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Biomedical subjects

S C Lin

Publications and source records attributed to S C Lin.

At least 73 records · Page 4Linked to original sources
PubMed1999

DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis.

Several newly identified tumor suppressor genes including ATM, NBS1, BRCA1 and BRCA2 are involved in DNA double-strand break repair (DSBR) and DNA damage-induced checkpoint activation. Many of the gene products involved in checkpoint control and DSBR have been studied in great detail in yeast. In addition to evolutionarily conserved proteins such as Chk1 and Chk2, studies in mammalian cells have identified novel proteins such as p53 in executing checkpoint control. DSBR proteins including Mre11, Rad50, Rad51, Rad54, and Ku are present in yeast and in mammals. Many of the tumor suppressor gene products interact with these repair proteins as well as checkpoint regulators, thus providing a biochemical explanation for the pleiotropic phenotypes of mutant cells. This review focuses on the proteins mediating G1/S, S, and G2/M checkpoint control in mammalian cells. In addition, mammalian DSBR proteins and their activities are discussed. An intricate network among DNA damage signal transducers, cell cycle regulators and the DSBR pathways is illustrated. Mouse knockout models for genes involved in these processes have provided valuable insights into their function, establishing genomic instability as a major contributing factor in tumorigenesis.

Animals↗
PubMed1999

Axin forms a complex with MEKK1 and activates c-Jun NH(2)-terminal kinase/stress-activated protein kinase through domains distinct from Wnt signaling.

Axin negatively regulates the Wnt pathway during axis formation and plays a central role in cell growth control and tumorigenesis. We found that Axin also serves as a scaffold protein for mitogen-activated protein kinase activation and further determined the structural requirement for this activation. Overexpression of Axin in 293T cells leads to differential activation of mitogen-activated protein kinases, with robust induction for c-Jun NH(2)-terminal kinase (JNK)/stress-activated protein kinase, moderate induction for p38, and negligible induction for extracellular signal-regulated kinase. Axin forms a complex with MEKK1 through a novel domain that we term MEKK1-interacting domain. MKK4 and MKK7, which act downstream of MEKK1, are also involved in Axin-mediated JNK activation. Domains essential in Wnt signaling, i. e. binding sites for adenomatous polyposis coli, glycogen synthase kinase-3beta, and beta-catenin, are not required for JNK activation, suggesting distinct domain utilization between the Wnt pathway and JNK signal transduction. Dimerization/oligomerization of Axin through its C terminus is required for JNK activation, although MEKK1 is capable of binding C terminus-deleted monomeric Axin. Furthermore, Axin without the MEKK1-interacting domain has a dominant-negative effect on JNK activation by wild-type Axin. Our results suggest that Axin, in addition to its function in the Wnt pathway, may play a dual role in cells through its activation of JNK/stress-activated protein kinase signaling cascade.

Axin Protein↗
PubMed1999

The membrane association domain of RGS16 contains unique amphipathic features that are conserved in RGS4 and RGS5.

Regulators of G protein signaling (RGS proteins) modulate G protein-mediated signaling pathways by acting as GTPase-activating proteins for Gi, Gq, and G12 alpha-subunits of heterotrimeric G proteins. Although it is known that membrane association is critical for the biological activities of many RGS proteins, the mechanism underlying this requirement remains unclear. We reported recently that the NH2 terminus of RGS16 is required for its function in vivo. In this study, we show that RGS16 lacking the NH2 terminus is no longer localized to the plasma membrane as is the wild type protein, suggesting that membrane association is important for biological function. The region of amino acids 7-32 is sufficient to confer the membrane-targeting activity, of which amino acids 12-30 are predicted to adopt an amphipathic alpha-helix. Site-directed mutagenesis experiments showed that the hydrophobic residues of the nonpolar face of the helix and the strips of positively charged side chains positioned along the polar/nonpolar interface of the helix are crucial for membrane association. Subcellular fractionation by differential centrifugation followed by conditions that distinguish peripheral membrane proteins from integral ones indicate that RGS16 is a peripheral membrane protein. We show further that RGS16 membrane association does not require palmitoylation. Our results, together with other recent findings, have defined a unique membrane association domain with amphipathic features. We believe that these structural features and the mechanism of membrane association of RGS16 are likely to apply to the homologous domains in RGS4 and RGS5.

Amino Acid Sequence↗
PubMed1999

STAT3 activation in stromal/osteoblastic cells is required for induction of the receptor activator of NF-kappaB ligand and stimulation of osteoclastogenesis by gp130-utilizing cytokines or interleukin-1 but not 1,25-dihydroxyvitamin D3 or parathyroid hormone.

Interleukin (IL)-6-type cytokines stimulate osteoclastogenesis by activating gp130 in stromal/osteoblastic cells and may mediate some of the osteoclastogenic effects of other cytokines and hormones. To determine whether STAT3 is a downstream effector of gp130 in the osteoclast support function of stromal/osteoblastic cells and whether the gp130/STAT3 pathway is utilized by other osteoclastogenic agents, we conditionally expressed dominant negative (dn)-STAT3 or dn-gp130 in a stromal/osteoblastic cell line (UAMS-32) that supports osteoclast formation. Expression of either dominant negative protein abolished osteoclast formation stimulated by IL-6 + soluble IL-6 receptor, oncostatin M, or IL-1 but not by parathyroid hormone or 1,25-dihydroxyvitamin D3. Because previous studies suggested that IL-6-type cytokines may stimulate osteoclastogenesis by inducing expression of the tumor necrosis factor-related protein, receptor activator of NF-kappaB ligand (RANKL), we conditionally expressed RANKL in UAMS-32 cells and found that this was sufficient to stimulate osteoclastogenesis. Moreover, dn-STAT3 blocked the ability of either IL-6 + soluble IL-6 receptor or oncostatin M to induce RANKL. These results establish that STAT3 is essential for gp130-mediated osteoclast formation and that the target of STAT3 during this process is induction of RANKL. In addition, this study demonstrates that activation of the gp130-STAT3 pathway in stromal/osteoblastic cells mediates the osteoclastogenic effects of IL-1, but not parathyroid hormone or 1, 25-dihydroxyvitamin D3.

Animals↗
PubMed1999

RGS16 attenuates galphaq-dependent p38 mitogen-activated protein kinase activation by platelet-activating factor.

The large gene family encoding the regulators of G protein signaling (RGS) proteins has been implicated in the fine tuning of a variety of cellular events in response to G protein-coupled receptor activation. Several studies have shown that the RGS proteins can attenuate G protein-activated extracellular signal-regulated kinase (ERK) group of mitogen-activated protein kinases. We demonstrate herein that the production of inositol trisphosphate and the activation of the p38 group of mitogen-activated protein kinases by the G protein-coupled platelet-activating factor (PAF) receptor was attenuated by RGS16 in both CHO cells transiently and stably expressing RGS16. The inhibition was not observed with RGS2, RGS5, and a functionally defective form of RGS16, RGS16(R169S/F170C). The PAF-induced p38 and ERK pathways appeared to be preferentially regulated by RGS16 and RGS1, respectively. Overexpression of a constitutively active form of Galpha11 (Galpha11Q209L) prevented the RGS16-mediated attenuation of p38 activity, suggesting that Galphaq/11 is involved in PAF activation of p38. The Galphaq/11 involvement is further supported by the observation that p38 activation by PAF was pertussis toxin-insensitive. These results demonstrate for the first time that apart from ERK, p38 activation by a G protein-coupled receptor can be attenuated by an RGS protein and provide further evidence for the specificity of RGS function in G protein signaling pathways.

Animals↗
PubMed1999

Temperature effect on nervous necrosis virus infection in grouper cell line and in grouper larvae.

This preliminary study elucidates the in vitro and in vivo effects of temperature on grouper nervous necrosis virus (GNNV) infection. A novel continuous cell line derived from the fin tissue of a grouper (Epinephelus coioides, Hamilton), named as GF-1 cell line, was used. Cytopathic effect was observed in GNNV-infected GF-1 cells incubated at 24-32 degrees C after viral adsorption, but not at 20 degrees C or 37 degrees C even though the viral adsorption temperature was 28 degrees C. Viral protein could be detected in the pellets of GNNV-infected GF-1 cells cultured at 20-32 degrees C, but not at 37 degrees C. In a challenge test, GNNV-challenged larvae which were maintained at a constant 28 degrees C began to die 1 day post challenge (p.c.) with a death rate of 80%. Mortality reached 100% by 50 h p.c., while the mortality of negative control fish was only 5%. The cumulative mortality of GNNV-challenged larvae at ambient temperature, i.e. 28 degrees C at noon and 24 degrees C at midnight, was 10% 1 day p.c., and increased to 100% by 80 h p.c. Based on the results, we concluded that temperature plays an important role in GNNV infection and pathogenicity.

Animals↗
PubMed1999

The effect of presynaptic catecholamine depletion on 6-hydroxymelatonin sulfate: a double blind study of alpha-methyl-para-tyrosine.

Because it is a competitive inhibitor of tyrosine hydroxylase, alpha-methyl-para-tyrosine (AMPT) is used to study psychiatric disorders. Melatonin serves as a biological marker of catecholamine function since its secretion is regulated by noradrenergic neurons via beta-adrenergic receptors in the pineal gland. Ten healthy volunteers were administered AMPT in a double-blind placebo controlled study. When subjects received AMPT, nocturnal 6-hydroxymelatonin sulfate (6-SM) decreased significantly as compared with promethazine (night 1 P=0.002; and night 2 P=0.001). Urinary MHPG also decreased on both study days (DF1,9 F=9.82, GG=0.0121). Nocturnal 6-SM excretion and melatonin secretion correlated highly (r=0.91, P=0.0007). Behavioral ratings did not reveal a difference in symptomatology and did not correlate with changes in 6-SM or MHPG. This study demonstrates in healthy controls that 6-SM reliably reflects presynaptic catecholamine depletion induced by AMPT without the emergence of behavioral symptoms.

Adult↗
PubMed1999

A simple splinting method for correction of supple congenital clasped thumbs in infants.

A splint has been designed to correct the congenital clasped thumb. It is like a short opponens splint that can keep the thumb in a position of abduction and extension without limiting wrist movement. The application of the splint was easy and adjustment for fit could be made at each visit if necessary. The device has been used in 11 infant patients (17 thumbs) with congenital clasped thumb of the supple type. The functional results were excellent in 15 of 17 thumbs, and the other two were good according to the grading system of Weckesser et al. (1968).

Female↗
PubMed1999

Some results on combinations of two binary screening tests.

When two medical screening tests for a disease exist, it may be appealing to combine them to increase screening accuracy. Combination of two valid screening tests, where each independently has screening performance, can increase the overall disease screening performance. Some results are obtained when two binary screening tests are combined according to the Boolean Any+ strategy, as defined by Maguire (1). These results are useful and provide investigators of two screening tests a sense of what to expect of the performance of the two tests when combined. This then may be followed by a clinical trial that directly demonstrates the benefit of the combined test.

Binomial Distribution↗
PubMed1999

Telomerase activity and in situ telomerase RNA expression in oral carcinogenesis.

To investigate the role of telomerase in oral carcinogenesis, we assayed telomerase activity in various oral tissues by a modified telomeric repeat amplification protocol (TRAP) analysis. Also, using digoxigenin-labeled probes, we measured the in situ expression of human telomerase RNA component (hTR) in paired oral squamous cell carcinomas (OSCC) and adjacent non-cancerous matched tissue (NCMT). We detected telomerase activity in three OSCC cell lines, but not in primary oral keratinocytes. In patient samples, most OSCC (36/42, 86%) and oral premalignant lesions (8/12, 67%) possessed telomerase activity. In addition, 6 of 27 (22%) NCMT contained weak telomerase activity. In situ hybridization showed that hTR was expressed in almost all OSCC (23/27, 85%) as well as in the majority of NCMT (20/25, 80%). In most cases, accumulation of hTR was observed both in the nucleus and cytoplasm of epithelial cells. A correlation between hTR expression and more advanced tumor grade was observed. The appearance of telomerase activation and hTR expression during oral carcinogenesis was different. This study indicates that the activation of telomerase is an early and frequent event in OSCC.

Adult↗
PubMed1999

The influence of propolis ethanol extract on liver microsomal enzymes and glutathione after chronic alcohol administration.

Propolis designates a series of gums, resins and balms of viscous consistency, which are gathered by honeybees from certain parts, mainly the buds and barks of plants, especially those found on coniferous trees. Bees bring propolis back to the hive, where it is modified and mixed with other substances including the bees' own wax and salivary secretions. In this study, the influences of propolis ethanol extract on chronic alcohol induced liver microsomal enzyme changes were investigated. Three grams of alcohol was added to rats' daily diet for four weeks to induce chronic alcohol liver injuries, and two different doses of propolis ethanol extract were p.o. administrated three times per day on the 28th, 29th, and 30th day. During the period of propolis administration, the ethanol diet was continued. After sacrifice, the rat livers were excised for assay of microsomal enzymes activity, glutathione (GSH) concentration, glutathione-S-transferase (GSTase) and gamma-glutamylcysteine synthetase (gamma-GCSase) activity. It was found that 30 mg/kg of propolis ethanol extract significantly prevented the elevations of total cytochrome P-450 enzymes, NADPH-dependent cytochrome C reductase, aniline hydroxylation, 7-ethoxyresorufin hydroxylation (7-ERH), 7-penthoxyresorufin hydroxylation (7-PRH), and lipid peroxidation induced by chronic ethanol administration. Additionally, propolis ethanol extract (100 mg/kg) also induced GSTase and gamma-GCSase activities and decreased glutathione levels in the liver.

Aniline Compounds↗
PubMed1999

Traumatic wound dehiscence after penetrating keratoplasty: clinical features and outcome in 21 cases.

PURPOSE: To describe the characteristics, causes, treatment, and outcome, particularly the fate of the intraocular implant and visual acuity, of traumatic wound dehiscence occurring in patients who had penetrating keratoplasty (PK). METHODS: Between 1989 and 1997, 21 corneal transplant patients sustained traumatic wound dehiscence and were treated at our hospital. Graft dehiscence was managed with primary wound closure in all patients, except in some who required some combination of anterior vitrectomy, intraocular lens removal and reimplantation, and corneal regrafting. RESULTS: The incidence of traumatic wound dehiscence among patients on whom we performed PK over a period of 9 years was 2.53%. This complication occurred, on average, 3.4 years (2 months to 13 years) after PK. Most patients (76%) were men, and the average age at dehiscence was 59 years (range, 15-82 years). All corneal ruptures occurred at the graft-host junction, which had neither particular site preference nor quadrant specificity. Of the 16 eyes that were pseudophakic, nine (56.3%) had either loss of implants or dislocation of intraocular lens so severe that lens removal was imperative. In the end, only five (23.8%) of the 21 grafts retained clarity. Of the remaining 16 eyes, seven were regrafted, of which five (71.4%) grafts remained clear. Of the nine grafts that became opaque, six eyes (28.6%) atrophied. At the last follow-up, only six eyes (28.6%) had visual acuity of 20/200 or better, and six eyes had no perception of light. Final visual acuity was found to correlate inversely with the severity and extent of wound separation. CONCLUSION: Traumatic wound dehiscence is not rare after PK. The elderly corneal transplant patient may be more prone to such an injury. Corneal rupture at the graft-host junction in all of our cases means the persistence of wound weakness after PK. Although graft survival and visual outcome are generally poor after the injury, the restoration of a satisfactory visual result is possible after regrafting, insofar as the involved eye is free of intractable glaucoma or posterior segment damage.

Adolescent↗
PubMed1999

Immunohistochemical studies of transforming growth factor-beta and its receptors in the gastric mucosa of patients with refractory gastric ulcer.

Transforming growth factor (TGF)-beta regulates cell growth and differentiation, and is known to play regulatory roles in the process of tissue repair and remodeling. However, the functional role of TGF-beta in gastric ulcer healing has not been addressed. In this study, we assayed the expression of TGF-beta and its receptors in the gastric mucosa of patients with healed or refractory gastric ulcers. Antibodies against TGF-beta and its receptors (both type I and type II) were employed to examine expression levels. Sixteen gastric ulcer patients, including four with completely healed ulcers and 12 with ulcers refractory to treatment were included in this study. All four patients with healed ulcers showed remarkable expression levels of both TGF-beta and its receptors. On the other hand, two of the 12 patients with refractory ulcers had weak or deficient TGF-beta expression in the gastric mucosa, and seven lacked expression of at least one of the TGF-beta receptors. The remaining three patients had normal (moderate to weak) expression levels of TGF-beta and its two receptors. These results suggest that both TGF-beta and its receptors are essential for gastric ulcer healing.

Adult↗
PubMed1998

The core domain of RGS16 retains G-protein binding and GAP activity in vitro, but is not functional in vivo.

The regulators of G-protein signaling (RGS) family members contain a conserved region, the RGS domain, and are GTPase-activating proteins for many members of G-protein alpha-subunits. We report here that the core domain of RGS16 is sufficient for in vitro biochemical functions as assayed by its G-protein binding affinity and its ability to stimulate GTP hydrolysis by G alpha(o) protein. RGS16 also requires, in addition to the RGS domain, the divergent N-terminus for its biological function in the attenuation of pheromone signaling in yeast, whereas its C-terminus region is dispensable. Together with other evidence, these data support the notion that RGS proteins interact with other cellular factors and may serve to link specific G-proteins to different downstream effectors in G-protein-mediated signaling pathways.

Binding Sites↗
PubMed1998

Age-related changes in blood lymphocyte subsets of Chinese children.

BACKGROUND: Flow cytometric analysis of major lymphocyte populations and their subsets reveals age-related changes in the human cellular immune system. SUBJECTS AND METHODS: Immunophenotypic markers were evaluated in 136 healthy pediatric subjects divided into groups of newborn infants (cord blood), children aged 1 to 2 years, 2 to 5 years, and 6 to 15 years. RESULTS: The percentage of T cells increased gradually with age and the evolution of the percentage of B and NK cells was found to be variable. The percentage of CD4+ cells remains relatively unchanged from infancy to adolescence, but the percentage of CD8+ T cells was lowest at birth and reached maximal levels in the one to two year-old period. The percentage of naive T cells declined with time, but the percentage of memory T cells increased with age. Similar trends were seen in T-cell receptor alphabeta- and gammadelta-bearing T cells. The percentage of CD 11b+CD8+ T cells increased gradually from birth and reached maximal levels from 6 to 15 years old. The expression of the activation markers CD25 and HLA-DR on CD4+ T cells increased with age. The percentage of CD16+CD56- NK cells declined with age, but the evolution of the percentage of CD 16-CD56+ NK cells was variable. The fraction of B cells that expressed CD5 was high at birth (72.9%) and was highest in one to two year olds (73.1%), then declined steadily over time. The CD23 antigen was expressed on 41.9% of B cells at birth and 68.6% during the first to second year, then declined steadily with age. CONCLUSION: These data may serve as a reference range for studies of Chinese pediatric subjects.

Adolescent↗
PubMed1998

p53 alterations in betel quid- and tobacco-associated oral squamous cell carcinomas from Taiwan.

Alterations of p53 have been explored in Taiwanese oral squamous cell carcinomas (OSCCs) consisting of a betel quid (BQ)/tobacco-related subgroup of 36 subjects and a tobacco-related subgroup of 13 subjects. Mutations in conserved exons were found in 12 tumors. Seven mutations were clustered in a hot-spot region mapped to a region between codons 273-282 in exon 8. The incidence of p53 mutation in BQ/tobacco tumors was 22% (8/36). The frequency of p53 allelic loss (21%, 3/14) in BQ/tobacco tumors approximates to the incidence of mutation. This is the first study demonstrating allelic deletion of p53 in such malignancies. Twenty-four of 43 samples showed positive p53 immunostaining. All tumors harboring mis-sense mutations of p53 in conserved exons exhibited nuclear protein accumulation. The incidence of mutation in conserved exons in BQ/tobacco-associated Asian OSCCs (15%) is significantly different from worldwide OSCCs (46%) related primarily to tobacco consumption (P=0.00001).

Adult↗