Inhibition of L- and P-selectin by a rationally synthesized novel core 2-like branched structure containing GalNAc-Lewisx and Neu5Acalpha2- 3Galbeta1-3GalNAc sequences

The selectins interact in important normal and pathological situations with certain sialylated, fucosylated glycoconjugate ligands containing sialyl Lewisx(Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3)GlcN Ac). Much effort has gone into the synthesis of sialylated and sulfated Lewisxanalogs as competitive ligands for the selectins. Since the natural selectin ligands GlyCAM-1 and PSGL-1 carry sialyl Lewisxas part of a branched Core 2 O-linked structure, we recently synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(SE-3Galbeta1++ +-3)GalNAc1alphaOMe and found it to be a moderately superior ligand for L and P-selectin (Koenig et al. , Glycobiology 7, 79-93, 1997). Other studies have shown that sulfate esters can replace sialic acid in some selectin ligands (Yeun et al. , Biochemistry, 31, 9126-9131, 1992; Imai et al. , Nature, 361, 555, 1993). Based upon these observations, we hypothesized that Neu5Acalpha2-3Galbeta1-3GalNAc might have the capability of interacting with L- and P-selectin. To examine this hypothesis, we synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(Neu5Acalpha2++ +-3Galbeta1-3)- GalNAc alpha1-OB, which was found to be 2- to 3-fold better than sialyl Lexfor P and L selectin, respectively. We also report the synthesis of an unusual structure GalNAcbeta1-4(Fucalpha1- 3)GlcNAcbeta1-OMe (GalNAc- Lewisx-O-methyl glycoside), which also proved to be a better inhibitor of L- and P-selectin than sialyl Lewisx-OMe. Combining this with our knowledge of Core 2 branched structures, we have synthesized a molecule that is 5- to 6-fold better at inhibiting L- and P-selectin than sialyl Lewisx-OMe, By contrast to unbranched structures, substitution of a sulfate ester group for a sialic acid residue in such a molecule resulted in a considerable loss of inhibition ability. Thus, the combination of a sialic acid residue on the primary (beta1-3) arm, and a modified Lexunit on the branched (beta1-6) arm on an O-linked Core 2 structure generated a monovalent synthetic oliogosaccharide inhibitor superior to SLexfor both L- and P-selectin.      

The use of zootherapeutics in folk veterinary medicine in the district of Cubati, Paraíba State, Brazil

Background

Viewed through the micro focus of an interpretive lens, medical anthropology remains mystified because interpretivist explanations seriously downplay the given context in which individual health seeking-behaviours occur. This paper draws upon both the interpretivist and political economy perspectives to reflect on the ethno medical practices within the Korean-Australian community in Sydney.

Methods

We draw on research data collected between 1995 and 1997 for an earlier study of the use of biomedical and traditional medicine by Korean-Australians in Sydney. A total of 120 interviews were conducted with a range of participants, including biomedical doctors, traditional health professionals, Korean community leaders and Korean migrants representing a range of socio-economic backgrounds and migration patterns.

Results and Discussion

First, the paper highlights the extent to which the social location of migrants in a host society alters or restructures their initial cultural practices they bring with them. Second, taking hanbang medicine in the Korean-Australian community as an illustrative case, the paper explores the transformation of the dominant biomedicine in Australia as a result of the influx of ethnomedicine in the era of global capitalism and global movement.

Conclusion

In seeking to explain the popularity and supply of alternative health care, it is important to go beyond the culture of each kind of health care itself and to take into consideration the changes occurring at societal, national and global levels as well as consequential individual response to the changes. New social conditions influence the choice of health care methods, including herbal/alternative medicine, health foods and what are often called New Age therapies.     

Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration

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Highlights? Cardiac injury induces structural and molecular changes in zebrafish endocardium ? Endocardial and epicardial cells at the site of injury synthesize retinoic acid (RA) ? The extent of this injury response correlates with a species' regenerative capacity ? Regenerative cardiomyocyte proliferation in zebrafish requires retinoic acid signaling     

Segregation Analysis of Body Mass Index in an Unselected French-Canadian Sample: The Québec Family Study

Interest in a single gene etiology for obesity, as assessed by the body mass index (BMI), has been spurred recently by reports of a putative recessive major gene for extreme values, which accounts for as much as 40% of the variance. The major gene hypothesis was evaluated here in the Québec Family Study, a random sample of 375 French-Canadian volunteer families. This report represents one component in a more complete investigation of obesity in these families. In contrast to the recent studies, a major gene hypothesis for BMI was not verified here. Although there was a major effect, it did not conform to a Mendelian pattern of transmission. A multifactorial component (i.e., polygenic and/or common environmental factors) accounted for 42% of the phenotypic variance. In addition, evidence of heterogeneity between the generations was found. The heterogeneity was traced to the major non-Mendelian component (which accounted for 0.01% of the variance in parents and over 40% in offspring) rather than to the multifactorial one. These results would suggest that a simple recessive gene mixed model may not be sufficient to explain the familial distribution of the BMI. Several factors which may have contributed to these results include temporal trends and surrogate effects such as those related to variation in body composition and energy balance components. (OBESITY RESEARCH 1993; 1:288–294)     

Bias Assessment of General Chemistry Analytes using Commutable Samples

Harmonisation of reference intervals for routine general chemistry analytes has been a goal for many years. Analytical bias may prevent this harmonisation. To determine if analytical bias is present when comparing methods, the use of commutable samples, or samples that have the same properties as the clinical samples routinely analysed, should be used as reference samples to eliminate the possibility of matrix effect. The use of commutable samples has improved the identification of unacceptable analytical performance in the Netherlands and Spain. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has undertaken a pilot study using commutable samples in an attempt to determine not only country specific reference intervals but to make them comparable between countries. Australia and New Zealand, through the Australasian Association of Clinical Biochemists (AACB), have also undertaken an assessment of analytical bias using commutable samples and determined that of the 27 general chemistry analytes studied, 19 showed sufficiently small between method biases as to not prevent harmonisation of reference intervals. Application of evidence based approaches including the determination of analytical bias using commutable material is necessary when seeking to harmonise reference intervals.     

Correcting eggshell indices of raptor eggs for hole size and eccentricity

Eggshell thickness is often expressed by means of an index based on the length, breadth and weight of the shell. The effect of the blow-hole and egg eccentricity on Ratcliffe's shell thickness index was investigated in a sample of 585 eggs from six raptor species. Corrections for the size of the hole and egg eccentricity are proposed, as is a combined formula to correct both sources of error at the same time. It is shown that by using these formulae, considerable improvements in estimates of shell thinning are obtained. These may be especially useful when sample sizes are small, which is often the case when working with species that have been reduced in numbers.     

Expression of Lex antigen in Schistosoma japonicum and S.haematobium and immune responses to Lex in infected animals: lack of Lex expression in other trematodes and nematodes

Adults of the human parasitic trematode Schistosoma mansoni, which causes hepatosplenic/intestinal complications in humans, synthesize glycoconjugates containing the Lewis x (Lex) Galbeta1-->4(Fucalpha1-- >3)GlcNAcbeta1-->R, but not sialyl Lewis x (sLex), antigen. We now report on our analyses of Lexand sLexexpression in S.haematobium and S.japonicum, which are two other major species of human schistosomes that cause disease, and the possible autoimmunity to these antigens in infected individuals. Antigen expression was evaluated by both ELISA and Western blot analyses of detergent extracts of parasites using monoclonal antibodies. Several high molecular weight glycoproteins in both S. haematobium and S. japonicum contain the Lexantigen, but no sialyl Lexantigen was detected. In addition, sera from humans and rodents infected with S.haematobium and S.japonicum contain antibodies reactive with Lex. These results led us to investigate whether Lexantigens are expressed in other helminths, including the parasitic trematode Fasciola hepatica , the parasitic nematode Dirofilaria immitis (dog heartworm), the ruminant nematode Haemonchus contortus , and the free-living nematode Caenorhabditis elegans . Neither Lexnor sialyl-Lexis detectable in these other helminths. Furthermore, none of the helminths, including schistosomes, express Lea, Leb, Ley, or the H- type 1 antigen. However, several glycoproteins from all helminths analyzed are bound by Lotus tetragonolobus agglutinin , which binds Fucalpha1-->3GlcNAc, and Wisteria floribunda agglutinin, which binds GalNAcbeta1-->4GlcNAc (lacdiNAc or LDN). Thus, schistosomes may be unique among helminths in expressing the Lexantigen, whereas many different helminths may express alpha1,3-fucosylated glycans and the LDN motif.