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Biomedical subjects

C H Yang

Publications and source records attributed to C H Yang.

At least 91 records · Page 5Linked to original sources

Genetic interactions of the Arabidopsis flowering time gene FCA, with genes regulating floral initiation.

The genes controlling the timing of the transition from vegetative to reproductive growth are likely candidates for regulators of genes initiating floral development. We have investigated the interaction of one particular gene controlling flowering time, FCA, with the meristem identity-genes TERMINAL FLOWER 1 (TFL1), APETALA 1 (AP1) and LEAFY (LFY) and the floral repression gene EMBRYONIC FLOWER 1 (EMF1). Double mutant combinations were generated and the phenotypes characterized. The influence of strong and intermediate fca mutant alleles on the phenotype conferred by a 35S-LFY transgene was also analysed. The results support a model where FCA function promotes flowering in multiple pathways, one leading to activation of LFY and AP1, and another acting in parallel with LFY and AP1. Only the latter pathway is predicted to be non-functional in the intermediate fca-4 allele. The results are also consistent with AP1 and TFL1 negatively regulating FCA function. Combination of Columbia fca and emf1 mutant alleles confirmed that FCA is required for the early flowering of emf1. EMF1 and FCA are therefore likely to operate in different floral pathways.

Alleles↗

Effects of retroviral-mediated herpes simplex virus thymidine kinase gene transfer to murine neuroblastoma cell lines in vitro and in vivo.

Selective introduction of genes conferring chemosensitivity on proliferating tumor cells can be used to treat cancer. We investigated the efficacy of retrovirus-mediated gene transfer of the herpes simplex virus thymidine kinase (HSV-TK) gene to murine neuroblastoma cell lines (neuro-2a) in vitro and in vivo. Retrovirus-mediated HSV-TK gene transfer to the neuro-2a cells resulted in sensitivity to ganciclovir (GCV) in vitro. In A/J mice, tumors produced from HSV-TK transduced neuro-2a cells regressed after GCV treatment. Intratumoral injection of recombinant retrovirus expressing HSV-TK gene also inhibited growth of the tumor established in A/J mice. These results demonstrate that HSV-TK gene therapy might be a feasible approach for inhibiting the growth of neuroblastoma.

Animals↗

FLD interacts with CO to affect both flowering time and floral initiation in Arabidopsis thaliana.

fld and co, both with significantly delayed flowering, are characterized as late-flowering mutations in Arabidopsis thaliana. Double mutants between fld-2 and co-3 were generated and the phenotypes characterized. Double mutants flower later than both single mutant parents, suggesting that there is an additive effect. In addition, the formation of flowers in double mutants was altered and showed a novel phenotype. Double mutant flowers contained a much longer stalk (pedicel). Sepals and petals were absent. Several leaf-like structures were produced in the position normally occupied by sepals and the organ numbers were reduced. The carpels were morphologically normal. The stamens produced were usually aborted in the early stage, thus, the flowers were sterile. The additive phenotype observed in double mutants provides evidence to support that these two genes, FLD and CO, are not only involved in rosette-to-inflorescence transition but also involved in the flower formation. This result also indicates that FLD and CO promote the reproductive program through two different pathways.

Arabidopsis↗

Late-flowering genes interact with early-flowering genes to regulate flowering time in Arabidopsis thaliana.

To investigate the genetic mechanisms regulating the transition from the vegetative to reproductive growth in Arabidopsis, double mutants between three different early-flowering mutants, early flowering 1-1, 2-1, 3-1, (elf 1-1, 2-1, 3-1) and five different late-flowering mutants, gi-1, ft-1, fwa-1, ld-1, and fca-9, were constructed and phenotypes analyzed. Double mutants in all combinations displayed the late-flowering phenotypes which resembled their respective late-flowering parents in both flowering time and the number of vegetative leaves produced. The results indicate that five late-flowering mutants are epistatic to all three early-flowering mutants tested here. This epistatic relationship suggests that ELF1, ELF2, and ELF3 genes function upstream of these five late-flowering genes no matter if they are functioning in autonomous or photoperiod pathways. These three early-flowering genes may negatively modify the activity of most late-flowering genes to influence the time of the vegetative-to-reproductive transition in Arabidopsis.

Arabidopsis↗

Inappropriate sexual behaviors in dementia: a preliminary report.

We investigated types of inappropriate sexual behavior (ISB) and patient characteristics in geriatric patients with dementia. The study group consisted of 133 consecutive geropsychiatric demented patients admitted to our ward. All patients underwent standardized diagnostic procedures for dementia, and ISB was assessed by a questionnaire completed by patients' caregivers and records during hospitalization. Patients were then subdivided on the basis of the presence or absence of ISB. Of the 133 demented patients, 20 (15.0%) were reported to demonstrate ISB at home or during hospitalization. Patients with ISB had various types of dementia. There were no significant differences in patients with and without ISB in regard to age, age of onset, gender, educational level, or Mini-Mental State Examination scores. ISB is not unusual in dementia patients and can be found in different types of dementia. Medical care providers need to be trained to discuss sexual issues with caregivers and offer ideas and training to help cope with patients with ISB.

Aged↗

Power spectral analysis of arterial and central venous pressure signals during graded hemorrhage in anesthetized rats.

Based on simultaneous power spectral analysis of systemic arterial pressure (SAP) and central venous pressure (CVP) signals in rats anesthetized with pentobarbital sodium, we assessed the hypotheses that subtle changes in the SAP spectrum exist during hemorrhagic shock, and that the CVP spectrum is a feasible index for central blood volume during acute graded blood loss. During Stage I hemorrhagic shock seen after reduction in 10% of total blood volume (TBV), there was a significant increase in the power of both the very low frequency (VLF, 0-.25 Hz) and low frequency (LF, .25-.8 Hz) components, along with a moderate decrease in the very high frequency (VHF, 5-9 Hz) component, of SAP signals. Substantial reduction in VLF, LF, and VHF components in the SAP spectrum occurred after a blood loss of 25% of TBV (Stage II), which persisted during Stage III hemorrhagic shock when the withdrawn blood reached 50% of TBV and the mean SAP maintained at 40 mm Hg. The depressed SAP-VLF and SAP-LF components sustained the period of spontaneous recovery and subsequent retransfusion of shed blood, although the power of SAP-VHF component gradually elevated during these two periods. The power of the high-frequency (HF, .8-2.4 Hz) component of SAP signals increased discernibly only during Stage III, became significant on spontaneous recovery, and declined during retransfusion. Although CVP and CVP-VHF component progressively declined, the power of the CVP-HF component manifested a gradual increase that was significantly and reversely correlated with the reduction in TBV. We conclude that differential changes in individual components of the SAP spectrum occur during hemorrhagic shock, and that the CVP-HF component may be a reliable indicator for central blood volume during acute graded blood loss.

Algorithms↗

Case of sepsis caused by Bifidobacterium longum.

We report a case of sepsis caused by Bifidobacterium longum in a 19-year-old male who had developed high fever, jaundice, and hepatomegaly after acupuncture therapy with small gold needles. Anaerobic, non-spore-forming, gram-positive bacilli were isolated from his blood and finally identified as B. longum. He recovered completely after treatment with ticarcillin and metronidazole. To our knowledge, this is the first report of incidental sepsis caused by B. longum.

Actinomycetales Infections↗

EGF induces nuclear translocation of STAT2 without tyrosine phosphorylation in intestinal epithelial cells.

Signal transducers and activators of transcription (STATs) are cytoplasmic proteins that bind to activated membrane receptors, undergo ligand-dependent phosphorylation on tyrosine residues, and translocate to the nucleus, where they induce transcription of specific genes in response to a variety of ligands, including cytokines and some growth factors. Using immunocytochemical and biochemical techniques, we investigated the localization and responses of STAT1 and STAT2 to epidermal growth factor (EGF) stimulation in IEC-6 intestinal epithelial cells and HeLa cells. These studies provide the first description of STAT activation and localization in response to EGF in intestinal epithelial cells and some novel findings regarding the activation and localization of STATs in general. These include the following. First, EGF promoted the tyrosine phosphorylation of STAT1 in IEC-6 cells and caused its translocation to the nucleus. Second, in the absence of EGF stimulation both STAT1 and STAT2 were localized to the Golgi apparatus in IEC-6 cells. Third, EGF caused the translocation of STAT2 to the nucleus in both IEC-6 and HeLa cells without inducing the tyrosine phosphorylation of STAT2.

Animals↗

mirror controls planar polarity and equator formation through repression of fringe expression and through control of cell affinities.

The Drosophila eye is divided into dorsal and ventral mirror image fields that are separated by a sharp boundary known as the equator. We have previously demonstrated that Mirror, a homeodomain-containing putative transcription factor with a dorsal-specific expression pattern in the eye, induces the formation of the equator at the boundary between mirror-expressing and non-expressing cells. Here, we provide evidence that suggests mirror regulates equator formation by two mechanisms. First, mirror defines the location of the equator by creating a boundary of fringe expression at the mid-point of the eye. We show that mirror creates this boundary by repressing fringe expression in the dorsal half of the eye. Significantly, a boundary of mirror expression cannot induce the formation of an equator unless a boundary of fringe expression is formed simultaneously. Second, mirror acts to sharpen the equator by reducing the mixing of dorsal and ventral cells at the equator. In support of this model, we show that clones of cells lacking mirror function tend not to mix with surrounding mirror-expressing cells. The tendency of mirror-expressing and non-expressing cells to avoid mixing with each other is not determined by their differences in fringe expression. Thus mirror acts to regulate equator formation by both physically separating the dorsal cells from ventral cells, and restricting the formation of a fng expression boundary to the border where the dorsal and ventral cells meet.

Animals↗

Persecutory delusions in dementia.

BACKGROUND: Persecutory delusions are common in dementia. This study was undertaken to investigate the prevalence, associated factors, and characteristics of persecutory delusions in demented patients. METHOD: The sample population included 167 demented patients (DSM-III-R criteria) admitted to a geropsychiatric ward. Patients were assessed for the occurrence of any persecutory delusions since the onset of dementia. The content of persecutory delusions, the patients' response to the delusions, and any concomitant psychiatric symptoms were also explored. RESULTS: Of the 167 demented patients, 45 (26.9%) showed symptoms of persecutory delusions. Patients with persecutory delusions had a higher prevalence of other delusions, hallucinations, and physically aggressive behaviors. The deluded patients often thought that their caregivers were their persecutors and had a wide range of responses to their delusions. After they were hospitalized, many of these patients attacked medical staff and were uncooperative with treatment. CONCLUSION: Persecutory delusions are common in dementia of various types. Deluded patients often have vigorous responses to their delusions including physically aggressive behaviors and suicide attempts. Careful evaluation is needed to assess the potential for violent and suicidal behaviors in these patients. Medical staff should be alert to clinical strategies for handling the treatment of such patients when they become violent or uncooperative.

Age of Onset↗

Bcl-2 prevents topoisomerase II inhibitor GL331-induced apoptosis is mediated by down-regulation of poly(ADP-ribose)polymerase activity.

Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme responsible for DNA strand breaks, has been recently suggested to be crucial for apoptosis induced by a number chemotherapeutic drugs. In this study, we demonstrated that the PARP activity could be evidently elevated with a peak at 6 h when HL-60 cells were treated with a new anticancer drug GL331. Coincident with the peak of PARP activity, an apparent DNA fragmentation and apoptotic morphology were observed in cells treated with GL331. The subsequent apoptotic DNA fragmentation induced by GL331 could be completely blocked by transfecting cells with anti-sense PARP retroviral vector or by treating cells with PARP inhibitor, 3-aminobenzamide (3-AB). This blocking effect thus suggests that activation of PARP was critically involved in GL331-induced apoptosis. The fact that Bcl-2 has been found to antagonize cell death induced by a wide variety of agents, accounts for why we examined whether if Bcl-2 could antagonize GL331 effects. Interestingly, ectopic overexpression of Bcl-2 in either HL-60 or U937 cells caused in resistance towards GL331-elicited DNA fragmentation and cytotoxic effect. Additionally, Bcl-2 also attenuated the poly(ADP-ribosyl)ation of PARP itself as well as Histone H1 at the early period of drug treatment. However, Bcl-2 did not influence the extent of DNA strand breaks induced by GL331 in either control or Bcl-2-overexpressing cells. In addition, analysis of basal PARP activity in control and several Bcl-2 overexpressing clones revealed that Bcl-2 down-regulated PARP activity under the condition without DNA damages. Above findings suggest that poly(ADP-ribosyl)ation of nuclear targets is important for apoptosis induced by DNA-reactive anticancer drugs.

Antineoplastic Agents↗

Inhibition of fos-jun-DNA complex formation by dihydroguaiaretic acid and in vitro cytotoxic effects on cancer cells.

The effect of dihydroguaiaretic acid (DHGA), isolated from the aryls of Myristica fragrans, on the transcription factor (fos-jun dimer) action was investigated via in vitro assay. DHGA showed an inhibitory effect against the complex formation of the fos-jun dimer and the DNA consensus sequence with an IC50 value of 0.21 micromol. Nordihydroguaiaretic acid (NDGA) and curcumin also inhibited fos-jun dimer action showing IC50 values of 7.9 and 6.9 nmol, respectively. DHGA and NDGA suppressed leukemia, lung cancer and colon cancer in an in vitro bioassay. The in vitro experiment suggested that inhibition of fos-jun-DNA complex formation could be due to the direct interference of fos-jun dimer binding onto the DNA consensus sequence by NDGA and curcumin.

Dimerization↗

STAT3 complements defects in an interferon-resistant cell line: evidence for an essential role for STAT3 in interferon signaling and biological activities.

STAT proteins play critical roles in the signal transduction pathways for various cytokines. The type I interferons (IFNalpha/beta) promote the DNA-binding activity of the transcription factors STAT1, STAT2, and STAT3. Although the requirement for STAT1 and STAT2 in IFNalpha/beta signaling and action is well documented, the biological importance of STAT3 to IFN action has not yet been addressed. We found that STAT3 plays a critical role in signal transduction by IFNalpha/beta. A human cell line that is resistant to the antiviral and antiproliferative activities of IFN but is still IFN-responsive by virtue of STAT1 and STAT2 activation was found to be defective in STAT3 activation and in induction of NF-kappaB DNA-binding activity. Expression of STAT3 in these resistant cells complemented these signaling defects and also markedly increased cellular sensitivity to the antiviral and antiproliferative effects of IFN. Because STAT3 is involved in the induction of NF-kappaB DNA-binding activity and in the induction of antiviral and antiproliferative activity, our results place STAT3 as an important upstream element in type I IFN signal transduction and in the induction of biological activities. Therefore, our results indicate that STAT1 and STAT2 are not the only STATs required for the expression of the key biological activities of IFNalpha/beta.

Antiviral Agents↗

Crystallization and preliminary X-ray studies of hORF6, a novel human antioxidant enzyme.

HORF6 is a member of the novel antioxidant enzyme family found in humans. A recombinant form of hORF6 expressed and purified from E. coli has been crystallized by the hanging-drop method using various PEG's as precipitating agents. HORF6 crystallizes in two different monoclinic space groups, P21 and C2. The P21 crystals have unit-cell dimensions of a = 47.85, b = 75.17, c = 63.30 A and beta = 110.21 degrees and contain two monomers per asymmetric unit, while the C2 crystals have unit-cell dimensions of a = 165.27, b = 95.44, c = 166.44 A and beta = 128.97 degrees and contain more than six monomers per asymmetric unit. The P21 crystals with the smaller unit cell diffract X-rays better and behave well for the X-ray analysis. A native data set from a single crystal of the P21 space group gas been collected to 2.0 A resolution.

Antioxidants↗

Differences in activity between alpha and beta type I interferons explored by mutational analysis.

Type I interferon (IFN) subtypes alpha and beta share a common multicomponent, cell surface receptor and elicit a similar range of biological responses, including antiviral, antiproliferative, and immunomodulatory activities. However, alpha and beta IFNs exhibit key differences in several biological properties. For example, IFN-beta, but not IFN-alpha, induces the association of tyrosine-phosphorylated receptor components ifnar1 and ifnar2, and has activity in cells lacking the IFN receptor-associated, Janus kinase tyk2. To define the structural basis for these functional differences we produced human IFN-beta with point mutations and compared them to wild-type IFN-beta in assays that distinguish alpha and beta IFN subtypes. IFN-beta mutants with charged residues (N86K, N86E, or Y92D) introduced at two positions in the C helix lost the ability to induce the association of tyrosine-phosphorylated receptor chains and had reduced activity on tyk2-deficient cells. The combination of negatively charged residues N86E and Y92D (homologous with IFN-alpha8) increased the cross-species activity of the mutant IFN-betas on bovine cells to a level comparable to that of human IFN-alphas. In contrast, point mutations in the AB loop and D helix had no significant effect on these subtype-specific activities. A subset of these latter mutations did, however, reduce activity in a manner analogous to IFN-alpha mutations. The effects of these mutations on IFN-beta activity are discussed in the context of a family of related ligands acting through a common receptor and signaling pathway.

Amino Acid Sequence↗

Induction of Jak/STAT signaling by activation of the type 1 TNF receptor.

Cellular responses to TNF are initiated by either of two cell surface receptors, the type 1 TNF receptor (TNFR1) and the type 2 TNF receptor (TNFR2). Although neither receptor contains an intrinsic protein tyrosine kinase, such activity has been implicated in TNF action. In this study, we show that murine TNF induces the tyrosine phosphorylation and activation of the intracellular Janus tyrosine kinases Jak1, Jak2, and Tyk2 in murine 3T3-L1 adipocytes. Activation of Jak kinases by TNF was associated with tyrosine phosphorylation of STAT1, STAT3, STAT5, and STAT6, but not STAT2 or STAT4, showing that TNF acts on a specific subset of these latent cytoplasmic transcription factors in 3T3-L1 adipocytes. Agonist antiserum to TNFR1 induced Jak kinase and STAT protein phosphorylation. Phosphorylation of Jak proteins was also induced by human TNF, which selectively binds to TNFR1 on murine cells. 35S-labeled Jak kinases were precipitated from a cell-free system and from lysates of 3T3-L1 adipocytes by a glutathione S-transferase fusion protein containing the cytoplasmic domain of TNFR1. These results suggest that the cytoplasmic domain of TNFR1 can directly interact with and form signaling complexes with Jak kinases. Jak2 was precipitated from HeLa cells by antiserum to TNFR1, directly demonstrating their association in vivo. Thus, TNF activates a Jak/STAT signal-transduction cascade by acting through TNFR1.

3T3 Cells↗

The antiviral action of interferon is potentiated by removal of the conserved IRTAM domain of the IFNAR1 chain of the interferon alpha/beta receptor: effects on JAK-STAT activation and receptor down-regulation.

The first cloned chain (IFNAR1) of the human interferon-alpha (IFN alpha) receptor acts as a species-specific transducer for type 1 IFN action when transfected into heterologous mouse cells. Stably transfected mouse L929 cell lines expressing truncation mutants of the intracellular domain of the human IFNAR1 chain were tested for biological responses to human IFN alpha. Deletion of the intracellular domain resulted in a complete loss of sensitivity to the biological activity of human IFN but markedly increased IFNAR1 cell surface expression, demonstrating that the intracellular domain is required for biological function and contains a domain that negatively regulates its cell surface expression. Removal of the conserved membrane distal 16-amino-acid IRTAM (Interferon Receptor Tyrosine Activation Motif) sequence: (1) increased sensitivity to IFN alpha's antiviral activity, (2) increased the rapid IFN alpha-dependent formation of STAT-containing DNA-binding complexes, (3) prolonged tyrosine phosphorylation kinetics of the JAK-STAT pathway, and (4) blocked the IFN-dependent down-regulation of the IFNAR1 chain. These results indicate that the IRTAM negatively regulates signalling events required for the induction of IFN's biological actions via regulating receptor down-regulation.

Amino Acid Sequence↗