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CA125 is a mucin commonly employed as a diagnostic marker for epithelial ovarian cancer. Induction of humoral responses to CA125 leads to increased survival times in patients with this form of cancer, suggesting a potential role for this mucin in tumor progression. In this study, oligosaccharides linked to CA125 derived from the human ovarian tumor cell line OVCAR-3 were subjected to rigorous biophysical analysis. Sequencing of the Oglycans indicates the presence of both core type 1 and type 2 glycans. An unusual feature is the expression of branched core 1 antennae in the core type 2 glycans. CA125 is also N-glycosylated, expressing primarily high mannose and complex bisecting type N-linked glycans. High mannose type glycans include Man 5 -Man 9 GlcNAc 2 . The predominant N-glycans are the biantennary, triantennary, and tetraantennary bisecting type oligosaccharides. Remarkably, the N-glycosylation profiles of CA125 and the envelope glycoprotein gp120 (derived from H9 lymphoblastoid cells chronically infected with HIV-1) are very similar. The CA125-associated N-glycans have also recently been implicated in crucial recognition events involved in both the innate and adaptive arms of the cell-mediated immune response. CA125 may therefore induce specific immunomodulatory effects by employing its carbohydrate sequences as functional groups, thereby promoting tumor progression. Immunotherapy directed against CA125 may attenuate these immunosuppressive effects, leading to the prolonged survival of patients with this extremely serious form of cancer.

Nanotechnology is the exploitation of the unique properties of materials at the nanoscale. Nanotechnology has gained popularity in several industries, as it offers better built and smarter products. The application of nanotechnology in medicine and healthcare is referred to as nanomedicine, and it has been used to combat some of the most common diseases, including cardiovascular diseases and cancer. The present review provides an overview of the recent advances of nanotechnology in the aspects of imaging and drug delivery. Contents 1. Introduction 2. Nanotechnology in medicine and healthcare 3. Types of nanoparticles 4. Nanotechnology in imaging and diagnosis 5. Nanotechnology and cancer treatment 6. Nanotechnologies for the treatment of cardiovascular diseases 7. Potential risks of nanotechnologies 8. Conclusion

Many proteins synthesized through the secretory pathway receive posttranslational modifications, including N-glycosylation. ␣-Mannosidase II (MII) is a key enzyme converting precursor high-mannose-type N-glycans to matured complex-type structures. Previous studies showed that MII-null mice synthesize complextype N-glycans, indicating the presence of an alternative pathway. Because ␣-mannosidase IIx (MX) is a candidate enzyme for this pathway, we asked whether MX functions in N-glycan processing by generating MII͞MX double-null mice. Some double-nulls died between embryonic days 15.5 and 18.5, but most survived until shortly after birth and died of respiratory failure, which represents a more severe phenotype than that seen in single-nulls for either gene. Structural analysis of N-glycans revealed that double-nulls completely lack complex-type N-glycans, demonstrating a critical role for at least one of these enzymes for effective N-glycan processing. Recombinant mouse MX and MII showed identical substrate specificities toward N-glycan substrates, suggesting that MX is an isozyme of MII. Thus, either MII or MX can biochemically compensate for the deficiency of the other in vivo, and either of two is required for late embryonic and early postnatal development.gene knockout ͉ mutation N -glycosylation is the major form of posttranslational modification of newly synthesized proteins through the secretory pathway. The major biosynthetic steps for N-glycans in vertebrates have been established (1, 2). A key conversion of highmannose to complex-type oligosaccharides occurs in the medial Golgi, where GlcNAc-transferase I (GlcNAc-TI) adds a GlcNAc residue to form a hybrid-type N-glycan, GlcNAc 1 Man 5 GlcNAc 2 (3). Golgi ␣-mannosidase II (MII) then removes two mannosyl residues to form GlcNAc 1 Man 3 GlcNAc 2 (4, 5), which is further modified by GlcNAc-transferase II (GlcNAc-TII) (6) to form GlcNAc 2 Man 3 GlcNAc 2 , the precursor of complex-type Nglycans.When the gene encoding GlcNAc-TI was disrupted in mouse, GlcNAc-TI-null embryos died between embryonic day 9 (E9) and E10 because of defects in morphogenic processes, including the establishment of left-right asymmetry, vascularization, and neural tube formation (7,8). The observation that GlcNAc-TInull embryos could synthesize only high-mannose-type Nglycans demonstrates that high-mannose-type N-glycans by themselves cannot support embryonic development beyond E9-E10 in the mouse. On the other hand, mice lacking GlcNAc-TII were born and synthesized hybrid-type N-glycans, implying that hybrid-type N-glycans can support embryogenesis (9). However, GlcNAc-TII-null mice showed severe gastrointestinal, hematopoietic, osteogenic, and neuronal dysfunction, with phenotypes similar to those seen in human congenital disorders of glycosylation IIa (10, 11). This evidence indicates that hybrid-type N-glycans are not sufficient to maintain normal postnatal development in the mouse and in humans (12).Although MII catalyzes the step after GlcNAc-TI and before GlcNAc-TII (1, 2), MII-n...

There are three mammalian Golgi ␣1,2-mannosidases, encoded by different genes, that form Man 5 GlcNAc 2 from Man 8-9 GlcNAc 2 for the biosynthesis of hybrid and complex N-glycans. Northern blot analysis and in situ hybridization indicate that the three paralogs display distinct developmental and tissue-specific expression. The physiological role of Golgi ␣1,2-mannosidase IB was investigated by targeted gene ablation. The null mice have normal gross appearance at birth, but they display respiratory distress and die within a few hours. Histology of fetal lungs the day before birth indicate some delay in development, whereas neonatal lungs show extensive pulmonary hemorrhage in the alveolar region. No significant histopathological changes occur in other tissues. No remarkable ultrastructural differences are detected between wild type and null lungs. The membranes of a subset of bronchiolar epithelial cells are stained with lectins from Phaseolus vulgaris (leukoagglutinin and erythroagglutinin) and Datura stramonium in wild type lungs, but this staining disappears in lungs from null mice. Mass spectrometry of N-glycans from different tissues shows no significant changes in global N-glycans of null mice. Therefore, only a few glycoproteins required for normal lung function depend on ␣1,2-mannosidase IB for maturation. There are no apparent differences in the expression of several lung epithelial cell and endothelial cell markers between null and wild type mice. The ␣1,2-mannosidase IB null phenotype differs from phenotypes caused by ablation of other enzymes in N-glycan biosynthesis and from other mouse gene disruptions that affect pulmonary development and function.

Murine sperm initiate fertilization by binding to the specialized extracellular matrix of their complementary eggs, known as the zona pellucida. On the basis of data reported in this study, mouse sperm also bind to rabbit erythrocytes with higher affinity than they do to murine eggs. This unusual interaction between a germ cell and a somatic cell ("sperm-somatic cell adhesion system") is also carbohydrate dependent based on its sensitivity to mild periodate oxidation. To determine what types of carbohydrate sequences could be involved in this interaction, the protein-linked oligosaccharides of rabbit erythrocytes were sequenced using novel matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry methods that enabled the analysis of individual components up to m/z 9000. The N-glycans are primarily complex biantennary and triantennary types terminated with Galalpha1-3Gal sequences. The majority of these oligosaccharides also possess one antenna consisting of a highly branched polylactosamine-type sequence that is also associated with many glycosphingolipids that coat rabbit erythrocytes. These erythrocytes also express Core 1 and Core 2 O-glycans terminated primarily with Galalpha1-3Gal sequences and to a lesser extent sialic acid. These results confirm that rabbit erythrocytes and mouse eggs present very different types of carbohydrate sequences on their surfaces. However, oligosaccharides terminated with beta1-6-linked N-acetyllactosamine or its alpha1-3 galactosylated analog are expressed on both the mouse zona pellucida and this somatic cell type. The far more abundant presentation of such sequences on rabbit erythrocytes compared with murine eggs could explain why mouse sperm display such exceptional affinity for this somatic cell type.

Osteoarthritis (OA) is a degenerative disorder of the cartilage and is one of the leading causes of disability, particularly amongst the elderly, wherein patients with advanced-stage OA experience chronic pain and functional impairment of the limbs, thus resulting in a significantly reduced quality of life. The currently available treatments primarily revolve around symptom management, and is thus palliative rather than curative. The aim of the present review is to briefly discuss the limitations of some of the currently available treatments for patients with OA, and highlight the value of the potential use of stem cells in cellular therapy, which is widely regarded as the breakthrough that can address the present unmet medical needs for treatment of degenerative diseases, such as OA. The advantages of stem cell therapy, particularly mesenchymal stem cells, and the challenges involved are also discussed in this review.

The persistence and breakdown of chlorinated insecticides in soil samples collected in the Atlantic Provinces of Canada were studied. Soxhlet extraction of the soil samples was achieved using hexane-2-propanol, 3 to 1. The 2-propanol was removed and the hexane layer purified using a Florisil column. The nature of the insecticide residues and their metabolites was studied using electron-capture gas chromatography with two column types. Thin-layer chromatography and chemical conversion to structurally related compounds confirmed the presence of some insecticides. The soil samples were taken from agri-cultural lands in 1965 where organochlorine insecticides had been used. Forty-five per cent of all the soil samples investigated contained residues of DDT plus metabolites between 1 and 9 p.p.m. DDD and DDE were the chief metabolites of DDT. Thirty-two per cent of the total soil samples contained 0.75 p.p.m. of aldrin plus dieldrin. Heptachlor, heptachlor epoxide, and -chlordan were found in 9% of the soils analyzed in concentrations between 0.06 and 0.86 p.p.m. 1 -Hydroxychlordene, a metabolite of heptachlor, was found in a small number of samples.The persistence and breakdown of pesticides in soil under controlled conditions have been the subject of considerable study in recent years (/, 2,11,14,18,21).Residues of organochlorine insecticides in farm soils have been investigated by several authors (5,10,20,21). The persistence and breakdown of insecticides in soils are related to a number of factors such as soil type and organic content, cultivation, rainfall, temperature, and soil microbial population (6). The conversion of aldrin and heptachlor to their epoxides ( 8) and DDT to DDE (21) in soil have been reported. Recently, Bowman, Schechter, and Carter (2) found that heptachlor was rapidly changed to 1 -hydroxychlordene in dry soils with low organic content and that no conversion of heptachlor to its epoxide was detected in these soils. In another study, under field conditions, Bowman, Young, and Barthel detected a small amount of heptachlor epoxide and 1 -hydroxychlordene in Norfolk fine sandy loam which had been exposed to heptachlor (3).Alexander (/) has indicated that many chemicals are resistant to degradation in the soil by microorganisms.The objectives of this project were to establish quantitatively the extent to which residues of the organochlorine insecticides were occurring in Canadian Atlantic soils collected in Nova Scotia, New Brunswick, Newfoundland, and Prince Edward Island and the nature of the metabolites resulting from them. Materials and MethodsChemicals. The chemicals used were: DDDE, l-chloro-2,2-bis(4-chlorophenyl)ethylene; -chlordan,