Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1.

We report the identification of mutations in lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) genes in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17. Linkage disequilibrium analysis of six families affected by NCIE permitted us to reduce a recently reported interval of 8.4 cM on chromosome 17p13.1 to a 600 kb region around the marker D17S1796, which contains LOX genes. LOX products have long been implicated in skin disorders. Two point mutations and one deletion were found in ALOXE3 and three point mutations were found in ALOX12B in these consanguineous families from the Mediterranean basin. ALOXE3 and ALOX12B are two genes which are physically linked and functionally related. They are separated by 38 kb, have one more exon than the other LOX genes and are mainly expressed in epithelial cells including keratinocytes. Although the main substrate(s) of the two enzymes is (are) still unknown, the products of ALOX12B obtained in experimental systems have been demonstrated to be of R-chirality. It seems likely that the product of one of these enzymes may be the substrate of the other, and that they belong to the same metabolic pathway.     

Comparative toxicity,protective, histamine sensitizing and leucocytosis promoting activities in mice ofBordetella pertussis culture fluid,bacterial cells and cell extracts

Bordetella pertussis bacterial cells, bacterial extracts, and concentrated culture supernatant fluid were comparatively examined for histamine sensitizing and leucocytosis promoting activities, toxicity (mouse weight gain test), immunoprotective potency and lipopolysaccharide bioassay. The activity of histamine sensitizing factor always paralleled that of leucocytosis promoting factor. In contrast, important differences were demonstrated regarding the toxicity and protective activity of the three preparations. Culture supernatant was more toxic and less protective than either bacterial cells or cell extract. Although the latter had lower protective potency than whole cells, its lower toxicity might lead to its consideration as a possible potential vaccine.     

The vascular lesions in vascular and mixed dementia: the weight of functional neuroanatomy

Vascular dementia appears rarer than previously thought, but the contribution of vascular lesions to cognitive impairment in Alzheimer's disease (AD) affected patients (mixed dementias) is now recognized as frequent. The role of strategic areas of the brain involved in the cognitive decline induced by vascular lesions and their relative contributions to the severity of the dementing process remain poorly understood. We determined the relationship between the severity of clinical dementia and the volume of different brain areas affected by infarcts in a prospective clinicopathological study in elderly patients. A volumetric study of the functional zones of Mesulam's human brain map affected by vascular lesions was made and correlations between quantified neuropathological data and the severity of dementia were performed in cases with large vascular lesions only, pure AD, and both lesions. The severity of cognitive impairment was significantly correlated with the total volume of infarcts but in a multi-variate model the volume destroyed in the limbic and heteromodal association areas, including the frontal cortex and in the white matter explained 50% of the variability in MMSE and GDS. The total volume of ischemic lesions explained only 0.1-5% of the variability in MMSE and GDS. Age only explained an extra of 0.1-1.6%. This study confirms that infarcts located in strategic areas have a role in the mechanism of cognitive impairment and brings a key for their quantification. It may be useful for developing neuropathological criteria in multi-infarct and mixed dementias.     

Antioxidant capacity and nitric oxide in patients with hepatic cirrhosis

This study investigated the relationship between the antioxidant capacity of blood and the serum level of nitric oxide (NO) in patients with hepatic cirrhosis. The study included 20 patients with compensated cirrhosis (group I), 30 with decompensated cirrhosis (group II), and 30 healthy controls (group III). The serum levels of NO, albumin, bilirubin, and uric acid, and the erythrocyte activity of superoxide dismutase (SOD) were measured in all groups. The mean erythrocyte SOD activity (5.94 +/- 3.21 U/mg protein) and serum NO level (25.19 +/- 8.15 micromol/L) in group I were similar to those of controls (6.86 +/- 2.47 U/mg protein and 21.67 +/- 6.51 micromol/L, respectively). However, erythrocyte SOD activity in group II was significantly lower than in groups I and III and mean serum NO level was significantly higher in group II than in groups I and III. In regard to non-enzymatic antioxidants, the mean serum albumin level was lower and the mean serum total bilirubin level was higher in group II than in groups I and III. As expected, group I had higher mean serum total bilirubin level than the control group. Correlation analysis showed that erythrocyte SOD activity in cirrhotic patients was negatively correlated with their serum levels of NO. These results suggest that disturbances of antioxidative mechanisms may diminish hepatic resistance to oxidative stress, thereby contributing to the development of fibrogenesis.     

The seroepidemiology of human T-lymphotropic viruses: types I and II in Europe: a prospective study of pregnant women

BACKGROUND: Up to 20 million persons are infected with the human retroviruses human T-lymphotropic virus (HTLV)-I and HTLV-II globally. Most data on the seroprevalence of HTLV-I and HTLV-II in Europe are from studies of low-risk blood donors or high-risk injection drug users (IDUs). Little is known about the general population. METHODS: A prospective anonymous study of HTLV-I and HTLV-II seroprevalence among 234,078 pregnant women in Belgium, France, Germany, Italy, Portugal, Spain, and the United Kingdom was conducted. Maternal antibody status was determined by standard methods using sera obtained for routine antenatal infection screens or eluted from infant heel prick dried blood spots obtained for routine neonatal metabolic screens. RESULTS: Anti-HTLV-I/II antibodies were detected and confirmed in 96 pregnant women (4.4 per 10,000, 95% confidence interval [CI]: 3.5-5.2). Of these, 73 were anti-HTLV-I, 17 were anti-HTLV-II, and 6 were specifically anti-HTLV but untyped. The seroprevalence ranged from 0.7 per 10,000 in Germany to 11.5 per 10,000 in France. CONCLUSIONS: Pregnant women better reflect the general population than blood donors or IDUs. The seroprevalence of HTLV-I and HTLV-II in Western Europe is 6-fold higher among pregnant women (4.4 per 10,000) than among blood donors (0.07 per 10,000). These data provide a robust baseline against which changes in HTLV-I and HTLV-II seroprevalence in Europe can be measured.     

Activation of group I mGluRs elicits different responses in murine CA1 and CA3 pyramidal cells

The group I metabotropic glutamate receptor agonist DHPG has been shown to produce two major effects on CA3 pyramidal cells at rest: a reduction in the background conductance and an activation of a voltage-gated inward current ( I _mGluR(V)). Both effects contribute to depolarising CA3 pyramidal cells and the latter has been implicated in eliciting prolonged epileptiform population bursts. We observed that DHPG-induced depolarisation was smaller in CA1 pyramidal cells than in CA3 cells. Voltage clamp studies revealed that while DHPG elicited I _mGluR(V) in CA3 pyramidal cells, such a response was absent in CA1 pyramidal cells. Both mGluR1 and mGluR5 have been localised in CA3 pyramidal cells, whereas only mGluR5 has been detected in CA1 pyramidal cells. Using mGluR1 knockout mice, we evaluated whether the absence of an I _mGluR(V) response can be correlated with the absence of mGluR1. In these experiments, DHPG failed to elicit I _mGluR(V) in CA3 pyramidal cells. This suggests that the smaller depolarising effects of DHPG on wild-type CA1 pyramidal cells is caused, at least in part, by the absence of I _mGluR(V) in these cells and that the difference in the responses of CA1 and CA3 cells may be attributable to the lack of mGluR1 in CA1 pyramidal cells.