Biomedical subjects

Y H Chen

Publications and source records attributed to Y H Chen.

At least 19 recordsLinked to original sources

PubMed2003

Actively Q-switched Nd:YVO4 laser using an electro-optic periodically poled lithium niobate crystal as a laser Q-switch.

We demonstrate a low-voltage and fast laser Q-switching by using an electro-optic periodically poled lithium niobate (EO PPLN) crystal. The half-wave voltage measured from the EO PPLN crystal was 0.36 V x d (microm)/L (cm), where d is the electrode separation and L is the electrode length. When a 13-mm-long EO PPLN was used as a laser Q switch at 7-kHz switching rate, we measured an approximately 12-ns pulse width and approximately 0.74-kW laser pulses at 1064-nm wavelength from a diode-pumped Nd:YVO4 laser with continuous 1.2-W pump power at 809-nm wavelength.

Journal Article↗

PubMed2003

Dynamic behavior of ozonation with pollutant in a countercurrent bubble column with oxygen mass transfer.

The dynamic behavior of ozonation with pollutants in a countercurrent bubble column is studied for the model establishment. Bubble columns have been widely used for an ozonation system in the plants and laboratories. In addition, a countercurrent bubble column has been commonly recommended than a cocurrent one because it has a higher ozone transfer efficiency. Therefore, the investigation of this paper focuses on the countercurrent bubble column. As an ozonation process starts, the gas mixture of ozone and oxygen is introduced into the bottom of a column, and then transferred into the liquid. The pollutants in the wastewater are eliminated subsequently via oxidation by the dissolved ozone. There certainly exists a temporary and unsteady period before the ozonation system reaches steady state. However, available ozonation models employed to describe ozone and pollutant profiles have commonly been developed for steady state. The treating qualities of wastewater in the early stage of ozonation are usually not predicted, and the time required for the steady-state establishment remains to be determined. Moreover, oxygen mass transfer is usually neglected in previous ozonation models so that the increase of dissolved oxygen is uncertain. These information is desirable for the proper design and operation of ozonation system in a bubble column. Thus, the aim of this study is to model and investigate the dynamic processes of ozonation with pollutants including oxygen mass transfer. The dynamic axial dispersion model proposed is employed to predict the variation of the ozone, pollutant, and oxygen concentrations profiles. The validity of the model was demonstrated by comparing the predicted results with the experimental data. The o-cresol was chosen as the model pollutant. The temporal concentration variations of the residual o-cresol and dissolved oxygen in the effluent liquid, and the off-gas ozone in the free volume were measured accordingly. Furthermore, the variation of the enhancement factor of ozone and the amount of off-gas were predicted. Note that it usually needs 2-5 hydraulic retention times to approach steady state under the conditions of this study. Further, the effects of dimensionless system parameters on the performance of the ozonation processes are examined. As a result, the proposed dynamic model of ozonation with pollutants is useful for proper prediction of the variables of an ozonation system in a countercurrent bubble column.

Gases↗

PubMed2003

Claudin-8 interacts with multi-PDZ domain protein 1 (MUPP1) and reduces paracellular conductance in epithelial cells.

The claudin family is a set of integral membrane proteins found at cell-cell interactions in tight junctions. To identify proteins that interact with claudin-8, we used the yeast two-hybrid system to search for binding partners. Using the C-terminal 37 amino acids of claudin-8 as bait, we screened a human kidney cDNA library and identified multi-PDZ domain protein 1 (MUPP1) as a claudin-8 binding protein. MUPP1 contains 13 PDZ domains and binds to claudin-8 though its PDZ9 domain. When MDCK cells were transfected with epitope-tagged claudin-8 or MUPP1, both molecules were concentrated at cell-cell junctions. The interaction of claudin-8 and MUPP1 in vivo was confirmed by co-immunolocalization and co-immunoprecipitation in MDCK cells. Expression of claudin-8-myc increased transepithelial electrical resistance (TER) and reduced paracellular flux using FITC-dextran as a tracer. Over-expression of FLAG-MUPP1 in MDCK cells also reduced the epithelial paracelhular conductance. Our results indicate that claudin-8 and MUPP1 interact in tight junctions of epithelial cells and are involved in the tight junction barrier function.

Animals↗

PubMed2002

Effects of cisapride on oesophageal transit of solids in patients with progressive systemic sclerosis.

In most patients with progressive systemic sclerosis (PSS) the oesophagus is affected. Reflux symptoms are most frequent, whilst dysphagia also occurs. Cisapride, a prokinetic agent, may enhance motility along the gastrointestinal tract. The effects of cisapride on oesophageal transit were evaluated in 12 PSS patient using a solid-phase radionuclide oesophageal transit study. Each PSS patient was given cisapride 10 mg or placebo orally three times a day in a random, double-blind, crossover fashion. The results show that cisapride does not seem to have any impact on oesophageal transit in patients with PSS.

Administration, Oral↗

PubMed2002

Decomposition of 2-naphthalenesulfonate in aqueous solution by ozonation with UV radiation.

This study investigates the ozonation of 2-naphthalenesulfonate (2-NS) combined with ultraviolet (UV) radiation. Naphthalenesulfonic acids are of importance as dye intermediates for the dye and textile auxiliary industries. Its derivatives, such as 2-NS, have been found in rivers and tannery effluents causing pollution problems. Thus, the 2-NS is of concern for the aquatic pollution control especially in the surface and waste waters. Ozonation combined with UV radiation is employed for the removal of 2-NS in the aqueous solution. Semibatch ozonation experiments were proceeded under different reaction conditions to study the effects of ozone dosage and UV radiation on the oxidation of 2-NS. The concentrations of 2-NS and sulfate are analyzed at specified time intervals to elucidate the decomposition of 2-NS. In addition, values of pH and oxidation reduction potential are continuously measured in the course of experiments. Total organic carbon is chosen as a mineralization index of the ozonation of 2-NS. The mineralization of 2-NS via the ozonation is remarkably enhanced by the UV radiation. These results can provide useful information for the proper removal of 2-NS in the aqueous solution by the ozonation with UV radiation.

Arylsulfonates↗

PubMed2002

Functional modulation of human brain Nav1.3 sodium channels, expressed in mammalian cells, by auxiliary beta 1, beta 2 and beta 3 subunits.

Voltage-gated sodium channels consist of a pore-forming alpha subunit and two auxiliary beta subunits. Excitable cells express multiple alpha subtypes, designated Na(v)1.1-Na(v)1.9, and three beta subunits, designated beta1, beta2 and beta3. Understanding how the different alpha subtypes, in combination with the various beta subunits, determine sodium channel behavior is important for elucidating the molecular basis of sodium channel functional diversity. In this study, we used whole-cell electrophysiological recording to examine the properties of the human Na(v)1.3 alpha subtype, stably expressed in Chinese hamster ovary cells, and to investigate modulation of Na(v)1.3 function by beta1, beta2 and beta3 subunits. In the absence of beta subunits, human Na(v)1.3 formed channels that inactivated rapidly (tau(inactivation) approximately equals 0.5 ms at 0 mV) and almost completely by the end of 190-ms-long depolarizations. Using an intracellular solution with aspartate as the main anion, the midpoint for channel activation was approximately -12 mV. The midpoint for inactivation, determined using 100-ms conditioning pulses, was approximately -47 mV. The time constant for repriming of inactivated channels at -80 mV was approximately 6 ms. Coexpression of beta1 or beta3 did not affect inactivation time course or the voltage dependence of activation, but shifted the inactivation curve approximately 10 mV negative, and slowed the repriming rate ca. three-fold. beta2 did not affect channel properties, either by itself or in combination with beta1 or beta3. Na(v)1.3 expression is increased in damaged nociceptive peripheral afferents. This change in channel expression levels is correlated with the emergence of a rapidly inactivating and rapidly repriming sodium current, which has been proposed to contribute to the pathophysiology of neuropathic pain. The results of this study support the hypothesis that Na(v)1.3 may mediate this fast sodium current.

Animals↗

PubMed2002

The effect of dexamethasone upon patient-controlled analgesia-related nausea and vomiting.

Ninety female patients were enrolled in this randomised, double-blind, placebo-controlled study to compare the anti-emetic effect of intravenous dexamethasone 8 mg with saline control in preventing patient-controlled analgesia-related nausea and vomiting following major orthopaedic surgery. The prophylactic administration of dexamethasone 8 mg significantly reduced the overall incidence of patient-controlled analgesia-related nausea and vomiting (p<0.001) and the need for rescue anti-emetics (p<0.01). Furthermore, patients who received dexamethasone showed a higher incidence of complete responses (no vomiting or need for rescue anti-emetic for a 24-h postoperative period) than those who received saline (p<0.05). We conclude that dexamethasone 8 mg may be valuable for preventing patient-controlled analgesia-related nausea and vomiting in women undergoing major orthopaedic surgery.

Adult↗

PubMed2002

Changes in vesicourethral function following laparoscopic hysterectomy versus abdominal hysterectomy.

OBJECTIVE: To assess whether total hysterectomy is associated with increased postoperative vesicourethral abnormalities. SAMPLE: Forty-five patients had a laparoscopic hysterectomy and 36 patients had a total abdominal hysterectomy. DESIGN: Before and after hysterectomy, patients underwent a urinalysis, a personal interview, and an urodynamic study. RESULTS: Of the laparoscopic hysterectomy group, 27 patients (60%) exhibited urinary symptoms preoperatively, and 22 patients (48.9%) remained symptomatic following surgery. There was no significant change in the number of women with one or more urinary symptoms, but the incidence of urinary frequency and stress incontinence decreased significantly following hysterectomy (p < 0.05). Of the total abdominal hysterectomy group, preoperative voiding symptoms were present in 22 patients (61.1%). After surgery, urinary symptoms were present in 19 patients (52.8%). Some patients did not complain of any urinary frequency or stress incontinence following hysterectomy, but this figure did not differ significantly (p > 0.05). Maximal urethral closure pressure and maximal cystometric capacity demonstrated significant increases for both groups following surgery. CONCLUSIONS: The results indicated that total hysterectomy, either laparoscopic or total abdominal hysterectomy, did not significantly increase the subjective and objective incidence of vesicourethral dysfunction. On the contrary, some patients experience a substantial improvement of pre-existing urinary frequency or stress incontinence, partly as a result of an increase in the maximal urethral closure pressure and total bladder capacity following hysterectomy.

Female↗

PubMed2001

Mutation analysis of the human NR4A2 gene, an essential gene for midbrain dopaminergic neurogenesis, in schizophrenic patients.

Recent studies have revealed that an orphan receptor gene of the steroid/thyroid hormone nuclear receptor superfamily, the Nurr1 gene, is essential for the neurogenesis and differentiation of dopaminergic neurons in the midbrain of mice. Transgenic mice lacking the Nurr1 gene soon die after birth and are devoid of dopaminergic neurons in the midbrain. Heterozygous mice survive postnatally without obvious locomotor deficits; however, they have increased vulnerability to dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In view of the importance of dopamine neurotransmission in brain function, we were interested to know if the human homologous gene of murine Nurr1, the NR4A2 gene, may play a role in the pathogenesis of schizophrenia. We systematically sequenced all the exons of the human NR4A2 gene to search for molecular variants in a cohort of Chinese schizophrenic patients from Taiwan. Two molecular variants were identified: a G-insertion in intron 6 (designated IVS6 + 17 [see text] + 18insG), and a G-deletion in the untranslated exon 1 (designated c.-469delG). The IVS6 + 17 [see text] + 18insG is a polymorphic one; further case control study, however, did not reveal association of this polymorphism with schizophrenia. The c.-469delG is a rare variant found in two unrelated patients among 177 schizophrenic patients, but not in 130 nonpsychotic controls. The result suggests that the c.-469delG and possibly other variants of the NR4A2 gene may be of relevance to the complex factors involved in the pathogenesis of schizophrenia.

DNA↗

PubMed2001

Pulsatility of ascending aorta and restenosis after coronary angioplasty in patients >60 years of age with stable angina pectoris.

A recent study has demonstrated that the pulsatility of the ascending aorta is a strong predictive factor for restenosis after coronary angioplasty. However, whether the pulsatility of the ascending aorta is still a significant predictor for restenosis in elderly patients with a stiffer aorta is unknown. We investigated the relation between arterial pulsatility in the ascending aorta and restenosis after coronary angioplasty in patients aged > 60 years. Eighty-seven consecutive patients (80 men, aged 72.5 +/- 5.1 years) with stable angina were included. Before angioplasty, the arterial systolic, diastolic, and mean pressure waveforms of the ascending aorta were measured. We used fractional pulse pressure (PPf, the ratio of pulse pressure to mean pressure) and pulsatility index (PI, the ratio of pulse pressure to diastolic pressure) to estimate the pulsatility of the ascending aorta. Angiographic restenosis occurred in 39 patients. Pulse pressure, PPf, and PI were significantly higher in patients with restenosis after coronary angioplasty (restenosis vs without restenosis: pulse pressure, 77.6 +/- 12.2 vs 66.1 +/- 15.4 mm Hg [p < 0.001]; PPf, 0.80 +/- 0.09 vs 0.69 +/- 0.11 [p < 0.001]; PI, 1.19 +/- 0.20 vs 0.98 +/- 0.21 [p < 0.001]). After multivariate stepwise adjustment of risk factors of restenosis and using receiver-operating characteristic analysis, the odds ratio (OR) of restenosis was: pulse pressure > 66 mm Hg, OR 5.88 (95% confidence interval [CI] 2.17 to 15.93); PPf > 0.72, OR 13.71 (95% CI 4.81 to 39.05); PI > 1.06, OR 13.56 (95% CI 4.67 to 39.38). Moreover, among patients aged > 70 years (n = 60), the predictive values of PPf and PI were even higher than those in patients aged < or = 70 years (n = 27). Thus, in elderly patients with stable angina, the pulsatility of the ascending aorta is a powerful predictor of restenosis after coronary angioplasty.

Aged↗

PubMed2001

Geometric parameters of the in vivo tissues at the lumbosacral joint of young Asian adults.

STUDY DESIGN: Magnetic resonance images (MRIs) were used to determine the geometry of the tissues studied. OBJECTIVE: To investigate the geometric parameters of tissues around the lumbosacral joint. SUMMARY OF BACKGROUND DATA: Cross-sectional area (CSA), moment arms, and line of action of the tissues located at lumbosacral joint (L5-S1), which are important in the study of spinal mechanics and models for the investigation of low back pain. It was insufficient information to describe the relative dimension of spinal tissues except muscles around the lumbar spine. METHODS: MRIs from eight asymptomatic young Taiwanese male adults were collected to present CSA, moment arms, and line of action of the tissues located at lumbosacral joint (L5-S1). Four pairs of trunk muscles, erector spinae, rectus abdominis, abdominal oblique externus, and psoas muscles, ligamentum flavum, and facet joints at the bilateral sides were studied. RESULTS: Spinal tissues at the level of lumbosacral joint were determined. The CSAs of the spinal elements at the L5-S1 normalized by the CSA of trunk ranged from 5.42% (the erector spinae) to 0.14% (the ligamentum flavum). The moment arm of the spinal elements relative to the trunk width and depth ranged from 40.91% (rectus abdominis at the y direction) to 0.38% (ligamentum flavum at the x direction). The profile of geometric elements of lumbosacral joint in the Asian male subjects was similar to the data collected from the white population. The data also showed that right-left symmetry in the aforementioned dimension. CONCLUSION: Normalized data of the CSA, moment arm, and line of action of the spinal tissues at the L5-S1 joint were reported in vivo through the MRI techniques. The profile of geometric elements of lumbosacral joint in the Asian male subjects did not differ from the white population. In addition to muscles, the geometry of facet joint and ligament was determined, which would be important to the calculation of force distribution on the lumbosacral joint.

Adult↗

PubMed2001

Upstream stimulatory factors regulate aortic preferentially expressed gene-1 expression in vascular smooth muscle cells.

The phenotypic modulation of vascular smooth muscle cells (VSMC) plays a central role in the pathogenesis of arteriosclerosis. Aortic preferentially expressed gene-1 (APEG-1), a VSMC-specific gene, is expressed highly in differentiated but not in dedifferentiated VSMC. Previously, we identified an E-box element in the mouse APEG-1 proximal promoter, which is essential for VSMC reporter activity. In this study, we investigated the role of upstream stimulatory factors (USF) in the regulation of APEG-1 transcription via this E-box element. By electrophoretic mobility shift assays, recombinant USF1 and USF2 homo- and heterodimers bound specifically to the APEG-1 E-box. Nuclear extracts prepared from primary cultures of rat aortic smooth muscle cells exhibited specific USF1 and USF2 binding to the APEG-1 E-box. To investigate the binding properties of USF during VSMC differentiation, nuclear extracts were prepared from the neural crest cell line, MONC-1, which differentiates into VSMC in culture. Maximal USF1 and USF2 protein levels and binding to the APEG-1 E-box occurred 3 h after the differentiation of MONC-1 cells was initiated. Co-transfection experiments demonstrated that dominant negative USF repressed APEG-1 promoter activity, and USF1, but not USF2, transactivated the APEG-1 promoter. Our studies demonstrate that USF factors contribute to the regulation of APEG-1 expression and may influence the differentiation of VSMC.

Animals↗

PubMed2001

Purification, sequencing, and phylogenetic analyses of novel Lys-49 phospholipases A(2) from the venoms of rattlesnakes and other pit vipers.

Basic phospholipase A(2) homologs with Lys49 substitution at the essential Ca(2+)-binding site are present in the venom of pit vipers under many genera. However, they have not been found in rattlesnake venoms before. We have now screened for this protein in the venom of rattlesnakes and other less studied pit vipers. By gel filtration chromatography and RP-HPLC, Lys49-phospholipase-like proteins were purified from the venoms of two rattlers, Crotalus atrox and Crotalus m. molossus, and five nonrattlers, Porthidium nummifer, Porthidium godmani, Bothriechis schlegelii, Trimeresurus puniceus, and Trimeresurus albolabris. Their N-terminal amino acid sequences were shown to be characteristic for this phospholipase subfamily. The purified basic proteins from rattlesnakes caused myonecrosis and edema in experimental animals. We have also cloned the cDNAs and solved the complete sequences of four novel Lys49-phospholipases from the venom glands of C. atrox, P. godmani, B. schlegelii, and Deinagkistrodon acutus (hundred-pace). Phylogenetic analyses based on the amino acid sequences of 28 Lys49-phospholipases separate the pitviper of the New World from those of the Old World, and the arboreal Asiatic species from the terrestrial Asiatic species. The implications of the phylogeny tree to the systematics of pit vipers, and structure-function relationship of the Lys49-phospholipases are discussed.

Amino Acid Substitution↗

PubMed2001

Role of macrophage-expressed adipocyte fatty acid binding protein in the development of accelerated atherosclerosis in hypercholesterolemic mice.

Atherosclerosis is an inflammatory disease process associated with elevated levels of plasma cholesterol, especially low-density lipoproteins. The latter become trapped within the arterial wall and are oxidized and taken up by macrophages to form foam cells. This process is an initiating event for atherosclerosis. Fatty acid binding proteins (FABP) are involved in fatty acid metabolism and cellular lipid transport, and adipocyte FABP (aP2) is also expressed in macrophages. We recently generated mice lacking both apolipoprotein (Apo)E and aP2 (ApoE-/-aP2-/-) and found that these mice, compared with ApoE-/- mice, developed markedly smaller atherosclerotic lesions that contained fewer macrophages. Here we investigated the mechanism(s) responsible for this prevention of atherosclerotic lesion formation. Bone marrow transplantations were performed in ApoE-/- mice, receiving cells from either ApoE-/- or ApoE-/-aP2-/- mice. The lack of aP2 in donor marrow cells led to the development of smaller (5.5-fold) atherosclerotic lesions in the recipient mice. No differences were found in plasma cholesterol, glucose, or insulin levels between recipients of bone marrow cells from ApoE-/- or ApoE-/-aP2-/- mice. However, the expression of chemoattractant and inflammatory cytokines was decreased in macrophages from ApoE-/-aP2-/- mice compared with ApoE-/- mice, which may contribute to the decrease in atherosclerotic lesion formation. Taken together, we demonstrate the importance of macrophage aP2 in the development of atherosclerotic lesions.

Animals↗

PubMed2001

E1A inhibition of radiation-induced NF-kappaB activity through suppression of IKK activity and IkappaB degradation, independent of Akt activation.

Activation of the transcription factor nuclear factor kappaB (NF-kappaB) has been implicated in the protection of cells from apoptosis. We have shown previously that the adenovirus type 5 E1A sensitizes cells to radiation-induced apoptosis by inhibiting NF-kappaB activity. However, the exact mechanism of inhibition is not known. In this study, we compared the activity of inhibitor of nuclear factor-kappaB (IkappaB) kinase (IKK) and the degradation of IkappaBalpha in E1A transfectants and parental human cancer cells after ionizing radiation treatment. We found that radiation-induced IKK activity and IkappaBalpha degradation were inhibited in the E1A transfectants. Recently, Akt has been implicated in NF-kappaB activation. To test whether Akt is regulated by E1A and is involved in radiation-induced NF-kappaB activity, we examined the phosphorylation status of Akt in the E1A transfectants and parental cells and in irradiated cells. The results indicated that radiation induced Akt phosphorylation and that E1A inhibited basal but not radiation-induced Akt phosphorylation. We additionally examined radiation-induced NF-kappaB activity in cells stably transfected with a dominant-negative, inactive Akt and in parental cancer cells treated with a phosphatidylinositol 3-kinase inhibitor, wortmannin. We found that dominant-negative Akt and wortmannin did not block radiation-induced NF-kappaB activity. Thus, our results suggest that inhibition of IKK activity and IkappaB degradation is the predominant mechanism for E1A-mediated inhibition of radiation-induced NF-kappaB activity and that radiation-induced Akt activation cannot be inhibited by E1A and is likely independent of radiation-induced NF-kappaB activity.

Adenoviridae↗

PubMed2001

Molecular cloning, developmental expression, and hormonal regulation of zebrafish (Danio rerio) beta crystallin B1, a member of the superfamily of beta crystallin proteins.

The cDNA sequence of beta crystallin B1 was determined from zebrafish (Danio rerio) and compared to the corresponding genes of bovine, rat, chicken, human, and Xenopus. Multispecies comparison of superfamily diversity demonstrated beta crystallin B1 homology between zebrafish, bovine, chicken, and rat, but large distances to beta crystallin B2 and B3. Zebrafish cDNA has a size of 943 nucleotides and encodes a polypeptide of 233 amino acids. Zebrafish beta crystallin B1 shares 71.30, 75.86, and 71.00% similarities with bovine, chicken, and rat beta crystallin B1, respectively. Northern blot analysis revealed a single 0.9-kb beta crystallin B1 transcript which was expressed and progressively increased in the first 20 h of zebrafish embryogenesis. Whole-mount in situ hybridization revealed that the beta crystallin B1 transcript was only specifically expressed in the lens region of the eye. A starvation experiment revealed no variation in mRNA levels after 14 and 21 days. An experiment in which hormone was injected showed that the beta crystallin B1 transcript first increased 24 h after the injection of insulin-like growth factor I, insulin-like growth factor II, or growth hormone, then decreased 48 h after injection. The beta crystallin B1 transcript continuously increased after insulin was injected. Taken together, our results identify the early specific expression of beta crystallin B1 within the lens. Despite small differences, these results indicate that both the structure of the beta crystallin B1 protein and its involvement with regulation by growth factors appear to have been remarkably conserved.

Amino Acid Sequence↗

PubMed2001

Epitope-vaccine as a new strategy against HIV-1 mutation.

An effective vaccine is urgently needed to stop AIDS-epidemic. Up to now none of the candidate HIV-vaccines has been developed to prevent HIV-1 infection. A few neutralizing antibodies against HIV-1 enveloping proteins proved to be highly effective to neutralize different strains in vitro. Unfortunately, these antibodies are rare in infected humans, and have never yet been raised by a vaccine. The multiple sequential and antigenic variability of HIV-1 led to unprecedented difficulties in development of effective vaccines and anti-viral drugs. More and more experimental evidences indicated that HIV-1 mutants resulted in immune evasion may be a grave challenge for conventional strategy to prepare effective vaccines. We suggested that epitope-vaccine could be a new strategy to induce high levels of neutralizing antibodies with predefined epitope-specificity against HIV-1. Several candidate epitope-vaccines including mono-epitope-vaccine, multi-epitope-vaccine, epitope-vaccines in combination, were prepared and systematically studied in animal experiments. These studies provided experimental evidences that epitope-vaccine could be a new strategy to develop effective vaccines for prevention and immunotherapy against viral infection of HIV-l or other viruses.

AIDS Vaccines↗

PubMed2001

Systematic search for mutations in the human tissue inhibitor of metalloproteinases-3 (TIMP-3) gene on chromosome 22 and association study with schizophrenia.

Several linkage studies have suggested that chromosome 22q12-q13 is a putative region for schizophrenic genes. In this study, the human tissue inhibitor of metalloproteinase-3 (TIMP-3) gene was investigated as positional candidate gene for schizophrenia because of its regulatory function on extracellular matrix proteins, cell adhesion molecules, and neural cell adhesion molecules in the brain. We systematically searched for the nucleotide variants by sequencing all the exons and their flanking intronic sequences in a sample of Chinese schizophrenic patients from Taiwan. Two silent mutations in the exon 3 were identified: c.249T-->C at codon 83 (His) and c.261C-->T at codon 87 (Ser). However, no mutations causing amino acid alteration or aberrant splicing of transcripts were observed. Hence, it is unlikely that the TIMP-3 gene itself may play an important role in the genetic susceptibility to schizophrenia. Further case control association study revealed a significant difference of genotype distribution of the c.249T-->C between schizophrenic patients and control. This finding supports that 22q12 is a schizophrenia susceptible region, and it is likely that there might be other genetic mutations in the neighborhood of the TIMP-3 gene locus that may contribute to the susceptibility of schizophrenia.

Adult↗