Human myeloid alpha 3-fucosyltransferase is involved in the expression of the sialyl-Lewis(x) determinant, a ligand for E- and P-selectin

The sialyl-Lex determinant (NeuAc alpha 2-->3Gal beta 1-->4[Fuc alpha- 1-->3]GlcNAc) has been identified as a major ligand in the selectin- mediated adhesion of neutrophils and monocytes to activated endothelium or platelets. This carbohydrate epitope is formed by the sequential action of alpha 3-sialyltransferase and alpha 3-fucosyltransferase on N- acetyllactosamine (Gal beta 1-->4GlcNAc) disaccharide termini of glycoconjugates. We have addressed the role of the human myeloid alpha 3-fucosyltransferase in the expression of this epitope at the leucocyte surface by determining its activity in human-mouse leukemic cell hybrids (WEGLI), normal human granulocytes and chronic myeloid leukemia (CML) cells using sialylated and desialylated glycoproteins and oligosaccharides as acceptor substrates. In contrast to what has been reported for the myeloid-type enzyme, we found that the alpha 3- fucosyltransferase of the cells studied can use sialylated acceptors be it that the activity is several times lower than with asialo- substrates. Characterization of the product obtained with a sialylated oligosaccharide indicated that the enzyme can catalyze the formation of the sialyl-Le(x) structure. Flow cytometry of the WEGLI cells using a sialyl-Le(x)-specific monoclonal antibody (MoAb) showed that these cells indeed express sialyl-Lex at their surface, provided that they contain human chromosome 11. Earlier the presence of this chromosome had been correlated with the expression of alpha 3-fucosyltransferase activity. In addition to sialyl-Le(x), WEGLI cells containing chromosome 11 showed high-expression levels of related structures recognized by antibodies VIM-2 and VIM-8, suggesting that fucose addition can occur at both distal and proximal GlcNAc residues in poly- N-acetyl-lactosaminoglycan sequences. Based on the human chromosome contents it could be ruled out that the alpha 3-fucosyltransferase of WEGLI cells is a Lewis-type alpha 3/4- or plasma-type alpha 3- fucosyltransferase, the genes of which have been mapped to chromosome 19. It is concluded that the enzyme studied is of the myeloid-type and indeed is involved in the synthesis of sialyl-Le(x) (and also VIM-2 and VIM-8 structures) in leukocytes provided that its expression is at a sufficiently high level.     

Alefacept: an expert review concerning the treatment of psoriasis

Psoriasis is a chronic, inflammatory skin disease. Historically, phototherapy or immunosuppressive agents have been the first line of treatment for patients with severe psoriasis; however, the long-term use of these agents is limited by dose-dependent toxicities. Alefacept was the first biological agent approved in both the US and Canada for the treatment of adults with moderate-to-severe chronic plaque psoriasis. Alefacept is a remittive therapy that selectively reduces memory T cells. The efficacy and safety of up to two courses of alefacept have been demonstrated in clinical trials, and thus, this review focuses on new data to optimise the use of this biological agent. Emerging data indicates that multiple courses of alefacept for the long-term treatment of psoriasis are safe and effective. In addition, data are reviewed on the use of alefacept in combination with other agents and in other diseases, including psoriatic arthritis.     

Mental disorder and violent victimization in a total birth cohort

OBJECTIVE: We examined the association between mental disorder and violent victimization in a general population sample. METHODS: We performed a multivariate analysis of violent victimization in a 12-month period on a total birth cohort with follow-up data that assessed, during their 21st year, males and females born in Dunedin, New Zealand, in the early 1970s. RESULTS: Compared with people with no mental disorder, (1) people with anxiety disorders experienced more sexual assaults, (2) people with schizophreniform disorders experienced more threatened and completed physical assaults, (3) people with alcohol dependence disorders experienced more completed physical assaults, and (4) people with marijuana dependence disorders experienced more attempted physical assaults. These results held after control for psychiatric comorbidity, demographic characteristics, and the study participants' own violent behavior. CONCLUSION: Mentally disordered young adults tend to experience more violent victimization in the community than those without a mental disorder.     

Erdheim-Chester disease of the breast: a case report and review of the literature

Erdheim-Chester disease (ECD) is a rare xanthomatous non-Langerhans cell histiocytosis which involves the marrow space of the long bones. Extraosseous sites most commonly affected include the eyes, lungs, pituitary glands, and kidneys. We report the case of a 49-year-old woman who presented with palpable breast nodules, followed by progressive soft tissue and subcutaneous disease, and involvement of the long bones, dysarthria, and dysphagia. The histopathologic features and skeletal radiography findings are consistent with ECD. This case represents an unusual presentation, which led to delayed diagnosis, as ECD of the breast has been rarely reported. ECD should be considered in the differential diagnosis of histiocytoid breast lesions, including fat necrosis and histiocytoid invasive mammary carcinoma.     

Episode-centred analysis of drinking to intoxication in university students

AIMS: To demonstrate the use of an internet-based retrospective diary to measure intoxication and to describe the epidemiology of intoxication in a university community. METHODS: A probability sample of 1564 New Zealand university students completed an Internet-based survey (82% response), including a retrospective diary in which the volume consumed on each of the preceding seven days and the duration of each episode were recorded, along with the respondent's gender, weight, and their typical quantity/frequency of consumption, as a measure of tolerance. These parameters were used to compute an estimated blood alcohol concentration (EBAC) for each episode. RESULTS: Using an EBAC of 0.08 g/100 ml as a criterion for intoxication produced lower estimates of incidence than binge drinking guidelines (>40 g for women, >60 g for men), or subjective reports. EBACs of 0.08 g per cent were exceeded at least weekly by 37% of women and 39% of men. Teenage females had higher EBACs than teenage males, despite lower consumption. Intoxication was positively associated with lower age, European or Maori ethnicity relative to Asian, Pacific, or other ethnicities, and with residential halls relative to other living arrangements. Faculty of study was inconsistently related to intoxication. Discussion: Frequent drinking to intoxication is normative behaviour in this population group. Of particular concern are intoxication levels in females aged 16-21 years and in males throughout their 20s. The web-based retrospective diary is a useful means of measuring intoxication by self-report. Where time permits it can be enhanced by specification of drinking locations and beverage-specific questions.