Biomedical subjects

Ping Jin

Publications and source records attributed to Ping Jin.

28 records · Page 2Linked to original sources

PubMed2004

[Subclassification of seronegative type 1 diabetic subjects with HLA-DQ genotypes].

OBJECTIVE: To reveal the relationship between disease phenotype and HLA-DQ genotype in autoantibody-negative type 1 diabetics and to explore whether HLA-DQ genotypes can reclassify seronegative type 1 diabetic patients. METHODS: Sixty-one diabetics with unprovoked ketosis or ketoacidosis at presentation were tested for glutamic acid decarboxylase antibody (GAD-Ab), tyrosine phosphatase antibody (IA2-Ab), thyroglobulin antibody (TGA), thyroid peroxidase antibody (TPO-Ab) and HLA-DQ genotype. GAD-Ab and IA2-Ab were measured with radioligand assay. TGA and TPO-Ab were evaluated using RIA. Sequence-based genotyping (SBT) was used to determine the alleles of HLA-DQA1 and DQB1. Autoantibody negative patients were subdivided into group A (with type 1 diabetes susceptible alleles) and group B (without type 1 diabetes susceptible alleles). Clinical characteristics, including age, sex, mode of presentation, body mass index (BMI), islet beta-cell function and current treatment were compared between the autoantibody-positive and autoantibody-negative patients and between group A and B. RESULTS: Among the 61 patients, 29 (47.5%) were negative for all the antibodies tested, while 31 (50.8%) were positive for one or more antibodies tested. 5 (8.2%) were positive for all those 4 antibodies. As for genetic analysis, 18 of the 29 seronegative patients carried 1-4 HLA-DQ risk alleles, while the other 11 did not carry any type 1 diabetes susceptible alleles tested. As compared with the autoantibody-negative patients, younger age at onset, less obesity, severer degree of diabetic ketoacidosis (DKA) and lower C peptide were found in the autoantibody-positive ones. As compared with group B, less obesity [BMI: (22.4 +/- 4.4) kg/m(2) vs (25.8 +/- 3.7) kg/m(2), P = 0.03], severer degree of DKA [CO(2)CP: (16.3 +/- 7.1) mmol/L vs (19.2 +/- 2.0) mmol/L, P = 0.01; pH: 7.26 +/- 0.20 vs 7.34 +/- 0.06, P = 0.03], and lower C peptide [fasting C peptide: (254.6 +/- 189.4) pmol/L vs (458.7 +/- 274.1) pmol/L, P = 0.06] were observed in group A. During follow-up, 73% (8/11) patients in group B discontinued insulin therapy and maintained acceptable glycemic control by either diet or oral hypoglycemic agents (OHA), while only 28% (5/18) of the patients in group A discontinued and maintained control with OHA (28% vs 73%, P < 0.01). Among those who kept on using insulin, group A patients required higher insulin dosage than those of group B [(0.43 +/- 0.16) U x kg(-1) x d(-1) vs (0.24 +/- 0.18) U x kg(-1) x d(-1), P = 0.07]. CONCLUSIONS: Autoantibody-negative diabetics, if with susceptible HLA-DQ genotypes, presented more type 1A-like features, implying possible existence of as yet unidentified immunologic abnormalities in these patients. HLA-DQ risk genotypes may reclassify seronegative type 1 diabetics. Those who are autoantibody negative but carry susceptible HLA-DQ genotypes, should not be diagnosed as type 1B diabetes.

Adolescent↗

PubMed2004

[Adult-onset latent autoimmune diabetes and autoimmune thyroid disease].

OBJECTIVE: To investigate the relationship between latent autoimmune diabetes in adults (LADA) and thyroid autoimmunity. METHODS: The frequency of thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab) was determined with radioimmunoassay in 394 subjects, including 90 LADA, 104 classic type 1 diabetics (T1DM), 100 type 2 diabetics (T2DM) and 100 controls. Glutamic acid decarboxylase antibody (GAD-Ab) was measured with radioligand immunoassay. RESULTS: (1) TPO-Ab existed more frequently in LADA (16.7%, 15/90) than in T2DM patients (7.0%, 7/100; P < 0.05). The frequency of thyroid antibody (TPO-Ab or TG-Ab positivity) in LADA and T1DM was 18.9% (17/90) and 25.0% (26/104) respectively, being higher than that in the control group (8/100, 8.0%; P < 0.05). (2) Thyroid antibodies occurred more frequently in LADA patients with higher titer of GAD-Ab (GAD-Ab > or = 0.5) than those with lower ones (50.0% vs 12.5%, P < 0.05). (3) 47.1% (8/17) of LADA patients with thyroid autoimmunity had thyroid dysfunction as compared with 17.6% (6/34) in the group without thyroid antibodies (P < 0.05). CONCLUSIONS: (1) LADA patients, especially those with high titer of GAD-Ab, have high risk for thyroid autoimmunity. (2) The presence of thyroid antibody may predict high risk for thyroid dysfunction in LADA patients. (3) LADA may be one of the components in autoimmune polyendocrine syndrome.

Adolescent↗

PubMed2003

Polymorphism in clinical immunology - From HLA typing to immunogenetic profiling.

The pathology of humans, in contrast to that of inbred laboratory animals faces the challenge of diversity addressed in genetic terms as polymorphism. Thus, unsurprisingly, treatment modalities that successfully can be applied to carefully-selected pre-clinical models only sporadically succeed in the clinical arena. Indeed, pre-fabricated experimental models purposefully avoid the basic essence of human pathology: the uncontrollable complexity of disease heterogeneity and the intrinsic diversity of human beings. Far from pontificating on this obvious point, this review presents emerging evidence that the study of complex system such as the cytokine network is further complicated by inter-individual differences dictated by increasingly recognized polymorphisms. Polymorphism appears widespread among genes of the immune system possibly resulting from an evolutionary adaptation of the organism facing an ever evolving environment. We will refer to this high variability of immune-related genes as immune polymorphism. In this review we will briefly highlight the possible clinical relevance of immune polymorphism and suggest a change in the approach to the study of human pathology, from the targeted study of individual systems to a broader view of the organism as a whole through immunogenetic profiling.

Journal Article↗

PubMed2003

Cleavage of the Pseudomonas syringae type III effector AvrRpt2 requires a host factor(s) common among eukaryotes and is important for AvrRpt2 localization in the host cell.

Many phytopathogenic bacteria use a type III secretion system to deliver type III effector proteins into the host plant cell. The Pseudomonas syringae type III effector AvrRpt2 is cleaved at a specific site when translocated into the host cell. In this study, we first demonstrate that the factor(s) required for AvrRpt2 cleavage is present in extracts from animal and yeast cells, as well as plant cells. The cleavage factor in animal and plant cell extracts was heat labile but relatively insensitive to protease inhibitors. Second, mutational analysis of AvrRpt2 was applied to identify features important for its cleavage. In addition to two of the amino acid residues in the immediate vicinity of the cleavage site, a large part of the region C-terminal to the cleavage site was required when AvrRpt2 was cleaved in animal cell extract. Most of these features were also important when AvrRpt2 was cleaved in plant cells. Third, we investigated the effect of cleavage in interactions of AvrRpt2 with plant cells. Cleavage of AvrRpt2 appeared to be important for proper interactions with Arabidopsis cells that lack the resistance gene product corresponding to AvrRpt2, RPS2. In addition, removal of the region N-terminal to the cleavage site was important for the correct localization of the C-terminal effector region of the protein in the host cell. We speculate that the virulence function of AvrRpt2 requires removal of the N-terminal region to redirect the effector protein to a specific subcellular location in the host cell after translocation of the protein.

Animals↗

PubMed2003

Diffuse reflection of ceramics coated with dielectric thin films.

We have studied the diffuse reflection properties of ceramics in the presence of dielectric thin films on the surface. A simple optical model was proposed in which interference effects in a thin film were considered for light scattered out of a ceramic in various directions. Measurements were performed on angle-resolved reflection spectra of a thin-film-coated alumina ceramic in the case of normal incidence. They showed that the presence of the thin film on the ceramic's surface modified the angular distributions of scattered radiation from that of a bare ceramic, which suggested a way to tailor the scattering properties of a diffuse reflector as needed.

Journal Article↗

PubMed2003

Segmental analysis of molecular surface electrostatic potentials: application to enzyme inhibition.

We have recently shown that the anti-HIV activities of reverse transcriptase inhibitors can be related quantitatively to properties of the electrostatic potentials on their molecular surfaces. We now introduce the technique of using only segments of the drug molecules in developing such expressions. If an improved correlation is obtained for a given family of compounds, it would suggest that the segment being used plays a key role in the interaction. We demonstrate the procedure for three groups of drugs, two acting on reverse transcriptase and one on HIV protease. Segmental analysis is found to be definitely beneficial in one case, less markedly so in another, and to have a negative effect in the third. The last result indicates that major portions of the molecular surfaces are involved in the interactions and that the entire molecules need to be considered, in contrast to the first two examples, in which certain segments appear to be of primary importance. This initial exploratory study shows that segmental analysis can provide insight into the nature of the process being investigated, as well as possibly enhancing the predictive capability.

Algorithms↗

PubMed2003

Active-specific immunization against melanoma: is the problem at the receiving end?

The recent progress in tumor immunology is a striking example of the successful application of modern biotechnology to understand the complex phenomenon of immune-mediated cancer rejection. Tumor antigens were identified and successfully utilized in active immunization trials to induce tumor antigen-specific T cells. This achievement has left, however, clinicians and researchers perplexed by the paradoxical observation that immunization-induced T cells can recognize tumor cells in standard assays but cannot induce tumor regression. A closer look at T cell physiology and tumor biology suggests that this observation is not so surprising. Here, we argue that successful immunization is one of several steps required for tumor clearance while more needs to be understood about how T cells localize and are effective within a tumor microenvironment impervious to the execution of their effector function.

Antigens, Neoplasm↗

PubMed2002

Reciprocal modulation between the alpha and beta 4 subunits of hSlo calcium-dependent potassium channels.

Large conductance Ca(2+)-dependent potassium (K(Ca) or maxi K) channels are composed of a pore-forming alpha subunit and an auxiliary beta subunit. We have shown that the brain-specific beta4 subunit modulates the voltage dependence, activation kinetics, and toxin sensitivity of the hSlo channel (Weiger, T. M., Holmqvist, M. H., Levitan, I. B., Clark, F. T., Sprague, S., Huang, W. J., Ge, P., Wang, C., Lawson, D., Jurman, M. E., Glucksmann, M. A., Silos-Santiago, I., DiStefano, P. S., and Curtis, R. (2000) J. Neurosci. 20, 3563-3570). We investigated here the N-linked glycosylation of the beta4 subunit and its effect on the modulation of the hSlo alpha subunit. When expressed alone in HEK293 cells, the beta4 subunit runs as a single molecular weight band on an SDS gel. However, when coexpressed with the hSlo alpha subunit, the beta4 subunit appears as two different molecular weight bands. Enzymatic deglycosylation or mutation of the N-linked glycosylation residues in beta4 converts it to a single lower molecular weight band, even in the presence of the hSlo alpha subunit, suggesting that the beta4 subunit can be present as an immature, core glycosylated form and a mature, highly glycosylated form. Blockage of protein transport from the endoplasmic reticulum to the Golgi compartment with brefeldin A abolishes the mature, highly glycosylated beta4 band. Glycosylation of the beta4 subunit is not required for its binding to the hSlo channel alpha subunit. It also is not necessary for cell membrane targeting of the beta4 subunit, as demonstrated by surface biotinylation experiments. However, the double glycosylation site mutant beta4 (beta4 N53A/N90A) protects the channel less against toxin blockade, as compared with the hSlo channel coexpressed with wild type beta4 subunit. Taken together, these data show that the pore-forming alpha subunit of the hSlo channel promotes N-linked glycosylation of its auxiliary beta4 subunit, and this in turn influences the modulation of the channel by the beta4 subunit.

Animals↗

PubMed2002

Phosphorylation-dependent functional coupling of hSlo calcium-dependent potassium channel and its hbeta 4 subunit.

The auxiliary beta4 subunit of the human slowpoke calciumdependent potassium (slo) channel is expressed predominantly in the brain. Co-expression of beta4 subunit with the slo channel alpha subunit in HEK293 and Chinese hamster ovary cells slows channel activation and deactivation and also shifts the voltage dependence of the channel to more depolarized potentials. We show here that the functional interaction between the hbeta4 subunit and the slo channel is influenced by the phosphorylation state of hbeta4. Treatment of cells with okadaic acid (OA) reduces the effect of hbeta4 on slo channel activation kinetics and voltage dependence but not on slo channel deactivation kinetics. The effect of OA can be blocked by mutating three putative serine/threonine phosphorylation sites in hbeta4 (Thr-11/Ser-17/Ser-210) to alanines, suggesting that OA potentiates phosphorylation of hbeta4 and thereby suppresses its functional coupling to the slo channel. Mutation of Ser-17 alone to a negatively charged residue (S17E) can mimic the effect of OA. Mutating all three phosphorylation sites in hbeta4 to negatively charged residues (T11D/S17E/S210E) not only suppresses the effect of hbeta4 on slo channel activation kinetics and voltage dependence, it also suppresses its effect on slo channel deactivation kinetics. Co-immunoprecipitation/Western blot experiments indicate that all of these hbeta4 mutants, as well as the wild-type hbeta4, bind to the slo channel. Taken together, these data suggest that phosphorylation of the beta4 subunit dynamically regulates the functional coupling between the beta4 subunit and the pore-forming alpha subunit of the slo channel. In addition, phosphorylation of different residues in hbeta4 differentially influences its effects on slo channel activation kinetics, deactivation kinetics, and voltage dependence.

Animals↗

PubMed2002

[Analysis of a family pedigree with primary shunt hyperbilirubinaemia].

OBJECTIVE: To identify whether primary shunt hyperbilirubinaemia is a genetic disorder or not and the pattern of the inheritance. METHOD: Clinical case data were studied with analysis of family pedigree of a case. RESULTS: Although the patient with primary shunt hyperbilirubinaemia presented an elevated unconjugated serum bilirubin, anemia and splenomegaly, the patient also presented decline of amount of peripheral white cells and normal amount of reticulocytes. The mature erythrocytes in peripheral blood and bone marrow were irregular in shape and size. There were also some target-, rod-, and mouth-shaped peripheral red cells in blood smear. With analysis of family pedigree, we can find that there were some patients with the primary shunt hyperbilirubinaemia in every generation of the family with equal distribution in male and female. The pattern of inheritance was transmitted from one generation to the next generation directly. Almost any manifestation of the disease may be found in adult patients, but the severity of the disorder was not the same among these patients. CONCLUSIONS: The primary shunt hyperbilirubinaemia is a genetic disease; its pattern of inheritance is autosomal dominant. It is suggested that the disease of primary shunt hyperbilirubinaemia could be renamed as hereditary shunt hyperbilirubinaemia.

Adult↗