Is the political system really related to health?

We analyze whether the political system and its stability are related to cross-country differences in health. We apply factor analysis on various national health indicators for a large sample of countries over the period 2000–2005 and use the outcomes of the factor analysis to construct two new health measures, i.e., the health of individuals and the quality of the health care sector. Using a cross-country structural equation model with various economic and demographic control variables, we examine the relationship between the type of regime and political stability on the one hand and health on the other. The political variables and the control variables are measured as averages over the period 1980–1999. Our results suggest that democracy has a positive relationship with the health of individuals, while regime instability has a negative relationship with the health of individuals. Government instability is negatively related to individual health via its link with the quality of the health care sector, while democracy is positively related with individual health through its link with income. Our main findings are confirmed by the results of a panel model and various sensitivity tests.     

Selective drop-out in successive in-vitro fertilization attempts: the pendulum danger.

Success rates from in-vitro fertilization (IVF) in the long term are dependent on selection procedures with regard to continuation into further IVF episodes. Publications on success rates in successive episodes will give incentives to adapt selection criteria, but if these publications do not deal explicitly with patient selection, the adaptations might change their direction every time: the pendulum danger.     

Hereditary cerebral hemorrhage with amyloidosis-Dutch type: a study of fibrinolysis.

In view of reported associations between increased bleeding tendency and systemically decreased alpha 2-antiplasmin in patients with systemic amyloid deposition we studied alpha 2-antiplasmin, fibrinogen, C-reactive protein and blood levels of locally produced endothelial hemostasis factors in the acute and quiescent phase in 16 patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). None of the factors measured in the quiescent phase of the disease was abnormal. In the acute phase, shortly after a stroke, only factor VIII:Ag was evidently elevated. We concluded that systemic abnormalities in the part of the fibrinolysis system studied are not likely to be responsible for multifocal and recurrent cerebral hemorrhages in HCHWA-D. The role of an elevated factor VIII:Ag level in the acute phase is unclear.     

The role of quinone reductase (NQO1) and quinone chemistry in quercetin cytotoxicity.

The effects of quercetin on viability and proliferation of Chinese Hamster Ovary (CHO) cells and CHO cells overexpressing human quinone reductase (CHO+NQO1) were studied to investigate the involvement of the pro-oxidant quinone chemistry of quercetin. The toxicity of menadione was significantly reduced in CHO+NQO1 cells compared to wild-type CHO cells, validating the NQO1-overexpression in the CHO+NQO1 transfectant. Quercetin inhibited the proliferation of wild-type CHO and CHO+NQO1 cells to a similar extent without affecting cell viability, indicating that NQO1 enrichment of CHO cells did not provide increased protection. On the other hand, inhibition of NQO1 in both types of cells by dicoumarol significantly potentiated the inhibitory effect of quercetin on cell proliferation, revealing the role of NQO1 in cellular protection against quercetin. Altogether, these results can be explained by the hypothesis that both wild-type CHO and CHO+NQO1 cells contain sufficient NQO1 activity for optimal protection against the pro-oxidant effect of quercetin on cell proliferation. The results also point at a cellular NQO1 threshold for optimal protection against quercetin. This NQO1 threshold seems to be in the range of NQO1 activities already present in various tissues.     

Characterisation of four novel fibrillin-1 (FBN1) mutations in Marfan syndrome.

Forty-four percent of the fibrillin-1 gene (FBN1) from 19 unrelated families with Marfan syndrome was screened for putative mutations by single strand conformational polymorphism (SSCP) analysis. Four novel mutations were identified and characterised in five people, three with classical Marfan syndrome (two from one family, and one from an unrelated family), one with a more severe phenotype, and one with neonatal Marfan syndrome. The base substitutions G2113A, G2132A, T3163G, and G3458A result in amino acid substitutions A705T, C711Y, C1055G, and C1152Y, respectively. C711Y, C1055G, and C1152Y lead to replacement of a cysteine by another amino acid; the latter two occur within epidermal growth factor-like motifs in exon 25 and 27, respectively. The A705T mutation occurs at exon 16 adjacent to the GT splice site. The A705T and C711Y mutations, at exon 16 and 17, respectively, are the first documented in the second transforming growth factor-beta 1 binding protein-like motif of FBN1.     

Dermatitis in bulb growers

A damaged skin forms a health hazard in flower-bulb growers as it enables higher permeation rates For pesticides than normal skin. Therefore, an investigation was performed into the skin condition of 103 bulb growers and 49 controls. Contact dermatitis of the hands was of the same order (11 and 10%) in both groups. However, minor signs of dermatitis were seen more often in bulb growers (30 versus 8%, p <0.05). Most growers had contact with narcissus sap during the investigation. This irritant sap, as well as many other skin contacts with irritants such as hyacinth dust and pesticides, seemed to be responsible for many skin complaints. Contact serialization was suspected in 19 growers and 3 controls. Patch tests showed that contact sensitization existed to pesticides in probably 10, and to flower-bulb extracts in 4 growers. Reactions to propachlor were not regarded as very reliable as the test concentration seemed to be marginally irritant. There were only a few allergic reactions to narcissus (3) and tulip (2) and none to hyacinth. This investigation showed that minor irritant contact dermatitis was frequent in bulb growers, and indicated that contact sensitization to pesticides and bulbs seemed to be a less frequent but important cause of dermatitis.     

Hepatic,intestinal and renal transport of 1-naphthol-β-d-glucuronide in mutant rats with hereditary-conjugated hyperbilirubinemia

Summary Recently, a mutant rat strain was described with a genetic defect for the biliary excretion of organic anions (TR^– rats). To determine the possible heterogeneity of the transport systems in liver, intestine and kidney we investigated the transport of the anion 1-naphthol--d-glucuronide (1-NG) in isolated vascularly perfused organ preparations of the rat liver, intestine and kidney of both Wistar rats and TR^– rats. 1-NG was administered as such (liver and kidney experiments) or formed intracellularly from 1-naphthol (1-N) (liver and gut experiments). Independent of the type of exposure to 1-NG, the biliary excretion was considerably impaired in TR^– rats. In the intestine the total appearance and the vascular/luminal distribution pattern of 1-NG were not significantly different from the values in control rats. Furthermore, no significant disturbance was found with respect to the renal clearance of 1-NG in the TR^– rat when compared with the Wistar rat. Thus, the genetic defect in the TR^– rat is restricted to an impaired hepatobiliary excretion of 1-NG and does not affect the excretory systems of the intestine and kidney. These results suggest that the excretion of 1-NG by the liver, intestine and kidney involves distinct organ-specific transport systems.     

Functional folding of a cytoplasmic single-chain variable fragment and its use as elutable protein purification tag

The variable fragment (Fv) of the monoclonal B1-8 antibody recognizes 3-nitro-4-hydroxy-phenylacetate (NP) and 5-iodo-NP (NIP) allowing for the affinity purification of the respective B cell antigen receptor with NP-sepharose and its specific elution with NIP-capronic acid (NIPcap). We generated an intracellular single-chain B1-8 Fv (iscFv), fused it to the N-terminus of the regulatory subunit (p85alpha) of phosphatidylinositol-3-kinase (PI3K) (isc-p85alpha), and examined the potential of this iscFv to serve as an intracellular elutable protein purification tag. The isc-p85alpha fusion protein could be specifically affinity-purified from the lysates of transfected Drosophila S2 cells with NP-sepharose and eluted with NIPcap, indicating the functional folding of the iscFv in the reducing environment of the cytosol. Furthermore, co-purification of the catalytic subunit of PI3K (p110) was achieved from lysates of co-transfected S2 cells as well as RBL-2H3 mast cells stably expressing isc-p85alpha. This indicates that the iscFv part of isc-p85alpha does not negatively influence p85alpha folding and interaction with p110. Moreover, successful incorporation of the p85alpha-moiety of isc-p85alpha into endogenous protein complexes in mast cells suggests the use of isc-containing fusion proteins for the native purification, elution, and analysis of intracellular signaling complexes.     

Direct molecular diagnosis of myotonic dystrophy

Hecht BK, Donnelly A, Gedeon AK, Byard RW, Haan EA, Mulley JC. Direct molecular diagnosis of myotonic dystrophy. Clin Genet 1993: 43: 276–285. © Munksgaard, 1993 Myotonic dystrophy (DM) arises from an unstable trinucleotide (CTG_n) repeat sequence within the DM locus at 19q13.3. Twenty-three myotonic dystrophy families containing 205 persons with no symptoms, minimal manifestations, classic DM or congenital DM were investigated to validate the application of the pM10M6 probe to direct molecular diagnosis. Affected family members had been diagnosed clinically and the unaffected family members had been assigned carrier probabilities close to either zero or 100%, using closely linked flanking markers. Southern analysis identified all 89 DM gene carriers as having expansions of the unstable element. PstI detected all small expansions of the repeat sequence as easily seen discrete bands; but large expansions were usually seen as diffuse smears, sometimes difficult to distinguish from lane background. EcoRI concentrated these diffuse smears, associated with somatic instability, into discrete bands which were easy to detect; but it did not resolve the smaller expansions present in 9 (10%) of the DM carriers. It is essential that PstI and EcoRI gels are run in parallel to detect all DM gene carriers. The extent of expansion of CTG correlated with age of onset and disease severity. Biopsies of various fetal tissues from two terminated pregnancies confirmed the diagnosis obtained by CVS and revealed no heterogeneity between tissues at this developmental stage. Further expansion occurred during the culture of CVS cells, indicating that direct prenatal diagnosis needs to be carried out on CVS tissue rather than on cultured cells. The intergenerational change of the repeat sequence from DM parent to DM offspring showed a significant parental sex difference for those parents with large expansions. Contraction of the unstable element was observed in the three males carrying the largest expansions and could explain why congenital DM is exclusively of maternal origin.