Search PubMed⌕ Search

Biomedical subjects

Y G Chen

Publications and source records attributed to Y G Chen.

52 records · Page 3Linked to original sources

Mechanism of TGFbeta receptor inhibition by FKBP12.

Transforming growth factor-beta (TGFbeta) signaling requires phosphorylation of the type I receptor TbetaR-I by TbetaR-II. Although TGFbeta promotes the association of TbetaR-I with TbetaR-II, these receptor components have affinity for each other which can lead to their ligand-independent activation. The immunophilin FKBP12 binds to TbetaR-I and inhibits its signaling function. We investigated the mechanism and functional significance of this effect. FKBP12 binding to TbetaR-I involves the rapamycin/Leu-Pro binding pocket of FKBP12 and a Leu-Pro sequence located next to the activating phosphorylation sites in TbetaR-I. Mutations in the binding sites of FKBP12 or TbetaR-I abolish the interaction between these proteins, leading to receptor activation in the absence of added ligand. FKBP12 does not inhibit TbetaR-I association with TbetaR-II, but inhibits TbetaR-I phosphorylation by TbetaR-II. Rapamycin, which blocks FKBP12 binding to TbetaR-I, reverses the inhibitory effect of FKBP12 on TbetaR-I phosphorylation. By impeding the activation of TGFbeta receptor complexes formed in the absence of ligand, FKBP12 may provide a safeguard against leaky signaling resulting from the innate tendency of TbetaR-I and TbetaR-II to interact with each other.

Activin Receptors, Type I↗

ADP-ribosylation factor-1 stimulates formation of nascent secretory vesicles from the trans-Golgi network of endocrine cells.

ADP-ribosylation factor (ARF) is a small GTP-binding protein that has been implicated in intracellular vesicular transport. ARF regulates the budding of vesicles that mediate endoplasmic reticulum to Golgi and intra-Golgi transport. It also plays an important role in maintaining the function and morphology of the Golgi apparatus. Using a permeabilized cell system derived from GH3 cells, we provide evidence that ARF-1 regulates the formation of nascent secretory vesicles from the trans-Golgi network. Both myristoylated and non-myristoylated forms of recombinant human ARF-1 enhanced secretory vesicle budding about 2-fold. A mutant lacking the first 17 N-terminal residues, as well as one that preferentially binds GDP (T31N) did not stimulate vesicle formation. In contrast, a mutant defective in GTP hydrolysis (Q71L) promoted vesicle budding. Strikingly, a peptide corresponding to the N terminus of human ARF-1 (amino acids 2-17) also stimulated vesicle budding from the trans-Golgi network, in marked contrast to its inhibitory effect on vesicular transport from the endoplasmic reticulum to Golgi. These data demonstrate that in endocrine cells, ARF-1 and in particular its N terminus play an essential role in the formation of secretory vesicles.

ADP-Ribosylation Factors↗

The propeptide of anglerfish preprosomatostatin-I rescues prosomatostatin-II from intracellular degradation.

Polypeptide hormones and neuropeptides are initially synthesized as precursors possessing one or several domains that constitute the propeptide. Previous work from our laboratory demonstrated that expression of anglerfish prosomatostatin-I (proSRIF-I) in rat anterior pituitary GH3 cells resulted in efficient and accurate cleavage of the prohormone to generate the mature 14-amino acid peptide, SRIF-I. We also implicated the propeptide in mediating intracellular sorting to the trans Golgi network where proteolytic processing is initiated. In contrast, expression of a second form of the precursor, proSRIF-II in GH3 cells resulted in its intracellular degradation in an acidic, post-trans Golgi network compartment, most probably lysosomes. To further investigate the positive sorting signal present in proSRIF-I, we constructed a chimera comprising the signal peptide and proregion of SRIF-I fused to proSRIF-II and expressed the cDNA in GH3 cells. Here we demonstrate that the propeptide of SRIF-I rescued proSRIF-II from intracellular degradation quantitatively and diverted it to secretory vesicles. Furthermore, the chimera was processed to SRIF-28, an amino-terminally extended form of the hormone that is the physiological cleavage product of proSRIF-II processing in vivo. Most significantly, the SRIF-I propeptide functioned only in cis as part of the fusion protein and not in trans when expressed as a separate polypeptide. These data suggest that the SRIF-I propeptide may possess a sorting signal for sequestration into the secretory pathway rather than functioning as an intramolecular chaperone to promote protein folding.

Amino Acid Sequence↗

Application of dot-immunogold-silver staining in the diagnosis of clonorchiasis.

All 35 confirmed clonorchiasis cases showed a positive reaction in dot-immunogold-silver staining (Dot-IGSS) with a mean serum titre of 1:1656, while none of the sera from 35 normal individuals reacted. A seroepidemiological survey of middle-school students revealed a positive rate of 17.0% (142/836), and 76.1% (105/138) of the serologically positive students were egg positive in stool examination. The egg positive rates in those with antibody at levels of 1+ to 4+ were 57.1% (28/49), 75.7% (28/37), 94.7% (36/38) and 92.9% (13/14) respectively. It is believed that Dot-IGSS can be used for the clinical diagnosis and epidemiological survey of clonorchiasis.

China↗

Effect of glucose on TGF-beta 1 expression in peritoneal mesothelial cells.

The peritoneum's response to peritoneal dialysis is a complex and poorly understood process that can result in fibrosis. The transforming growth factor beta(TGF-beta 1) plays a central role in regulating tissue repair and remodeling after injury. To determine the role of mesothelial cells during peritoneal dialysis in the alteration of the peritoneum, we studied the effect of glucose on TGF-beta 1 expression by mesothelial cells. Human mesothelial cells were cultured in serum-free DMEM with different glucose concentrations for 48 hours. TGF-beta 1 messenger (mRNA) was measured by slot-blot hybridization using a TGF-beta 1 cDNA probe. The result was that glucose stimulates TGF-beta 1 mRNA expression in a dose-dependent way. The expression was more profound in high glucose concentrations. This suggests that TGF-beta 1 mRNA may overexpress by mesothelial cells due to the procedure of dialysis, which may be the most important mechanism of alteration of the peritoneum during peritoneal dialysis.

Autoradiography↗

[A study on histopathology of iris with Nd: YAG and/or argon laser iridotomy].

Laser iridotomy including Nd: YAG, argon and Nd: YAG combined with argon was performed on 42 eyes of 25 chinchilla rabbits. The postoperative follow-up was 8 months. The histopathological changes of the irides at the sites of the various laser shots under light, transmission and scanning electron microscopic examinations were compared. The results show: (1) In regard to the Nd: YAG laser effect on the target tissue, the inherent elasticity of the tissue may play a more important role in curative effects of the therapy than the thickness of the tissue. (2) Every iris hole, < 200 microns in diameter, performed by Nd: YAG or < 450 microns, by argon or argon combined with Nd: YAG was closed by the first postoperative week. The histopathological findings demonstrate that the pigment epithelial proliferation and migration are more marked in the irides with argon laser iridotomy. (3) An insufficient coagulative burn of the argon laser may cause congestion of iris blood vessels and possibly, result in more severe bleeding during succedent Nd: YAG laser shots.

Animals↗

[Biomechanics of traction for treatment of lumber disc prolapse].

The intervertebral distance in 31 prolapsed discs under traction increased on the average by 1.34 mm, but in normal discs 0.87 mm. Of 47 prolapsed discs without traction, 29 had negative intradisc pressure, 10 zero, and 8 positive. The total average value of the pressure before traction was -1.3 kPa. Under lumber traction, the pressure decreased in 30 discs, unchanged in 8, and increased in 9, with the average value being -3.2 kPa. The intradisc pressure in 7 normal discs was contrary to the pressure in the prolapsed disc. The difference between the two groups was highly significant (P < 0.01). The pressure unchanged when the intervertebral distance of prolapsed disc unchanged under traction, but the pressure decreased as the distance increased in most cases under traction.

Adolescent↗

[Epidemiological studies on human cryptosporidiosis in rural and urban areas of Jiangsu].

A survey of cryptosporidiosis in outpatients and inhabitants in Xuzhou city and 6 rural areas of Jiangsu Province was carried out from 1989 to 1991. Cryptosporidium oocysts (CSO) were found in 97 (1.6%) of 6,221 individuals as a whole, and were detected in 39 (3.3%) of 1,172 outpatients among the examinees. 39 cases were from 31 towns and villages of 8 counties near Xuzhou city. Among the 136 cases, 83 were males and 53 females, of them 89 (65.4%) were infants and young children. The incidence was evidently higher in the group of children under 4 than in that aged 4 to 15 (P < 0.01). Diarrhea, intermittent or persistent, was the main symptom of cryptosporidiosis, being present in 94 (69.1%) of the 136 positive cases, while the other 42 were asymptomatic carriers. The results of routine blood examination and immunoassay performed in a part of the infected children indicated that more than half of them had anemia and lessened cellular immunity. Stool examination of the domestic animals of the affected households showed that a pig and a dog were CSO positive.

Adolescent↗

Cryptosporidium infection and diarrhea in rural and urban areas of Jiangsu, People's Republic of China.

Screening of infants and children under age 15 years for Cryptosporidium oocysts in their stools was carried out in the suburb of Xuzhou City and six rural areas of Jiangsu Province. The infection rate varied from 0.7 to 5.06%. Of the total of 5,089 children examined, 89 (1.75%) were oocyst positive. The incidence was evidently higher in the group of children under age 4 years than it was in children from 4 to 15 years (P less than 0.01). Routine blood examination and immunoassay performed on blood samples from some of the infected children indicated that more than half of them had anemia and lower cellular immunity. Diarrhea was the main symptom of cryptosporidiosis. It was intermittent or persistent and was present in 57 of the 89 children positive for Cryptosporidium oocysts, while the other 32 children were asymptomatic carriers. Examination of stool specimens of adult members and domestic animals of about half of the infected families showed that two mothers, one pig, and one dog were positive for Cryptosporidium oocysts.

Adolescent↗

Computer-based solution to a clinical education problem in a physical therapy course.

This article describes the solution to a logistical problem involving the assignment of multiple clinical experiences to students in an undergraduate physical therapy course. Physical therapy faculty members collaborated with a computer programmer to formulate a computer program that would satisfy the organizational needs imposed by this problem. We suggest that the skills of the physical therapist combined with those of a computer programmer can be used to generate effective, computer-based solutions to many other problems related to the organization of data and to decision making in physical therapy.

Clinical Clerkship↗