Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using spleen cells of mice infected or immunized respectively with cercariae or antigen preparations of Schistosoma mansoni, S. haematobium or S. japonicum monoclonal antibodies (mAbs) were produced against the schistosome gut-associated antigens CAA (circulating anodic antigen) and CCA (circulating cathodic antigen). Fusions nearly exclusively produced either anti-CAA (n = 25) or anti-CCA mAbs (n = 55) with a strong isotype restriction (IgM, IgG1 and IgG3) against both antigens, the majority of anti-CAA mAbs being IgG1 and the majority of anti-CCA mAbs being IgM. The mAbs, which on the basis of their selection were reactive with multiple carbohydrate epitopes of CAA or CCA, were applied in different immunological techniques including immunofluorescence, a dot immunobinding assay and immunoelectrophoresis to study the epitope repertoire. Anti-CAA mAbs were found to be reactive with 5 different epitopes, none of which occurred as multiple epitopes on eggs. Anti-CCA mAbs, on the other hand, recognized at least 10 different epitopes, while 44% of anti-CCA mAbs recognized epitopes common to the adult worm and the egg. Both CAA- and CCA-epitopes were found to be developmentally expressed at the level of the tegument in cercariae, schistosomula and 5-day-old lung worms, but in the adult worm were primarily found in the gut. Thus, the production of panels of mAbs has not only resulted in the selection of reagents optimally performing in diagnostic immunoassays, but also allowed a more detailed study of the epitope repertoire of these important schistosome antigens.
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PMID:Schistosoma: analysis of monoclonal antibodies reactive with the circulating antigens CAA and CCA. 858 99

Thirty Syrian golden hamsters were infected with Schistosoma mansoni and 10 were used as negative controls. Hamsters were infected by 100 cercariae; 15 were treated by praziquantel in doses of 100 mg/kg at 12, 13, 14 and 15 weeks postinfection, and 15 hamsters were left as positive control. Five from each subgroup were sacrificed at 24, 28 and 32 weeks after infection. Animals were subjected to weekly analysis for total plasma protein, serum albumin and urinary total protein excretion. At the end point, animals were sacrificed and the mesenteric venous plexus was explored for adult worms. Liver and splenic specimens were examined by light microscopy, and immunofluorescence microscopy. Complete parasite eradication was achieved in the treated animals. Although, there were significantly higher plasma total protein and albumin in the treated group, there was no significant differences in proteinuria. Histopathological examination of liver specimens showed highly significant reduction of granulomas, CAA and CCA, while amyeloid deposition showed minimal reduction in treated animals. Histopathological examination of splenic specimens showed highly significant reduction of fibrosis, granulomas, CAA and CCA, while follicular hyperplasia and amyeloid deposition showed non significant reduction.
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PMID:Effect of anti-schistosomal treatment on schistosomal hepatic pathology: an experimental study in Syrian golden hamsters. 875 59

Circulating antigen levels and antibody responses in Schistosoma bovis-infected West African Dwarf goats were evaluated during infection and following treatment with praziquantel (60 mg/kg) 13 weeks post-infection. One day, 1 week and 4 weeks post-treatment, subgroups of goats were sacrificed and perfused for worm recovery. For comparison, parasite-free control animals were included. Blood and faecal samples were collected biweekly. Two gut-associated schistosome antigens, circulating cathodic and circulating anodic antigen (CCA and CAA) and 3 specific antibody responses (total Ig, IgG and IgM) were measured. For specific antibody detection, crude S. bovis adult worm and egg homogenates were used. The level of CCA in the infected groups was significantly elevated from the time of onset of egg excretion onwards. However, following treatment, the CCA titres dropped to control levels within 1 week post-treatment. Strong positive correlations were found between CCA levels and worm counts and faecal egg counts during peak egg excretion. The correlations of CAA and specific antibody titres to egg and worm counts were poor. The antibody responses were all significantly elevated in the infected goats during patency, but only marginally affected by the treatment. Hence, CCA proved to be superior by correlating strongly to the level of infection and by being a sensitive indicator of the effect of treatment.
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PMID:Experimental Schistosoma bovis infection in goats. Circulating antigen and antibody responses to egg and adult worm antigens during infection and following treatment with praziquantel. 887 76

We analysed the molecular basis of Glanzmann thrombasthenia (GT) in four Japanese patients with type I or type II disease. Polymerase chain reaction (PCR) and subsequent direct sequencing of platelet RNA and genomic DNA revealed three single nucleotide substitutions of the alphaIIb gene, which were confirmed by allele-specific PCR or restriction analysis. One patient with type I GT had a T to C base substitution in exon 11 resulting in a Phe (TTT)-289 to Ser (TCT) mutation (F289S) of the subunit. Another type I patient had a G to A base substitution in exon 12 resulting in a Glu (GAA)-324 to Lys (AAA) mutation (E324K). Interestingly, two unrelated patients with type II GT shared an A to C base substitution in exon 2 3, a region previously not associated with GT, resulting in a Gln (CAA)-747 to Pro (CCA) mutation (Q747P). To analyse the effects of these mutations on alphaII(b)beta3 surface expression, the wild-type alphaIIb cDNA or mutant alphaIIb cDNAs were transfected into Chinese hamster ovary (CHO) cells together with a wild-type beta3 cDNA. Flow cytometric analysis using an anti-alphaII(b)beta3 complex antibody revealed that 50.6% of CHO cells with wild-type alphaII(b)beta3 expressed complexes, whereas only 1 6%, 7.7% and 31.3% of cells, with IIb(F289S)beta3, alphaIIb(E324K)beta3 and alphaIIb(Q747P)beta3 expressed complexes, respectively. Our data indicate that these three novel point mutations in the alphaIIb subunit may hamper surface expression of the alphaII(b)beta3 complex, thus resulting in the quantitative GT phenotypes of platelets from these patients.
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PMID:Novel point mutations in the alphaIIb subunit (Phe289-->Ser, Glu324-->Lys and Gln747-->Pro) causing thrombasthenic phenotypes in four Japanese patients. 972 14

To further investigate the factors involved in the modulation of the schistosomal granuloma, mice were primed with immunogenic carbohydrates which were common to soluble egg antigen (SEA) and adult worm antigen. Mice sensitized with LewisX trisaccharide or lacto-N-fucopentaose-III (LNFP-III) displayed an increased cellular response towards SEA-coupled beads implanted in the liver by mesenteric injection, resulting in the formation of larger periparticular granulomas. When animals were sensitized with bovine serum albumin or a structurally related carbohydrate, an accelerated response was not seen. Since LNFP-III is built up of LewisX molecules, and LewisX carbohydrates are common to SEA and worm antigens such as the gut-secreted antigens CCA and CAA (two antigens that could prime egg-antigen-induced granuloma formation), this may explain why adult, live Schistosoma mansoni worms positively modulate egg-antigen-induced hepatic granuloma formation in the murine host. These observations provide new insights into the role of carbohydrates in parasite-host immunity and may yield important implications for choosing worm-derived antigens for the development of anti-schistosome vaccines.
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PMID:Schistosomal granuloma modulation. II. Specific immunogenic carbohydrates can modulate schistosome-egg-antigen-induced hepatic granuloma formation. 995 Feb 22

A cohort of Schistosoma haematobium infected schoolchildren from Cameroon (n = 146) was studied for urine circulating soluble egg antigen (SEA), in comparison to other urine infection parameters: the circulating adult worm-derived antigens, circulating anodic and cathodic antigens (CAA and CCA), egg counts and the reagent strip index (RSI). Before treatment, SEA prevalence was 90%, while 89% and 65% of the children were positive for CCA and CAA respectively. The children were treated with 2 doses of praziquantel (2 x 40 mg/kg bodyweight) at an interval of 10 days and followed-up at 1, 2, 3, 5 and 12 months after treatment. Urine SEA correlated significantly with egg counts and RSI; levels of CAA and CCA were also significantly correlated with those of SEA. The levels of SEA showed a better correlation to both egg counts and RSI than did the levels of CAA and CCA. SEA levels dropped sharply 1 month after treatment, with few children excreting any SEA whereas egg counts decreased less rapidly. The prevalence and levels of SEA remained low during the whole post-treatment period whereas egg counts, RSI and CCA in urine rose progressively in the post-treatment period with a final egg count prevalence of 78%. The results of the present study indicate that for S. haematobium infections, measurement of SEA in urine is a valuable additional diagnostic parameter.
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PMID:The dynamics of a soluble egg antigen of Schistosoma haematobium in relation to egg counts, circulating anodic and cathodic antigens and pathology markers before and after chemotherapy. 1032 6

Genetic variations in the locus encoding the transporter associated with antigen processing, subunit 1 (TAP1), were systematically studied using samples from Caucasians, Africans, Brazilians, and compared with data from chimpanzees. PCR-amplified genomic sequences corresponding to the 11 exons were analyzed by single-strand conformation polymorphism (SSCP) and sequencing. Six nonsynonymous and 2 synonymous single nucleotide polymorphisms (SNPs) were found to be common in one ethnic group or another, and they involved codons 254 (Gly-GGC/Gly-GGT) in exon 3, 333 (Ile-ATC/Val-GTC) in exon 4, 370 (Ala-GCT/Val-GTT) in exon 5, 458 (Val-GTG/Leu-TTG) in exon 6, 518 (Val-GTC/Ile-ATC) in exon 7, 637 (Asp-GAC/Gly-GGC), 648 (Arg-CGA/Gln-CAA) and 661 (Pro-CCG/Pro-CCA) in exon 10. At each SNP site the sequence listed first was predominant in all ethnic groups. Several SNPs segregated on the same chromosome regardless of populations and species. Together, the SNPs produced 5 major human TAP1 alleles, 4 of which matched the officially recognized alleles *0101, *02011, *0301, and *0401; the 5th allele differed from each of those by at least 4 SNPs. Overall, TAP1*0101 was the predominant allele in all ethnic groups, with frequencies ranging from 0.667 in Zambians to 0.808 in US Caucasians. The TAP1*0401 frequency showed the greatest difference between Africans (0.221-0.254) and Caucasians (0.033), with Brazilians (0.058) fitting in the middle. Consistent with earlier work based on Caucasians and gorillas, *0101 appeared to be the newest human TAP1 allele, suggesting a dramatic spread of *0101 into all human populations examined. Characterization of TAP1 polymorphisms allowed the design of a PCR-based genotyping scheme that targeted 7 SNP sites and required 2 separate genotyping techniques.
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PMID:TAPI polymorphisms in several human ethnic groups: characteristics, evolution, and genotyping strategies. 1125 43

Regression analysis of the relationship of serum circulating anodic and cathodic antigens (CAA and CCA), as a possible direct measure of worm burden, and fecal egg counts allows the study of phenomena like density-dependent fecundity in human Schistosoma mansoni infections. For a reliable analysis, variations in egg count measurements as well as in circulating antigen levels have to be taken into account, and an accurate estimation of these variations (represented by parameter lambda in the so-called Deming regression) is of great importance. From a new, extensive data set of repeated measurements of fecal egg counts and CAA and CCA concentrations we determined the respective values for parameter lambda, and (re)analysed the relationship between circulating antigens and egg counts in 3 data sets from Burundi, Senegal and Zaire by Deming regression. For comparison, ordinary linear regression was performed as well, which considerably biased the regression lines for CCA, but not for CAA. The analyses resulted in a clearly non-proportional relationship between egg counts and CAA, and, to a lesser extent, CCA. Assuming that egg counts and antigen measurements directly reflect egg production and worm burdens, respectively, our findings reinforce the indication of density-dependent fecundity in schistosomiasis mansoni, as suggested by others.
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PMID:Evaluation of density-dependent fecundity in human Schistosoma mansoni infections by relating egg counts to circulating antigens through Deming regression. 1127 46

During the metaphase-anaphase transition, the spindle checkpoint prevents segregation of chromosomes if the spindle assembly is perturbed. Critical components of this checkpoint are the MAD and BUB families of proteins, which prevent the proteolysis of Pds1 and B cyclins, producing mitotic arrest. In the present study, we first intended to resolve the role of the hsMAD2 gene in human cancer by determining the potential presence of hsMAD2 mutations in 44 primary bladder tumors, 42 soft-tissue sarcomas and 10 hepatocellular carcinomas. The entire coding region of the hsMAD2 gene was analyzed using PCR-SSCP and sequencing. One of the bladder tumor samples showed a point mutation consisting of a transition, ATC-->GTC (Ile-->Val) in codon 190 of hsMAD2. However, no differences were found in the mitotic arrest between cells transfected with mutant and wild-type MAD2 cDNA. We also identified mobility shifts in hsMAD2 in both normal and tumor DNA in 3 bladder tumors, 3 soft-tissue sarcomas and 1 hepatocellular carcinoma, consistent with a polymorphism at codon 143, CCA-->CCG (Pro-->Pro). Another polymorphism was identified in a hepatocellular carcinoma case at codon 22, GAG-->GAA (Glu-->Glu). In addition, a subgroup of 67 primary tumors was analyzed by Southern blot hybridization. No deletion or visible re-arrangements were detected by comparing tumor and normal DNA band signals. Two other important components of the spindle mitotic checkpoint, hBUB1 and hBUB3, were also screened for mutations: hBUB1 in 43 bladder tumors and 9 bladder cell lines and hBUB3 only in the cell lines. Two polymorphisms were found in hBUB1 at positions 144, CAG-->CAA (Gln-->Gln) in 1 primary tumor and 1 bladder cell line, and 913 (ATC-->ATT, Ile-->Ile) in 1 primary tumor. We did not find sequence alterations in hBUB3. These results suggest that mutations of the hsMAD2, hBUB1 and hBUB3 genes are very rare in bladder tumors and that hsMAD2 alterations are also infrequent in soft-tissue sarcomas and hepatocellular carcinomas.
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PMID:Molecular analyses of the mitotic checkpoint components hsMAD2, hBUB1 and hBUB3 in human cancer. 1140 Jan 14

Scid mice are defective in the ability to repair DNA double strand breaks and, as a consequence, their cells are radiosensitive. Further, they have been shown to be prone to develop thymic lymphomas (TLs) after small doses of ionizing radiation. Little is known, however, on the role of scid mutation in chemical carcinogenesis. To determine if scid mutation increased predisposition to chemical carcinogenesis, we examined both the susceptibility of scid mice to N-ethyl-N-nitrosourea (ENU)-induced lymphomagenesis and the involvement of ras gene activation. Adult female mice at 8 weeks of age were given ENU in their drinking water at 400 ppm for 2-10 weeks. Contrary to expectations, we observed a two to three-fold reduction in TL development in the scid mice. The highest incidence was achieved by ENU treatment for 8 weeks for scid and wild-type C.B-17 mice, of 42 and 85%, respectively (P<0.05). We investigated whether this was attributable to the usage of the ras mutation pathway. There was, however, no significant difference in the frequency and spectrum of K-ras mutation between the scid and wild-type C.B-17 mice. Most of the K-ras mutations were either GGT to GAT transition in codon 12 (11/23: 48%) or CAA to CCA transversion in codon 61 (8/23: 35%) that was independent of scid background. The incidence of N-ras mutation was very low. These results indicate that scid mice are less susceptible to ENU-induced lymphomagenesis and ras gene mutation frequently occurs in both scid and wild-type C.B-17 mice.
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PMID:Reduced sensitivity to and ras mutation spectrum of N-ethyl-N-nitrosourea-induced thymic lymphomas in adult C.B-17 scid mice. 1151 30


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