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Biomedical subjects

J S Lin

Publications and source records attributed to J S Lin.

At least 91 records · Page 5Linked to original sources
PubMed1997

Interaction of a synthetic peptide based on the neutrophil-derived antimicrobial protein CAP37 with dipalmitoyl-phosphatidylcholine membranes.

CAP37, a cationic antimicrobial protein of Mr 37 kDa is constitutively expressed in human neutrophils. A synthetic peptide, CAP37 P20-44, corresponding to amino acid residues 20 through 44 of the native CAP37 molecule has been shown to mimic the antimicrobial activity of the native protein. An analog of peptide CAP37 P20-44 was synthesized in which the cysteine residues at positions 26 and 42 were replaced with serine residues (CAP37 P20-44Ser). This resulted in a peptide that no longer exhibited bactericidal activity. The effect of different concentrations of the active CAP37 peptide, CAP37 P20-44, and its inactive analog, CAP37 P20-44Ser, on artificial lipid membranes composed of dipalmitoyl phosphatidylcholine (DPPC) was studied using small-angle X-ray scattering and differential scanning calorimetry. The results indicated that CAP37 P20-44 perturbs the periodicity of the lamellar structure as shown by small angle X-ray diffraction, while the effect of the inactive peptide is not as strong. Differential scanning calorimetry further confirms that CAP37 P20-44 interacts with lipid membranes as indicated by increased width of the transition and decreased peak height. Moreover, it completely abolishes the pretransition temperature of the DPPC membranes. The effect of the inactive peptide, CAP37 P20-44Ser on the thermotropic properties of DPPC was small. These studies suggest that CAP37 perturbs the lamellar structure of lipid bilayers and further suggests that the antibiotic action of the molecule may be through its interactions with the lipid components of the Gram negative bacterial membrane.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1997

High prevalence of antithrombin III, protein C and protein S deficiency, but no factor V Leiden mutation in venous thrombophilic Chinese patients in Taiwan.

We studied the prevalence of antithrombin III (AT III), protein C (PC) and protein S (PS) deficiencies and factor V Leiden mutation in thrombophilia in Taiwan. Eighty-five consecutive and unrelated patients with otherwise unexplained venous thrombophilia were studied. Both antigen and activity of inhibitors were determined using commercial kits (Stago), activated PC sensitivity ratio (APC SR) by Coatest (Chromogenix), and factor V mutation by polymerase chain reaction with sequence specific primer. Of 85 patients, 41 were male, 44 female, and mean age 49.4 years (17-82 years). None had factor V mutation, or APC SR of less than 2; 50 (58.8%) showed a deficiency of inhibitor proteins; 34 (68.0%) were hereditary, 16 (32.0%) non-hereditary; 3 had an AT III deficiency, 16 a PC deficiency, 28 a PS deficiency, and 3 a combined deficiency. Thirty-five were non-deficient without a known cause. The average age at the first thrombotic episode was 48.5 years (13-81 years). Thrombosis occurred spontaneously in 39 (78.0%) of 50 deficient patients. In conclusion, a relatively higher prevalence of AT III, PC and PS deficiency (59%), but no factor V Leiden mutation, was found in venous thrombophilic Chinese patients in Taiwan compared to that in western countries. Screening for inhibitor protein deficiency in Chinese thrombophilic patients is highly recommended.

Adolescent↗
PubMed1997

Synthesis and anti-hepatitis B virus activity of 9-(2-deoxy-2-fluoro-beta-L-arabinofuranosyl) purine nucleosides.

Since the discovery of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU) as a potent anti-HBV and anti-EBV agent, we have studied the structure-activity relationships of 2'-deoxy-2'-fluoro-beta-L-arabinofuranosylpyrimidine nucleosides as anti-HBV agents. Therefore it is rational to extend this study to the purine nucleosides. Thus, 3,5-di-O-benzoyl-2-deoxy-2-fluoro-beta-L-arabinofuranosyl bromide (1), which was prepared from L-xylose via a multistep procedure, was coupled with several purines by the sodium salt method. From this general synthesis, 10 purine nucleosides containing the 2-deoxy-2-fluoro-beta-L-arabinofuranosyl moiety have been obtained. The anti-HBV activity and toxicity of the synthesized nucleosides were evaluated in HepG2 2.2.15 cells. Among them, the adenine (10) and hypoxanthine (15) derivatives exhibit good in vitro anti-HBV activity (EC50 = 1.5 and 8 microM, respectively) without significant toxicity up to 200 microM.

Antiviral Agents↗
PubMed1997

Structure of the monophosphoryl lipid A moiety obtained from the lipopolysaccharide of Chlamydia trachomatis.

Monophosphoryl lipid A was prepared from the lipopolysaccharide of Chlamydia trachomatis, converted to the methyl ester, and fractionated by reverse-phase high-performance liquid chromatography. The peak fractions were collected and analyzed by mass spectrometry. Matrix-assisted laser desorption/ionization and liquid secondary ion mass spectrometry of the first of two major high-performance liquid chromatographic fractions showed multiple quasi-molecular ions of MNa+ at m/z 1780, 1794, 1808, 1822, and 1836. The positive-ion liquid secondary ion mass spectrometry spectrum also showed a minor series of peaks at m/z 1916, 1930, 1944, 1958, and 1971, consistent with the formation of matrix adducts with 3-nitrobenzyl alcohol. Oxonium ions representing the distal subunit were observed at m/z 1057, 1071, 1085, 1099, and 1113. The second fraction was similarly analyzed and found to contain structural homologs of the first fraction. Based on this study, the major lipid A component of chlamydial lipopolysaccharide is a glucosamine disaccharide that contains five fatty acids and a phosphate in the distal segment. Three fatty acyl groups are in the distal segment, and two are in the reducing end segment. The acyloxyacyl group is located in the distal segment in amide linkage. Two structural series, differing by 14 atomic mass units in the reducing subunit, were observed. Chlamydial lipid A is complex and consists of at least 20 homologous structural components. The relatively low potency of Chlamydia trachomatis lipopolysaccharide in activating lipopolysaccharide-responsive cells might be related to the unusual fatty acid composition of the lipid A moiety.

Chlamydia trachomatis↗
PubMed1997

Primary transplantation of allogeneic peripheral blood stem cell for severe aplastic anemia.

Primary allogeneic peripheral blood stem cell transplantation (allo-PBSCT) has not been previously described in the treatment of severe aplastic anemia (SAA). We report a patient with SAA who underwent primary allo-PBSCT with cells from her HLA-identical sibling and achieved rapid bone marrow reconstitution. The patient has been in complete remission with normal blood counts for 9 months following allo-PBSCT. This suggests that primary allo-PBSCT is a safe and effective alternative in the treatment of SAA.

Adolescent↗
PubMed1997

Retreatment with nafarelin for recurrent endometriosis symptoms: efficacy, safety, and bone mineral density.

OBJECTIVE: To assess the efficacy, safety, and effect on bone mineral density of a 3-month course of retreatment with intranasal nafarelin acetate for recurrent symptoms of endometriosis. DESIGN: Multicenter, open-label, nonrandomized clinical trial. SETTING: Eleven hospital-based and private practices. PATIENT(S): Thirty-six women with endometriosis symptoms recurring after 3 or 6 months of treatment with nafarelin. INTERVENTION(S): Nasal nafarelin 200 micrograms twice daily for 3 months. MAIN OUTCOME MEASURE(S): Assessments for dysmenorrhea, dyspareunia, pelvic pain, tenderness, and induration. Measurement of bone mineral density of the lumbar spine. RESULT(S): Improvements from admission to the end of retreatment were significant for dysmenorrhea, pelvic pain, tenderness, induration, and dyspareunia. Three months after retreatment ended, mean symptom scores for dysmenorrhea and pelvic tenderness, although worse than at the end of retreatment, were still significantly better than scores at admission. Mean bone mineral density 3 months after retreatment was 0.56% lower than before retreatment and 1.94% lower than before initial treatment. CONCLUSION(S): Three-month nafarelin retreatment for recurrent endometriosis symptoms was effective and safe.

Administration, Intranasal↗
PubMed1997

Clinicopathological features of bladder cancer associated with chronic exposure to arsenic.

A high incidence of bladder cancer has been documented in an area of chronic arsenic (As) exposure. This study investigates the characteristics of As-associated (n = 49) and other (n = 64) bladder cancers. A higher histological grading was observed for the As-exposed tumours (P = 0.04), but no other difference in pathobiological features or prognosis was found between the two groups.

Aged↗
PubMed1997

Processing of the gap junction protein connexin50 in the ocular lens is accomplished by calpain.

Gap junction channel forming connexins share a common membrane topology which has four transmembrane spanning segments with the amino- and carboxy termini both located on the cytoplasmic side. Both, mutation and truncation of the carboxyl tail of some connexins have been shown previously to have profound effects on channel function. Truncation of the carboxyl tail of connexin50 (Cx50) and connexin46 (Cx46) occurs naturally during the maturation of fiber cells in the mammalian lens. This system therefore offers the unique opportunity to study not only the cleavage process but also the functional role played by the cleaved domain, in a physiologically relevant context. As a first step, we now report on the cleavage of the 70 kDa ovine isoform of Cx50. The calcium-activated neutral protease calpain (EC 3.4.22.17) was identified as the enzyme which removed a 32 kDa carboxyl portion from the Cx50 molecule in mature lens fiber cells. The amino-terminal 38 kDa portion remained embedded in the plasma membrane and was isolated and visualized as channel structures. The amino-terminal sequence of the cleaved 32 kDa portion matched an interior portion of the published amino acid sequence of the ovine Cx50 isoform. Thus, two closely spaced calpain cleavage sites were identified in the Cx50 molecule which were located carboxy-terminal from the predicted exit of the fourth transmembrane spanning segment by 62 or 72 amino acid residues, respectively. These data provide the basic information required for the future construction of Cx50 mutants to explore the functional consequences of this cleavage.

Amino Acid Sequence↗
PubMed1996

Effect of strychnine on rat locus coeruleus neurones during sleep and wakefulness.

The noradrenergic neurones of the locus coeruleus (LC) discharge tonically during wakefulness, decrease their activity during slow wave sleep and are virtually quiescent during paradoxical sleep. We recently demonstrated an inhibitory glycinergic input to the locus coeruleus and proposed that this could be responsible for inhibition of the LC during paradoxical sleep. To test this proposal, we developed a method combining polygraphic recordings, iontophoresis and single-unit extracellular recordings in the unanaesthetized head-restrained rat. Iontophoretically applied strychnine, a specific glycine antagonist, induced strong excitation of LC neurones during paradoxical sleep, but also during slow wave sleep and wakefulness. These results suggest that glycine tonically inhibits noradrenergic LC neurones throughout the entire sleep-waking cycle and not only during paradoxical sleep.

Anesthesia↗
PubMed1996

Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat.

Much experimental and clinical data suggest that the pharmacological profile of modafinil, a newly discovered waking substance, differs from those of amphetamine and methylphenidate, two classical psychostimulants. The brain targets on which modafinil acts to induce wakefulness, however, remain unknown. A double-blind study using the protooncogene c-fos as experimental marker in the cat was, therefore, carried out to identify the potential target neurons of modafinil and compare them with those for amphetamine and methylphenidate. Cats were sacrificed after a single oral administration of amphetamine, methylphenidate, or modafinil at equivalent doses for wake induction (1, 2.5, or 5 mg/kg, respectively) and brain sections examined for Fos by immunocytochemistry. Administration of either amphetamine or methylphenidate evoked Fos-like immunoreactivity in a large number of neurons in the striatum and whole cortex, especially in the caudate nucleus and mediofrontal cortex, which are known to be dopaminergic targets. In contrast, administration of modafinil resulted in the labeling of few cells in these structures, but did induce marked Fos labeling in neurons of the anterior hypothalamic nucleus and adjacent areas. These results provide evidence for the potential brain targets of modafinil, which differ from those of amphetamine or methylphenidate, and suggest that modafinil induces wakefulness by mechanisms distinct from those of the two stimulants.

Amphetamine↗
PubMed1996

The caudo ventral pontine tegmentum is involved in the generation of high velocity eye saccades in bursts during paradoxical sleep in the cat.

Cat eye movements were recorded in the head restrained condition, with the technique of the scleral search coil in a magnetic field, and the maximum velocity/amplitude relationships were analyzed for saccades in the following conditions, (1) during waking (W); (2) during paradoxical sleep (PS); and (3) during W following carbachol microinjections in the medioventral part of the caudal pontine tegmentum. These findings indicate that (1) the neurophysiological mechanisms underlying carbachol induced events are similar to those acting during PS and that the caudal pontine tegmentum might be the generator of high velocity eye saccades in bursts accompanied by ponto geniculo occipital waves (PGOw) during PS, and (2) caudal pontine tegmentum neurons show 'state-dependent' responsiveness to cholinergic inputs, suggesting that a change in the synaptic inputs and/or the membrane properties of these neurons during PS may be responsible for the induction of saccadic eye movements in bursts and associated PGOw.

Animals↗
PubMed1996

Structure--activity relationships of 1-(2-Deoxy-2-fluoro-beta-L-arabinofuranosyl)pyrimidine nucleosides as anti-hepatitis B virus agents.

Since 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU) has been shown to be a potent anti-HBV agent in vitro, it was of interest to study the structure-activity relationships of related nucleosides. Thus, a series of 1-(2-deoxy-2-fluoro-beta-L-arabinofuranosyl)pyrimidine nucleosides have been synthesized and evaluated for antiviral activity against HBV in 2.2.15 cells. For this study, L-ribose was initially used as the starting material. Due to the commercial cost of L-ribose, we have developed an efficient procedure for the preparation of L-ribose derivative 6. Starting from L-xylose, 6 was obtained in an excellent total yield (70%) through the pyridinium dichromate oxidation of the 3-OH group followed by stereoselective reduction with NaBH4. It was further converted to the 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-alpha-L-arabinofuranose (10), which was then condensed with various 5-substituted pyrimidine bases to give the nucleosides. Among the compounds synthesized, the lead compound, L-FMAU (13), exhibited the most potent anti-HBV activity (EC50 0.1 microM). None of the other uracil derivatives showed significant anti-HBV activity up to 10 microM. Among the cytosine analogues, the cytosine (27) and 5-iodocytosine (35) derivatives showed moderately potent anti-HBV activity (EC50 1.4 and 5 microM, respectively). The cytotoxicity of these nucleoside analogues has also been assessed in 2.2.15 cells as well as CEM cells. None of these compounds displayed any toxicity up to 200 microM in 2.2.15 cells. Thus, compound 13 (L-FMAU), 27, and 35 showed a selectivity of over 2000, 140, and 40, respectively.

Antiviral Agents↗
PubMed1996

Histaminergic descending inputs to the mesopontine tegmentum and their role in the control of cortical activation and wakefulness in the cat.

We have demonstrated previously the importance of histaminergic neurons in arousal mechanisms. In addition to their ascending axons, these neurons also send heavy descending inputs to the mesopontine tegmentum (MPT), which plays a key role in cortical activation during wakefulness (W). This anatomical link suggests histaminergic control of the mechanisms of the MPT relevant to behavioral states. In this study, we sought to demonstrate, at the light microscopy level, hypothalamotegmental histaminergic pathways and their topographical interaction with MPT neurons in the cat and to explore further their involvement in sleep-wake control. Using immunohistochemistry of histamine (HA), either alone or together with that of choline-acetyltransferase or tyrosine hydroxylase, a large number of very fine, short and varicose HA-positive fibers and terminal-like dots were detected in the MPT, including the laterodorsal tegmental nucleus, locus coeruleus (LC), LC alpha, and peri-LC alpha. Furthermore, these fibers and terminal-like structures were found in close proximity to a great number of cholinergic or noradrenergic neurons. We also investigated the effects of microadministration of HA agonists and antagonist into the mediodorsal pontine tegmentum on the cortical electroencephalogram (EEG) power spectra and the sleep-wake cycle in freely moving cats. Microinjection of HA or 2-thiazolylethylamine (an H1-receptor agonist) caused a long-lasting suppression of cortical slow activity and an increase in quiet wakefulness (W). Paradoxical sleep, however, was less affected. The effects of HA were attenuated by systemic or in situ pretreatment with mepyramine (an H1-receptor antagonist), which when injected alone produced an increase in slow wave sleep. Microinjection of impromidine (an H2-receptor agonist) into the same area had no effect on either the cortical EEG or W. Because MPT ascending and presumed cholinergic neurons discharge tonically during cortical activation of W and because HA causes excitation of MPT cholinergic neurons via H1 receptors, we hypothesize that the histaminergic descending afferents in the MPT would promote cortical desynchronization and W, at least partially, via activation of H1 receptors situated on cholinergic neurons and that the interactions between histaminergic and cholinergic neurons constitute an important circuit in cortical activation during W.

Animals↗
PubMed1996

Segmentation of multispectral magnetic resonance image using penalized fuzzy competitive learning network.

Segmentation (tissue classification) of the medical images obtained from Magnetic resonance (MR) images is a primary step in most applications of computer vision to medical image analysis. This paper describes a penalized fuzzy competitive learning network designed to segment multispectral MR spin echo images. The proposed approach is a new unsupervised and winner-takes-all scheme based on a neural network using the penalized fuzzy clustering technique. Its implementation consists of the combination of a competitive learning network and penalized fuzzy clustering methods in order to make parallel implementation feasible. The penalized fuzzy competitive learning network could provide an acceptable result for medical image segmentation in parallel processing using the hardware implementation. The experimental results show that a promising solution can be obtained using the penalized fuzzy competitive learning neural network based on least squares criteria.

Adult↗
PubMed1996

Modulation of antitumor immunity of tumor-bearing mice with low-dose cyclophosphamide.

As a tumor progressively grows, the tumor-bearing host usually is under a tumor-mediated immune suppression status. Although surgical resection of the tumor may immediately eliminate most tumor-induced detrimental influences, perioperatively the antitumor immunity of the host remains temporarily suppressed. The major purpose of this study is to investigate the modulation effect of low-dose cyclophosphamide (CY) on the antitumor immunity of tumor-bearing mice (TBM). Using the C3H/He-MBT-2 murine bladder tumor model, we demonstrate that low-dose CY (100 mg/kg) intraperitoneal injection 2 days before tumor resection can significantly enhance the specific antitumor immunity of the TBM. It consequently suppresses the outgrowth of perioperative rechallenged tumor cells and improves the survival of the animals. Phenotypic analysis of cellular subset of spleen by flow cytometry revealed that low-dose CY, when given to both naive and tumor-bearing mice, causes significant reduction of both absolute number and percentage of cells with CD4-CD8- subset in the spleens of TBM. As a result of a parallel increase in the percentage of both CD4+CD8- and CD4-CD8+ subsets, the CD4+/CD8+ ratio remains unchanged. However, after short-term in vitro culture with IL-2 the percentage of the CD4-CD8- subset and CD4+/CD8+ ratio markedly decreased because of the relatively predominant proliferation of the CD4-CD8+ subset. Evidence from in vitro cytotoxicity assays on panel tumor cells and phenotypic analysis revealed that this enhancement of host antitumor immunity, following low-dose CY pretreatment, may be due to augmenting the activity of NK, LAK, and CD11b+ myeloid/macrophages in addition to cytotoxic T lymphocytes.

Animals↗
PubMed1996

The rabbit as an intracavernous injection study model.

We investigated the feasibility of using the rabbit as an animal model for intracavernous injection studies. The rabbit, having a penile structure rather similar to that of humans, offers the advantage of being a strain-specific, adequately sized, and easily controlled experimental animal. Using intracavernous injections of the two vasoactive drugs prostaglandin E1 (PGE1, 0.2-1.6 micrograms/kg) and papaverine (PAP, 0.25-1 mg/kg), which have been commonly used in the management of erectile dysfunction in man, increases intracavernous pressure (delta ICP) were induced. After intracavernous injection of PGE1, the maximal delta ICP ranged from 18 to 44 mmHg (mean 29.25 +/- 7.85 mmHg) with a duration of tumescence from 3.1 to 13.3 min (mean 8.61 +/- 3.71 min). Intracavernous injection of PAP also induced increases in ICP, with a maximal delta ICP ranging from 24 to 56 mmHg (mean 43.5 +/- 11.35 mmHg) and a duration of tumescence from 5.3 to 15 min (mean 10.25 +/- 3.39 min). The systemic blood pressures were unchanged after all intracavernous injections. In addition, administration of cAMP antagonist in combination with PGE1 inhibited the relaxing effects of PGE1 in a dose-dependent manner. Our results suggest that the effects of vasoactive drugs on the rabbit's corpus cavernosum are similar to those in humans; thus the rabbit model is a suitable alternative for further physiological and pharmacological studies of penile erection.

Alprostadil↗