Influence of serum paraoxonase polymorphism on serum lipids and apolipoproteins

One hundred and sixty-three healthy Chinese subjects of both sexes were studied for serum paraoxonase (PON) polymorphism, and levels of lipids and apolipoproteins in order to examine effects of PON alleles on these parameters. The level of serum triglyceride was significantly higher in high activity allele (PON*B) compared with that in low activity allele (PON*A) in both sexes (P less than 0.01). The subjects with PON A had significantly higher LDL cholesterol (P less than 0.05) and lower Apo A-II and ApoB levels. The influence of serum paraoxonase on serum lipids was estimated further by Spearman's rank correlation. In the males, there was a significant negative correlation of serum paraoxonase activity with total (P less than 0.05) and LDL (P less than 0.01) cholesterol levels, and positive correlation with HDL cholesterol and Apo A-II levels (P less than 0.05). Serum paraoxonase activity had a high positive correlation with serum triglyceride levels in both sexes (P less than 0.001). Serum ApoB level had a positive correlation with the enzyme activity only in females (P less than 0.01). The allelic effect of PON on these parameters was studied by multiple regression analysis. The high activity allele (PON*B) was associated with higher serum triglyceride level (P less than 0.001) and ApoB (P less than 0.001), while it had lowering influence on total cholesterol (P less than 0.05) and LDL cholesterol (P less than 0.005) in men. The average allelic effect of PON was found to be about 22% for serum triglycerides, 11% for LDL cholesterol, 14% for Apo A-II and 19% for Apo B in the present study. This study suggests a possible significant role of serum paraoxonase alleles in the metabolism of serum lipids and apolipoproteins.     

Evaluation of three simple and rapid immunological tests for detection of heat-labile enterotoxin of enterotoxigenic Escherichia coli.

Three simple immunological tests, the modified Elek (Biken) test, the modified staphylococcal coagglutination test, and the rapid GM1-horseradish peroxidase-enzyme-linked immunosorbent assay have been evaluated for detection of heat-labile enterotoxin of enterotoxigenic Escherichia coli. Of the 100 coded E. coli strains tested, 94 gave consistent results with all the three immunological tests; a discrepancy was observed in only 6 strains. Identical results were obtained when the Biken test was conducted with complete and incomplete Biken kits (Meguro Institute Ltd., Osaka, Japan). All three immunological tests evaluated in this study were found to be sensitive and simple and can be easily adopted by any laboratory for detection of heat-labile enterotoxins of enterotoxigenic E. coli strains.     

Rapid identification and antibiotic susceptibility testing of Salmonella enterica serovar Typhi isolated from blood: implications for therapy

The turnaround time (TAT) for Salmonella enterica serovar Typhi identification and reporting of the antibiotic susceptibility profile was determined for 391 cases of typhoid fever, using the lysis direct plating or lysis centrifugation method of blood culture along with rapid antimicrobial susceptibility testing. The TAT was more rapid (TAT for 90% of the patients [TAT(90)] = 30 h; TAT(100) 相似文献   

The trypanosome alternative oxidase exists as a monomer in Trypanosoma brucei mitochondria

The bloodstream forms of African trypanosomes solely depend on trypanosome alternative oxidase (TAO), for respiration. Similar to alternative oxidases (AOXs) found in plants and fungi, TAO is a membrane-bound diiron protein. Here, we investigated if TAO exists as a dimer like plant AOXs, or as a monomer like that of fungi. We have found that TAO forms a homo-dimer on a regular SDS-PAGE in the absence of any reducing agent and exists as a monomer under reducing condition. However, TAO does not form a dimer upon treatment of mitochondria with diamide. TAO was found as a higher molecular mass complex on a Blue-native gel after solubilization with digitonin. In the detergent soluble form, TAO activity was stimulated under reducing and inhibited under oxidizing condition. However, these conditions have no effect on the TAO activity in the mitochondria. Moreover, chemical cross-linking analysis revealed that TAO could not be cross-linked when present in the mitochondria. Together, it suggests that like certain other hydrophobic membrane proteins, TAO forms a dimer or oligomer when solubilized with detergents, and the TAO-dimer is SDS-resistant. However, it exists as a monomer in Trypanosoma brucei mitochondria.     

The E3-11.6K protein of adenovirus is an Asn-glycosylated integral membrane protein that localizes to the nuclear membrane.

The 11,600 MW (101 amino acids; 11.6K) protein of adenovirus 2 (Ad2) is a protein of unknown function which is synthesized in low amounts during early stages of infection but in very high amounts at late stages. The 11.6K protein migrates as three major groupings of diffuse bands of ca. 14K, 21K, and 31K on SDS-PAGE, indicating that 11.6K undergoes post-translational modification. We show here that 11.6K is Asn-glycosylated with complex (endo H-resistant) oligosaccharides and that 11.6K is an integral membrane protein. Immunofluorescence indicated that 11.6K initially is associated with the endoplasmic reticulum and Golgi apparatus and that it ultimately localizes to the nuclear membrane. The 11.6K protein is predicted to have a single signal-anchor sequence at residues 41-62 and only one potential Asn-linked glycosylation site at residue 14; thus, 11.6K must be oriented in the membranes with its NH2-terminus in the lumen and its COOH-terminus in the cytoplasm. The signal-anchor and glycosylation features of 11.6K are preserved in Ad2 and Ad5 (group C), and in Ad3 and Ad7 (group B), but the sequence of 11.6K is more diverged among these serotypes than is the sequence of most other adenovirus proteins.     

Adverse effects of early dexamethasone in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network

BACKGROUND: Early administration of high doses of dexamethasone may reduce the risk of chronic lung disease in premature infants but can cause complications. Whether moderate doses would be as effective but safer is not known. METHODS: We randomly assigned 220 infants with a birth weight of 501 to 1000 g who were treated with mechanical ventilation within 12 hours after birth to receive dexamethasone or placebo with either routine ventilatory support or permissive hypercapnia. The dexamethasone was administered within 24 hours after birth at a dose of 0.15 mg per kilogram of body weight per day for three days, followed by a tapering of the dose over a period of seven days. The primary outcome was death or chronic lung disease at 36 weeks' postmenstrual age. RESULTS: The relative risk of death or chronic lung disease in the dexamethasone-treated infants, as compared with those who received placebo, was 0.9 (95 percent confidence interval, 0.8 to 1.1). Since the effect of dexamethasone treatment did not vary according to the ventilatory approach, the two dexamethasone groups and the two placebo groups were combined. The infants in the dexamethasone group were less likely than those in the placebo group to be receiving oxygen supplementation 28 days after birth (P=0.004) or open-label dexamethasone (P=0.01), were more likely to have hypertension (P<0.001), and were more likely to be receiving insulin treatment for hyperglycemia (P=0.02). During the first 14 days, spontaneous gastrointestinal perforation occurred in a larger proportion of infants in the dexamethasone group (13 percent, vs. 4 percent in the placebo group; P=0.02). The dexamethasone-treated infants had a lower weight (P=0.02) and a smaller head circumference (P=0.04) at 36 weeks' postmenstrual age. CONCLUSIONS: In preterm infants, early administration of dexamethasone at a moderate dose has no effect on death or chronic lung disease and is associated with gastrointestinal perforation and decreased growth.     

Optimedin: a novel olfactomedin-related protein that interacts with myocilin

Mutations in the MYOC gene may lead to juvenile open-angle glaucoma with high intraocular pressure, and are detected in about 4% of people with adult onset glaucoma. Most of these mutations are found in the third exon of the gene encoding the olfactomedin-like domain located at the C terminus of the protein. Another olfactomedin-related protein, known as noelin or pancortin, is involved in the generation of neural crest cells. Here we describe the identification of a novel olfactomedin-related gene, named optimedin, located on chromosome 1p21 in humans. Optimedin and noelin are both expressed in brain and retina. However, unlike noelin, rat optimedin is also highly expressed in the epithelial cells of the iris and the ciliary body in close proximity to the sites of Myoc expression. In the human eye, optimedin is expressed in the retina and the trabecular meshwork. Both optimedin and myocilin are localized in Golgi and are secreted proteins. The presence of mutant myocilin interferes with secretion of optimedin in transfected cells. Optimedin and myocilin interact with each other in vitro as judged by the GST pulldown, co-immunoprecipitation and far-western binding assays. The C-terminal olfactomedin domains are essential for interaction between optimedin and myocilin, while the N-terminal domains of both proteins are involved in the formation of protein homodimers. We suggest that optimedin may be a candidate gene for disorders involving the anterior segment of the eye and the retina.     

Validity of a modified Born approximation for a pulsed plane wave in acoustic scattering problems

The validity domain of a modified Born approximation (MBA) has been examined for the scattering of a pulsed plane wave (PPW). This new approximation has been compared with exact results and also with the conventional Born approximation (BA). Comparisons have been made for the scattering by a homogeneous sphere. Error charts have been presented for various scatterer sizes and acoustic properties for forward as well as back scattering. The pulse width has also been varied. Our study shows that the modified Born approximation is generally preferable to the conventional Born approximation in the forward direction. In the backward direction both approximations have a similar kind of validity domain. These observations are important in view of the fact that the Born approximation has been widely used in acoustic scattering problems.     

Leishmania promastigote membrane antigen-based enzyme-linked immunosorbent assay and immunoblotting for differential diagnosis of Indian post-kala-azar dermal leishmaniasis

Diagnosis of post-kala-azar dermal leishmaniasis (PKDL), caused by Leishmania donovani, is difficult, as the dermal lesions are of several types and resemble those caused by other skin diseases, especially leprosy. Since the disease generally appears very late after the clinical cure of kala-azar in India, it is also difficult to correlate PKDL with a previous exposure to L. donovani. Very few attempts have been made so far to diagnose PKDL serologically, and the diagnostic methods vary in their sensitivities and specificities. Diagnosis of PKDL through sophisticated PCR methods, although highly sensitive, has limited practical use. We have developed a serodiagnostic method using an enzyme-linked immunosorbent assay to detect specific immunoglobulin (Ig) isotypes and IgG subclass antibodies in the sera of Indian PKDL patients. Our assay, which uses L. donovani promastigote membrane antigens, was 100% sensitive for the detection of IgG and 96.7% specific for the detection of IgG and IgG1. Optical density values for individual patients, however, demonstrated wide variations. Western blot analysis based on IgG reactivity could differentiate patients with PKDL from control subjects, which included patients with leprosy, patients from areas where kala-azar is endemic, and healthy subjects, by the detection of polypeptides of 67, 72, and 120 kDa. The recognition patterns of the majority of serum samples from patients with PKDL were also distinct from those of the serum samples from patients with visceral leishmaniasis (VL), at least for a 31-kDa polypeptide. To further differentiate patients with PKDL from those with active and cured VL, we analyzed the specific titers of the Ig isotypes and IgG subclasses. High levels of IgG, IgG1, IgG2, and IgG3 antibodies significantly differentiated patients with PKDL from patients cured of VL. The absence of antileishmanial IgE and IgG4 in patients with PKDL differentiated these patients from those with active VL. These results imply intrinsic differences in the antibodies generated in the sera from patients with PKDL and VL.     

Polymorphism of germ-line immunoglobulin VH genes correlates with allotype and idiotype markers

The polymorphic nature of the immunoglobulin V_H genes was investigated by Southern blot analysis of liver DNA of sixteen different mouse strains and hybridization with V_H probes. Differences in restriction enzyme pattern (REP) were observed and six different patterns of restriction fragments were found for the sixteen strains analyzed. No equivalent polymorphism was observed in another multigene family, the actins. The six patterns correlate with immunoglobin constant region allotypes (Igh-1). Experiments with Igh-1-congenic strains suggest that the V_H REP is linked to immunoglobulin constant region haplotype. Mouse strains which share inherited idiotypes also share identical V_H restriction pattern. This provides a structural basis for the genetic linkage between idiotypes and allotypes. It also indicates that different strains carry different VH gene repertoires, which may be the basis for the expression of different inherited idiotypes in various strains. We propose that a V_H group is a set of linked genes that are coinherited as a cluster with the constant region genes and that V_H and C_H can be regarded as an extended haplotype.