Association between the interleukin 4 gene -590C>T promoter polymorphism and asthma in Xinjiang Uighur children.

We investigated the association between the interleukin 4 gene (IL-4) -590C>T polymorphism and forced expiratory volume in one second (FEV1) values, immunoglobulin E (IgE) levels, and susceptibility to asthma in Uighur children. IL-4 -590C>T frequencies were analyzed in 38 bronchial asthmatic patients and 35 non-asthmatic controls. Polymerase chain reaction and direct sequencing were applied to determine the residue at position -590 of IL-4. Total serum IgE levels were detected by enzyme-linked immunosorbent assay, while lung function was examined by professionals. There were significant differences in the distribution of IL-4 -590C>T genotypes and alleles between patient and control groups (genotypes: chi-square = 11.476, P < 0.05; alleles: chi-square = 14.572, P < 0.05). Frequencies of CC, CT, and TT genotypes were 21, 29, and 50% among patients, and 49, 37, and 14% among controls, respectively, indicating that the T allele was significantly more frequent in the asthma group than in the control group. Total serum IgE levels were significantly higher (P < 0.05) and FEV1 values were significantly lower (F = 13.294, P < 0.05) in patients than in control subjects of the same genotype. In conclusion, the IL-4 -590C>T polymorphism is related to bronchial asthma in Uighur children, and the T allele may constitute a susceptibility factor in this group. Furthermore, this genetic variant can result in raised IgE levels and decreased FEV1 values, suggesting that both factors are associated with bronchial asthma in Uighur children.

Clostridium sporogenes delivers interleukin-12 to hypoxic tumours, producing antitumour activity without significant toxicity.

UNLABELLED: Clostridium sporogenes ATCC 3584 is an obligate anaerobe that has been reported to possess excellent tumour-targeting capacity. Here, we use Cl. sporogenes as a vector to deliver IL-12, a potent antitumour cytokine that bears numerous antitumour properties but that has limited clinical applications due to its strong toxicity when delivered systemically. In this study, Cl. sporogenes was genetically engineered to secrete murine IL-12, and its antitumour efficacy and toxicity were investigated in a murine EMT6 mammary carcinoma model. After intravenous injection, Cl. sporogenes was able to selectively settle and reproduce in the tumours without encroaching on normal tissues, resulting in a clear delay of tumour growth and a 14·3% cure rate. Importantly, the mice showed no obvious toxicity-associated side effects, such as diarrhoea and weight loss, during the treatment process. The significant antitumour efficacy and low toxicity of this treatment may be explained by the selective tumour-targeting properties of Cl. sporogenes and by the sustained release of IL-12 accompanying bacterial proliferation. This moderate local IL-12 concentration would not induce the severe response in the entire body, that is inevitable when IL-12 is administered directly. SIGNIFICANCE AND IMPACT OF THE STUDY: Interleukin-12 (IL-12) is a potent antitumour cytokine, but it is toxic when administrated systemically. This study demonstrates that murine IL-12 can be systemically delivered to hypoxic sites in solid tumours by Clostridium sporogenes, producing a clear delay in tumour growth and a 14·3% cure rate in a mouse tumour model. Importantly, there is no obvious toxicity associated with IL-12 during the treatment process. This result may be accounted for by the excellent tumour-targeting capacity of Cl. sporogenes, targeting IL-12 directly to the tumour site instead of to the entire body.

[Intrahepatic biliary lithiasis : role of Ascaris infection in 150 cases. Experimental study on bile stone formation (author's transl)]. / Lithiase biliaire intra-hépatique. 150 cas. Rôle de l'infestation ascaridienne. Expérimentation sur la formation des calculs biliaires.

Biliary infection was the cause of intrahepatic biliary lithiasis in 150 patients operated upon over the last twenty years. Diagnosis was established during operation in the majority of cases, but cholangiography, or ultrasound and/or scintiscan examinations were required in a few patients. To determine the mechanism of formation of these biliary stones, a study was conducted in 30 rabbits divided into three groups, each forming a model of lithogenesis. Pathological examination of the liver demonstrated the presence of multiple abscesses, fibrosis, bile duct stenosis, and perihepatitis. The results of the different types of operative techniques employed in these patients are described.

Gene sequencing for identification of Paragonimus eggs from a human case.

OBJECTIVE: To identify the etiologic agent from a paragonimiasis patient using molecular techniques. METHODS: The complete nuclear ribosomal DNA second internal transcribed spacer (ITS2) gene sequence of eggs in sputum from a paragonimiasis patient was obtained by directly auto-sequencing its PCR product. ITS2 genes from eggs of Paragonimus westermani and Pagumogonimus skrjabini (both from animal hosts) were also sequenced for comparison. In addition, morphological comparisons were made with the eggs of the two species. RESULTS: The ITS2 gene from the human case was 100% identical with the sequence from the eggs of P. westermani from an experimentally infected dog but only 92% identical with the sequence from the eggs of P. skrjabini. Morphologically, the eggs from the human case more resembled those from P. westermani infected dog. CONCLUSION: The patient was diagnosed to be suffered from paragonimiasis westermani by gene sequence analysis.

[Study on molecular phylogeny of Schistosoma sinensium based on nuclear ribosomal DNA].

OBJECTIVE: To determine the phylogenetic relationships between Schistosoma sinensium and other Schistosomatid species using DNA sequence data. Two segments of the nuclear rDNA repeat, the second internal spacer (ITS2) and large subunit (LSU/12S) were selected for sequencing. METHODS: Adult worms stored in 100% methanol were washed 3 times with 0.1 x TE (pH8.0) and the genomic DNA was extracted by the GNT-K method. The target regions were amplified by PCR using specific primers. The PCR products were purified before ligation into the plasmid pT-adv (Clontech). Recombinant plasmids were amplified in E. coli (strain TOP10), extracted and purified using routine methods and then sequenced using M13 primers (F/R) on a Licor long-read auto-sequencer. Sequences of related schistosomes were retrieved from GenBank and aligned with our data in the sequence editor ESEE. Gene trees were constructed in PHYLIP (Version 3.6 alpha July, 2,000) and MEGA (version 2.0 beta build 3) using both Maximum Parsimony and Neighbor-Joining methods. For parsimony analysis, all characters were treated as unordered and with equal weights. At least 3,000 cycles of bootstrapping were carried out. For analysis in MEGA, all gap columns were deleted. Schistosomatium douthitti and Trichobilharzia were used as outgroups. RESULTS: The ITS2 and LSU sequences of Schistosoma sinensium were obtained. The ITS2 sequence of Trichobilharzia sp. was reported here for the first time. CONCLUSION: The phylogenetic trees from these data of nuclear rDNA suggested that S. sinensium belongs to the Asian schistosome group. And this species might be an ancient member in the Asian clade.

A molecular perspective on the genera Paragonimus Braun, Euparagonimus Chen and Pagumogonimus Chen.

The status of the genera Euparagonimus Chen, 1963 and Pagumogonimus Chen, 1963 relative to Paragonimus Braun, 1899 was investigated using DNA sequences from the mitochondrial cytochrome c oxidase subunit I (CO1) gene (partial) and the nuclear ribosomal DNA second internal transcribed spacer (ITS2). In the phylogenetic trees constructed, the genus Pagumogonimus is clearly not monophyletic and therefore not a natural taxon. Indeed, the type species of Pagumogonimus, P. skrjabini from China, is very closely related to Paragonimus miyazakii from Japan. The status of Euparagonimus is less obvious. Euparagonimus cenocopiosus lies distant from other lungflukes included in the analysis. It can be placed as sister to Paragonimus in some analyses and falls within the genus in others. A recently published morphological study placed E. cenocopiosus within the genus Paragonimus and probably this is where it should remain.