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Biomedical subjects

J S Lin

Publications and source records attributed to J S Lin.

At least 19 recordsLinked to original sources
PubMed2006

Modafinil inhibits rat midbrain dopaminergic neurons through D2-like receptors.

Modafinil is a well-tolerated medication for excessive sleepiness, attention-deficit disorder, cocaine dependence and as an adjunct to antidepressants with low propensity for abuse. We investigated the modafinil action on identified dopaminergic and GABAergic neurons in the ventral tegmental area (VTA) and substantia nigra (SN) of rat brain slices. Modafinil (20 microM) inhibited the firing of dopaminergic, but not GABAergic neurons. This inhibition was maintained in the presence of tetrodotoxin and was accompanied by hyperpolarization. Sulpiride (10 microM), a D2-receptor antagonist, but not prazosine (20 microM, an alpha1-adrenoreceptor blocker) abolished the modafinil action. Inhibition of dopamine reuptake with a low dose of nomifensine (1 microM) reduced the firing of DA neurons in a sulpiride-dependent manner and blunted the effect of modafinil. On acutely isolated neurons, modafinil evoked D2-receptor-mediated outward currents in tyrosine-hydroxylase positive cells, identified by single-cell RT-PCR, which reversed polarity near the K(+) equilibrium potential and were unchanged in the presence of nomifensine. Thus modafinil directly inhibits DA neurons through D2 receptors.

Action Potentials↗
PubMed2006

Novel polymorphisms in exons 6 and 7 of A/B alleles detected by polymerase chain reaction-single strand conformation polymorphism.

BACKGROUND AND OBJECTIVES: The ABO blood group system is the most important blood group system in transfusion medicine. In addition to the major A, B and O alleles, many rare alleles have been defined. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and analysis by PCR sequence specific primers (SSP) are commonly conducted for genotyping but have the limitation of being unable to detect unknown substitution(s) in amplified DNA fragments, whereas PCR-single strand conformation polymorphism (SSCP) can be used for both. MATERIALS AND METHODS: Three-hundred unrelated blood donors of the AB phenotype were enrolled. Four pairs of primers were designed to constitute two sets of multiplex PCRs: this amplifies four fragments spanning the entire exon 6 and its immediate flanking regions, nucleotides 432-1065, as well as the 3' untranslated region of exon 7 of the ABO gene. The SSCP electrophoresis was carried out on a 12.5% polyacrylamide gel in a GenePhor electrophoresis unit. For those with unexpected banding patterns, SSCP analyses were performed in duplicate and samples were cloned and sequenced for exons 6 and 7. RESULTS: Seven samples were noted to have six variant alleles, of which five have not been previously reported in the literature. Of these five novel variants, four were derived from the B allele, while the other derived from the A allele. CONCLUSIONS: By using PCR-SSCP, five novel A/B alleles were found.

ABO Blood-Group System↗
PubMed2004

A two-state model for the multilamellar structure of a DNA/cationic lipid complex in the bulk.

Polyanionic DNA can bind electrostatically with cationic lipids to form a complex used for gene delivery and nanostructure construction. Here, we reveal two multilamellar phases, L(I) and L(II), characterized by distinct states of lipid packing and DNA conformation in a DNA/cationic lipid complex in the bulk state. The L(II) phase, formed when the lipids are in excess of DNA in terms of overall ionic charge, is composed of B-DNA confined between the bilayers with the lipid tails aligning normal to the lamellar interface. When DNA becomes in excess of the lipids, the L(I) phase in which the DNA is bound with the tilted lipid chains adopting the A conformation is favored because this configuration offers more economical electrostatic binding between these two components.

DNA↗
PubMed2004

Changes in motoric, exploratory and emotional behaviours and neuronal acetylcholine content and 5-HT turnover in histidine decarboxylase-KO mice.

Histamine has been implicated, inter alia, in mechanisms underlying arousal, exploratory behaviour and emotionality. Here, we investigated behavioural and neurochemical parameters related to these concepts, including open-field activity, rotarod performance and anxiety, as well as brain acetylcholine and 5-HT concentrations of mice deficient for the histidine decarboxylase (HDC) gene. These mice are unable to synthesize histamine from its precursor histidine. The HDC-knockout mice showed reduced exploratory activity in an open-field, but normal habituation to a novel environment. They behaved more anxious than the controls, as assessed by the height-fear task and the graded anxiety test, a modified elevated plus-maze. Furthermore, motor coordination on the rotarod was superior to controls. Biochemical assessments revealed that the HDC-knockout mice had higher acetylcholine concentrations and a significantly higher 5-HT turnover in the frontal cortex, but reduced acetylcholine levels in the neostriatum. These results are suggestive of important interactions between neuronal histamine and these site-specific neurotransmitters, which may be related to the behavioural changes found in the HDC-deficient animals.

Acetylcholine↗
PubMed2003

Size, volume fraction, and nucleation of Stober silica nanoparticles.

29Si NMR, small-angle X-ray scattering (SAXS), and dynamic light scattering (DLS) are used to monitor the synthesis of silica nanoparticles from the base-catalyzed hydrolysis of TEOS in methanol and ethanol. The reactions are conducted at a [TEOS] =0.5 M, low concentrations of ammonia ([NH(3)] =0.01-0.1 M), and [H(2)O] =1.1-4.4 M to resolve the initial size of the first nuclei and to follow their structural evolution. It is found that after an induction period where there is a buildup of singly hydrolyzed monomer, the first nuclei are fractal and open in structure. Interestingly, the nuclei are twice as large in ethanol (R(g) approximately 8 nm) as those in methanol (R(g) approximately 4 nm). The data suggest that the difference in primary particle size is possibly caused by a higher supersaturation ratio of the singly hydrolyzed monomer in methanol than in ethanol if it is assumed that the surface energy of the first nuclei is the same in methanol and ethanol. The particle number concentration and the volume fraction of the silica particles are calculated independently from the SAXS, DLS, and 29Si NMR results. Finally, the rate of nucleation is obtained from the particle number concentrations.

Journal Article↗
PubMed2003

Waking selective neurons in the posterior hypothalamus and their response to histamine H3-receptor ligands: an electrophysiological study in freely moving cats.

Neurons which discharge selectively during waking (waking selective) have been found in the tuberomamillary nucleus (TM) and adjacent areas of the posterior hypothalamus. Although they share some electrophysiological properties with aminergic neurons, there is no direct evidence that they are histaminergic. We have recorded from posterior hypothalamic neurons during the sleep-wake cycle in freely moving cats, and investigated the effects on waking selective neurons of specific ligands of histaminergic H3-receptors, which autoregulate the activity of histaminergic neurons. Two types of neurons were seen. Waking selective neurons, termed "waking-on (W-on)," were located exclusively within the TM and adjacent areas, and discharged at a low regular rate during waking (1.71-2.97 Hz), decreased firing during light slow wave sleep (SWS), became silent during deep SWS and paradoxical sleep (PS) and resumed their activity on, or a few seconds before, awakening. "Waking-related" neurons, located in an area dorsal to the TM, displayed a similar, although less regular, low rate of firing (1.74-5.41 Hz) and a similar discharge profile during the sleep-wake cycle; however, unlike "W-on" neurons, they did not completely stop firing during deep SWS and PS. Intramuscular (i.m.) injection of ciproxifan (an H3-receptor antagonist, 1mg/kg), significantly increased the discharge rate of W-on neurons and induced c-fos expression in histamine-immunoreactive neurons, whereas i.m. injection of imetit (an H3-receptor agonist, 1mg/kg) or microinjection of alpha-methylhistamine (another H3-receptor agonist, 0.025-0.1 microg/0.2 microl) in the vicinity of these cells significantly decreased their discharge rate. Moreover, the effect of the antagonist was reversed by the agonists and vice versa. In contrast, "waking-related" neurons were unaffected by these H3-receptor ligands. These data provide evidence for the histaminergic nature of "W-on" neurons and their role in cortical desynchronization during waking, and highlight the heterogeneity of posterior hypothalamic neuronal populations, which might serve different functions during the wakefulness.

Action Potentials↗
PubMed2003

Production of biologically active tethered ovine FSHbetaalpha by the methylotrophic yeast Pichia pastoris.

The pituitary-derived glycoprotein hormone FSH plays a central role in controlling vertebrate gonadal function. In female mammals the maturation of ovarian follicles is critically dependent upon stimulation by FSH. Moreover, injection of exogenous FSH is used extensively to stimulate increased numbers of follicles to ovulate. Structurally FSH is a heterodimeric glycoprotein composed of two non-covalently associated polypeptide subunits. The tertiary structures of both the alpha- and beta-subunits are constrained by intramolecular disulphide bonds and are post-translationally modified with two N-linked carbohydrate moieties, the structure of which appears to modulate in vivo biological activity. Here we report the expression of ovine FSH (oFSH) as a biologically active single-chain polypeptide using the methylotrophic yeast Pichia pastoris. Sequences encoding the mature oFSH alpha- and beta-proteins were fused to form a gene encoding a fusion protein with the C-terminus of the beta-chain joined to the N-terminus of the alpha-chain, with the chains separated by a two amino acid linker sequence. This fusion gene was itself fused to two alternative Pichia leader sequences (mating factor alpha and acid phosphatase) and transformed into the Pichia strains GS115 and SMD1168. The recombinant fusion protein (oFSHbetaalpha) was expressed at approximately 0.1 microg/ml in 'shake-flask' cultures. The Pichia-expressed tethered protein was biologically active in an in vitro bioassay, had a molecular mass of 28 kDa, as determined by SDS-PAGE, and bound the bovine FSH receptor with a binding profile similar to that of native oFSH.

Animals↗
PubMed2002

Homogeneity of a supersaturated solid solution.

Extended x-ray absorption fine structures, small-angle x-ray scattering, and atomistic model calculations have been employed to probe the homogeneity of the fcc solution created in Ag-Cu, a classical system demonstrating the extension of solubility across the entire miscibility gap through rapid quenching. Our results reveal that in many cases the supersaturated solutions formed have decomposition features on the scale of 1 nm. Conventional diffraction methods are inadequate in determining the level of supersaturation or the uniformity of such solid solution alloys.

Journal Article↗
PubMed2001

Catalytic nucleophilic acyl substitution of anhydrides by amphoteric vanadyl triflate.

[reaction--see text] Among four vanadyl species examined, vanadyl triflate was the most efficient catalyst to facilitate nucleophilic acyl substitution of anhydrides with a myriad array of alcohols, amines, and thiols in high yields and high chemoselectivity. By using mixed-anhydride technique, one can achieve oleate and peptide syntheses. In marked contrast to common metal triflates, the amphoteric character of the V=O unit in vanadyl species was proven to be responsible for the catalytic profile in this process.

Journal Article↗
PubMed2001

Inner ear localization of mRNA and protein products of COCH, mutated in the sensorineural deafness and vestibular disorder, DFNA9.

Missense mutations in the COCH gene, which is expressed preferentially at high levels in the inner ear, cause the autosomal dominant sensorineural deafness and vestibular disorder, DFNA9 (OMIM 601369). By in situ hybridization of mouse and human inner ear sections, we find high-level expression of COCH mRNA in the fibrocytes of the spiral limbus and of the spiral ligament in the cochlea, and in the fibrocytes of the connective tissue stroma underlying the sensory epithelium of the crista ampullaris of the semicircular canals. A polyclonal antibody against the human COCH protein product, cochlin, was raised against the N-terminal 135 amino acid residues of cochlin, corresponding to the Limulus factor C-homology (cochFCH) domain; this domain harbors all five known point mutations in DFNA9. On western blots of human fetal cochlear extracts, anti-cochlin reacts with a cochlin band of the predicted full-length size as well as a smaller isoform. Immunohistochemistry performed with anti-cochlin shows staining predominantly in the regions of the fibrocytes of the spiral limbus and of the spiral ligament in mouse and in human fetal and adult tissue sections. These sites correspond to those areas that express COCH mRNA as determined by in situ hybridization, and to the regions of the inner ear which show histological abnormalities in DFNA9. The fibrocytes expressing mRNA and protein products of COCH are the very cell types which are either absent or markedly reduced and replaced by eosinophilic acellular material in temporal bone sections of individuals affected with DFNA9.

Adult↗
PubMed2001

Distinct CD8 T cell functions mediate susceptibility to histoplasmosis during chronic viral infection.

It has long been recognized that some viral infections result in generalized immune suppression. In acute infections, this period of suppressed immunity is relatively short. However, chronic infections associated with a prolonged period of immune suppression present far greater risks. Here, we examined the role of CD8 T cell responses following viral infection in immunity to systemic histoplasmosis. Although wild-type mice with systemic histoplasmosis were able to control the infection, those simultaneously infected with lymphocytic choriomeningitis virus clone 13 showed reduced immunity with greater fungal burden and high mortality. The immune suppression was associated with loss of CD4 T cells and B cells, generalized splenic atrophy, and inability to mount a granulomatous response. Removing the anti-viral CD8 T cells in the coinfected mice enabled them to reduce the fungal burden and survive the infection. Their lymphoid organs were replenished with CD4 T and B cells. In contrast to wild-type mice, perforin-deficient mice infected with lymphocytic choriomeningitis virus clone 13 and Histoplasma showed an absence of immunopathology, but the animals still died. These results show that CD8 T cells can suppress immunity through different mechanisms; although immunopathology is perforin-dependent, lethality is perforin-independent.

Animals↗
PubMed2001

Bioinformatics and mass spectrometry for microorganism identification: proteome-wide post-translational modifications and database search algorithms for characterization of intact H. pylori.

MALDI-TOF mass spectrometry has been coupled with Internet-based proteome database search algorithms in an approach for direct microorganism identification. This approach is applied here to characterize intact H. pylori (strain 26695) Gram-negative bacteria, the most ubiquitous human pathogen. A procedure for including a specific and common posttranslational modification, N-terminal Met cleavage, in the search algorithm is described. Accounting for posttranslational modifications in putative protein biomarkers improves the identification reliability by at least an order of magnitude. The influence of other factors, such as number of detected biomarker peaks, proteome size, spectral calibration, and mass accuracy, on the microorganism identification success rate is illustrated as well.

Algorithms↗
PubMed2001

Correlations between osteocalcin content, degree of mineralization, and mechanical properties of C. carpio rib bone.

Osteocalcin is one of the most abundant noncollagenous proteins in bone. It is strongly associated with the mineral phase of bone, and has long been associated as a marker of bone turnover. However, its relationship to bone composition, strength, and structure is unclear. Carp rib bone is an excellent model for the study, because osteocalcin represents almost 60% of the total extractable noncollagenous proteins found in it. Because of the abundance of osteocalcin relative to other extractable proteins, any changes in the properties of carp rib bone would be more likely influenced by the osteocalcin concentration. To test the hypotheses that the concentration of osteocalcin is reflected in other properties of bone, the correlations between the osteocalcin concentration and the mineral content, microstructural properties, and physical characteristics of the bone mineral crystals were determined utilizing radioimmunoassay (RIA), spectrophotometry, nanoindentation, and small-angle X-ray scattering (SAXS) techniques, respectively. Osteocalcin concentration was found to be correlated to the molar Ca/P ratio and inversely correlated to the elastic modulus and hardness in the longitudinal plane. This study provides evidence for a putative relationship between the concentration of osteocalcin and the microstructural mechanical properties of bone. Correlations were also found between the mechanical properties in the longitudinal plane and both the phosphate content and the molar Ca/P ratio. However, no relationships could be identified between osteocalcin concentration and several parameters of bone crystals, as determined by SAXS.

Animals↗
PubMed2001

Extravesical cryosurgical approach for VX2 bladder tumor in rabbits.

This study characterized the VX2 bladder cancer model in rabbits and tested the feasibility of treating bladder cancer by extravesical cryosurgery. After the growth characteristics of the VX2 bladder tumor model were determined, the VX2 tumor was inoculated into rabbits at the dome of the bladder. One week later, three freeze/thaw cycles were followed by immediate surgical repair. The control group underwent a sham operation without freezing. When the VX2 tumor is injected into the bladder wall, invasion and central necrosis occurred within I week, lymphatic metastases by 2 weeks, and lung metastases by 3 weeks after inoculation. By 4 weeks, all control rabbits had large VX2 tumors in their bladders and advanced lung metastases. Nine of the ten rabbits in the cryosurgical group had mild to moderate degrees of lung metastases, and six of them had relatively small local recurrences. One rabbit had no tumor in the bladder and only microscopic lung metastasis. The extravesical approach to cryosurgery employing bladder inversion is well tolerated. Cryosurgery exhibits modest efficacy in treating local tumors and delaying lung metastasis in this aggressive tumor model.

Animals↗
PubMed2001

Successful testicular sperm extraction and paternity in an azoospermic man after bilateral postpubertal orchiopexy.

Postpubertal orchiopexy is usually considered a cosmetic operation and unlikely to have any effect on fertility. We describe a 32-year-old patient with bilateral undescended testes who underwent bilateral orchiopexy at 18 years of age. He presented with primary infertility and azoospermia. After fertility counseling, testicular sperm extraction in conjunction with intracytoplasmic sperm injection was performed. A few spermatozoa were recovered and produced a fertilization rate of 42.9%. Pregnancy resulted and a healthy baby girl was delivered. We suggest that orchiopexy be recommended in infertile men with bilateral cryptorchidism, and that testicular sperm extraction be recommended if azoospermia persists after surgery.

Adult↗
PubMed2001

Age-associated changes in collagen content and its subtypes within rat corpora cavernosa with computerized histomorphometric analysis.

OBJECTIVES: To study the age-associated changes in the percentage of collagen and subtypes I, III, and IV within the corpora cavernosa in a rat model. METHODS: The corpora cavernosa tissues were obtained from 30 male Wistar rats at three different ages. Processed with Masson's trichrome staining for collagen and with immunohistochemical staining for the collagen subtypes, the values of the collagen percentage, the percentage of area, and relative proportion of each collagen subtype within the rat corpora cavernosa were measured using an automatic image analysis system. The relationships between an increase in age and these parameters were analyzed. RESULTS: The percentage of collagen within the corpora cavernosa was higher in the old rats (80 weeks) than in the young (20 weeks) and intermediate-age (40 weeks) rats (P = 0.02 and P = 0.25, respectively) and significantly increased with age (P = 0.021). The values of the percentage of area of collagen subtypes III and IV also increased significantly with age (P = 0.039 and P = 0.019, respectively). The value of the percentage of area of collagen subtype I was not significantly increased (P = 0.159). Also, no significant differences were found in the relative proportions of all three collagen subtypes with age among the three age groups. CONCLUSIONS: The percentages of collagen within rat corpora cavernosa significantly increased, but not strongly, with age, especially collagen subtypes III and IV. However, the relative proportion of each subtype did not change with age. Therefore, we conclude that the amount of collagen may only partly contribute to erectile dysfunction in the aging process of the rat.

Aging↗
PubMed2001

ASSESS-3: a randomised, double-blind, flexible-dose clinical trial of the efficacy and safety of oral sildenafil in the treatment of men with erectile dysfunction in Taiwan.

The efficacy and safety of sildenafil were evaluated in a randomised, double-blind, placebo-controlled, flexible-dose study in Taiwanese men aged 26 to 80 y with erectile dysfunction (ED) of broad-spectrum aetiology and more than 6 months' duration. A total of 236 patients were randomised at six medical centres in Taiwan to receive either sildenafil (50 mg initially increased if necessary to 100 mg or decreased to 25 mg depending on efficacy and toleration) (n=119) or matching placebo (n=117) taken on an 'as needed' basis 1 h prior to anticipated sexual activity for a period of 12 weeks. At the end of 12 weeks, the primary efficacy variables relating to the achievement and maintenance of erections sufficient for sexual intercourse, and the secondary efficacy variables, which included: (1) the five separate domains of sexual functioning of the IIEF (International Index of Erectile Function) scale, (2) the percentage of successful intercourse attempts; and (3) a global assessment of erections, were all statistically significantly improved by sildenafil in comparison with placebo (P<0.0001). Treatment-related adverse events occurred in 43.7% of patients receiving sildenafil and 18.8% receiving placebo. The most common adverse events with sildenafil were flushing, dizziness and headache (25.2, 6.7 and 5.9% of patients, respectively), and most were mild in nature. The efficacy and safety of sildenafil in the population of Taiwanese men appears similar to that reported in other studies in western populations.

Administration, Oral↗