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Biomedical subjects

W Min

Publications and source records attributed to W Min.

64 records · Page 4Linked to original sources

Inhibition of calcium oxalate crystal growth in vitro by uropontin: another member of the aspartic acid-rich protein superfamily.

The majority of human urinary stones are primarily composed of calcium salts. Although normal urine is frequently supersaturated with respect to calcium oxalate, most humans do not form stones. Inhibitors are among the multiple factors that may influence the complex process of urinary stone formation. We have isolated an inhibitor of calcium oxalate crystal growth from human urine by monoclonal antibody immunoaffinity chromatography. The N-terminal amino acid sequence and acidic amino acid content of this aspartic acid-rich protein, uropontin, are similar to those of other pontin proteins from bone, plasma, breast milk, and cells. The inhibitory effect of uropontin on calcium oxalate crystal growth in vitro supports the concept that pontins may have a regulatory role. This function would be analogous to that of other members of the aspartic acid-rich protein superfamily, which stereospecifically regulate the mineralization fronts of calcium-containing crystals.

Amino Acid Sequence↗

Non-glycosylated recombinant pro-concanavalin A is active without polypeptide cleavage.

The complex post-translational processing of concanavalin A (Con A) in maturing jackbeans is unique because the non-glycosylated mature active protein is circularly permuted in primary sequence relative to its own inactive precursor (glycosylated pro-Con A) and to other legume lectins. We show here that non-glycosylated pro-Con A expressed in bacteria from recombinant cDNA (rec-pro-Con A) folds in vivo and in vitro to a stable form which is active without further processing. N-glycosylation alone must therefore be sufficient to inactivate pro-Con A--a novel role for glycosylation in regulating activity during protein maturation.

Base Sequence↗

[Mesangial proliferative changes and mesangiolysis. Habu-snake venom induced glomerular lesions of the kidney].

Proliferative changes of the glomerular mesangium of the kidney are generally considered to be a progressive inflammatory process of glomerulonephritis. There are several reports on experimental glomerulonephritis induced by snake venom which is known to cause demonstrable mesangiolytic changes in the glomerulus. The author investigated the sequential morphological changes of the renal glomerulus by light and electron microscopy after administration of 1.0 mg/kg of Habu (Trimeresurus flavoviridis) snake venom to 56 guinea-pigs via tail vein injection. In addition, an analysis of proliferated cells in the glomerulus was attempted by applying the immunostaining method for the antibody to BrdU as the marker of the dividing cells. Various degrees of mesangiolytic changes of the glomerulus were induced after Habu venom injection. In this model, however, the majority of mesangiolytic changes were mild. Subsequent segmental nodular proliferation of the mesangial cells was observed in mesangiolytic areas. Mitotic figures appeared from 24 hours to 7 days after the venom injection, as shown by BrdU staining. New capillary lumens were formed among the proliferated cells of the postmesangiolytic segment 4 to 5 days after the venom injection. Formation of capillary lumens and reconstruction of the glomerular loops had been gradually established through the time course. The histological structure of the glomeruli returned almost to normal 15 weeks after the venom injection, with occasional features of remolded-healing, although a small number of glomeruli still showed persisted mild segmental mesangial proliferation as well as mild increase of PAM-positive substance in the mesangial area. These results suggest that mesangial proliferation is related to the reconstruction of the glomerulus rather than the progression of the glomerular lesions, at least in this model. The author postulates that the mesangial cell has the functional ability to repair the injured glomerular structure. The application of the BrdU immunostaining method turns out to be a useful tool for analyzing the relationship between cell mitosis and cell proliferation. In the guinea-pig, the Habu-snake venom induced mesangiolytic lesions are milder than those in the rabbit and the rat and the degree of subsequent mesangial proliferative changes is less prominent.

Animals↗

Metabolic effects of acarbose in normal and diabetic rats: long- and short-term administration.

The effects of acarbose administration to normal and streptozotocin-diabetic rats were studied in animals given the drug for 3 or 21 days. The acarbose was incorporated into control diets or diets fortified with sucrose and starch. After extirpating the hearts, they were perfused by the Langendorff procedure and ventricular rate and isometric force of contraction were recorded in the presence or absence of isoproterenol. Frozen samples of heart and liver were used for metabolic measurements. At a low dose of isoproterenol (0.01 microgram) the positive inotropic response was the same in control and diabetic animals. With a higher dose of the amine (0.1 microgram) the contractile response was increased further in hearts from normal animals but not enhanced in hearts from diabetic rats. Cardiac phosphorylase activation by isoproterenol was accentuated by diabetes only when the smaller dose of the amine was given. The markedly elevated heart glycogen content of diabetic rats was decreased in response to a high carbohydrate diet. Inclusion of acarbose in the diet prevented this diminution in cardiac glycogen. In normal and diabetic rats fed the high carbohydrate diet for 3 weeks, liver glycogen was elevated. The increase in hepatic glycogen was not observed when acarbose was present in the diet. A comparison of the results of the short- and long term-administration of acarbose show that the onset of action of the drug is prompt and that the effect of the treatment is undiminished over an extended period of time.

Acarbose↗

Chemically-induced in vitro malignant transformation of human esophagus fibroblasts.

Neoplastic transformation of primary fibroblast culture derived from esophagus tissue of a 52-year old male esophageal cancer patient was induced by chemical carcinogen (N-methyl-N'-nitro-N-nitrosoguanidine, MNNG) treatment. The transformed cells showed the biological and morphological properties characteristic of malignant cells, such as loss of contact inhibition, unlimited growth in vitro, aneuploidy, agglutinability by concanavalin A, formation of microvilli on the cell surface, growth on solid agar medium and tumor (fibrosarcoma) formation after heterotransplantation into immunosuppressed newborn mice.

Aneuploidy↗

In vitro and in vivo antineoplastic effects of orthovanadate.

In the present study we have demonstrated that orthovanadate at concentrations of 5-10 uM is cytotoxic to proliferating cells including primary cultures and tumour cell lines. However, concentrations of up to 50 uM did not affect the viability of non-proliferating cells. The cytotoxicity appears to be dependent on the vanadium concentration rather than on the oxidation state of vanadium or the vanadium compound. Furthermore, tumour cell lines with different proliferative rates were equally sensitive to orthovanadate cytotoxicity. Although the mechanisms responsible for the cytotoxicity are not known, addition of H2O2 potentiated orthovanadate cytotoxicity suggesting that hydroxyl or vanadium radicals may be involved. In vivo subcutaneous injections of orthovanadate into mice containing MDAY-D2 tumours resulted in the inhibition of tumour growth by 85-100%. These data indicated that orthovanadate at concentrations greater than 5 uM has antineoplastic properties and may be useful as a chemotherapeutic agent.

Animals↗

Kinetic differences in intestinal and systemic interferon-gamma and antigen-specific antibodies in chickens experimentally infected with Eimeria maxima.

Kinetic differences between systemic vs. intestinal and humoral vs. cellular immune responses were elucidated in chickens experimentally infected with Eimeria maxima by comparing interferon-gamma (IFN-gamma) and parasite-specific antibody levels in the intestine and serum during the course of infection. The level of serum IFN-gamma correlated significantly with fecal oocyst shedding (r2 = 0.97), thereby establishing the importance of cell-mediated immunity in coccidia infection. Moreover, intestinal IFN-gamma levels increased sooner than those in sera (4 vs. 6 days postinfection) and both were observed prior to the appearance of parasite-specific antibodies (8-10 days postinfection), again indicating the importance of intestinal cellular immunity in coccidiosis. Although immunoglobulin (Ig)G, IgA, and IgM isotypes of the antigen-specific antibody response increased significantly in both the intestine and serum after E. maxima infection, intestinal IgA-specific antibodies showed the most dramatic increase. However, the relevance of this observation in the context of primary Eimeria infection is unclear because the coccidia parasites have reached the final stages of their life cycle by this time. These results thus demonstrate the importance of T-cell immune responses against coccidia, characterized by local IFN-gamma secretion in the intestine, in mediating host protective immune response to coccidia.

Animals↗