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Biomedical subjects

J M Lin

Publications and source records attributed to J M Lin.

At least 19 recordsLinked to original sources

Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo.

Several hormones that regulate nutritional status also impact on bone metabolism. Preptin is a recently isolated 34-amino acid peptide hormone that is cosecreted with insulin and amylin from the pancreatic beta-cells. Preptin corresponds to Asp(69)-Leu(102) of pro-IGF-II. Increased circulating levels of a pro-IGF-II peptide complexed with IGF-binding protein-2 have been implicated in the high bone mass phenotype observed in patients with chronic hepatitis C infection. We have assessed preptin's activities on bone. Preptin dose-dependently stimulated the proliferation (cell number and DNA synthesis) of primary fetal rat osteoblasts and osteoblast-like cell lines at periphysiological concentrations (>10(-11) M). In addition, thymidine incorporation was stimulated in murine neonatal calvarial organ culture, likely reflecting the proliferation of cells from the osteoblast lineage. Preptin did not affect bone resorption in this model. Preptin induced phosphorylation of p42/p44 MAP kinases in osteoblastic cells in a dose-dependent manner (10(-8)-10(-10) M), and its proliferative effects on primary osteoblasts were blocked by MAP kinase kinase inhibitors. Preptin also reduced osteoblast apoptosis induced by serum deprivation, reducing the number of apoptotic cells by >20%. In vivo administration of preptin increased bone area and mineralizing surface in adult mice. These data demonstrate that preptin, which is cosecreted from the pancreatic beta-cell with amylin and insulin, is anabolic to bone and may contribute to the preservation of bone mass observed in hyperinsulinemic states such as obesity.

Animals↗

Lactoferrin and bone; structure-activity relationships.

The maintenance of the mechanical integrity of the skeleton depends on bone remodeling, the well-coordinated balance between bone formation by osteoblasts and bone resorption by osteoclasts. The coupled action of osteoblasts and osteoclasts is regulated by the action of many local and circulating hormones and factors as well as central regulation by a neurological mechanism. We have previously shown that lactoferrin can promote bone growth. At physiological concentrations, lactoferrin potently stimulates the proliferation and differentiation of primary osteoblasts and acts as a survival factor. Lactoferrin also affects osteoclasts, potently inhibiting their formation. In vivo, local injection of lactoferrin results in substantial increases in bone formation and bone area. In a critical bone-defect model in vivo, lactoferrin was also seen to promote bone growth. The mitogenic effect of lactoferrin in osteoblast-like cells is mediated mainly through low-density lipoprotein-receptor protein-1 (LRP1), a member of the low-density lipoprotein-receptor-related proteins that are primarily known as endocytic receptors; however, LRP1 is not necessary for the anti-apoptotic actions of lactoferrin. Lactoferrin also induces the activation of p42/44 mitogen-activated protein kinase (MAPK) signalling and the PI3-kinase-dependent phosphorylation of Akt in osteoblasts. In this study, we examined other properties of lactoferrin and the way they affect osteogenic activity. The degree of glycosylation, iron-binding, and the structure-activity relationships indicate that lactoferrin maintains osteogenic activity in deglycosylated, holo, and apo forms, and in with various small fragments of the molecule. These data suggest that lactoferrin signals through more than 1 membrane-bound receptor to produce its anabolic skeletal effects, and that it signals through diverse pathways. We conclude that lactoferrin might have a physiological role in bone growth and healing and a potential therapeutic role as an anabolic factor in osteoporosis.

Amino Acid Sequence↗

Luminol chemiluminescence in unbuffered solutions with a cobalt(II)-ethanolamine complex immobilized on resin as catalyst and its application to analysis.

Using a heterogeneous catalyst, Co(II)-ethanolamine complex sorbed on Dowex-50W resin, the chemiluminescence (CL) of luminol in unbuffered or weakly acidic solution was studied in the presence of H2O2. The maximum luminol CL wavelength at pH 5.7 was 448 nm, 23 nm longer than that in a basic solution (pH 10.5). Three different ligands, mono-, di-, and triethanolamine, and six transition metal ions, Co(II), Cu(II), Ni(II), Mn-(II), Fe(II), and Fe(III) were compared by CL measurements. The CL intensity decreased in the order mono- > di- > triethanolamine and Co(II) > Cu(II) > Ni(II) > Fe-(III) > Mn(II) > Fe(II). This heterogeneous CL system was developed as H2O2 and glucose flow-through sensors. Detection limits (S/N = 3) of H2O2 and glucose using Dowex-50W-X4-Co(II)-monoethanolamine as catalyst are 1 x 10(-7) M and 1 x 10(-6) M, respectively. On the basis of the studies of the CL, fluorescence, UV-vis and ESCA spectra and the effect of dissolved oxygen in luminol solution, a mechanism for CL emission in unbuffered solution was considered as the formation of a superoxide radical ion during the decomposition of H2O2 catalyzed by the Co(II)-ethanolamine immobilized resin. Then the superoxide radical ion acted on luminol and the CL was emitted. The applications of the proposed method to determine H2O2 in rainwater without any special pretreatment and glucose in human urine and orange juice samples give satisfactory results.

Anion Exchange Resins↗

Continuous preconcentration system for nitrate ions using anionic reverse osmosis tubes coupled to an ion chromatograph.

A continuous preconcentration system for nitrate ions was developed using cation exchange tubing made from Nafion perfluorosulfonic acid membrane. This method is based on ion exclusion effects and reverse osmosis phenomena. The system was evaluated by connecting it to an ion chromatograph. The concentration ratios could be increased by raising the pressures between the two sides of the cation exchange tubing. Twenty-fold concentration of nitrate ion was achieved when the pump pressure was 20 x 10(5) Pa. The relative standard deviations of the preconcentration ratio at four different pump pressures, 5, 10, 15 and 20 x 10(5) Pa were 1.2-2.8% (n = 5).

Journal Article↗

Inspection of the reversal of enantiomer migration order in ligand exchange micellar electrokinetic capillary chromatography.

Enantiometers of D,L-phenylalanine were separated by capillary electrophoresis based on the principle of ligand exchange. Copper (II) complex of 4-hydroxy-L-proline was used as chiral selector. The separation and the migration order of D- and L-phenylalanine were strongly affected by adding an anion surfactant sodium dodecylsulfate (SDS). Without SDS in the electrolyte, the separation was also carried out but the resolution was very small. With SDS added into the electrolyte, the resolution decreased with increasing concentration of SDS until 5.0 mM. When the concentration of SDS in the electrolyte was over 5.0 mM, inversion of the migration order of DL-phenylalanine was observed and the resolution was also increased with increasing concentration up to 20 mM. It was interesting to find that the inversion of the migration order took place not only in the enantioscparation but also in the positional isomers. A family of a fluorinated amino acid, o-, m- and p-fluoro-D,L-phenylalanine was separated and the inversion of the migration order is discussed.

Chromatography, Micellar Electrokinetic Capillary↗

Color vision after laser in situ keratomileusis.

PURPOSE: To evaluate the effect of laser in situ keratomileusis (LASIK) on color vision. SETTING: Department of Ophthalmology, China Medical College Hospital, Taichung, Taiwan. METHOD: This prospective study comprised consecutive patients having LASIK. Patients were eligible for inclusion if they had a best corrected visual acuity of 20/20 or better and a normal color vision test preoperatively and an uncorrected near visual acuity of 20/40 or better postoperatively. Color vision was tested using the Farnsworth-Munsell 100-hue test (FM 100 test) preoperatively and 1 day, 1 week, and 1 month postoperatively. RESULTS: Twenty-nine eyes of 15 patients having LASIK were enrolled in the study. The mean patient age was 29.2 years +/- 2.9 (SD). The mean preoperative spherical equivalent refractive error was -5.6 +/- 1.8 diopters, and the mean preoperative error score of the FM 100 test was 3.79 +/- 1.55. After surgery, no significant change in the error score was observed at 1 day (4.30 +/- 1.07, P =.1039, paired t test), 1 week (3.72 +/- 1.25, P =.8125, paired t test), or 1 month (3.97 +/- 1.29, P =.6149, paired t test). CONCLUSION: Laser in situ keratomileusis did not affect color vision evaluated by the FM 100 test.

Adult↗

Treatment and outcome of Taiwanese patients with 6-pyruvoyltetrahydropterin synthase gene mutations.

Ten cases of tetrahydrobiopterin (BH4) deficiency were identified in 1,337,490 newborns screened in a Chinese population in Taiwan. The high incidence of BH4 deficiency in the Taiwanese population may be explained by a founder effect, since all of the patients revealed 6-pyruvoyltetrahydropterin synthase gene mutations, and grouping N52S and P87S mutations together constituted 88.9% of the disease alleles. BH4 supplementation with restriction of high-protein foods gave control of plasma phenylalanine within normal range, and levodopa itself prevented seizure. However, the average intelligence quotient (IQ) score of these patients was only 76 +/- 14 (56-98). Statistically, the age of starting medication, including 5-hydroxytryptophan (5-HTP), was inversely correlated to IQ scores of these patients. We suggest the combination of BH4, levodopa and 5-HTP as the standard protocol to commence the treatment of BH4 deficiency as early as possible, although prenatal brain damage could have existed.

5-Hydroxytryptophan↗

Chemiluminescent flow-through sensor for 1,10-phenanthroline based on the combination of molecular imprinting and chemiluminescence.

A functional polymer for the catalysis of the chemiluminescent reaction and molecular recognition ability of 1,10-phenanthroline was prepared based on the molecular imprinting method. The structural and catalytic roles of transition metal ion interactions were applied in the material design. A ternary complex, 4-vinylpyridine-Cu(II)-1,10-phenanthroline (2:1:1), was synthesized and used as a functional monomer. The ligand 1,10-phenanthroline in the ternary complex was the template used to form the molecularly imprinted polymer. Another monomer, styrene, and the cross-linking reagent divinylbenzene were copolymerized with the ternary complex. The polymer containing the ternary complex is an efficient catalyst for the decomposition of hydrogen peroxide. During the hydrogen peroxide decomposition, superoxide radical ion is formed, which reacts with 1,10-phenanthroline and gives a chemiluminescent emission. The 1,10-phenanthroline was destroyed during the chemiluminescent reaction, leaving a cavity and copper binding sites for another 1,10-phenanthroline molecule. The prepared polymer particles were packed into a glass tube and developed as a molecular recognition chemiluminescent flow-through sensor for 1,10-phenanthroline. The sensitivity and selectivity of the sensor were tested.

Journal Article↗

Phenotyping of individual pancreatic islets locates genetic defects in stimulus secretion coupling to Niddm1i within the major diabetes locus in GK rats.

The major diabetes quantitative trait locus (Niddm1), which segregates in crosses between GK rats affected with spontaneous type 2-like diabetes and normoglycemic F344 rats, encodes at least two different diabetes susceptibility genes. Congenic strains for the two subloci (Niddm1f and Niddm1i) have been generated by transfer of GK alleles onto the genome of F344 rats. Whereas the Niddm1f phenotype implicated insulin resistance, the Niddm1i phenotype displayed diabetes related to insulin deficiency. Individual islets from 16-week-old congenic rats were characterized for insulin release and oxygen tension (pO(2)). In the presence of 3 mmol/l glucose, insulin release from Niddm1f and Niddm1i islets was approximately 5 pmol. g(-1). s(-1) and pO(2) was 120 mmHg. Similar recordings were obtained from GK and F344 islets. When glucose was raised to 11 mmol/l, insulin release increased significantly in Niddm1f and F344 islets but was essentially unchanged in islets from GK and Niddm1i. The high glucose concentration lowered pO(2) to the same extent in islets from all strains. Addition of 1 mmol/l tolbutamide to the perifusion medium further increased pulsatile insulin release threefold in all islets. The pulse frequency was approximately 0.4 min(-1). alpha-Ketoisocaproate (11 mmol/l) alone increased pulsatile insulin release eightfold in islets from Niddm1f, Niddm1i, and control F344 rats but had no effect on insulin release from GK islets. These secretory patterns in response to alpha-ketoisocaproate were paralleled by reduction of pO(2) in Niddm1f, Niddm1i, and control F344 islets and no change of pO(2) in GK islets. The results demonstrate that Niddm1i carries alleles of gene(s) that reduce glucose-induced insulin release and that are amenable to molecular identification by genetic fine mapping.

Alleles↗

Giant tear retinal detachment after laser in situ keratomileusis--a case report.

A 42-year-old woman with a refractive error of -10.00S - 2.00C x 105 degrees in the right eye underwent laser in situ keratomileusis (LASIK) at our hospital. LASIK was performed using the Schwind excimer laser (Keratom Multiscan, Schwind, Kleinostheim, Germany) and Moria LSK--One manual microkeratome with a 130 microns ablation plate. The uncorrected visual acuity improved postoperatively, and the patient was very satisfied. However, nine months later, she complained of sudden loss of visual acuity in the right eye. Indirect ophthalmoscopy revealed a giant retinal tear extending from 10:00 to 2:00 o'clock position with retinal detachment and vitreous hemorrhage. We performed scleral buckling procedure (with silicone band encircling), vitrectomy, and fluid-gas exchange with air/SF6 mixture. The retina attached postoperatively and remained so during 3-month follow-up period, but cellophane maculopathy was noted.

Adult↗

[Determination of coenzyme Q and alpha-tocopherol in mouse plasma and tissue mitochondria by liquid chromatography with electrochemical detection].

A convenient and reliable liquid chromatographic method with electrochemical detection was developed for the simultaneous determination of reduced coenzyme Q(ubiquinol), oxidized coenzyme Q(ubiquinone) and alpha-tocopherol in various tissues. The compounds of interest were separated on a reverse-phase C18 column under the mobile phase of 7 g/L NaClO4 in ethanol-methanol-70% HClO4 (800:200:1, volume ratio) and detected simultaneously by using a series of detection cells. Electrochemical guard cell (upstream of the injector) was used for eliminating interference for mobile phase. Ubiquinones were reduced in the -550 mV conditioning cell (downstream of the column). The resultant ubiquinols and original ubiquinols and alpha-tocopherol existing in the sample were easily oxidized in the 150 mV analytical cell. The linear range of the compounds were from 5 micrograms/L to 200 micrograms/L with correlation coefficients from 0.9976 to 0.9999. The detection limits were from 0.23 microgram/L to 0.68 microgram/L. The method was applied satisfactorily to the simultaneous determination of the amounts of ubiquinol-9, ubiquinol-10, ubiquinone-9, ubiquinone-10 and alpha-tocopherol in mice plasma and tissue mitochondria.

Animals↗

Studies on the synthesis of trans-dihydrodiols of polycyclic aromatic thiaarenes as potential proximate carcinogenic metabolites: first synthesis of trans-10,11-dihydroxy-10,11-dihydroacenaphtho[1, 2-b]benzo[d]thiophene and 6,7-dihydroxy-6,7-dihydronaphtho[1, 2-b]thiophene.

Polyaromatic thiophene compounds are found to occur concomitantly with numerous coal-derived products and shale oils and are suspected mutagens and/or carcinogens. The first synthesis of the two title compounds 9 and 16 has been achieved in five or four steps starting from 8,9-dihydroacenaphtho[1,2-b]benzo[d]thiophene (1) and 7-methoxynaphtho[1,2-b]thiophene (12), respectively. Compound 1 was converted to the cis-diol (11) (via treatment with OsO(4)/pyridine) or to trans-diol (3) [via Prevost reaction (PhCOOAg/I(2)) followed by hydrolysis] in 95-98% yield, respectively. Subsequent dehydration (PTS/benzene) of the diol followed by aromatization of the resulting ketone (5) produced the phenolic compound 6 in 97% yield. Oxidation of the phenol with phenyl iododiacetate followed by hydrolysis of the o-quinone monoketal 7 gave the o-quinone (8) in 86% yield. Stereoselective reduction of 8 with NaBH(4)/EtOH under oxygen afforded trans-10,11-dihydroxy-10,11-dihydroacenaphtho[1,2-b]benzo[d]thi oph ene(9) (orange yellow solid) in 55% yield. Compound 16 was obtained as a colorless solid, through the stereoselective reduction of the o-quinone 15 (with NaBH(4)), which in turn was prepared from 12 following the protocol of functional group transformation of methoxy --> phenol --> o-quinone monoketal --> o-quinone, as used in the previous case. The yields for all the steps are very good. The mutagenicity assay of compound 9 and 16 as well as their parent thiaarenes have been performed. The results showed that 9 may not be the proximate carcinogen of acenaphtho[1,2-b]benzo[d]thiophene, while it is likely that compound 16 is one of the possible proximate carcinogens for naphtho[1,2-b]thiophene.

Animals↗

Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines.

BACKGROUND: A number of recent studies have identified interleukin (IL)-6 as an important regulator of prostate cancer growth. Here, we investigate the potential interaction of IL-6 with phosphatidylinositol (PI)-3 kinase, a key growth regulatory enzyme, in prostate cancer cell lines. METHODS: Tyrosine phosphorylation of p85, the regulatory subunit of PI-3 kinase, in the human prostate cancer cell lines LNCaP and PC-3 was assessed by sequential immunoprecipitation with anti-p85 antibody and immunoblotting with anti-phosphotyrosine. The effects of wortmannin, an inhibitor of PI-3 kinase, and/or IL-6 on cell growth were assessed by MTT assays. DNA laddering experiments were performed to assay for programmed cell death. RESULTS: Tyrosine phosphorylation of p85 is upregulated by IL-6 in both LNCaP and PC-3. IL-6 promotes coprecipitation of p85 with gp130, the signal-transducing component of the IL-6 receptor. Inhibition of PI-3 kinase with wortmannin induces programmed cell death in PC-3 cells. In contrast, wortmannin has no effect on LNCaP growth when used alone; however, combined with IL-6, wortmannin promotes apoptosis in these cells. CONCLUSIONS: PI-3 kinase is involved in IL-6 signal transduction and delivers an antiapoptotic signal in human prostate cancer cell lines.

Androstadienes↗

Natural history of central islands after laser in situ keratomileusis.

PURPOSE: To assess the incidence and natural history of central islands following laser in situ keratomileusis (LASIK) and evaluate the association of central island characteristics with visual acuity. SETTING: Department of Ophthalmology, China Medical College Hospital, Taichung, Taiwan. METHODS: A consecutive series of 406 eyes of 212 patients who had LASIK was retrospectively evaluated. Uncorrected visual acuity (UCVA) was measured and corneal topography performed preoperatively and 1 week and 1, 3, 6, and 9 months postoperatively. Best spectacle-corrected visual acuity (BSCVA) was evaluated preoperatively and 1, 3, and 6 months postoperatively. RESULTS: The topographic images obtained at 1 week demonstrated central islands in 23 eyes of 20 patients (5.7%). No new cases of central island formation were identified after 1 week. Of the 23 eyes with central islands, the 6 month post-LASIK maps were available in 20 eyes of 18 patients. There was a significant difference in the size and power of the central islands between 1 week and 6 months. However, the power and size decreased slowly. Within 6 months, only 5 of 20 central islands (25.0%) had resolved. Eight eyes were undercorrected, and 1 eye lost 2 lines of BSCVA. Central islands larger than 1.8 mm or 3.0 diopters (D) were significantly correlated with lower UCVA. CONCLUSION: Most central islands that occur with LASIK persist more than 6 months. Large central islands (>/=1.8 mm or >/=3.0 D) are risk factors for lower UCVA. Preventive measures are necessary.

Adult↗