Biomedical subjects

H M Chen

Publications and source records attributed to H M Chen.

At least 19 recordsLinked to original sources

PubMed2006

Endothelin-1 regulates parathyroid hormone expression of human parathyroid cells.

OBJECTIVE: Parathyroid cells synthesize and release endothelin-1 (ET-1). ET-1 displays an in vitro inhibitory effect on basal parathyroid hormone (PTH) secretion and also counteracts PTH hypersecretion stimulated by low calcium. Such effects are further demonstrated in vivo, independent of the changes in calcitonin. We propose that ET-1 may regulate the pathogenesis of uremic hyperparathyroidism. However, this was not directly demonstrated in human parathyroid glands. DESIGN: Hyperplastic parathyroid glands are obtained from the surgical operation for uremic hyperparathyroidism. Cells are isolated by enzyme digestion and treated with ET-1, and are assessed for PTH mRNA expression. PTH in the plasma and the medium is measured by a newly developed method to detect the whole PTH (1-84). PATIENTS: Uremic patients with severe secondary hyperparathyroidism and ultrasonography-proved hypertrophy of parathyroid glands received elective surgical approaches under general anesthesia. The resected glands were immediately taken to the laboratory for fresh isolation. MEASUREMENTS: Following ET-1 treatment, PTH mRNA expression is evaluated by RT-PCR method. ET-1 is detected with radioimmunoassay kit and PTH is measured by a new commercially available Duo PTH kit. RESULTS: ET-1 exhibited a dose-dependent inhibitory effect (from 10(-12) - 10(-7) M) on PTH mRNA expression of parathyroid cells, either in the basal or in the low-calcium-stimulated states. Release of PTH into the medium is also gradually inhibited by the increase in ET-1 concentrations. CONCLUSIONS: Our results demonstrate that ET-1 attenuates PTH mRNA expression in freshly isolated human parathyroid cells, and PTH release is also decreased. This result is consistent with our previously reported in vitro and in vivo experiments.

Adult↗

PubMed2005

Decreased annexin I expression in prostatic adenocarcinoma and in high-grade prostatic intraepithelial neoplasia.

AIMS: To analyse annexin I expression in prostatic carcinoma. Annexin I belongs to a family of structurally related calcium and phospholipid-binding proteins implicated in signal transduction, DNA replication, cell proliferation and apoptosis. The decreased expression of annexin I, II and VII proteins has been reported in different types of cancer. METHODS AND RESULTS: Using immunohistochemistry, we analysed annexin I expression in 77 cases of prostatic adenocarcinoma (Gleason score 6, N = 40; Gleason scores 7-8, N = 27; and Gleason scores 9-10, N = 10) and high-grade prostatic intraepithelial neoplasia (PIN, N = 50). Immunoreactivity of annexin I in tumour cells was evaluated as negative (< 5% of cells), focally positive (5-25% of cells) or positive (> 25% of cells). In contrast to positive staining in adjacent benign prostatic epithelium, annexin I expression was decreased (focally positive) in 76% of cases of high-grade PIN (P < 0.0001) and was decreased or absent in 81% of prostatic adenocarcinomas (P < 0.0001). Annexin I expression in all higher grade tumours (Gleason scores 7-10) was only focally positive or absent. CONCLUSIONS: Expression of annexin I inversely correlates with the increasing histological grade of prostatic adenocarcinoma. By showing a progressive loss of annexin I expression in high-grade PIN, intermediate-grade and high-grade cancer, our findings suggest that the loss of annexin I expression occurs early in prostatic tumorigenesis and becomes more prominent throughout tumour progression. The loss of expression of annexin I may serve as a useful marker of prostate cancer development and progression.

Adenocarcinoma↗

PubMed2003

Motorcycle emissions and fuel consumption in urban and rural driving conditions.

This work reports sampling of motorcycle on-road driving cycles in actual urban and rural environments and the development of representative driving cycles using the principle of least total variance in individual regions. Based on the representative driving cycles in individual regions, emission factors for carbon monoxide (CO), hydrocarbons (HC), nitrogen oxides (NO(x)=NO+NO(2)) and carbon dioxide (CO(2)), as well as fuel consumption, were determined using a chassis dynamometer. The measurement results show that the representative driving cycles are almost identical in the three largest cities in Taiwan, but they differ significantly from the rural driving cycle. Irrespective of driving conditions, emission factors differ insignificantly between the urban and rural regions at a 95% confidence level. However, the fuel consumption in urban centers is approximately 30% higher than in the rural regions, with driving conditions in the former usually poor compared to the latter. Two-stroke motorcycles generally have considerably higher HC emissions and quite lower NO(x) emissions than those of four-stroke motorcycles. Comparisons with other studies suggest that factors such as road characteristics, traffic volume, vehicle type, driving conditions and driver behavior may affect motorcycle emission levels in real traffic situations.

Air Pollutants↗

PubMed2003

Chemical behavior of Cd in rice rhizosphere.

Chemical behavior of Cd in rice rhizosphere as affected or not by Pb was investigated. The NH4OAc extractable Cd in the rhizosphere was distinctly lower than that in bulk soil. The depletion of Cd in the rhizosphere could not be simply attributed to Cd uptake by rice. The observed phenomena could be attributed to the decreasing pH in the rhizosphere and the complexing capabilities of soluble exudates for Cd. Extractable Cd increased in both the rhizosphere and bulk soil after the addition of Pb, which might be caused by the replacement of Pb for Cd. The extractable Cd in the non-rhizosphere varied with the distance from the root surface, especially within 0-1 mm, which was greatly affected by the combined effects of mass flow, activation and fixation, and had the lowest extractable Cd. Pb addition affected the distribution of extractable Cd in the non-rhizosphere, implying that the affinity of Pb for organic matter was greater than that of Cd. The difference of Cd species between rhizosphere and bulk soil demonstrated that the transformation of exchangeable Cd (EXC-Cd) to OM-Cd (bound to organic matter) and FMO-Cd (bound to iron and manganese oxide) occurred in the rice rhizosphere due to the exudations from the rice root, the activity of microorganisms on the root surface and the activation of Fe and Mn oxides. The interaction between Pb and Cd resulted in the content of EXC-Cd being higher in the presence of Pb, whereas the OM-Cd content was lower in the presence of Pb.

Cadmium↗

PubMed2003

Forms and distribution of selenium at different depths and among particle size fractions of three Taiwan soils.

The bioavailability of selenium in soils for plants depends more on its forms than on its total concentration. The purpose of the present study was to examine the solid-phase forms of selenium at different depths of three soil series representing major farming soil groups in Taiwan as well as the amounts of selenium in sand, silt and clay fractions of the soils. The study was conducted by means of sequential extraction to obtain the amounts of selenium and the distribution of various solid-phase forms of selenium at different depths of Pinchen (121 degrees 11(')E, 24 degrees 55(')N), Toulun-Sheto (120 degrees 55(')E, 24 degrees 50(')N), and Chunliao (120 degrees 25(')E, 23 degrees 57(')N) soil series. The amounts of metal oxide-bound form of selenium in the three soil series were the largest, with those of Pinchen and Toulun-Sheto soil series exceeding 50% of the total amounts of selenium and that of Chunliao soil series maintained at 30-40%. In the Pinchen and Toulun-Sheto soil series, the amounts of selenium in clay fractions were the largest, with a significant difference between the clays with and without metal oxides and organic matter removed. The amounts of selenium remained high in silt and/or sand fractions of the Chunliao soil series with metal oxides and organic matter removed. Metal oxide and organic matter contents of the three soil series mainly affect the amounts of various solid-phase forms of selenium and their distribution in different depths and particle size fractions of the soils. This observation of selenium associated with soil constituents was in good agreement with the results of the adsorption of selenite and selenate by the three soil series.

Adsorption↗

PubMed2003

Twenty-year follow-up of the Carpentier-Edwards standard porcine bioprosthesis in the Oriental population.

AIM: The 20-year period long-term results of porcine bioprosthetic valve use are limited. In addition, the majority of these reports come from Western countries. Given the scanty information reported in Oriental countries, this study was therefore designed to examine 20-year long-term results in patients who received a Carpentier-Edwards porcine bioprosthetic valve in an effort to contribute further information on the long-term clinical performance of porcine prosthetic valves from a viewpoint of results in the Oriental population. METHODS: From July 1979 to April 2001, 82 patients received valve replacement with a standard Carpentier-Edwards porcine valve. There were 40 men and 42 women with a mean age of 42.3+/-15.1 years (range 16 to 73 years). Follow-up time extended more than 20 years (mean 10.9+/-3.2 years, range 0.5 to 21.5 years ) for a total of 719.5 patient-years. RESULTS: The overall operative mortality was 16.9% (14 of 83 procedures). At 5, 10, 15, and 20 years, the actuarial survival rate of patients was 71.7%, 66.9%, 55.5%, and 44.4%, respectively. Actuarial estimates of freedom from structural valvular deterioration (SVD) at 5, 10, 15, and 17 years were 96.3%, 64.0%, 24.3%, and 24.3%, respectively; from reoperation 96.3%, 64.5%, 24.5%, and 24.5%; from operated valvular endocarditis 96.8%, 92.6%, 92.6%, and 92.6%; and from overall thromboembolism 96.3%, 88.5%, 67.2%, and 52.2%. In normal sinus rhythm, actuarial estimates of freedom from thromboembolism at 5, 10, 15, and 17 years were 100.0%, 100.0%, 81.8%, and 81.8%, respectively. Whereas for those in patients with atrial fibrillation, the estimates of freedom from thromboembolism were 94.5%, 82.4%, 57.7%, and 38.5%. CONCLUSION: This study demonstrates the very satisfactory 20-year period long-term performance of freedom from bleeding events, thromboembolism (except in patients with atrial fibrillation), and valvular endocarditis in Oriental patients undergoing replacement with a porcine valve. However, the remarkable rate of SVD and reoperation ensued at 6 years after bioprosthesis implanted which does not differ from the series reported from Western countries.

Adolescent↗

PubMed2001

Significance of local electrostatic interactions in staphylococcal nuclease studied by site-directed mutagenesis.

In this paper, we show that amino acids Glu(73) and Asp(77) of staphylococcal nuclease cooperate unequally with Glu(75) to stabilize its structure located between the C-terminal helix and beta-barrel of the protein. Amino acid substitutions E73G and D77G cause losses of the catalytic efficiency of 24 and 16% and cause thermal stability losses of 22 and 26%, respectively, in comparison with the wild type (WT) protein. However, these changes do not significantly change global and local secondary structures, based on measurements of fluorescence and CD(222 nm). Furthermore, x-ray diffraction analysis of the E75G protein shows that the overall structure of mutant and WT proteins is similar. However, this mutation does cause a loss of essential hydrogen bonding and charge interactions between Glu(75) and Lys(9), Tyr(93), and His(121). In experiments using double point mutations, E73G/D77G, E73G/E75G, and E75G/D77G, significant changes are seen in all mutants in comparison with WT protein as measured by fluorescence and CD spectroscopy. The losses of thermal stability are 47, 59, and 58%, for E73G/D77G, E73G/E75G, and E75G/D77G, respectively. The triple mutant, E73G/E75G/D77G, results in fluorescence intensity and CD(222 nm) close to those of the denatured state and in a thermal stability loss of 65% relative to the WT protein. Based on these results, we propose a model in which significant electrostatic interactions result in the formation of a locally stable structure in staphylococcal nuclease.

Calorimetry, Differential Scanning↗

PubMed2001

Early microcirculatory derangement in mild and severe pancreatitis models in mice.

An in vivo microscopic technique was used to clarify the increase in microvascular permeability and enhanced leukocyte-endothelium interaction of pancreatic microcirculation in experimental pancreatitis of differing severity. Using bovine albumin fluorescein isothiocyanate (FITC) and carboxyfluorescein diacetate succinimidyl ester (CFDASE) as tracers, the change in permeability and the behavior of leukocytes in the acinar microcirculation were quantified during the initial 1, 2, 6, and 12h after the induction of caerulein pancreatitis in mice. Cold stress was added to produce the severe model. It was revealed that the early microcirculatory changes in the pancreas of caerulein pancreatitis included the increased permeability of endothelial lining and an accumulation of extravasated fluid in the perilobular space, which were more severe if cold stress was added. A decrease in flow velocity was also noted 2h after the onset of severe pancreatitis. Leukocyte adherence to the endothelial cells was not observed during the first 12h in either model of severity. In contrast, observation of the hepatic microcirculation revealed a significant number of adherent leukocytes 2h after the induction of severe pancreatitis. These results suggest that during the early course of acute pancreatitis, leukocyte adherence in the pancreatic microcirculation is a secondary event following the increase in pancreatic vascular permeability.

Acute Disease↗

PubMed2001

Catalytic effect of soil colloids on the reaction between CrVI and p-methoxyphenol.

Adsorption of CrVI and p-methoxyphenol (PMP) on soil colloids at different pH media was studied. The resulting k1 and n of 1.89 x 10(2) and 0.53 (r2 = 0.99) and k2 and b of 0.13 and 1.25 x 10(3) (r2 = 0.96) were obtained from Freundlich (Q = k1Caqn) and Langmuir [Q = k2bCaq/(1 + k2Caq)] simulation equations, respectively, for CrVI adsorption on soil colloids (pH 4.20). The adsorption of PMP on soil colloids in pH 5.72 media was simulated by five different equations and the results indicated that the Fritz-Schluender one (r2 = 1.00) was the most suitable among them. Adsorption quantity of CrVI and PMP on colloids increased with increasing acidity in the pH range of 3.5-9.0. Study of CrVI adsorption kinetics indicated that the adsorption equilibrium of CrVI was reached rapidly within 2 h. In pure aqueous solution, CrVI reduction by PMP was observed only when the media's pH was lower than 4.0. Oxidation and reduction reaction between CrVI and p-methoxyphenol obviously occurred when soil colloids were involved in this system, even at pH > or = 7.0, which strongly suggested that minerals in soil colloids acted as catalysts to speed the reaction of CrVI and PMP. The oxidized product of PMP by CrVI, extracted by chloroform in acid media and analyzed by gas chromatography-mass spectrometry, was identified as benzoquinone. The reaction included two steps of one electron process.

Adsorption↗

PubMed2001

Kinetics of membrane lysis by custom lytic peptides and peptide orientations in membrane.

To aid the development of custom peptide antibiotics, a kinetic study of membrane lysis by cecropin B (CB) and its analogs, cecropin B1 (CB1) and cecropin B3 (CB3) was carried out to determine the mechanism by which these peptides disrupt the bilayer structure of liposomes of defined composition. Disruption of the phospholipid bilayer was determined by a fluorescence assay involving the use of dithionite to quench the fluorescence of lipids labeled with N-7-nitro-2,1,3-benzoxadiazol-4-yl. Lytic peptides caused the disruption of liposomes to occur in two kinetic steps. For liposomes composed of mixtures of phosphatidylcholine and phosphatidic acid, the time constants for each kinetic step were shorter for CB and CB1 than for CB3. Oriented circular dichroism experiments showed that the peptides could exist in at least two different membrane-associated states that differed primarily in the orientation of the helical segments with respect to the bilayer surface. The results are discussed in terms of kinetic mechanisms of membrane lysis. The mode of actions of these peptides used for the interpretation of their kinetic mechanisms were supported by surface plasmon resonance experiments including or excluding the pore-forming activities.

Amino Acid Sequence↗

PubMed2001

Crumpled structure of the custom hydrophobic lytic peptide cecropin B3.

The solution structure of a custom lytic peptide, cecropin B3 (CB3), having two identical hydrophobic segments on both the N- and C-termini, was investigated by two-dimensional NMR spectroscopy. The need to determine the structure of this peptide is rooted in its specific ability to lyse lipid layers that have a high content of anionic lipid. The lytic activities of CB3 on cell membranes including cancer cells and bacteria is found to be less than cecropin B1. The results show that CB3 has four discrete segments forming alpha helical structures. The crumpled structure of CB3 provides evidence for the lysis of the lipid layer being via a pathway that differs from pore formation. The results in this study provide strong clues towards a rational design for a potent antimicrobial and antitumor peptide.

3T3 Cells↗

PubMed2001

Structure stability of lytic peptides during their interactions with lipid bilayers.

In this work, molecular dynamics simulations were used to examine the consequences of a variety of analogs of cecropin A on lipid bilayers. Analog sequences were constructed by replacing either the N- or C-terminal helix with the other helix in native or reverse sequence order, by making palindromic peptides based on both the N- and C-terminal helices, and by deleting the hinge region. The structure of the peptides was monitored throughout the simulation. The hinge region appeared not to assist in maintaining helical structure but help in motion flexibility. In general, the N-terminal helix of peptides was less stable than the C-terminal one during the interaction with anionic lipid bilayers. Sequences with hydrophobic helices tended to regain helical structure after an initial loss while sequences with amphipathic helices were less able to do this. The results suggests that hydrophobic design peptides have a high structural stability in an anionic membrane and are the candidates for experimental investigation.

Amino Acid Sequence↗

PubMed2001

Acyclic nucleoside/nucleotide analogues with an imidazole ring skeleton.

Syntheses of a few acyclic nucleoside and acyclic nucleoside phosphonate analogues containing an imidazole ring have been reported. These analogues include methyl 1-(2-hydroxyethoxymethyl)imidazole-4, 5-dicarbo-xylate (1), 4,5-dicarbamoyl-1-(2-hydroxyethoxymethyl)imidazole (2), 4,5-dicyano-1-(2-hydroxyethoxymethyl)imidazole (4), Methyl 1-(2-bromoethoxymethyl)imidazole-4,5-dicarboxylate (7), 4,5-dicyano-(2-bromoethoxymethyl)imidazole (8), and Methyl 1-(2-phosphonomethoxyethyl)imidazole (10). Also reported are a few potential prodrugs of the above compounds, including the acetyl derivatives 5 and 6 (of 1 and 4, respectively), and the diethyl phosphonate ester 9 (of 10). In addition, the corresponding benzyl-protected precursors 11 and 12 (of 1 and 4, respectively), along with their common hydrolysis product, 1-(2-benzyloxy-ethoxymethyl)-4,5-imidazoledicarboxylic acid (3), are reported. Another potential prodrug included in the list is 1-(2-acetoxyethyl)-4,5-dicyanoimidazole (15). The compounds were screened for in vitro antiviral activity against a wide variety of herpes and respiratory viruses. The most active compound was the phosphonate analogue 9 which exhibited an anti-measles virus activity with an EC50 of <2.5 microg/mL and an SI value of > 176.

Antiviral Agents↗

PubMed2001

Distinct regulation of gene expression by prostaglandin F(2alpha) (PGF(2alpha)) is associated with PGF(2alpha) resistance or susceptibility in human granulosa-luteal cells.

The effects of human chorionic gonadotrophin (HCG) and prostaglandin F(2alpha) (PGF(2alpha)) on regulation of human granulosa-luteal cell (GLC) function at different stages of differentiation (day 2 versus day 8 of culture) were studied. Expression of LH receptor mRNA and biosynthesis of progesterone were HCG dependent in human GLC at all stages (n = 6, P < 0.05). Steady-state concentrations of mRNA encoding for FP (a specific high-affinity plasma membrane receptor for PGF(2alpha)) were not dependent on, but were stimulated by, addition of HCG (10 IU/ml) or 8-bromo-cAMP (0.5 mmol/l) (n = 6, P < 0.05). Treatment with PGF(2alpha) (100 nmol/l) decreased FP mRNA concentration, but had no effect on LH receptor and cyclo oxygenase-2 (COX-2) expression on day 2 of cultured GLC (n = 8). As a result, the progesterone biosynthesis by GLC was not affected. On day 8, PGF(2alpha) induced FP and PGHS-2 expression and at the same time decreased LH receptor expression, resulting in inhibition of progesterone output by GLC. Our data demonstrated that early stage GLC (day 2 of culture) are resistant to PGF(2alpha)-induced inhibition of progesterone synthesis but underwent further differentiation and acquired luteolytic capacity after 8 days culture in vitro. We conclude that, via distinct gene regulation at different stages of differentiation, human GLC may become resistant or susceptible to PGF(2alpha)-induced luteolysis.

Cell Division↗

PubMed2001

Prostacyclin analogue (OP-2507) induces delayed ex vivo neutrophil apoptosis and attenuates reperfusion-induced hepatic microcirculatory derangement in rats.

Leukocyte-endothelial adherence and changes of blood flow in microcirculation are associated with the development of ischemia-reperfusion injury in the liver. Polymorphonuclear neutrophil (PMN) apoptosis is essential to maintain homeostasis and plays a major role in limiting the reperfusion-related systemic effects. This study investigates the effects of a prostacyclin analogue (OP-2507) on hepatic ischemia-reperfusion injury. Adult, male Sprague-Dawley rats were used. Five groups were evaluated: (1) sham-operated control, n = 8; (2) ischemia control (1-h ischemia, 5-h reperfusion), n = 8; (3) intravenous infusion with OP-2507 ([15 cis-14-propylcyclohexyl]-16,17,18,19,20-pentanor-9-deoxy-9alpha,6-ni-trilo-PGF, methyl eater) at a dose of 1 microg/kg/min plus ischemia, n = 8; (4) intravenous infusion with OP-2507 at a dose of 0.1 microg/kg/min plus ischemia, n = 8, and (5) sham-operated control and intravenous infusion with OP-2507 at a dose of 1 microg/kg/min, N =8. Laser-Doppler flowmetry and an in vivo microscopy were used to investigate hepatic microcirculation. PMN apoptosis was quantitated by flow-cytometric labeling of DNA strand breaks. Tissue malondialdehyde and adenosine triphosphate were determined at the end of the experiment. Compared with the ischemia control group, OP-2507 significantly improved harmful insults following ischemia-reperfusion. The changes of mean systemic arterial pressure following ischemia-reperfusion have been significantly attenuated by OP- 2507 at both doses. OP-2507 lessened adherent leukocyte count in the post-sinusoid venules, and improved flow velocity in these areas. OP-2507 at both doses reduced malondialdehyde and increased adenosine triphosphate levels and this effect was dose-related. The activity of delayed ex vivo PMN apoptosis was significantly lower in the ischemia group than that of control and treatment groups. OP-2507 induced the activity of PMN apoptosis and its effect is dose-related, also. The PMN apoptosis activity is strongly correlated with parenchymal damages. This study demonstrates that OP-2507 treatment with ischemia may ameliorate the ischemia-reperfusion injury of the liver in the rat model, and increase spontaneous neutrophil apoptosis ex vivo.

Animals↗

PubMed2001

Effect of N(G)-nitro-L-arginine methyl ester on intestinal permeability following intestinal ischemia-reperfusion injury in a rat model.

Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis in premature infants. Previous studies suggested that continuous, endogenous formation of nitric oxide (NO) maintains the mucosal integrity of the intestine, thus protecting the gut from injuries from blood-borne toxins and tissue-destructive mediators. This study was undertaken to assess whether the inhibition of NO production causes an increase in intestinal permeability in rats following IRI. Sprague-Dawley rats weighing 200-300 g were divided into 4 groups: (1) untreated group (normal control); (2) ischemia-reperfusion group; (3) early N(G)-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO production, treatment group, and (4) late L-NAME treatment group. Transient IRI was induced by 30-min occlusion, followed by reperfusion of the isolated ileal loop. The L-NAME was administered 15 min before and after mesenteric ischemia as a 25-mg/kg bolus. Fluorescein isothiocyanate-dextran (FITC-D) was used to quantitatively assess the alteration in mucosal permeability of the intestine. There was no significant increase in the portal vein FITC-D level among normal controls, ischemia-reperfusion group and late L-NAME-treated group, but there was an approximately 6-fold increase in the early L-NAME treatment group. The pathological features of the intestine following IRI include denudation of the villus epithelium and reduction of villus height, associated with marked inflammatory cell infiltration over the lamina propria. These results suggest that endogenous NO may play a role in the protecting intestinal integrity after IRI.

Animals↗

PubMed2001

Association between the Ser9Gly polymorphism of the dopamine D3 receptor gene and tardive dyskinesia in Chinese schizophrenic patients.

It has been suggested that dopamine D3 receptor (DRD3) may have important implications for antipsychotic-induced tardive dyskinesia (TD). Previous studies have demonstrated an association between a serine to glycine polymorphism in the first exon of the DRD3 gene and TD; however, the results have been inconsistent. Therefore, we have replicated these studies using a Chinese sample population. A total of 115 schizophrenic patients from chronic wards were assessed for TD severity using the Abnormal Involuntary Movements Scale (AIMS) and were subsequently genotyped for the DRD3 polymorphism. The mean AIMS score for patients carrying the heterozygote (DRD3(ser-gly)) was significantly greater than for those with the homozygotes (DRD3(ser-ser) and DRD3(gly-gly)). Our results are in line with a previous report, the results of which suggest that the presence of the DRD3(ser-gly) genotype may be a risk factor for the development of TD in patients treated with antipsychotics.

Adolescent↗

PubMed2001

The regulation of T cell homeostasis and autoimmunity by T cell-derived LIGHT.

Costimulatory molecules on antigen-presenting cells (APCs) play an important role in T cell activation and expansion. However, little is known about the surface molecules involved in direct T-T cell interaction required for their activation and expansion. LIGHT, a newly discovered TNF superfamily member (TNFSF14), is expressed on activated T cells and immature dendritic cells. Here we demonstrate that blockade of LIGHT activity can reduce anti-CD3-mediated proliferation of purified T cells, suggesting that T cell-T cell interaction is essential for this proliferation. To test the in vivo activity of T cell-derived LIGHT in immune homeostasis and function, transgenic (Tg) mice expressing LIGHT in the T cell lineage were generated. LIGHT Tg mice have a significantly enlarged T cell compartment and a hyperactivated peripheral T cell population. LIGHT Tg mice spontaneously develop severe autoimmune disease manifested by splenomegaly, lymphadenopathy, glomerulonephritis, elevated autoantibodies, and severe infiltration of various peripheral tissues. Furthermore, the blockade of LIGHT activity ameliorates the severity of T cell-mediated diseases. Collectively, these findings establish a crucial role for this T cell-derived costimulatory ligand in T cell activation and expansion; moreover, the dysregulation of T cell-derived LIGHT leads to altered T cell homeostasis and autoimmune disease.

Animals↗