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Biomedical subjects

S H Yang

Publications and source records attributed to S H Yang.

At least 73 records · Page 4Linked to original sources

DOH1, a class 1 knox gene, is required for maintenance of the basic plant architecture and floral transition in orchid.

We report here the isolation and identification of an orchid homeobox gene, DOH1, from Dendrobium Madame Thong-In. Analyses of its sequence and genomic organization suggest that DOH1 may be the only class 1 knox gene in the genome. DOH1 mRNA accumulates in meristem-rich tissues, and its expression is greatly downregulated during floral transition. In situ hybridization analysis demonstrates that DOH1 is also expressed in the incipient leaf primordia and is later detected in the same region of the inflorescence apex, as in DOMADS1. Overexpression of DOH1 in orchid plants completely suppresses shoot organization and development. Transgenic orchid plants expressing antisense mRNA for DOH1 show multiple shoot apical meristem (SAM) formations and early flowering. In addition, both the sense and antisense transformants exhibit defects in leaf development. These findings suggest that DOH1 plays a key role in maintaining the basic plant architecture of orchid through control of the formation and development of the SAM and shoot structure. Investigations of DOMADS1 expression in the SAM during floral transition reveal that the precocious flowering phenotype exhibited by DOH1 antisense transformants is coupled with the early onset of DOMADS1 expression. This fact, together with the reciprocal expression of DOH1 and DOMADS1 during floral transition, indicates that downregulation of DOH1 in the SAM is required for floral transition in orchid and that DOH1 is a possible upstream regulator of DOMADS1.

Amino Acid Sequence↗

Estradiol exerts neuroprotective effects when administered after ischemic insult.

BACKGROUND AND PURPOSE: 17beta-Estradiol (E2) has been reported to exert neuroprotective effects when administered before an ischemic insult. This study was designed to determine whether E2 treatment after ischemia exerts the same effects and, if so, how long this therapeutic window remains open, and whether the effects are related to changes in cerebral blood flow (CBF). METHODS: Female Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO). In protocol 1, E2 was administered (100 microg/kg IV followed immediately by subcutaneous implantation of crystalline E2 in a silicone elastomer tube) to ovariectomized females (OVX+E2) at 0.5 (n=8), 1 (n=6), 2 (n=7), 3 (n=6), or 4 (n=9) hours after MCAO. Intact (INT; n=6) and ovariectomized females (OVX; n=12) were subjected to MCAO and received vehicle instead of E2. Two days after MCAO the animals were killed, and ischemic lesion volume was determined by 2,3,5-triphenyltetrazolium chloride staining. In protocol 2, CBF was monitored before and at 1, 24, and 48 hours in a group of animals receiving E2 or vehicle 0.5 hour after ischemia induction (INT, n=6; OVX, n=8; OVX+E2, n=6). RESULTS: Lesion volume was 20.9+/-2.2% and 21.8+/-1.2% in the INT and OVX groups, respectively. E2 was found to decrease lesion volume significantly when administered within 3 hours after MCAO. The lesion volumes were 6.3+/-0.5%, 10.3+/-2.1%, 11.8+/-1.8%, 13.5+/-1.6%, and 17.9+/-2.8% when E2 was administered at 0.5, 1, 2, 3, or 4 hours after MCAO, respectively. CBF decreased to 43.1+/-2.2% and 25.4+/-1.0% in the INT and OVX animals, respectively, at 5 minutes after MCAO. In comparison to OVX rats, CBF was not different at 1 hour after E2 administration but was increased significantly in the OVX+E2 group 1 and 2 days after E2 administration. CONCLUSIONS: E2 exerts neuroprotective effects when administered after ischemia, with a therapeutic window in a permanent focal cerebral ischemia model of approximately 3 hours. This effect of estradiol was associated with no immediate change in blood flow but with a delayed increase in CBF.

Animals↗

Expression of transforming growth factor beta-1 in chronic hepatitis and hepatocellular carcinoma associated with hepatitis C virus infection.

BACKGROUND: Transforming growth factor beta-1 (TGF beta 1) has been suggested to play a role in the development, growth or progression of hepatocellular carcinoma (HCC). Genotype and serum titer of HCV also affect the occurrence of HCC in chronic hepatitis C. In this study, we were to evaluate the effects of genotype or serum titer of HCV on the expression of TGF beta 1. We also intended to examine the correlation between the up-regulation of TGF beta 1 and the association with HCC in patients with chronic hepatitis C. METHODS: We studied 19 patients with chronic hepatitis C and 18 with HCC associated with HCV infection. HCV genotype was determined by line probe reverse hybridization assay and the amount of HCV-RNA was quantitated by branched DNA signal amplification assay. Serum TGF beta 1 level was measured by enzyme linked immunosorbent assay. RESULTS: HCV genotypes of patients with HCC were similar to those without it. Serum HCV-RNA titer was higher in genotype 1b than in non-1b (p < 0.05). Serum TGF beta 1 levels were higher in HCC than in chronic hepatitis (p < 0.05). However, there was no significant difference in the serum TGF beta 1 level between genotype 1b and non-1b. Also, it was not correlated with the serum HCV-RNA titer or alanine aminotransferase levels. CONCLUSION: TGF beta 1 seems to be overexpressed in HCC compared to that of chronic hepatitis C: it was not affected by serum ALT levels, genotype or serum HCV titer. It is suggested that TGF beta 1 may be associated with the malignant transformation of hepatocyte or the progression of HCV-associated HCC.

Adult↗

Cecal volvulus: report of seven cases and literature review.

BACKGROUND: Cecal volvulus is an abdominal emergency and delay in its diagnosis and treatment can result in severe complications. We reviewed these cases in order to increase the understanding of cecal volvulus (CV) to promote early diagnosis and better management. METHODS: In this retrospective study of seven patients (all male; mean age +/- standard deviation, 63.4 +/- 17.3 years) over a 16-year period, we reviewed radiographs, for diagnostic accuracy, and the results of surgical procedures for better future management. RESULTS: The symptoms of CV related to obstruction had a mean of duration of 6.85 days (range, 2-20 days). The preoperative diagnosis rate was 57.1%. Three types of CV (bascule, clockwise and counterclockwise) were found. There were three treatment failures resulting in two deaths. There were two cases of metachronous volvulus, one in the sigmoid colon and one in the small intestine. CONCLUSIONS: Resection is indicated for gangrene or perforation and is highly suggested in underlying bowel disease or recurrent operative procedures. For uncomplicated viable CV, cecopexy provides fair results. Metachronous volvulus should always be considered when obstruction recurs.

Adult↗

Intracortical osteosarcoma: report of a case.

Intracortical osteosarcoma is the rarest anatomic variation of osteosarcoma. There have been only 12 cases reported in the English-language literature. We present a case of osteosarcoma in an 18-year-old Taiwanese man that originated within the cortex of the tibial diaphysis. The initial radiograph revealed a lytic mass confined to the cortex, mimicking a benign bone lesion. Histopathologic examination of the biopsy specimen showed an osteoblastic osteosarcoma mingled with some fibroblastic foci. He underwent en bloc resection, and a metallic prosthetic intercalary stem was used to replace the larger bone defect. Adjuvant chemotherapy was administered before and after the operation. He was free of disease during 40 months of follow-up. A review of all reported cases of intracortical osteosarcoma revealed that the initial method of treatment plays an important role in local recurrence and distant metastasis. Local excision and curettage leads to the worst results. The outcomes of more recently reported cases have improved because of early awareness of the possibility of malignancy and advances in chemotherapy. However, whether patients with intracortical osteosarcoma have a different prognosis from those with conventional osteosarcoma cannot be determined, because of the small number of intracortical osteosarcoma cases available for analysis.

Adolescent↗

Molecular characterization of a zebrafish TCF ETS-domain transcription factor.

The ternary complex factor (TCF) subfamily of ETS-transcription factors represent key nuclear targets of the MAP kinase pathways. Members of this subfamily are classified by the presence of several conserved domains for DNA binding, interaction with SRF, interaction with MAP kinases and transcriptional activation. In this study we have isolated a further member of this subfamily (TCF-1) from zebrafish. The protein product of zebrafish TCF-1 (zTCF-1), shares sequence similarity with the mammalian TCFs in all four conserved domains, with highest overall similarity to SAP-1. Zebrafish TCF-1 is expressed throughout zebrafish embryonic development and exhibits typical TCF DNA binding characteristics, with the B-box being required for interaction with SRF. Of the mammalian TCFs, its DNA binding specificity resembles Elk-1. zTCF-1 is a target for both the growth factor/mitogen-activated and stress-activated MAP kinase cascades in vitro and in vivo. However, differential targeting occurs, with the profile of its activation closely resembling that of mammalian SAP-1. Together, our results demonstrate that the TCFs have been functionally conserved during vertebrate development.

Amino Acid Sequence↗

TATA element recognition by the TATA box-binding protein has been conserved throughout evolution.

Cocrystal structures of wild-type TATA box-binding protein (TBP) recognizing 10 naturally occurring TATA elements have been determined at 2.3-1.8 A resolution, and compared with our 1.9 A resolution structure of TBP bound to the Adenovirus major late promoter (AdMLP) TATA box (5'-TATAAAAG-3'). Minor-groove recognition by the saddle-shaped protein induces the same conformational change in each of these oligonucleotides, despite variations in promoter sequence that reduce the efficiency of transcription initiation. Three molecular mechanisms explain assembly of diverse TBP-TATA element complexes. (1) T --> A and A --> T transversions leave the minor-groove face unchanged, permitting formation of TBP-DNA complexes on many A/T-rich core promoter sequences. (2) Cavities in the interface between TBP and the minor-groove face of the AdMLP TATA box accommodate the exocyclic NH(2) groups of G in a TACA box and in a TATAAG box. (3) Formation of a C:G Hoogsteen basepair in a TATAAAC box eliminates steric clashes that would be produced by the Watson-Crick base pair. We conclude that the structure of the TBP-TATA box complex found at the heart of the polymerase II (pol II) transcription machinery has remained constant over the course of evolution, despite variations in TBP and its DNA targets.

Amino Acid Sequence↗

The mechanism of phosphorylation-inducible activation of the ETS-domain transcription factor Elk-1.

Protein phosphorylation represents one of the major mechanisms for transcription factor activation. Here we demonstrate a molecular mechanism by which phosphorylation by mitogen-activated protein (MAP) kinases leads to changes in transcription factor activity. MAP kinases stimulate DNA binding and transcriptional activation mediated by the mammalian ETS-domain transcription factor Elk-1. Phosphorylation of the C-terminal transcriptional activation domain induces a conformational change in Elk-1, which accompanies the stimulation of DNA binding. C-terminal phosphorylation is coupled to activation of DNA binding by the N-terminal DNA-binding domain via an additional intermediary domain. Activation of DNA binding is mediated by an allosteric mechanism involving the key phosphoacceptor residues. Together, these results provide a molecular model for how phosphorylation induces changes in Elk-1 activity.

Allosteric Regulation↗

Trilinolein potentiates the pro-aggregating effect of phorbol-12-myristate 13-acetate in human polymorphonuclear leukocytes.

Trilinolein, a triacylglycerol with linoleic acid as the only type of fatty acid residue in all three of the glycerol esterified positions, was recently reported to have an antiplatelet effect, mediated through stimulating nitric oxide and cyclic guanosine monophosphate (GMP) formation. In our study, trilinolein induced aggregation of human polymorphonuclear neutrophils (PMNs) and, pretreatment with 0.1 nM trilinolein enhanced phorbol-12-myristate 13-acetate (PMA) induced aggregation. Further investigation showed that trilinolein at concentrations ranging from 0.1 nM to 10 microM increased cyclic GMP formation after 10 min of incubation with PMNs. Pretreatment of trilinolein with 10 microM d-sphingosine, before being incubated with PMNs, attenuated the stimulatory effect of trilinolein on cyclic GMP formation, and pretreatment of 10 microM d-sphingosine also attenuated the aggregation induced by PMA and trilinolein. We conclude that trilinolein can induce the aggregation of human PMNs, and enhance the aggregation induced by PMA.

Cell Aggregation↗

Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors.

Mitogen-activated protein (MAP) kinase-mediated signalling to the nucleus is an important event in the conversion of extracellular signals into a cellular response. However, the existence of multiple MAP kinases which phosphorylate similar phosphoacceptor motifs poses a problem in maintaining substrate specificity and hence the correct biological response. Both the extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) subfamilies of MAP kinases use a second specificity determinant and require docking to their transcription factor substrates to achieve maximal substrate activation. In this study, we demonstrate that among the different MAP kinases, the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2. The efficiency of phosphorylation in vitro and transcriptional activation in vivo of MEF2A and MEF2C by these p38 subtypes requires the presence of a kinase docking domain (D-domain). Furthermore, the D-domain from MEF2A is sufficient to confer p38 responsiveness on different transcription factors, and reciprocal effects are observed upon the introduction of alternative D-domains into MEF2A. These results therefore contribute to our understanding of signalling to MEF2 transcription factors and demonstrate that the requirement for substrate binding by MAP kinases is an important facet of three different subclasses of MAP kinases (ERK, JNK, and p38).

Animals↗

Effects of acupuncture on exercise-induced muscle soreness and serum creatine kinase activity.

The purpose of this study was to determine the effects of acupuncture on delayed onset muscle soreness (DOMS) produced by exercise. Baseline data were collected on 20 male subjects for intensity of muscle soreness and serum creatine kinase (CK) activity. All values were subsequently reassessed 24, 48 and 72 hours after exercise. The experimental group received acupuncture treatment while the control group received no treatment. Muscle soreness perception was significantly less (P < 0.05) at 72 hours in the acupuncture treated group compared to control group. However, the change in CK was not significantly different between groups. These results suggest that acupuncture is effective in decreasing muscle soreness but does not prevent CK release from muscle.

Acupuncture Therapy↗

Estrogen attenuates over-expression of beta-amyloid precursor protein messager RNA in an animal model of focal ischemia.

Cerebral ischemia is a risk factor for late onset Alzheimer's disease. Since estrogen replacement therapy benefits the outcome of cerebral stroke in post-menopausal women, we designed the present study to investigate the effects of estrogen on the expression of beta-amyloid precursor protein (APP) mRNA following focal ischemia in female rats. Female rats were ovariectomized (OVX) for two weeks. A single dose of 17 beta-estradiol (E2) (100 microgram/kg) was injected s.c. two hours before a unilateral middle cerebral artery (MCA) occlusion. Brain samples were harvested from ischemic core and penumbra of cortices at one hour and twenty-four hours following MCA occlusion. The expression of APP mRNA was assessed by RT-PCR. At one hour after MCA occlusion, OVX rats had a 67.9% (p<0.05) increase in APP mRNA in the penumbra. E2 treatment reduced this APP mRNA over-expression by 26.3% at that region. At twenty four hours following MCA occlusion, OVX rats had increases in APP mRNA of 52.9% and 57.0% (p<0.05) in the core and penumbra, respectively. E2 treatment reduced the APP mRNA over-expression by 61.0% and 48.6% (p<0.05) in these two regions, respectively. These effects appeared to reflect an interaction between hormonal environment and ischemia, since in the absence of MCA occlusion, there were no significant differences in APP mRNA expression among OVX, OVX-E2 treated and intact female rats. The present study demonstrates that estrogen may have an important role in reducing the over-expression of APP mRNA following focal ischemia.

Amyloid beta-Protein Precursor↗

Differential targeting of MAP kinases to the ETS-domain transcription factor Elk-1.

The activation of MAP kinase (MAPK) signal transduction pathways results in the phosphorylation of transcription factors by the terminal kinases in these cascades. Different pathways are activated by mitogenic and stress stimuli, which lead to the activation of distinct groups of target proteins. The ETS-domain transcription factor Elk-1 is a substrate for three distinct classes of MAPKs. Elk-1 contains a targeting domain, the D-domain, which is distinct from the phosphoacceptor motifs and is required for efficient phosphorylation and activation by the ERK MAPKs. In this study, we demonstrate that members of the JNK subfamily of MAPKs are also targeted to Elk-1 by this domain. Targeting via this domain is essential for the efficient and rapid phosphorylation and activation of Elk-1 both in vitro and in vivo. The ERK and JNK MAPKs use overlapping yet distinct determinants in the D-domain for targeting to Elk-1. In contrast, members of the p38 subfamily of MAPKs are not targeted to Elk-1 via this domain. Our data therefore demonstrate that different classes of MAPKs exhibit differential requirements for targeting to Elk-1.

3T3 Cells↗

In vivo assay for hepatitis C viral serine protease activity using a secreted protein.

Hepatitis C virus (HCV) is a major pathogen of community-acquired and post-transfusional non-A, non-B hepatitis. Since an in vitro replication system is not available, it is crucial to develop an efficient and sensitive assay system for screening inhibitors of HCV. The fact that the activity of HCV NS3 protease is responsible for the maturation of the nonstructural proteins and viral replication, suggests that NS3 protease is a suitable target for anti-HCV drug development. To devise an assay system in cell culture, we constructed NS3/4A-SEAP (secreted alkaline phosphatase) chimeric gene, in which the SEAP gene was fused in-frame to downstream of NS4A/4B cleavage site. In this system, the SEAP would be secreted into the extracellular media depending on the cleavage activity of the NS3 protease. Our results demonstrate that the NS3/4A-SEAP expression vector encoding wild type NS3 protease, but not mutant NS3 protease, could produce high SEAP activity in the media of both transfected cells and stable expression cell lines. Since the activity of SEAP in the culture media can be monitored quantitatively and continuously by the chemiluminescent method, this assay system will be useful for screening potential inhibitors of HCV protease.

3T3 Cells↗

Neural network computer program to determine photorefractive keratectomy nomograms.

PURPOSE: To evaluate a commercially available neural network program for calculation of photorefractive keratectomy treatment nomograms. SETTING: University referral refractive surgery clinic. METHODS: PRK/LASIK Brain, a commercial neural network computer program, was trained using the demographics, preoperative clinical data, surgical parameters, and 1 year postoperative clinical data of 44 patients treated with a Summit Technology excimer laser using a 5.0 mm optical zone. The neural-network derived nomogram was compared with the standard treatment nomogram for each patient. The relative contribution of age, sex, keratometry, and intraocular pressure (IOP) to the predicted nomograms was also assessed. RESULTS: Nomograms produced by the neural network were qualitatively similar to the standard nomogram. The sequence of data entry during training affected the network's predictions. Entry ordered by outcome (as opposed to entry by chronological order) yielded a nomogram that was more consistent with the standard nomogram. However, both outcome- and chronologically ordered network-derived nomograms diverged from the standard nomogram in individual patients, including a subset for whom use of the standard nomogram yielded desired refractive results (within 0.25 diopter of emmetropia). Further analysis of the neural-network-derived nomograms revealed marked sensitivity to sex, age, keratometry readings, and IOP. CONCLUSIONS: Neural networks offer a potential means of individualizing treatment nomograms, to account for patient demographics, preoperative examination, surgeon style, and equipment bias. However, a data set of 44 patients was not sufficient to train the PRK/LASIK Brain network to accurately predict treatment parameters in individual cases in the training set. A larger training set or a different learning algorithm may be required to improve the neural network's performance.

Adult↗

Hepatitis C virus core from two different genotypes has an oncogenic potential but is not sufficient for transforming primary rat embryo fibroblasts in cooperation with the H-ras oncogene.

Persistent infection with hepatitis C virus (HCV) is associated with the development of liver cirrhosis and hepatocellular carcinoma. To examine the oncogenic potential of the HCV core gene product, primary rat embryo fibroblasts (REFs) were transfected with the core gene in the presence or absence of the H-ras oncogene. In contrast to a previous report (R. B. Ray, L. M. Lagging, K. Meyer, and R. Ray, J. Virol. 70:4438-4443, 1996), HCV core proteins from two different genotypes (type 1a and type 1b) were not found to transform REFs to tumorigenic phenotype in cooperation with the H-ras oncogene, although the core protein was successfully expressed 20 days after transfection. In addition, REFs transfected with E1A- but not core-expressing plasmid showed the phenotype of immortalized cells when selected with G418. The biological activity was confirmed by observing the transcription activation from two viral promoters, Rous sarcoma virus long terminal repeat and simian virus 40 promoter, which are known to be activated by the core protein from HCV-1 isolate. In contrast to the result with primary cells, the Rat-1 cell line, stably expressing HCV core protein, exhibited focus formation, anchorage-independent growth, and tumor formation in nude mice. HCV core protein was able to induce the transformation of Rat-1 cells with various efficiencies depending on the expression level of the core protein. These results indicate that HCV core protein has an oncogenic potential to transform the Rat-1 cell line but is not sufficient to either immortalize primary REFs by itself or transform primary cells in conjunction with the H-ras oncogene.

Animals↗

The Elk-1 ETS-domain transcription factor contains a mitogen-activated protein kinase targeting motif.

The phosphorylation of transcription factors by mitogen-activated protein kinases (MAP) is a pivotal event in the cellular response to the activation of MAP kinase signal transduction pathways. Mitogenic and stress stimuli activate different pathways and lead to the activation of distinct groups of target proteins. Elk-1 is targeted by three distinct MAP kinase pathways. In this study, we demonstrate that the MAP kinase ERK2 is targeted to Elk-1 by a domain which is distinct from, and located N-terminally to, its phosphoacceptor motifs. Targeting via this domain is essential for the efficient and rapid phosphorylation of Elk-1 in vitro and full and rapid activation in vivo. Specific residues involved in ERK targeting have been identified. Our data indicate that the targeting of different classes of MAP kinases to their nuclear substrates may be a common mechanism to increase the specificity and efficiency of this signal transduction pathway.

Amino Acid Sequence↗

Pheochromocytoma complicated with cardiomyopathy after delivery--a case report and literature review.

Pheochromocytoma in pregnancy is very rare but it is associated with very high maternal and fetal mortality. Therefore, it is important to include pheochromocytoma in the differential diagnosis of hypertension associated with pregnancy. It is difficult to make a diagnosis of pheochromocytoma in pregnancy before delivery. The characteristic symptoms of pheochromocytoma could be initiated during delivery because the process of delivery, general anesthesia, fetal movement, induce acute surge of catecholamine release, which could also induce cardiomyopathy. Early diagnosis and intensive care can affect the prognosis of cardiomyopathy induced by pheochromocytoma. Proper management with alpha-blockade, beta-blockade and angiotension converting enzyme inhibitor could acutely reverse the course of cardiomyopathy.

Adrenal Gland Neoplasms↗