation of PrPsc on follicular dendritic cells within the germinal centre of B-cell follicles. Because accumulation of PrPsc in the nervous system leads to neuronal cell loss we have examined PrPsc accumulation in the prescapular and mesenteric lymph nodes in relation to lymph node architecture of scrapie-challenged sheep. We demonstrate that an accumulation of PrPsc in the lymph node fails to result in gross defects in the microanatomy and phenotype of T- and B-cell areas in the lymph nodes.     

Identification of a common variant in the lipoprotein lipase gene in a large Utah kindred ascertained for coronary heart disease: the -93G/D9N variant predisposes to low HDL-C/high triglycerides

Defects in the lipoprotein lipase (LPL) gene are associated with dyslipidemia in the general population. Several rare mutations in the gene, as well as two common coding region polymorphisms, D9N and N291S, exhibit deleterious effects on circulating lipid levels. Using a linkage-based approach, we have identified a large Utah kindred segregating the D9N variant in the LPL gene. The kindred was ascertained for premature coronary heart disease and was expanded based on familial dyslipidemia. A genomic scan identified a region of linkage including LPL, and mutation screening identified the segregating variant. In the kindred, the variant shows high penetrance for a hypoalphalipoproteinemia phenotype, but is also associated with hypertriglyceridemia and elevated insulin levels. The strength of linkage was dependent on the combination of phenotype definition and model parameters, favoring the use of a MOD score approach. Most other studies of LPL have proceeded by mutation screening of randomly chosen individuals or selected affected probands; this is the first example identifying a segregating LPL mutation using direct linkage.     

Direct Detection of Legionella Species from Bronchoalveolar Lavage and Open Lung Biopsy Specimens: Comparison of LightCycler PCR, In Situ Hybridization, Direct Fluorescence Antigen Detection, and Culture

We developed a rapid thermocycling, real-time detection (also known as real-time PCR) method for the detection of Legionella species directly from clinical specimens. This method uses the LightCycler (Roche Molecular Biochemicals, Indianapolis, Ind.) and requires approximately 1 to 2 h to perform. Both a Legionella genus PCR assay and Legionella pneumophila species-specific PCR assay were designed. A total of 43 archived specimens from 35 patients were evaluated, including 19 bronchoalveolar lavage (BAL) specimens and 24 formalin-fixed, paraffin-embedded open lung biopsy specimens. Twenty-five of the specimens were culture-positive for Legionella (9 BAL specimens and 16 tissue specimens). BAL specimens were tested by LightCycler PCR (LC-PCR) methods and by a direct fluorescent antibody (DFA) assay, which detects L. pneumophila serogroups 1 to 6 and several other Legionella species. Tissue sections were tested by the two LC-PCR methods, by DFA, by an in situ hybridization (ISH) assay, specifically designed to detect L. pneumophila, and by Warthin-Starry (WS) staining. The results were compared to the "gold standard" method of bacterial culture. With BAL specimens the following assays yielded the indicated sensitivities and specificities, respectively: Legionella genus detection by Legionella genus LC-PCR, 100 and 100%; Legionella genus detection by DFA assay, 33 and 100%; and L. pneumophila detection by L. pneumophila species-specific LC-PCR, 100 and 100%. With open lung biopsy specimens the following assays yielded the indicated sensitivities and specificities, respectively: Legionella genus detection by LC-PCR 68.8 and 100%; Legionella genus detection by DFA assay, 44 and 100%; Legionella genus detection by WS staining, 63 and 100%; L. pneumophila species-specific detection by LC-PCR, 17 and 100%; and L. pneumophila species-specific detection by ISH, 100 and 100%. The analytical sensitivity of both LC-PCR assays was <10 CFU/reaction. LC-PCR is a reliable method for the direct detection of Legionella species from BAL specimens. The Legionella genus LC-PCR assay could be performed initially; if positive, L. pneumophila species-specific LC-PCR could then be performed (if species differentiation is desired). The speed with which the LC-PCR procedure can be performed offers significant advantages over both culture-based methods and conventional PCR techniques. In contrast, for the methods evaluated, culture was the best for detecting multiple Legionella species in lung tissue. WS staining, Legionella genus LC-PCR, and L. pneumophila species-specific ISH were useful as rapid tests with lung tissue.     

Physical fitness of blind and sighted children

Summary Twenty-seven children (age 7–17 years) with varying degrees of blindness but with no other known disorder were assessed for physical fitness. Twenty-seven randomly selected children with normal eyesight were also assessed. Maximum oxygen uptake ( ) was measured directly during a progressive exercise test on a treadmill. There was a significant and substantial reduction in in totally blind children (mean ± standard deviation 35.0±7.5 ml · min^–1 · kg^–1) compared with normal children (45.9±6.6 ml · min^–1 · kg^–1). Partially sighted children had a significant but smaller reduction in . Fitness assessed by a step-test was significantly reduced in the visually impaired children, and skin-fold thickness was also significantly greater in totally blind children.The level of habitual physical activity for each child, as assessed by a questionnaire, correlated with (r=0.53,p<0.0001). Blind children were significantly less active than normal children, and the difference between mean for blind and normal children became non-significant when their different activity levels were taken into account. It is concluded that totally blind children are less fit than other children at least partly because of their lower level of habitual activity.     

IL-2-like activity in lymph fluid following in vivo antigen challenge.

The majority of studies that characterize lymphokines utilize in vitro activation of lymphocytes. In an attempt to identify and characterize lymphokines released from tissue sites, we have cannulated sheep lymphatic vessels and collected lymph that drains a site of in vivo antigen challenge. Lymph draining directly from a site of intradermal antigen challenge (afferent lymph) and lymph draining an antigen-stimulated lymph node (efferent lymph) were assayed for lymphokine activity by the ability of cell-free lymph fluid to stimulate the proliferation of sheep Con A-blasts. Afferent and efferent lymph, both collected at 24 and 48 hr following in vivo antigen challenge, with either ovalbumin or PPD in primed animals, stimulates the proliferation of sheep Con A-blast cells. This in vivo-derived lymphokine activity and in vitro-generated sheep Con A supernatant has an active component with properties similar to interleukin-2 (IL-2) that has been described in several other species. The IL-2-like material is precipitated by 40-80% ammonium sulphate saturation, has a molecular weight (MW) of 20,000 MW as judged by gel filtration chromatography, and is eluted from an anion-exchange HPLC column with 125 mM NaCl. HPLC ion-exchange fractionation of the 20,000 MW material from lymph fluid shows differences between afferent and efferent lymph material. The fractionation of afferent material is similar to that of in vitro generated Con A supernatant material with a single peak of activity eluted by 125 mM NaCl. In contrast, the 20,000 MW material from efferent lymph elutes with peaks of activity at 125 and 300 mM NaCl.     

Genetic control of serum IgE levels: a study of low molecular weight protein tyrosine phosphatase

Protein tyrosine phosphatases (PTPases) have recently been recognized as important modulators of various signal transduction pathways in immune cells. Genetic polymorphisms have been described in genes codifying for members of this family of enzymes, and the genetics of PTPases is predicted to play an important role in the etiology of immune diseases and of their clinical variability. The low molecular weight protein tyrosine phosphatase (ACP1 or LMPTP) is one of the few PTPases with a known genetic polymorphism, and has been proposed to be associated with atopic dermatitis in a small sample from an Italian population. In this paper we describe the association of the ACP1 polymorphism with total IgE levels in two independent samples from English and Italian populations. In both the samples the mean value of serum IgE is lower among subjects carrying the BC genotype than in other ACP1 genotypes. The BC genotype is associated with the highest total ACP1 enzymatic activity. Our data suggest that one or both of the ACP1 isoforms exert an inhibitory role on some signal transduction pathway relevant for IgE hyperproduction.