Tumor necrosis factor alpha induced protein 3, interleukin 10, tumor necrosis factor alpha, and interleukin 17 F genes polymorphisms in Algerian patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation. Its pathogenesis involves immunological, genetic, and environmental factors. We investigate the association between Tumor Necrosis Factor α Protein 3 (TNFAIP3), Interleukin 10 (IL10), Tumor Necrosis Factor α (TNF α), and Interleukin 17 F (IL17F) polymorphisms with susceptibility to RA. METHODS AND RESULTS: 191 patients with RA diagnosed according to the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification and 190 healthy subjects were recruited. Rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), and C-reactive protein (CRP) were measured. Genotyping of the polymorphisms was performed by real-time PCR. Analysis of the allelic frequencies of TNFAIP3 showed a positive association OR (95% CI) = 1.46 (1.01-2.09); p = 0.04, but failed to meet the criteria of significance after Bonferroni Correction. The genotypic and allelic distribution of the IL10, IL17F, and TNFα showed no significant difference when comparing the RA group with controls. Furthermore, the genotype codominant model shows a moderate positive association in the presence of ACPA (OR (95% CI) = 2.82 (1.22-6.24); p = 0.01. None of the polymorphisms studied was associated with RF and CRP production. CONCLUSION: Our results show that there is a tendency for the AG genotype of IL10-1082 to be associated with the production of ACPA in patients with RA. None of the variants studied were associated with RA susceptibility in Algerians.

Phenobarbital increases DNA adduct and metabolites formed by ochratoxin A: role of CYP 2C9 and microsomal glutathione-S-transferase.

Ochratoxin A (OTA), a mycotoxin that induces nephrotoxicity and urinary tract tumors, is genotoxic and can be metabolized not only by different cytochromes P450 (CYP) but also by peroxidases involved in the arachidonic cascade, although the exact nature of the metabolites involved in the genotoxic process is still unknown. In order to establish the relation between OTA genotoxicity and the formation of metabolites, we chose three experimental models: kidney microsomes from rabbit, human bronchial epithelial cells, and microsomes from yeast that specifically express the human cytochrome P450 2C9 or 2B6 genes. OTA-DNA adducts were analyzed by (32)P postlabeling and the OTA derivatives formed were isolated by HPLC after incubation of OTA in the presence of: (1) kidney microsomes from rabbit pretreated or not with phenobarbital (PB); (2) human pulmonary epithelial cells simultaneously pretreated (or not) with PB alone or in the presence of ethacrynic acid (EA); (3) microsomes expressing CYP 2B6 and 2C9. PB pretreatment significantly increased DNA adducts formed after OTA treatment, both in the presence of kidney microsomes and bronchial epithelial cells, and induced the formation of new adducts. Ethacrynic acid, which inhibits microsomal glutathione-S-transferase, reduced DNA adduct level. DNA adducts were detected when OTA were incubated with microsomes expressing human CYP 2C9 but not with those expressing CYP 2B6. Several metabolites detected by HPLC were increased after PB treatment. Some of them could be related to DNA-adduct formation. In conclusion, OTA biotransformation, enhanced by PB pretreatment, increased DNA-adduct formation through pathways involving microsomal glutathion-S-transferase and CYP 2C9.

Red cell enzyme polymorphisms in Moroccans and southern Spaniards: new data for the genetic history of the western Mediterranean.

Population samples from Morocco (El Jadida, south Atlantic coast) and La Alpujarra (Granada mountains, Spain), located on both shores of the western Mediterranean, were typed for 8 erythrocyte genetic markers: ACP1, ESD, PGD, AK1, GLO1, PGM1, SODA, and DIA. Genetic heterogeneity within western Mediterranean groups was investigated on the basis of allele frequencies of these 8 polymorphisms plus ABO and Rh (CDE). Only slight peculiarities for the ACP1, GLO1, and AK1 systems were observed in the 2 samples compared with other Mediterranean data. The new data are consistent with a main north to south genetic differentiation in the Mediterranean region. However, with regard to other European groups, the La Alpujarra population shows a particular affinity with North Africans that may be compatible with both an ancient common substratum and/or a special historical influence during the Muslim domination of the Iberian Peninsula.

Genetic relationships between southeastern Spain and Morocco: New data on ABO, RH, MNSs, and DUFFY polymorphisms.

The genetic polymorphism of four blood group systems (ABO, RH, MNSs, and DUFFY) was analyzed in two well-defined population samples coming from south-central Morocco and southeastern Spain. Both a controversial ancient common substrate and the long period of coexistence between North Africa and southern Spain during the eight centuries of the Islamic invasion of the Iberian Peninsula suggest a particular genetic relationship between northwestern Africa and southern Spain. Allele distributions in each sample are in general agreement with that expected according to the geographical and historical characteristics in the Mediterranean region. However, the differences between the Moroccan sample and other north African groups illustrate considerable genetic variability in this geographical region. In comparison with other samples from different regions of the Iberian Peninsula, the markers examined fail to demonstrate any particular affinity between the southern Spanish sample of La Alpujarra and Moroccan populations. Am. J. Hum. Biol. 11:745-752, 1999. Copyright 1999 Wiley-Liss, Inc.

Digital dermatoglyphic patterns of Moroccan Arabs: relationships with Mediterranean populations.

Dermatoglyphic finger patterns and pattern intensity were examined in a sample of 204 (105 males and 99 females) adults from the authochthonous Arab population of south central Morocco. No significant sex differences were found for the overall finger pattern incidence or for the pattern intensity index. A high incidence of arches is the most remarkable characteristic of this population as compared to other Mediterranean groups. The significant differences from two previous sets of Moroccan data indicate a remarkable heterogeneity within the present day Moroccan population. Also important is the differentiation of this sample from other north African ethnic groups such as Berbers and Tuaregs. An analysis of the dermatoglyphic relationships using R-matrix analysis, shows a relative proximity between this Moroccan series and other southwest European groups as compared to north African populations.

Cost effectiveness of noninvasive oxygen saturation measurement during exercise for the diagnosis of Pneumocystis carinii pneumonia.

We assessed (1) the sensitivity and specificity of exercise oxygen saturation measurement (EOS) for the diagnosis of Pneumocystis carinii pneumonia (PCP); and (2) the cost of introducing this indirect diagnostic test compared with that of standard diagnostic strategies for PCP. In a prospective study, 85 HIV-infected patients with suspected PCP underwent EOS, followed by induced sputum (IS) and bronchoalveolar lavage (BAL) if IS was negative for P. carinii. The prevalence of PCP was 0.22, the sensitivity of IS was 0.6, and its specificity was perfect. The cost ratios of IS to BAL and EOS to BAL were 0.1 and 0.2, respectively. A desaturation of three points was the best cutoff point, giving perfect sensitivity and a specificity of 0.77. The cost analysis showed that the introduction of EOS into diagnostic strategies for PCP is highly justified when the local prevalence is low. Exercise oxygen saturation measurement is simple and safe, and the results are available rapidly; its sensitivity is perfect and its specificity good. Its economic utility depends on its cost and the local prevalence of PCP in the test population.

Effects of carotid denervation and decerebration on ventilatory response to CO.

To clarify the mechanisms involved in the ventilatory response to the inhalation of low concentrations of CO (0.18-0.22% in air), the roles of the arterial chemoreceptors and the forebrain structures have been investigated in unanesthetized adult cats. The ventilatory response was observed in conscious animals intact, after carotid denervation (CD), and after midcollicular decerebration. The results show that the initial small ventilatory depression was unaffected by CD but that the subsequent characteristic tachypnea was blunted after CD even after more prolonged exposure to CO. The CO tachypnea was not observed after decerebration, but a residual hyperventilation was noted with the higher concentration used. It may be concluded that carotid chemoreceptors do not mediate the CO tachypnea, which may then originate in suprapontine structures as shown by comparison of intact and decerebrate animals. The blunting of the tachypnea after CD may be caused by the relative hypercapnia observed in CD animals. The residual hyperventilation observed in decerebrate animals may be caused by central acidosis and/or some peripheral potentiation of chemoreceptor activity resulting from the decrease in arterial blood pressure that accompanied CO inhalation in decerebrate animals.

Cell cycle-specific variation of intracellular plasminogen activator activity in cultured human alveolar epithelial carcinoma and rat hepatoma cells.

Plasminogen activator activity was demonstrated in two carcinoma cell lines: A549 cells derived from a human alveolar epithelial carcinoma; and ZHC cells derived from a rat hepatoma. Both cells had intracellular plasminogen activator activity throughout their cell cycles and in each case this activity reached a maximum. For A549 cells the maximal activity took place either during the G2 phase or in the course of the S to G2 transition, suggesting that plasminogen activator might play a role in cell division. For ZHC cells, the maximal activity occurred at the start of the S phase, suggesting that in these cells plasminogen activator might be involved in DNA replication.

Influence of halothane on control of breathing in intact and decerebrated cats.

The effects of halothane anesthesia have been investigated in intact and in decerebrated cats. Pulmonary ventilation and breathing pattern were studied during room-air breathing, hypercapnia, and O2 inhalation. The following results have been demonstrated. First, halothane anesthesia does not modify pulmonary ventilation, but a tachypnea much more intense in intact than in decerebrated cats is observed. This indicates that halothane-induced tachypnea originates mainly in structures rostral to the brain stem. Second, decerebrated animals exhibit a breathing pattern and a ventilatory response to CO2 similar to those of intact conscious cats, suggesting that forebrain facilitatory and inhibitory influences on brain stem are cancelled out by decerebration. However, the tidal volume vs. inspiratory duration relationship observed in decerebrated cats differs from that in conscious cats. Finally, during halothane anesthesia, ventilatory response to CO2 is markedly depressed. Third, during O2 inhalation, except in decerebrated, anesthetized animals, ventilation is only slightly depressed. This suggests that central stimulatory effect of O2 is enhanced and/or that peripheral chemoreceptor drive is reduced.

Smoking does not reduce the functional activity of serum alpha-1-proteinase inhibitor. An epidemiologic study of 719 healthy men.

The present study was aimed at testing the hypothesis that smoking, the major risk factor for the development of pulmonary emphysema, impairs the functional activity of alpha 1-proteinase inhibitor (alpha 1-antitrypsin). We used a population of 719 apparently healthy subjects. The serum concentrations of immunoreactive and functionally active alpha 1-proteinase inhibitor were measured by radial immunodiffusion and inhibition of porcine pancreatic elastase, respectively. Both the immunoreactive and functionally active levels of serum alpha 1-proteinase inhibitor were found to increase with tobacco consumption, but the ratio between the 2 concentrations was independent of smoking. Smoking does not, therefore, impair the functional activity of alpha1-proteinase inhibitor.

A simple spectrophotometric assay of plasminogen activator: comparison with the fibrinolytic method.

We describe a simple assay of plasminogen activator in which the enzyme reacts with a mixture of plasminogen and H-D-valyl-L-leucyl-L-lysine-p-nitroanilide for 1 h at 37 degrees C after which the absorbance is measured at 405 nm. The method detects as little as 2 CTA milliunits of activator and is linear over a 100-fold range of enzyme concentration. The new procedure has been used successfully for the assay of activator in breast tumor cytosols, cell culture supernatants, and pleural or ascitic fluids. Thirty-two biological samples have been assayed for plasminogen activator activity with both the spectrophotometric method and a classical fibrinolytic technique using radiolabeled fibrin. Although the two series of results are significantly correlated, the activities measured with the former assay are significantly different from those determined with the latter. It is shown that the spectrophotometric method is, in many respects, superior to the fibrinolytic procedure.

Gas exchanges during exercise in normoxia and hyperoxia.

Exercises of constant workload (90 watt) have been carried out during normoxia or hyperoxia FIO2 = 0.45). It has been shown that, in spite of a significant dispersion in the values of O2 deficit and O2 debt calculated, these values are related to the increased blood lactate level which contributes to the marked acidosis observed in both conditions of oxygenation. Hyperoxia reduces lactate level as well as the O2 debt. In addition to the significant increase in arterial [H+] and PCO2, exercise provokes a slight decrease in PO2. It is suggested that the significant variations of these humoral factors might contribute to the control of ventilation during exercise in both conditions of oxygenation.