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Biomedical subjects

C J Lin

Publications and source records attributed to C J Lin.

At least 37 records · Page 2Linked to original sources

Tst-1, a member of the POU domain gene family, binds the promoter of the gene encoding the cell surface adhesion molecule P0.

Tst-1, a member of the POU domain gene family, is expressed in specific neurons and in myelinating glia in the mammalian nervous system. Bacterially expressed Tst-1 binds specifically to the promoter of the gene encoding myelin protein P0, a Schwann cell surface adhesion molecule. In cotransfection assays, Tst-1 can specifically repress the P0 promoter. The N-terminal part of Tst-1 protein is highly glycine- and alanine-rich, a structural feature shared by the helix-loop-helix protein TFEB.

Amino Acid Sequence

Ectopic ACTH syndrome due to clear cell sarcoma of the kidney.

The 7-year-old girl presenting with cushingoid appearance and gross hematuria was found to have a right renal tumor. Preoperative hormonal assay revealed an extremely high plasma ACTH level and elevated plasma cortisol levels. Right radical nephrectomy was performed, and pathology proved the tumor to be a clear cell sarcoma, a sarcomatous variant of Wilms' tumor, of the kidney. Postoperative plasma ACTH level declined dramatically and cortisol levels returned to normal, too. She received chemotherapy and radiotherapy then and gradually lost her cushingoid appearance. This is the first reported case of clear cell sarcoma of the kidney with ectopic ACTH syndrome.

ACTH Syndrome, Ectopic

Tissue culture, DNA flow cytometric and cytogenetic studies of a giant cell tumor of bone.

An in vitro tissue culture was established using a giant cell bone tumor derived from a 66-year-old female. The tumor was clinically classified as stage 2, and grade 1 histologically. Morphological observations including, in vitro growth character, histochemical and immunohistochemical staining, and ultrastructural studies, support that the giant cell originated from the mononucleated stromal cell. They do not belong to the monocyte-macrophage system. In this aggressive case, we also tried to evaluate the significance of using DNA ploidy flow cytometry, and chromosomal study in predicting its clinical outcome. The DNA ploidies of both the primary and cultured tumor cells were diploid. The chromosomal analyses revealed its chromosome number ranging from 43 to 46 with three clonal structural changes; dic (19;20) (p13;q13), dic (19;22) (q13;q13) and dic (12;?) (p13;?). As previously compared and reported, cases with marker chromosomes usually had a more aggressive clinical course than those without marker chromosomes. Instability of the terminal portion of the F- and G- chromosome groups were reported in other studies and were also detected in our case. Possible association of clinical aggressiveness with the clonal structural changes, especially dic (19;20) (p;q) and dic (19;22) (q;q), needed further investigation.

Aged

Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 1. Initial structure-activity relationships.

This series of reports describes the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. Described in this first report are the structure-activity relationships that led to a more than a 20-fold improvement of the potency and selectivity of the initial chemical lead (RG 5901). From this series of compounds, RG 7152 (16) was identified and selected for further evaluation in the clinic as an antiasthmatic agent. Compound 16 competitively inhibits [3H]LTD4 binding to membranes from guinea pig lung (Ki = 38 +/- 6 nM) and the spasmogenic activity of LTC4, LTD4, and LTE4 in parenchymal lung strips from guinea pigs. Unlike the original lead (RG 5901), compound 16 does not inhibit 5-lipoxygenase from guinea pig PMNs. Following oral administration to guinea pigs, 16 blocks LTD4-induced dermal permeability (ED50 = 6.9 mg/kg), LTD4-induced bronchoconstriction (ED50 = 1.1 mg/kg), antigen-induced bronchoconstriction (ED50 = 2.5 mg/kg), and anaphylactic-induced mortality (ED50 = 16 mg/kg). These studies on structure-activity relationships indicate that there is a requirement for an acidic function and the presence of the (2-quinolinylmethoxy)phenyl moiety in a specific geometric arrangement.

Animals

Differential effects of a series of hydroxamic acid derivatives on 5-lipoxygenase and cyclooxygenase from neutrophils and 12-lipoxygenase from platelets and their in vivo effects on inflammation and anaphylaxis.

The synthesis of a series of novel substituted hydroxamates has been described along with their profile of inhibitory activity against 5-lipoxygenase, 12-lipoxygenase, and cyclooxygenase enzymes. The structure--activity relationship suggests that future molecules could be designed to specifically inhibit one or more of these enzymes since there were definite differences in structure--activity relationships for these different enzymes. A representative number of these compounds have been tested in vivo and found to possess potent oral activity in a systemic anaphylaxis model mediated by leukotrienes and topical activity in an arachidonic acid induced inflammation model. One of these molecules, compound 20, demonstrated that a leukotriene antagonist pharmacophore can be modified such that it contains both antagonist activity and 5-lipoxygenase inhibitory activity.

Anaphylaxis

[Process of regeneration of cementum observed by various fluorescent-labeling methods].

The purpose of this study was to evaluate the effect of various fluorescent-labeling methods on longitudinal information associated with the process of regeneration of cementum after periodontal therapy. Mandibular bilateral premolars and molars in three monkeys were used. Prior to the labeling, experimental periodontitis was surgically produced at the mesial site of each tooth. In four weeks, scaling and root planing were carried out, and time marking was performed by injection of 3 kinds of fluorescent-labeling materials, tetracycline hydrochloride (30 mg/kg), calcein (8 mg/kg), and alizarin complexon (20 mg/kg), intramuscularly. The animals were sacrificed 4 days after the last injection and serial sections without decalcification were prepared. They were examined under a fluorescence microscope and further observed by contact microradiography (CMR) and staining with toluidine blue. According to the observations made by fluorescence microscopy, marked regeneration of the cementum was revealed by each of the 3 labeling agents. Also, the presence of regenerated cementum was supported by the observations by CMR and after toluidine blue staining. In addition, the regeneration of new cementum was shown to start in about 2 weeks after scaling and root planing. Judging from the results of this experiment, the various fluorescent-labeling methods seem to be effective for observing the process of regeneration of cementum.

Animals

Effect of porous and dense hydroxyapatite implantation on periodontal tissue regeneration in monkeys.

Two different kinds of hydroxyapatite (HA) granules (size: 400-630 microns), 1) porous HA fabricated by the H2O2 bubbling method and 2) dense HA, were placed into the experimentally created, 3-wall, wide periodontal defects in two monkeys to evaluate whether the different structures of hydroxyapatite influence the periodontal response after implantation. Defects without HA implantation served as controls. The HA implant groups showed excellent biocompatibility. Both the porous HA and the dense HA showed a greater amount of "connective tissue attachment or adhesion" than the control group. The amount of the increase by the porous HA group was statistically significant when compared with the control group. However, the three groups showed a similar amount of new cementum formation. These results indicate that the improvement of tissue regeneration by hydroxyapatite implantation was probably due to the prevention of the epithelial downgrowth rather than to the acceleration of the coronal proliferation of the periodontal ligament cells. In the porous HA group, ingrowth of fibrous and osseous tissue in the HA and indefinite tissue-apatite interface were observed. These findings suggest that the porous HA granules formed a firmer attachment to the surrounding periodontal tissue.

Alveolar Process

Molecular mechanism of retinoblastoma gene inactivation in retinoblastoma cell line Y79.

Formation of retinoblastoma, a cancer arising in the retinas of young children, is determined by mutational inactivation of an autosomal gene (RB), which has been molecularly cloned. Whereas all normal tissues and many tumor cells express an RB mRNA of 4.7 kilobases, six of six retinoblastomas were previously found either to lack RB gene expression or to have RB transcripts of abnormal (reduced) length. To further characterize the latter type of mutation, we chose to examine retinoblastoma cell line Y79, which expressed a shortened RB mRNA of about 4.0 kilobases. RB cDNA clones isolated from a library constructed with Y79 mRNA demonstrated an internal loss of 470 nucleotides near the 5' end, which corresponded to a deletion of exons 2-6. Genomic clones containing the deletion junction were isolated from a library made with Y79 DNA, which allowed precise localization and sequencing of deletion endpoints in introns 1 and 6. These regions had no apparent homology to each other or to the Alu family of repetitive sequences, implying that the deletion must have occurred by a mechanism other than recombination of homologous sequences. Deletion of exons 2-6 would interrupt the open reading frame in RB mRNA and would result in premature termination of translation. Since no normal RB protein was detected by immunoprecipitation with specific antibody, the other, apparently normal RB allele in Y79 cells was necessarily inactivated by a different mutation.

Base Sequence

Picric acid-evoked release of [14C]acetylcholine from the isolated synaptosome of rat cerebral cortex.

Picric acid stimulated, in a dose-dependent manner, the release of [14C]acetylcholine (ACh) from isolated synaptosomes of rat cerebral cortex pre-loaded with labelled choline. Radioactive ACh was separated for counting from choline in the synaptosomal supernatants by a liquid cation-exchange method. Neither the nicotinic antagonist (hexamethonium) nor the muscarinic antagonists (atropine and scopolamine) affected the effectiveness of picric acid, suggesting that the action of picric acid does not occur through a cholinoceptor-mediated mechanism. Moreover, oxotremorine, but not pilocarpine, inhibited ACh release in a concentration-dependent manner in either basal- or picric acid-evoked conditions, indicating the presence of muscarinic M2-receptors for auto-regulation of ACh release. The effect of picric acid was compared with high-K+ depolarization which also initiated a non-receptor-mediated release of ACh. Deletion of calcium ion from the medium negated the effects of both drugs. The ACh-releasing effect of picric acid was totally abolished, whereas high-K+ depolarization was reduced to some extent, when tetrodotoxin was added to the medium. These results indicate that picric acid acts as a releaser of ACh in the cerebrocortex of rat.

Acetylcholine

The fatty acid composition of glycerolipids in nerve, brain, and other tissues of the streptozotocin diabetic rat.

The fatty acid composition of individual glycerolipids in brain and sciatic nerve of rats made diabetic with streptozotocin and sacrificed 8 weeks later was determined and compared to the alterations that occurred in liver and kidney glycerolipids. A substantial decrease in the proportion of arachidonic acid and increases in the relative content of linoleic and docosahexenoic (22:6n3) acids occurred in the phosphoglycerides of visceral tissues from diabetic animals as reported by others. In contrast, except for a small rise in the percentage of linoleic acid, no consistent changes in fatty acid composition of phosphatidylcholine, phosphatidylethanolamine, ethanolamine plasmalogen, phosphatidylinositol or phosphatidylserine from brain or nerve were detected. The fatty acids of triacylglycerol associated with nerve exhibited alterations similar to those characteristic of liver. The differences which developed as a result of diabetes were completely prevented if animals were maintained continuously on insulin commencing shortly after administration of streptozotocin. It is concluded that the fatty acid composition of brain and nerve phosphoglycerides are unusually resistant to alteration in the diabetic animal and that consequently, changes in bulk membrane fluidity are unlikely to contribute to functional abnormalities displayed by diabetic peripheral nerve.

Animals