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Biomedical subjects

S H Lin

Publications and source records attributed to S H Lin.

At least 73 records · Page 4Linked to original sources

Propranolol rapidly reverses paralysis, hypokalemia, and hypophosphatemia in thyrotoxic periodic paralysis.

Hypokalemia and hypophosphatemia are commonly encountered during paralysis in patients with thyrotoxic periodic paralysis (TPP) and may contribute to neuromuscular manifestations. Potassium and phosphate supplements have been recommended to hasten recovery and prevent cardiopulmonary complications. However, this recommendation has not yet proven efficacious. Hyperadrenergic activity has been implicated in the pathogenesis of TPP. We tested whether nonselective beta-blockers could terminate neuromuscular symptoms rapidly while reducing an intracellular shift of potassium and phosphate. We describe two patients who had an acute attack of TPP with characteristic hypokalemia and hypophosphatemia associated with low urinary potassium and phosphate excretion. After oral propranolol, 3 mg/kg, serum potassium and phosphate concentrations increased promptly in 2 hours in both patients, and there was complete amelioration of paralysis. No rebound hyperkalemia or hyperphosphatemia was detected. Given their efficacy in this pilot study, they should be considered as a first-line therapy for TPP.

Administration, Oral↗

Persistent hyperendemicity of hepatitis C virus infection in Taiwan: the important role of iatrogenic risk factors.

The purpose of this study was to investigate determinants of endemic hepatitis C virus (HCV) infection within communities in Taiwan. A two-phase study, including a seroprevalence survey and a prevalent case-control study at the first phase, which has been published previously, and a follow-up seroconversion determination and an incident case-control study during the second phase, was carried out to evaluate correlates of persistent endemic HCV infection. At the first phase, a total of 12,021 men and 1,819 women who were 30-64 years old and living in seven townships in Taiwan were tested for the seroprevalence of antibodies to HCV (anti-HCV). In addition, a prevalent case-control study involving 272 HCV-positive cases and 282 seronegative controls identified from the anti-HCV testing was conducted to investigate risk factors associated with HCV prevalence. During the second phase, a total of 2,728 men and 834 women who were seronegative at recruitment participated in the 1-year prospective study on anti-HCV seroconversion. Subsequently, an incident case-control study based on 39 seroconverters and 81 persistently seronegative controls were carried out to elucidate determinants of HCV seroconvertion. Antibodies to HCV were tested by the second-generation enzyme immunoassay. Information on risk factors of HCV infection was collected from subject interviews. The prevalence of anti-HCV consistently increased with age (range 2.9-5.4%), whereas no apparent age trend was observed for anti-HCV seroconversion rate (range 0.9-1.7%). A striking geographical variation in seroprevalence and seroconversion rates of anti-HCV was observed in the study townships. Furthermore, a significant geographical correlation between HCV seroprevalence and seroconversion rates was noted (r = 0.962, P = 0.001). From the results of both prevalent and incident case-control comparisons, medical injections were found to be the main mode to sustain the persistent endemic state of HCV infection within a community (odds ratios for prevalent and incident case-control studies were 2.5 (95% CI = 1.7-3.6) and 3.1 (95% CI = 1.4-7.1), respectively. The data indicate that the basis for HCV transmission has already been existed in study areas and the iatrogenic risk factor tended to be the major determinant for sustaining persistent endemicity within a community.

Adult↗

Preparation of Na,K-ATPase specifically modified on the anti-fluorescein antibody-inaccessible site by fluorescein 5'-isothiocyanate.

Specific labeling is required for energy transfer measurements and to avoid artifacts in the use of fluorophores as reporter groups. Therefore, a method for specific modification by one of the most popular reagents for P-type ATPases (fluorescein 5'-isothiocyanate) has been developed. Sulfhydryl reagents protected against modification of cysteine residues, and treatment with dithiothreitol eliminated a slow doubling of the fluorescence of conventionally modified Na,K-ATPase upon dilution that is attributed to disappearance of self-energy transfer. Removal of nonspecifically bound fluorescein was also confirmed by titration of the modified Na, K-ATPase with anti-fluorescein antibody and by time resolution of the fluorescence change when the modified enzyme was mixed with Na(+) in a stopped-flow instrument. The only fluorescence change when specifically modified Na,K-ATPase was mixed with Na(+) was the signal from fluorescein at the antibody-inaccessible, substrate-protectable site that reports the conformational change in unphosphorylated enzyme. The magnitude of the fluorescence change reporting the conformational change increased from between 8 and 12% to between 25 and 30% without affecting the kinetic constants estimated from titrations with Na(+) and K(+). The method should be generally applicable to the preparation of specifically labeled P-type pumps for use in kinetic and equilibrium titrations or energy transfer measurements.

Animals↗

Group I and group III metabotropic glutamate receptor subtypes provide enhanced neuroprotection.

Neuroprotection by the metabotropic glutamate receptor (mGluR) system has been linked to the modulation of both the free radical nitric oxide (NO) and programmed cell death (PCD). Because the cellular mechanisms that ultimately determine neuronal PCD rely upon the independent pathways of genomic DNA degradation, externalization of membrane phosphatidylserine (PS) residues, and the activation of associated cysteine proteases, we investigated the ability of the individual mGluR subtypes to modulate the distinct pathways of NO-induced PCD in primary rat hippocampal neurons. Membrane PS residue externalization occurred within the initial 3 hr after exposure to the NO donors (300 microM SNP or 300 microM NOC-9), preceded genomic DNA fragmentation, and was present in 80 +/- 2% of the neurons within a 24-hr period. NO exposure also led to the rapid induction of both caspase 1-like and caspase 3-like activities that were determined to be necessary, at least in part, for the generation of NO-induced genomic DNA degradation, but distinct from the detrimental effects of intracellular acidification. Yet, only caspase 1-like activity was necessary for the modulation of PS residue externalization. Activation of group I mGluR subtypes utilized an effective, "upstream" mechanism for the inhibition of cysteine protease activity that offered an enhanced level of neuroprotection through both the preservation of genomic DNA integrity and the maintenance of PS membrane asymmetry. Group II and Group III mGluR subtypes maintained DNA integrity and group III mGluR subtypes additionally prevented PS residue externalization through mechanisms that were targeted below the level of caspase activation. Our work elucidates the independent nature of the mGluR subtypes to not only provide discrete levels of protection against neuronal PCD, but also offer robust therapeutic strategies for neurodegenerative disease.

Animals↗

Dynamical principles in biological processes: a model of charge migration in proteins and DNA.

The generalized master equations (GMEs) that contain multiple time scales have been derived quantum mechanically. The GME method has then been applied to a model of charge migration in proteins that invokes the hole hopping between local amino acid sites driven by the torsional motions of the floppy backbones. This model is then applied to analyze the experimental results for sequence-dependent long-range hole transport in DNA reported by Meggers et al. [Meggers, E., Michel-Beyerle, M. E., & Giese, B. (1998) J. Am. Chem. Soc. 120, 12950-12955]. The model has also been applied to analyze the experimental results of femtosecond dynamics of DNA-mediated electron transfer reported by Zewail and co-workers [Wan, C., Fiebig, T., Kelley, S. O., Treadway, C. R., Barton, J. K. & Zewail, A. H. (1999) Proc. Natl. Acad. Sci. USA 96, 6014-6019]. The initial events in the dynamics of protein folding have begun to attract attention. The GME obtained in this paper will be applicable to this problem.

Base Sequence↗

Removal of heavy metals from aqueous solution by chelating resin in a multistage adsorption process.

Copper and zinc removal from aqueous solution by chelating resin was investigated theoretically and experimentally in the present study. A multistage process was proposed as an alternative for enhancement of the heavy removal of the single-stage process. Heavy metal mass balance equations with empirical Freundlich adsorption isotherm were developed to represent the multistage process and the theoretical model permits determination of the inter-stage heavy metal concentrations and the total amount of chelating resin required for achieving a desired level of heavy metal removal. Optimization of the linearized theoretical model shows that equal division of the total amount of chelating resin among all stages of the multistage process yields the best results in terms of saving of chelating resin for a given heavy metal removal or enhanced heavy metal removal for a given total amount of chelating resin. Experimental tests were also conducted to establish the equilibrium adsorption of heavy metal by the chelating resin and to empirically verify the advantages of the multistage adsorption process.

Adsorption↗

Charge conductivity in peptides: dynamic simulations of a bifunctional model supporting experimental data.

Our previous finding and the given mechanism of charge and electron transfer in polypeptides are here integrated in a bifunctional model involving electronic charge transfer coupled to special internal rotations. Present molecular dynamics simulations that describe these motions in the chain result in the mean first passage times for the hopping process of an individual step. This "rest and fire" mechanism is formulated in detail-i.e., individual amino acids are weakly coupled and must first undergo alignment to reach the special strong coupling. This bifunctional model contains the essential features demanded by our prior experiments. The molecular dynamics results yield a mean first passage time distribution peaked at about 140 fs, in close agreement with our direct femtosecond measurements. In logic gate language this is a strongly conducting ON state resulting from small firing energies, the system otherwise being a quiescent OFF state. The observed time scale of about 200 fs provides confirmation of our simulations of transport, a model of extreme transduction efficiency. It explains the high efficiency of charge transport observed in polypeptides. We contend that the moderate speed of weak coupling is required in our model by the bifunctionality of peptides. This bifunctional mechanism agrees with our data and contains valuable features for a general model of long-range conductivity, final reactivity, and binding at a long distance.

Computer Simulation↗

Insulin sensitivity in normotensive offspring of hypertensive parents.

OBJECTIVES: To investigate the insulin sensitivity in normotensive offspring of hypertensive parents. SUBJECTS: Fifteen young normotensive offspring of hypertensive parents were paired with 15 controls matched for age, sex and body mass index. METHODS: The insulin sensitivity was investigated by 75 g oral glucose tolerance test (OGTT) and modified insulin suppression test. A high-fat mixed meal was administered to observe the changes of TG levels. RESULTS: The plasma glucose and serum insulin responses to oral glucose challenge were comparable between both groups. High-fat mixed meal made no difference in the plasma glucose, serum triglyceride or insulin between the 2 groups. With the modified insulin suppression test, the steady-state plasma glucose levels (SSPG) were higher in the offspring of parents with essential hypertension (138+/-43 mg/dl) than in the control group (95+/-26 mg/dl). The diastolic blood pressure and heart rate of the offspring of hypertensive parents are also higher than the control group. CONCLUSIONS: Insulin resistance exists in young normotensive offspring of hypertensive parents, and the impairment of insulin-mediated glucose uptake in these subjects develop before any alteration of fasting and postprandial triglyceride.

Adult↗

Prevention of nitric oxide-induced neuronal injury through the modulation of independent pathways of programmed cell death.

Neuronal injury may be dependent upon the generation of the free radical nitric oxide (NO) and the subsequent induction of programmed cell death (PCD). Although the nature of this injury may be both preventable and reversible, the underlying mechanisms that mediate PCD are not well understood. Using the agent nicotinamide as an investigative tool in primary rat hippocampal neurons, the authors examined the ability to modulate two independent components of PCD, namely the degradation of genomic DNA and the early exposure of membrane phosphatidylserine (PS) residues. Neuronal injury was determined through trypan blue dye exclusion, DNA fragmentation, externalization of membrane PS residues, cysteine protease activation, and the measurement of intracellular pH (pHi). Exposure to the NO donors SIN-1 and NOC-9 (300 micromol/L) alone rapidly increased genomic DNA fragmentation from 20 +/- 4% to 71 +/- 5% and membrane PS exposure from 14 +/- 3% to 76 +/- 9% over a 24-hour period. Administration of a neuroprotective concentration of nicotinamide (12.5 mmol/L) consistently maintained DNA integrity and prevented the progression of membrane PS exposure. Posttreatment paradigms with nicotinamide at 2, 4, and 6 hours after NO exposure further demonstrated the ability of this agent to prevent and reverse neuronal PCD. Although not dependent upon pHi, neuroprotection by nicotinamide was linked to the modulation of two independent components of neuronal PCD through the regulation of caspase 1 and caspase 3-like activities and the DNA repair enzyme poly(ADP-ribose) polymerase. The current work lays the foundation for the development of therapeutic strategies that may not only prevent the course of PCD, but may also offer the ability for the repair of neurons that have been identified through the loss of membrane asymmetry for subsequent destruction.

Animals↗

Molecular cloning and characterization of a second human cysteinyl leukotriene receptor: discovery of a subtype selective agonist.

The cysteinyl leukotrienes (CysLTs) are potent biological mediators in the pathophysiology of inflammatory diseases, in particular of airway obstruction in asthma. Pharmacological studies have suggested the existence of at least two types of CysLT receptors, designated CysLT(1) and CysLT(2). The CysLT(1) receptor has been cloned recently. Here we report the molecular cloning, expression, localization, and functional characterization of a human G protein-coupled receptor that has the expected characteristics of a CysLT(2) receptor. This new receptor is selectively activated by nanomolar concentrations of CysLTs with a rank order potency of LTC(4) = LTD(4) >> LTE(4). The leukotriene analog BAY u9773, reported to be a dual CysLT(1)/CysLT(2) antagonist, was found to be an antagonist at CysLT(1) sites but acted as a partial agonist at this new receptor. The structurally different CysLT(1) receptor-selective antagonists zafirlukast, montelukast, and MK-571 did not inhibit the agonist-mediated calcium mobilization of CysLT(2) receptors at physiological concentrations. Localization studies indicate highest expression of CysLT(2) receptors in adrenal glands, heart, and placenta; moderate levels in spleen, peripheral blood leukocytes, and lymph nodes; and low levels in the central nervous system and pituitary. The human CysLT(2) receptor gene is located on chromosome 13q14.12-21.1. The new receptor exhibits all characteristics of the thus far poorly defined CysLT(2) receptor. Moreover, we have identified BAY u9773 as a CysLT(2) selective agonist, which could prove to be of immediate use in understanding the functional roles of the CysLT(2) receptor.

Amino Acid Sequence↗

Childhood trauma and dissociative symptoms in panic disorder.

OBJECTIVE: Childhood trauma has been associated with increased risk for both panic disorder and dissociative symptoms in adulthood. The authors hypothesized that among individuals with a primary diagnosis of panic disorder, those experiencing depersonalization/derealization during panic attacks would be more likely to have a history of childhood trauma. METHOD: Rates of traumatic events were compared between panic disorder patients with (N=34) and without (N=40) prominent depersonalization/derealization during panic attacks. Symptom severity in the two groups was also examined. RESULTS: Contrary to the authors' hypothesis, no evidence was found that depersonalization/derealization during panic attacks was associated with childhood trauma. Minimal differences in severity of illness were found between patients with dissociative symptoms and those without such symptoms. CONCLUSIONS: This finding is consistent with a multifactorial model of dissociation. Factors other than childhood trauma and general psychopathology may underlie vulnerability to dissociative symptoms in panic disorder.

Adolescent↗

Low dopamine D(2) receptor binding potential in social phobia.

OBJECTIVE: This study compared dopamine D(2) receptor binding potential in patients with social phobia and healthy comparison subjects. METHOD: Dopamine D(2) receptor binding potential was assessed in 10 unmedicated subjects with generalized social phobia and no significant lifetime psychiatric comorbidity and 10 healthy comparison subjects matched for age and sex. Binding potential was measured in the striatum by using single photon emission computerized tomography and constant infusion of the D(2) receptor radiotracer [(123)I]iodobenzamide ([(123)I]IBZM). RESULTS: Mean D(2) receptor binding potential was significantly lower in the subjects with social phobia than in the comparison subjects. Within the social phobia group, there was a nonsignificant correlation of binding potential with the Liebowitz Social Anxiety Scale score. CONCLUSIONS: Generalized social phobia may be associated with low binding of [(123)I]IBZM to D(2) receptors in the striatum.

Adult↗

C-CAM1, a candidate tumor suppressor gene, is abnormally expressed in primary lung cancers.

Previous studies have shown that the expression of the cell-cell adhesion molecule (C-CAM1), located at chromosome 19, is down-regulated in several types of human cancers, including prostate and breast cancers. Two major isoforms of C-CAM1, the long or L-form C-CAM1 and the short or S-form C-CAM1, are derived from the C-CAM1 gene through alternative splicing. Tumor cells transfected with L-form C-CAM1, which contains a cytoplasmic domain, display significantly lower growth rates and less tumorigenicity in both in vitro and in vivo models compared with untransfected tumor cells, suggesting that L-form C-CAM1 may be a tumor suppressor. The transfection of the cytoplasmic domain of L-form C-CAM1 could also cause suppression of tumor growth, further supporting the role of L-form C-CAM1 in tumorigenesis. In contrast to reports of most of the tumor types tested, Ohwada et al. (Am. J. Respir. Cell Mol. Biol., 11: 214-220, 1994) reported that C-CAM1 was not down-regulated or even up-regulated in lung cancer. Because the cytoplasmic domain of L-form C-CAM1 is critical for the tumor suppressor function of C-CAM1, we hypothesized that switching of the isoform rather than down- regulation of C-CAM1 gene expression occurs during lung tumorigenesis. To test this hypothesis, we analyzed pairs of tumor tissue and corresponding normal-appearing lung tissue from 51 patients with non-small cell lung cancer (NSCLC) and 43 cell lines to determine expression profiles of L-form C-CAM1 and S-form C-CAM1 using reverse transcription-PCR. We found that L-form C-CAM1 was the predominant form (75%; 38 of 51) in normal-appearing lung tissue, whereas most (84%; 43 of 51) of the primary NSCLC tissue samples expressed predominantly S-form C-CAM1 (P < 0.0001). Similarly, 19 (79%) of the 24 NSCLC cell lines and 17 (85%) of the 20 small cell lung cancer cell lines expressed predominantly S-form C-CAM1. The frequent alteration of the C-CAM1 expression pattern suggests that C-CAM1 has an important role in lung tumorigenesis.

Adenosine Triphosphatases↗

Effect of oral clonidine premedication on perioperative hemodynamic response and postoperative analgesic requirement for patients undergoing laparoscopic cholecystectomy.

BACKGROUND: To investigate the clinical efficacy of oral clonidine premedication in anesthesia and analgesia in patients undergoing laparoscopic cholecystectomy (LC). METHODS: One hundred and ten patients, scheduled for elective laparoscopic cholecystectomy, were recruited for the prospective, randomized, single-blind, comparative study. They were randomly allotted to either of the placebo or clonidine group. Patients of the placebo group (n = 65) were premedicated with oral antacid (alugel hydroxide 300 mg), while those in the clonidine group (n = 45) were premedicated with oral clonidine 150 micrograms prior to anesthesia. The premedication was given 60 to 90 min before the anticipated time of induction of anesthesia. Normocapnia was maintained throughout the perioperative period. Mass spectrometer was used to assess the inspired and expiratory concentrations of isoflurane, the anesthetic used for maintenance of anesthesia. Postoperative pain intensity, sedation scores, adverse events, time to the first dose of postoperative analgesic and cumulative analgesic requirement in 24 hours were recorded. Data were expressed as mean +/- SD. RESULTS: Patients in the clonidine group displayed greater hemodynamic stability perioperatively and the isoflurane requirement was also reduced (30% less). The postoperative analgesic requirement was less (1.5 +/- 1.3 vs. 2.2 +/- 1.3 dose, P < 0.05) and the time for the first dose of analgesic was prolonged (411 +/- 565 vs. 264 +/- 441 min) in comparison with the placebo group but no statistic difference was found. CONCLUSIONS: Oral clonidine premedication helped to provide perioperative hemodynamic stability, spared the use of isoflurane and reduced the requirement of postoperative analgesia so as to smoother the way to recovery in patients undergoing LC.

Administration, Oral↗

Coronary artery bypass grafting on the beating heart using the octopus method--a case report.

A 74-year-old male was admitted due to chest tightness for one month. He had received percutaneous transilluminal coronary angioplasty (PTCA) because of single-vessel disease one year ago. Cardiac catheterization examination carried out during this admission revealed 90% stenosis of the left anterior descending coronary artery (LAD) and circumflex branch (CX). Because another attempt of PTCA was considered not optimal, the patient was advised to undergo surgical grafting to which he consented. After expediently balancing the merits and demerits of every practicable surgical procedure--the essential determinant in selection of which was that the patient's condition and criteria of indication of that procedure were in perfect harmony--we decided to carry out minimally invasive direct coronary artery bypass (MIDCAB) with the application of Octopus tissue stabilizer. We report the surgical course and anesthetic management of the patient and discourse some detail in MIDCAB.

Aged↗

Adsorption of BTEX from aqueous solution by macroreticular resins.

Theoretical and experimental investigations were conducted on the adsorption of benzene, toluene, ethylbenzene and xylene (BTEX) by macroreticular resins. A mass transfer model based on the squared-driving force principle is presented for describing the BTEX transfer between the aqueous and solid phases. Also proposed is a theoretical model for describing the BTEX breakthrough curves of the adsorption column. While the mass transfer model involves only an overall mass transfer coefficient, the column adsorption model has two model parameters. Those parameters are conveniently estimated using the observed mass transfer and breakthrough data. The predictions using the proposed models were found to compare well with the experimental data of batch and column BTEX adsorption tests.

Adsorption↗