Localization of the genes encoding the type I diabetes autoantigens, protein-tyrosine phosphatases IA2 and IAR.
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Autoantigens↗
Biomedical subjects
L Cui
Publications and source records attributed to L Cui.
Relationships between polydnavirus genomes and viral gene expression.
Polydnavirus genomes and viral gene functions are atypical for viruses. Polydnaviruses are the only group of viruses with segmented DNA genomes and have an unusual obligate mutualistic association with parasitic Hymenoptera, in which the virus is required for survival of the wasp host and vice versa. The virus replicates asymptomatically in the wasp host but severely disrupts lepidopteran host physiology in the absence of viral DNA replication. It is not surprising then that viral gene expression is divergent in its two insect hosts and that differences in viral gene expression are linked to these divergent functions. Some viral genes are expressed only in the wasp host while other viral genes are expressed only in the lepidopteran host and are presumed to be involved in the disruption of host physiological systems. Our laboratory has described the expression and regulation of a family of viral genes implicated in suppressing the lepidopteran immune system, the cys-motif genes. In conjunction with these studies we have described the physical organization of additional viral gene segments. We have cloned, mapped and begun the sequence analysis of selected viral DNA segments. We have noted that some viral DNA segments are nested and that nested viral DNA segments encode the abundantly expressed, secreted cys-motif genes. Conversely, other viral segments are not nested, encode less abundantly expressed genes and may be targeted intra-cellularly. These results suggest that nesting of segments in polydnavirus genomes may be linked to the levels of gene expression. By extension, the unique, segmented organization of polydnavirus genomes may be associated, in part, with the requirement for divergent levels of viral gene expression in lepidopteran hosts in the absence of viral DNA replication.
Journal Article↗
Zinc deficiency enhances interleukin-1alpha-induced metallothionein-1 expression in rats.
This study investigated whether interleukin-1alpha-induced metallothionein gene expression is affected by zinc deficiency. Weaning male rats were fed a zinc-deficient (ZD) diet (2 mg zinc/kg) or a zinc-supplemented diet [50.8 mg zinc/kg; controls for the diet included pair-fed (PF) and ad libitum consumption groups (AL)] for 4 wk. All rats except those that served as controls for interleukin-1alpha administration, (injected with vehicle and killed at 0 h) were then injected subcutaneously with interleukin-1alpha (2 x 10(7) units/kg body wt) and killed at 3, 6, 12, 24 and 72 h after the injection. Compared with AL and/or PF rats, zinc depletion significantly reduced zinc concentrations in plasma and liver but not in kidney or intestine, and significantly reduced hepatic, renal, and intestinal metallothionein-1 mRNA levels analyzed by competitive reverse transcription-polymerase chain reaction (RT-PCR). Interleukin-1alpha injection reduced plasma zinc concentration and enhanced liver zinc concentration, but did not affect zinc levels in kidney or intestine. Metallothionein-1 mRNA was significantly elevated by interleukin-1alpha in liver, kidney and intestine of all groups; the levels in liver and kidney of ZD rats 6 h after the injection were significantly higher than those of AL or PF rats. Liver metallothionein protein levels were enhanced after interleukin-1alpha injection in both AL and ZD rats. Semiquantitative RT-PCR revealed significantly higher hepatic levels of interleukin-1 receptor type-I mRNA in ZD rats than in AL and PF rats but no differences in renal or intestinal tissues among groups before interleukin-1alpha challenge. In conclusion, zinc deficiency induces upregulation of metallothionein-1 gene expression in response to interleukin-1alpha challenge in rats.
Animals↗
Polydnavirus-mediated inhibition of lysozyme gene expression and the antibacterial response.
Parasitism of lepidopteran host larvae by hymenopteran parasitoids impairs the cellular immune response via expression of polydnavirus genes. Encapsulation of parasitoid eggs is thereby prevented. Parasitized insects are susceptible to opportunistic infections, suggesting that additional components of the immune system are affected. Insects normally respond to infection by inducing the synthesis of an array of antibacterial factors, including cecropins and lysozyme via a NFkappaB/lkappaB-like signal transduction pathway. To characterize the effects of PDVs on the antibacterial immune response, plasma antibacterial activities were assayed in H. virescens larvae infected with the C. sonorensis PDV. Plasma lysozyme activity in Heliothis virescens was reduced in parasitized and PDV-infected larvae after immune challenge. To examine the regulation of lysozyme after CsPDV injection, the Heliothis virescens lysozyme cDNA was cloned. In contrast to plasma lysozyme activity, the 1.1 kb lysozyme mRNA was induced in fat body and haemocytes by known elicitors. The data suggest that CsPDV, like some other viruses, regulates host cell gene expression at the level of translation. We propose that the immunodeficiencies caused by CsPDV injection are caused, in part, by the targeted translational inhibition of specific humoral immune response transcripts.
Amino Acid Sequence↗
Antibodies to the protein tyrosine phosphatases IAR and IA-2 are associated with progression to insulin-dependent diabetes (IDDM) in first-degree relatives at-risk for IDDM.
Insulin-dependent diabetes mellitus (IDDM) is preceded by the presence of antibodies against islet proteins including a protein tyrosine phosphatase (PTP) designated IA-2. Recently, we cloned a novel PTP named IAR which shares 43% sequence identity with IA-2 and is recognised by antibodies from a majority of patients with IDDM. The aim of the present study was to determine whether IAR antibodies (IAR Ab) or IA-2 antibodies (IA-2 Ab) are associated with progression to IDDM in first-degree relatives "at-risk" for IDDM (operationally defined as those with islet cell antibodies [ICA] > or = 20JDFU or insulin autoantibodies [IAA] > or = 100 nU/ml), and to examine combinations of IAR Ab and IA-2 Ab in these subjects. The sensitivity and specificity of these antibodies were also examined in patients with recent-onset IDDM. Using Cox's Proportional Hazards Model, the number of siblings with IDDM was associated with progression to IDDM in "at-risk" relatives, but other covariables (age, sex, number of affected offspring or parents) were not significantly associated. Using number of affected siblings as a covariable, both IAR and IA-2 antibodies were significantly associated with progression to IDDM (p < 0.005). Combinations of both antibodies, however, did not result in a significantly stronger association with progression to IDDM. The threshold of positivity for IAR Ab (0.5 units) and IA-2 Ab (3.0 units) assays was adjusted to give the same specificity (97.9%) for each assay in 144 healthy control subjects, to allow standardised comparisons. Levels of IAR Ab and IA-2 Ab were strongly correlated in 53 recent-onset IDDM patients (r = 0.70, p < 0.0001) but 11.3% had IAR Ab in the absence of IA-2 Ab and 16.9% had IA-2 Ab in the absence of IAR Ab. The sensitivity for IDDM (defined as the proportion of IDDM patients positive) was 56.6% for IAR Ab and 62.3% for IA-2 Ab. We conclude that there is considerable overlap in IA-2 Ab and IAR Ab positivity, although either antibody can occur independently in IDDM patients. Both IAR Ab and IA-2 antibodies are associated with progression to IDDM in first-degree relatives at-risk of IDDM, but the use of IAR and IA-2 antibodies in combination are not significantly more strongly associated with progression than single antibodies. IAR Ab may play an important role in the prediction of IDDM.
Adolescent↗
[In vitro susceptibilities of clinical isolates of coagulase-negative staphylococci to glycopeptide antibiotics].
Two hundred and thirteen clinical strains of coagulase-negative staphylococci isolated in Japan between 1980 and 1997 were analyzed for glycopeptide susceptibility by determining MIC using both Mueller-Hinton agar (MHA) and Brain Heart Infusion agar (BHIA) plates. Of 37 Staphylococcus epidermidis strains isolated between 1980 and 1981, all were susceptible to vancomycin and teicoplanin on both MHA and BHIA. However, of 122 isolates of Staphylococcus epidermidis isolated between 1994 and 1997, 1 (0.8%) was intermediate to vancomycin on MHA and 39 (32%) were intermediate on BHIA, while 3 (2.5%) and 27 (22.1%) were intermediate or resistant to teicoplanin on MHA and BHIA, respectively. It was demonstrated that the susceptibilities of the strains in 1990s to vancomycin and teicoplanin were significantly decreased compared with those in 1980s. Population analysis was performed with six strains each of Staphylococcus epidermidis and Staphylococcus haemolyticus (three with vancomycin MIC > or = 8 micrograms/ml and three with vancomycin MIC < or = 4 micrograms/ml using BHIA). The population curves of the Staphylococcus epidermidis strains showed a homogeneous pattern of susceptibility. Whereas, those for two Staphylococcus haemolyticus strains (vancomycin MIC = 8 micrograms/ml using BHIA) showed a typical heterogeneous pattern. Vancomycin-resistant mutants (MIC > or = 32 micrograms/ml) were obtained with a high frequency of 10(-4)-(-5) from the strains by one-step selection with 16 micrograms/ml of vancomycin.
Anti-Bacterial Agents↗
[Determination of intracellular calcium ions in fibroblasts of contractured scar].
Free calcium ions, as a kind of message-transport substance, is important in cellular activity such as cell movement, cell differentiation and cell proliferation. In order to investigate the relationship between free calcium ions and scar contracture, the fibroblasts which originated from hypertrophic scar, keloid and normal skin were used as the experimental target. The fibroblasts from 4th-6th generations of different sources were used; Then the intracellular free calcium ions concentrations were measured respectively by the fluorescent Ca2+ indicator Fura-2/AM and Image analysis system. The results showed that the level of Ca2+ in fibroblasts of hypertrophic scar was higher than that in keloid and normal skin (P < 0.01). There was no significant difference between the level of Ca2+ in keloid and in normal skin. The conclusion was that the concentration of intracellular free calcium ions played an important role in the scar contract, but the exact mechanism was still unclear and required further study.
Biological Transport, Active↗
[Assessment of fetal maturation by epithelial growth factor in serum of pregnant women].
OBJECTIVE: To study the concentrations of human epithelial growth factor (EGF), progesterone (P) in serum, and EGF, P, amylase (Ams), creatinine (Cr) and total bilirubin (TB) in amniotic fluid at different trimester normal pregnancy. METHODS: The concentrations of EGF, P in serum of 181 cases of pregnant women (first trimester 35, midtrimester 69, late trimester 77) and the concentrations of EGF, P, Ams, Cr, TB in amniotic fluid of 87 cases (mid-trimester 44, late trimester 43) were determined. At the same time, the concentrations of EGF, P in serum of umbilical veins and arteries from 23 full term neonates were determined as well. The concentrations of EGF and P were measured by radioimmunoassay and Ams, Cr, TB in amniotic fluid by PA110 autobiochemistry analyzer. RESULTS: (1) The concentrations of EGF, P in serum increased as pregnancy advanced. (2) There were significant correlations between EGF level and Ams, Cr levels in amniotic fluid. After 32 gestational weeks, the fetal maturity rate was 70.59% when EGF was > or = 4.5 micrograms/L. There were significant positive correlations between EGF in maternal serum and in amniotic fluid, (3) The maternal serum EGF concentration was significantly higher than that in the umbilical vessels, and there was positive correlations between them. CONCLUSION: The change of maternal serum concentration could be used to determine the fetal maturation.
Amniotic Fluid↗
[Strategy on the prevention and treatment of chronic diseases among residents in Dongcheng District, Beijing].
Chronic diseases, in particular, circulatory diseases characterized by high mortality, morbidity, and lack of special treatment have become serious problems to the residents living in the Beijing communities. To learn the above mentioned diseases among people at the community level and to investigate treatment and preventive method concerned studies on chronic circulatory system diseases among people living in communities in Dongcheng where few disease were under special control studies were carried out between 1981 and 1997. We found that the studied residents who had received and adopted a series of preventive measures as health education, giving up smoking, reducing alcohol and salt consumption, diet balance and practicing physical exercises, had greatly improved their health condition. Because of the positive results, we addressed some long-termed suggestions on the treatment and prevention for chronic patients with circulatory system diseases which is believed to have established a solid ground for the future.
Cardiovascular Diseases↗
[Olfactory event-related potentials to isoamyl acetate in congenital anosmia].
OBJECTIVE: To investigate the olfactory origin of the event-related potential (OEP) by evaluating OEP and standardized psychophysical measures in patients with congenital anosmia. METHODS: Olfactory function was evaluated by OEP and standardized psychophysical measures including smell identification test and odor detection threshold tests for 3 chemosensory stimulants: phenylethyl alcohol (PEA), isoamyl acetate (IAA), and chloracetyl phenone (CAP) in 9 subjects with isolated congenital anosmia and 9 age- and gender-matched normosmic controls. RESULTS: There was a significant difference in the smell identification test score (P < 0.001) and odor detection thresholds for PEA and IAA (P < 0.001) between the anosmic and normosmic subjects. Detection thresholds for CAP, a trigeminal stimulant, did not differ between the 2 groups. In the control subjects, OEP to IAA was characterized by 4 reproducible components (P1, N1, P2 and N2). In the subjects with congenital anosmia, no reproducible evoked potential components were identified in response to IAA. No reproducible evoked potential components were seen in response to the air control stimulus in either the anosmic or normosmic groups. CONCLUSION: These data suggest that OEP provide a specific and objective measure of olfactory function.
Adult↗
EMG study in the diagnosis and differential diagnosis of lipid storage myopathy.
Clinical, electromyographic and pathological features were studied in 18 patients with lipid storage myopathy (group I) and 18 patients with polymyositis and dermatomyositis (group II). The results showed a remarkable lower spontaneous activity(SA) incidence (14%) in group I than that (55%) in group II; 46% and 34% short-duration motor unit potentials(MUAPs) with polyphasic potentials and 74% and 71% short-duration MUAPs without polyphasic potentials respectively; the percentages of increased polyphasic MUAPs were same in the two groups. The reduced or pathologic interference patterns accounted for 61% in the group I and 50% in group II. Increased CPK, LDH and HBD were also found in both of them. It is suggested that the lipid storage myopathy may be diagnosed when patients have muscle weakness and myalgia with short-duration and low-amplitude and polyphasic MUAPs without or with occasional spontaneous activities, and increased CPK, LDH and HBD.
Adolescent↗
[Treatment of portal hypertension by using pericardial vascular disconnection and mesocaval side-to-side shunting].
OBJECTIVE: To prevent post-operative bleeding, to maintain the blood supply to the liver from the portal vein and to reduce the incidence of hepatic encephalopathy. METHOD: The blood vessel was cut around the cardial opening and the venae cavae was anastomosed in 37 patients with portal hypertension. RESULT: The success rate of surgery was 100%. The free portal pressure (FPP) was 3.16 +/- 0.581 kPa, which was lower than the FPP (3.91 +/- 0.642 kPa) before operation (P < 0.01). Follow-up for 5 to 22 months showed that liver function recovered from III to I in 5 patients, and from III to II in 7. Ascites disappeared in all and varix improved in 82.9% patients. CONCLUSION: Cutting flow combined with fraction flow can effectively maintain the blood supply to the liver in treating portal hypertension.
Adolescent↗
A more flexible regression-to-the-mean model with possible stratification.
We consider a regression-to-the-mean model that includes both additive and multiplicative treatment effects. We allow either or both of these treatment effects to be stratified by ranges of the first measurement. We focus on the situation where there is a very large sample on the first measurement and a relatively small subsample for the second measurement is selected, which often occurs in screening trials. We propose some asymptotically efficient estimators for the parameters of the model that are very simple to compute. We begin with a discussion of the full model, and more on tests and estimation for reduced models follows. An example from a large screening trial is discussed.
Biometry↗
Regulation of callus status and cell-suspending culture in naked seed oat (Avena nuda).
The original calli were obtained by inducing culture of mature embryos of naked seed oat on N6 medium. The original calli were white-colored tumor forms, soft outside and hard inside. These kinds of calli are easy to differentiate into plantlets, and they are not the friable type. Friable embryogenic calli could be obtained by cycled regulated culture on IM1-IM4 medium for 7-8 months from the original calli. They became vigorous, lightish yellow in color, with small grainy forms. Well-separated and fast-growing suspending cell lines have been obtained from the above-mentioned embryogenic calli in the liquid medium. Regenerated plants have been obtained for this kind of suspension line by culturing on the medium for differentiation. The surviving percentage for such plantlets was over 95% after planting in the soil.
Avena↗
Ability of early acting cytokines to directly promote survival and suppress apoptosis of human primitive CD34+CD38- bone marrow cells with multilineage potential at the single-cell level: key role of thrombopoietin.
Purified primitive progenitor/stem cells from bone marrow represent likely target populations for ex vivo expansion of stem cells to be used in high-dose chemotherapy or gene therapy. Whereas such primitive progenitor cells require combined stimulation by multiple cytokines for growth, some cytokines selectively promote viability rather than growth when acting individually. We investigated here for the first time the direct effects of cytokines on survival of primitive CD34+CD38- human bone marrow progenitor cells at the single-cell level. Interleukin-3 (IL-3) and the ligands for c-kit (KL) and flt3 (FL) had direct and selective viability-promoting effects on a small fraction of CD34+CD38- but not CD34+CD38+ progenitor cells. Interestingly, the recently cloned thrombopoietin (Tpo), although stimulating little growth, kept most CD34+CD38- progenitors viable after prolonged culture, maintaining twofold and fourfold more progenitors viable than KL and IL-3, respectively. A high fraction of these progenitors had a combined myeloid and erythroid differentiation potential, as well as capacity for prolonged production of progenitor cells under stroma-independent conditions. In addition, Tpo promoted viability of CD34+CD38- long-term culture-initiating cells, further supporting the idea that Tpo promotes viability of primitive human progenitor cells. Finally, Tpo suppressed apoptosis of CD34+CD38- cells in culture. Thus, the present studies show a novel effect of Tpo, implicating a potential role of this cytokine in maintaining quiescent primitive human progenitor cells viable.
ADP-ribosyl Cyclase↗
Thrombopoietin promotes adhesion of primitive human hemopoietic cells to fibronectin and vascular cell adhesion molecule-1: role of activation of very late antigen (VLA)-4 and VLA-5.
Thrombopoietin (Tpo), the ligand for c-mpl and a principal regulator of megakaryocytopoiesis and platelet production, has been demonstrated to stimulate the growth and differentiation of megakaryocyte as well as multipotent hemopoietic progenitor cells. In the present study we demonstrate that Tpo can stimulate the adhesion of the Mo7e progenitor cell line to fibronectin (Fn) as well as vascular cell adhesion molecule-1 through activation of very late antigen (VLA)-4 and VLA-5, adhesion molecules previously demonstrated to be involved in regulation of steady state hemopoiesis. Tpo-induced adhesion was concentration dependent, reached a maximum following 30 min, and appeared to be dependent on adenylate cyclase, and tyrosine kinase activity. Furthermore, second messenger inhibitors implicated essential and complimentary roles of phosphatidylinositol-3-kinase and protein kinase C in mediating Tpo-induced adhesion. The ability of Tpo to promote adhesion to fibronectin was comparable to that of IL-3, but less than that of stem cell factor. Unlike the ability of these cytokines to synergistically enhance growth of Mo7e as well as normal progenitor cells, no synergy was observed with regard to their ability to enhance adhesion. Finally, Tpo stimulated adhesion of primitive (CD34+ CD38-) human bone marrow cells to fibronectin, predominantly through activation of VLA-5, whereas no such effect could be observed on CD34+ CD38+ bone marrow cells. Thus, Tpo might play an important role in early hemopoiesis, at least in part through its ability to promote adhesion through activation of adhesion molecules on hemopoietic progenitor cells.
ADP-ribosyl Cyclase↗
Thrombopoietin directly and potently stimulates multilineage growth and progenitor cell expansion from primitive (CD34+ CD38-) human bone marrow progenitor cells: distinct and key interactions with the ligands for c-kit and flt3, and inhibitory effects of TGF-beta and TNF-alpha.
Thrombopoietin (Tpo) is a primary regulator of megakaryocyte and platelet production. However, studies in c-mpl-deficient mice suggest that Tpo might also play an important role in early hemopoiesis. Here, the direct ability of Tpo to stimulate stroma-independent growth, multilineage differentiation, and progenitor cell expansion from single primitive CD34+ CD38- human bone marrow cells was investigated. Tpo alone stimulated limited clonal growth, but synergized with c-kit ligand (KL), flt3 ligand (FL), or IL-3 to potently enhance clonogenic growth. Whereas KL and FL in combination stimulated the clonal growth of only 3% of CD34+ CD38- cells, 40% of CD34+ CD38- cells were recruited by KL+FL+Tpo, demonstrating that Tpo promotes the growth of a high fraction of CD34+ CD38- progenitor cells. Additional cytokines (IL-3, IL-6, and erythropoietin (Epo)) did not significantly enhance clonal growth above that observed in response to KL+FL+Tpo. In contrast, Tpo enhanced clonogenic growth in response to KL+FL+IL-3+IL-6+Epo by as much as 80%, implicating a key role for this cytokine in early hemopoiesis. Importantly, we also demonstrate that the majority of Tpo-recruited CD34+ CD38- progenitor cells have a multilineage differentiation potential, and that Tpo promotes prolonged expansion of multipotent progenitors. Specifically, whereas progenitor cells were reduced in cultures containing only KL+FL, addition of Tpo resulted in 40-fold expansion of multipotent progenitors following a 14-day incubation. Finally, we identified inhibitors of Tpo-induced progenitor cell growth, in that TGF-beta as well as TNF-alpha almost completely abrogated the growth of CD34+ CD38- progenitor cells in response to Tpo alone as well as KL+FL+Tpo.
Animals↗
Expression and hemocyte-targeting of a Campoletis sonorensis polydnavirus cysteine-rich gene in Heliothis virescens larvae.
The polydnavirus associated with the parasitic wasp Campoletis sonorensis is injected into the lepidopteran insect, Heliothis virescens, during parasitization, after which viral gene products suppress the cellular immune system of the hosts. Four related cysteine-rich polydnavirus gene have been identified in parasitized H. virescens larvae and grouped into a family. In this study, we investigated the expression and hemocyte targeting of the cysteine-rich VHv1.4 protein. Full-length and truncated VHv1.4 proteins were produced in a bacterial expression system, and the purified proteins were used to raise polyclonal antisera. In immunoblots the VHv1.4 protein was detected in parasitized insects as early as 6 h and throughout the entire course of parasitism. The VHv1.4 protein appeared predominantly in the plasma fraction of hemolymph from parasitized larvae, suggesting that this protein is secreted. The VHv1.4 protein expressed from a recombinant baculovirus was secreted in two lepidopteran cell lines and in larvae injected with the recombinant virus. Digestion with endoglycosidases suggests that the VHv1.4 protein is glycosylated at multiple N-glycosylation sites. Immunofluorescence assays showed that the VHv1.4 protein binds to the hemocytes, most notably the granulocytes, in H. virescens larvae. After binding, the VHv1.4 protein was internalized, probably by endocytosis. Specific binding of the VHv1.4 to granulocytes implies an important function in the suppression of host cellular encapsulation response.
Animals↗