• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.65-66
• /
• 2003

The cause of Huntington's disease (HD) is a pathological expansion of the polyglutamine domain within the N-terminal region of huntingtin. Neuronal aggregates composed of mutant huntingtin within certain neuronal populations are a characteristic hallmark of HD. Because tissue transglutaminase (tTG) cross-links proteins into aggregates and polypeptide-bound glutamines are primary determining factors for tTG-catalyzed reactions, it has been hypothesized that tTG may contribute to the formation of aggregates. (omitted)

• Biomedical Science Letters
• /
• v.22 no.4
• /
• pp.160-166
• /
• 2016

To provide a basis for a homogeneous fluorescence resonance energy transfer (FRET) immunoassay for celiac disease, we carried out a FRET experiment using guinea pig tissue transglutaminase (tTG) and antibodies to tTG (anti-tTG) purified from rat serum. Fluorescein was utilized as the probe, and a nonfluorescent dye, QSY 7 served as the quencher. We labeled anti-tTG and tTG with fluorescein isothiocyanate and QSY 7 succinimidyl ester, respectively. Fluorescein-labeled anti-tTG was the donor, and QSY 7-labeled tTG was the acceptor of the FRET experiment. When we titrated fluorescein-labeled anti-tTG with QSY 7-labeled tTG, we observed a large decrease in the steady-state fluorescence intensity, which was due to strong FRET from fluorescein-labeled anti-tTG to QSY 7-labeled tTG. Using time-resolved fluorescence spectroscopy, we could also observe a decrease in the fluorescence lifetime, which confirms the steady-state data. We expect that these results might be useful in the development of a novel fluorescence immunoassay for an easy screening and follow-up of celiac patients.

• Proceedings of the KSAR Conference
• /
• 2003.06a
• /
• pp.61-61
• /
• 2003

We have investigated the novel function of tissue transglutaminase (tTG) in the germinal vesicle breakdown (GVBD) of mouse oocyte. tTG was identified in ooplasm and germinal vesicle by immunostaining assay. Spontaneous maturation of the oocytes elevated in situ activity of tTG by over 2.5 fold at 3 hr, which was determined by a confocal microscopic assay. However, incubation with monodansylcadaverine (MDC), a tTG inhibitor, blocked the activation of tTG. The possible role of tTG in GVBD was investigated by the use of two tTG inhibitors, MDC and cystamine. MDC largely inhibited the GVBD by a concentration dependent manner. GV-stage oocytes were matured to the GVBD stage by 78% at 3 hr in BWW culture medium. However, in the oocytes incubated with MDC for 3 hr, the GVBD rates were 43 and 11% by 50 and 100 mM, respectively. MDC also blocked the entry of 70 kDa TRITC-dextran from the ooplasm to the compartment of germinal vesicle, indicating a possible inhibition of nuclear pore disassembly by MDC. The role of tTG in GVBD was further investigated by microinjection with cystamine. The control oocytes, injected with DPBS, showed about 80 % of GVBD at 3 hr. But the oocytes injected with cystamine showed 15% of GVBD at 3 hr and a little higher rate at 6 hr. In addition, the inhibition of GVBD maturation by MDC was reversible by washing. These results suggested that tTG was involved in the early event of mouse oocyte maturation

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.23 no.4
• /
• pp.397-404
• /
• 2020

Purpose: Synbiotics can alleviate some intestinal pathologies or prevent trigger mechanisms for some diseases such as celiac disease (CD). If patients with high levels of anti-tissue transglutaminase (anti-tTG) immunoglobulin A (IgA) antibodies have normal duodenal histology, they are followed as potential CD patients. The aim of this study was to investigate the effect of synbiotic use on the blood levels of anti-tTG antibodies in children. Methods: Eighty-two patients with high anti-tTG levels were included in this study. Patients were randomly divided into two groups. The synbiotic group was treated with a daily dose of a synbiotic including multi-strain probiotics for 20 days. The control group was not administered any medication. Anti-tTG values at baseline and repeat measurements and the percentage change in anti-tTG levels between groups were compared. Results: The anti-tTG level at baseline was 36 U/mL (interquartile range [IQR], 26.4-68 U/mL) in the synbiotic group, and it decreased significantly to 13 U/mL (IQR, 6.5-27.5 U/mL) after 20 days (p<0.05). The anti-tTG level at baseline was 46 U/mL (IQR, 31-89 U/mL) in the control group, which also decreased significantly to 23 U/mL (IQR, 7-41 U/mL) after 20 days (p<0.05). Anti-tTG levels exhibited 73% and 56% decreases in the synbiotic and control groups, respectively (p<0.05). Conclusion: It may be speculated that a synbiotic supplementation can contribute to decreasing anti-tTG levels in children with potential CD.

• Archives of Pharmacal Research
• /
• v.27 no.8
• /
• pp.850-856
• /
• 2004

Intraneuronal deposition containing $\alpha$-synuclein is implicated in the pathogenesis of synuclein-opathies including Parkinsons disease (PD). Although it has been demonstrated that cytoplas-mic inclusions of wild type $\alpha$-synuclein are observed in the brain of PD patients and that $\alpha$-synuclein mutations such as A30P and A53T accelerate aggregate formation, the exact mech-anism by which $\alpha$-synuclein forms insoluble aggregates is still controversial. In the present study, to understand the possible involvement of tissue transglutaminase (tTG) in aggregate formation of $\alpha$-synuclein, SH-SY5Y cell lines stably expressing wild type or mutant (A30P or A53T) $\alpha$-synuclein were created and aggregate formation of $\alpha$-synuclein was observed upon activation of tTG. The data demonstrated that $\alpha$-synuclein negligibly interacted with tTG and that activation of tTG did not result in the aggregate formation of $\alpha$-synuclein in SH-SY5Y cells overexpressing either wild type or mutant $\alpha$-synuclein. In addition, $\alpha$-synuclein was not modi-fied by activated tTG in situ. These data suggest that tTG is unlikely to be a contributing factor to the formation of aggregates of $\alpha$-synuclein in a stable cell model.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.22 no.4
• /
• pp.350-357
• /
• 2019

Purpose: This study aimed to evaluate a possible association between the anti-tissue transglutaminase antibody (anti-tTG) titer and stage of duodenal mucosal damage and assess a possible cut-off value of anti-tTG at which celiac disease (CD) may be diagnosed in children in conjunction with clinical judgment. Methods: This observational study was conducted at a gastroenterology clinic in a tertiary hospital from April 2012 to May 2013. Seventy children between 6-months and 18-years-old with suspected CD underwent celiac serology and duodenal biopsy. Statistical analyses were done using SPSS 16. Diagnostic test values were determined for comparing the anti-tTG titer with duodenal biopsy. An analysis of variance and Tukey-Kramer tests were performed for comparing the means between groups. A receiver operating characteristics curve was plotted to determine various cut-off values of anti-tTG. Results: The mean antibody titer increased with severity of Marsh staging (p<0.001). An immunoglobulin (Ig) A-tTG value at 115 AU/mL had 76% sensitivity and 100% specificity with a 100% positive predictive value (PPV) and 17% negative predictive value (NPV) for diagnosis of CD (p<0.001, 95% confidence interval [CI], 0.75-1). Conclusion: There is an association between the anti-tTG titer and stage of duodenal mucosal injury in children with CD. An anti-tTG value of 115 AU/mL (6.4 times the upper normal limit) had 76% sensitivity, 100% specificity, with a 100% PPV, and 17% NPV for diagnosing CD (95% CI, 0.75-1). This cut-off may be used in combination with clinical judgment to diagnose CD.

• BMB Reports
• /
• v.34 no.1
• /
• pp.66-72
• /
• 2001

To investigate the mechanism of adriamycin (ADM) resistance in the ADM resistant subline PC-14/ADM, we examined the expressions of p-glycoprotein (P-gp), topoisomerase I (Topo I) and II (Topo II), glutathione-S-transferases (GSTs), tissue transglutaminase (t-TG), epidermal growth factor receptor (EGFR), and E-cadherin and the activity of superoxide dismutase (SOD) in PC-14 and PC-14/ADM cells. There was no change in the cellular levels of P-gp, Topo I, Topo II, and the two isoforms of GSTs. However, SOD activity in PC-14/ADM cells was 2.38 fold higher than that in PC-14 cells. A marked induction of the t-TG expression was also observed in PC-14/ADM cells. In addition to those changes, expressions of EGFR and E-cadherin were down regulated in PC-14/ADM cells. Therefore, molecular modifications such as an increase in SOD activity, induction of the t-TG expression, and down regulation of EGFR and E-cadherin expressions may play important roles in PC-14/ADM cells during the development of ADM resistance.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.25 no.4
• /
• pp.312-320
• /
• 2022

Purpose: Screening serologic tests are important tools for the diagnosis of celiac disease (CD). Immunoglobulin (Ig)G anti-deamidated gliadin peptide (anti-DGP) is a relatively new autoantibody thought to have good diagnostic accuracy, comparable to that of anti-tissue transglutaminase (anti-tTG) antibody. Methods: Pediatric patients (n=86) with a clinical suspicion of CD were included. Duodenal biopsy, anti-tTG, and IgG anti-DGP antibody tests were performed. The patients were divided into CD and control groups based on the pathological evaluation of duodenal biopsies. The diagnostic accuracy of serological tests was determined. Results: IgA anti-tTG and IgG anti-DGP antibodies were positive in 86.3% and 95.4% of patients, respectively. The sensitivity, specificity, and diagnostic accuracy of the IgA anti-tTG test were 86.3%, 50.0%, and 68.6%, respectively, and those of the IgG anti-DGP test were 95.4%, 85.7%, and 90.7%, respectively. The area under the receiver operating characteristic (ROC) curve was 0.84 (95% confidence interval [CI], 0.74-0.91) for IgA anti-tTG test and 0.93 (95% CI, 0.86-0.97) for IgG anti-DGP test. The comparison of IgA anti-tTG and IgG anti-DGP ROC curves showed a higher sensitivity and specificity of the IgG anti-DGP test. Conclusion: IgG anti-DGP is a reliable serological test for CD diagnosis in children. High tTG and DGP titers in the serum are suggestive of severe duodenal atrophy. The combined use of IgA anti-tTG and IgG anti-DGP tests for the initial screening of CD can improve diagnostic sensitivity.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.20 no.4
• /
• pp.222-226
• /
• 2017

Purpose: Celiac disease, an autoimmune enteropathy triggered by exposure to gluten, is not uncommon in South Jordan. However, its prevalence is underestimated due to lack of physician awareness of the diversity of disease presentation. The clinical spectrum includes classic gastrointestinal manifestations, as well as rickets, iron-deficiency anemia, short stature, elevated liver enzymes, and edema. Our goal was to evaluate celiac disease presentation in clinically diagnosed children. Methods: Retrospective study included all children diagnosed with celiac disease between September 2009 and September 2015. Hospital charts were reviewed. Demographic data, clinical characteristics, and follow-up were recorded. Results: Thirty-five children were diagnosed with celiac disease during the study period. Mean age${\pm}$standard deviation was $6.7{\pm}3.8$ years (range, 2.0-14 years). There were 17 (48.6%) female patients. The average duration between onset of symptoms and diagnosis was $16.3{\pm}18.7$ months. Fifteen (42.9%) patients presented with classic malabsorption symptoms, whereas 7 (20.0%) patients presented with short stature. Positive tissue transglutaminase antibodies (tTg)-immunoglobulin A (IgA) was seen in 34 (97.1%) patients. The one patient with negative tTg-IgA had IgA deficiency. Although tTG-IgA values were not available for objective documentation of compliance, clinical data (resolution of presenting abnormalities and growth improvement) assured acceptable compliance in 22 (62.9%) patients. Conclusion: CD in children may present with diverse picture. Although of the small number, the non-classical presentations are not uncommon in our rural community. Gluten-free diet is the main strategy for treatment and associated with usually correction of laboratory abnormalities and improvement of growth.