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Biomedical subjects

X Lin

Publications and source records attributed to X Lin.

At least 37 records · Page 2Linked to original sources
PubMed2005

Efficiency and efficacy of multi-channel gastric electrical stimulation.

Gastric electrical stimulation (GES) using single channel has been under investigation for its therapeutic potential for gastroparesis. The aim of this study was to study the efficacy and efficiency of multi-channel GES in accelerating gastric emptying in dogs. The study was performed in eight dogs, and gastric emptying of liquid was assessed in three randomized sessions of control, one-channel GES and four-channel GES. It was found that (i) GES of both one-channel and four-channel was able to completely entrain the slow waves in the entire stomach. However, the stimulation energy required by four-channel GES was only 1% of that required by one-channel GES. (ii) Four-channel, but not one-channel, GES significantly and substantially accelerated gastric emptying. An increase of 121.0 and 93.9% was noted with four-channel GES at 30 and 60 min after the meal, respectively. It was concluded that four-channel GES is substantially more efficient and effective than conventional single-channel GES in improving gastric emptying. It is worthy to explore its therapeutic potential for gastroparesis in clinical settings.

Animals↗
PubMed2005

Influence of hydroxyethyl starch on lipopolysaccharide-induced tissue nuclear factor kappa B activation and systemic TNF-alpha expression.

BACKGROUND: Several studies have shown beneficial effects of hydroxyethyl starch (HES) on organ damage in the treatment of severe inflammatory situations, but the mechanisms remain unclear. Nuclear factor-kappa B (NF-kappaB) activation is known to contribute to many aspects of inflammatory injury and organ dysfunction in critical illness, and tumor necrosis factor-alpha (TNF-alpha) is considered the most important pro-inflammatory cytokine. The present study was undertaken to test whether HES (200/0.5) has some effects on tissue NF-kappaB activity and systemic TNF-alpha expression induced by lipopolysaccharide in order to define a possible mechanism of the beneficial effects of HES. METHODS: Male Wistar rats were randomly divided into seven groups treated with saline, lipopolysaccharide (LPS, 6 mg/kg), LPS plus HES (3.75, 7.5, 15, 30 ml/kg), or HES (30 ml/kg) alone. Two hours after LPS challenge, NF-kappaB activation in the lungs, hearts, livers, and kidneys were examined with an electrophoretic mobility shift assay. Four hours after LPS challenge, plasma TNF-alpha concentrations were measured using an enzyme-linked immunosorbance assay. RESULTS: 3.75 and 7.5 ml/kg HES suppressed LPS-induced NF-kappaB activation in the four tissues and decreased plasma TNF-alpha elevation. The effects of 15 ml/kg HES was only significant in inhibiting NF-kappaB activity in the lung and liver. No effect of 30 ml/kg HES was revealed in all the cases. CONCLUSION: Lower doses of HES may inhibit tissue NF-kappaB activation and systemic TNF-alpha elevation after LPS challenge, which might be helpful during sepsis.

Animals↗
PubMed2005

MRI results from the European Study on Intravenous Immunoglobulin in Secondary Progressive Multiple Sclerosis (ESIMS).

BACKGROUND: Monthly application of high-dose intravenous immunoglobulin (IVIG) to patients with secondary progressive multiple sclerosis (MS) showed no clinical benefit in the European Study on Immunoglobulin in MS (ESIMS). Magnetic resonance imaging (MRI) results may provide insights into the morphologic consequences of such treatment. METHODS: A total of 318 patients (mean age 44 +/- 7 years) were enrolled in 31 European and Canadian centres and treated monthly with 1 g/kg body weight of IVIG or equivalent amounts of albumin 0.1% for 27 months. MRI was performed at baseline and after 12 and 24 months and comprised of conventional dual-echo T2-weighted and T1-weighted scans before and after application of 0.1 mmol/kg Gd-DTPA. RESULTS: Similar to clinical variables, MRI measures at baseline were well comparable between treatment groups except for a somewhat lower mean number of contrast-enhancing lesions and number of active scans in IVIG-treated patients. Over the trial period there was almost no change of the T2-lesion load and the 'black hole' volume in both treatment groups and the cumulative number of contrast-enhancing lesions were similar. There was only a trend for fewer new or enlarged T2-lesions in IVIG patients, which disappeared after correction for the imbalance in the number of contrast-enhancing lesions at baseline. Brain volume in terms of a partial cerebral fraction decreased significantly less with IVIG than placebo treatment (final visit: -0.62 -/+ 0.88% versus -0.88 +/- 0.91%; P=0.009). This difference remained statistically significant with correction for active lesions at baseline (P=0.02) and was seen primarily in male patients and those with an Expanded Disability Status Scale score > or = 6 and no relapses in the two years before the study. CONCLUSION: The absence of significant differences in conventional MRI measures between both treatment groups parallels the negative clinical results of ESIMS. The causes for and possible long-term clinical effects of a lower rate of brain volume loss in IVIG patients should be explored further.

Adult↗
PubMed2004

Halogen-substituted thiophenol molecules on Cu(111).

Para-halosubstituted thiophenols (X-TPs, where X is Br, Cl, or F) form ordered islands and monolayers on Cu(111) at temperatures as low as 81 K. At incomplete coverages, all X-TPs adsorb with the dehydrogenated thiol group attached to the substrate and the substituted ring inclined toward the surface, as verified experimentally and theoretically. The structure of ordered islands has a pronounced dependence on the nature of the halogen substituent: while unsubstituted TP and pentafluoro-TP molecules do not self-assemble into extended ordered patterns at 81 K, X-TP molecules form a range of different structures which depend both on the size and electronegativity of the substituent, as well as on the coverage.

Adsorption↗
PubMed2004

In vivo MRS measurement of liver lipid levels in mice.

A magnetic resonance spectroscopy (MRS) procedure for in vivo measurement of lipid levels in mouse liver is described and validated. The method uses respiratory-gated, localized spectroscopy to collect proton spectra from voxels within the mouse liver. Bayesian probability theory analysis of these spectra allows the relative intensities of the lipid and water resonances within the liver to be accurately measured. All spectral data were corrected for measured spin-spin relaxation. A total of 48 mice were used in this study, including wild-type mice and two different transgenic mouse strains. Different groups of these mice were fed high-fat or low-fat diets or liquid diets with and without the addition of alcohol. Proton spectra were collected at baseline and, subsequently, every 4 weeks for up to 16 weeks. Immediately after the last MRS measurement, mice were killed and their livers analyzed for triglyceride level by conventional wet-chemistry methods. The excellent correlation between in vivo MRS and ex vivo wet-chemistry determinations of liver lipids validates the MRS method. These results clearly demonstrate that in vivo MRS will be an extremely valuable technique for longitudinal studies aimed at providing important insights into the genetic, environmental, and dietary factors affecting fat deposition and accumulation within the mouse liver.

Animals↗
PubMed2004

The internal comparator method.

An internal comparator method is proposed which offers reliable instrumental neutron activation analysis (INAA) results for samples with an irregular geometry and/or measured at the closest position to the Ge detector. Because the selected internal comparator in the sample analyzed will receive exactly the same thermal neutron flux as the other components, this method can be applied to the INAA of materials suffering from thermal neutron self-shielding. To apply the internal comparator method, the k(0)-method must be installed and the analytes, including the internal comparator, should be homogeneously distributed in the test portion.

Journal Article↗
PubMed2004

Scanning for MODY5 gene mutations in Chinese early onset or multiple affected diabetes pedigrees.

Mutation of HNF-1beta gene has been reported in early onset diabetes or MODY families and this gene has been defined as MODY5 gene. The aim of our study was to examine whether HNF-1beta mutation contribute to early onset or multiple affected diabetes pedigrees in Chinese. Molecular scanning of HNF-1beta gene promoter region, nine exons and flanking introns was performed in 154 unrelated probands from early onset and multiple affected diabetes Chinese pedigrees. The family members of probands with mutations or variants and 58 nondiabetics were also examined. Clinical examinations of renal morphology, renal function and beta-cell function were performed in the HNF-1beta gene mutation carriers and family members. Mutation of HNF-1beta gene causing the substitution S36F was found in two subjects of an early onset diabetic family. One carrier has early onset diabetes, renal function impairment and renal cyst, while the other has impaired glucose tolerance only. This is the first case of MODY5 gene mutation diabetes found in the Chinese. Three HNF-1beta variants were identified and no significant differences in allele frequencies for these variants were detected between the nondiabetic and diabetic groups. Nucleotide 66 of intron 8 of HNF-1beta gene was G in the Chinese population rather than A as noted in the GenBank sequence. These results suggest that HNF-1beta gene mutations may be associated with nondiabetic renal dysfunction and diabetes in Chinese, but they are responsible for only a small percentage of early onset or multiple affected diabetes pedigrees including MODY.

Adenine↗
PubMed2004

Improved targeting of platinum chemotherapeutics. the antitumour activity of the HPMA copolymer platinum agent AP5280 in murine tumour models.

AP5280 is a novel N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound platinum (Pt) therapeutic designed to increase the therapeutic index relative to conventional, small-molecule platinum agents. The platinum-polymer construct accumulates in solid tumours on the basis of increased capillary permeability. The bound platinum moiety is present as an N,O-Pt chelate at the distal end of a tetrapeptide linker, glycine-phenylalanine-leucine-glycine, and the weight-average molecular weight (Mw) of the construct is 22 kDa. The antitumour activity and toxicity of AP5280 were assessed in the syngeneic murine B16F10 and Lewis lung tumour models, and in the human ovarian carcinoma 2008 and head and neck squamous carcinoma UMSCC10b xenograft models. The maximum tolerated dose (MTD) of AP5280 was 6-fold greater than that of carboplatin (CBDCA) in vivo. AP5280 was active in all four tumour models, and it displayed a higher therapeutic index than CBDCA in each of these tumour models. The antitumour effect of AP5280 given at 16% of its MTD was equivalent to that produced by a MTD of CBDCA. Thus, consistent with the design goal for this drug, and despite being less potent than CBDCA, AP5280 produced less systemic toxicity relative to its antitumour activity and thus has a greater therapeutic index. On the basis of the improved therapeutic index evidenced in these models, AP5280 has been advanced into clinical trials.

Acrylamides↗
PubMed2004

Group I metabotropic glutamate receptors in spiral ganglion neurons contribute to excitatory neurotransmissions in the cochlea.

Evidence has accumulated over the years supporting glutamate as the primary neurotransmitter used by hair cells in afferent cochlear neurotransmission. Besides acting on ionotropic glutamate receptors, glutamate also activates second messenger systems via G-protein-coupled metabotropic glutamate receptors (mGluRs) to modulate neuronal excitability. However, it is unclear whether mGluRs participate in cochlear neurotransmission. We present evidence directly supporting a functional role for group I metabotropic glutamate receptors (mGluRIs) in spiral ganglion (SG) neurons. The presence of mGluRI and downstream G-protein subunits was demonstrated by molecular biology and immunolabeling methods. Direct activation of mGluRIs in cultured SG neurons resulted in transient increases of intracellular Ca(++) concentration and transient inward currents that gave rise to firings of multiple action potentials. These responses showed mGluRI pharmacological specificity and quickly desensitized. We next examined changes in cochlear function after noise exposure as a result of pharmacologically manipulating cochlear glutamate neurotransmission. These in vivo tests showed that blocking non-N-methyl-D-aspartic acid glutamate receptors was sufficient to eliminate compound action potentials of the auditory nerve, and pharmacologically inhibiting mGluRIs in the cochlea did not significantly affect the hearing threshold. In contrast, blocking mGluRIs lowered the amplitude of compound action potentials at louder sound levels and reduced the noise-induced temporary threshold shift. Our results suggest that although mGluRIs did not initiate fast excitatory cochlear neurotransmission, their activation contributed to the growth of excitatory responses of the cochlea. As a result, the cochlea was more resistant to noise-induced temporary hearing losses without the activation of mGluRIs in SG neurons.

Action Potentials↗
PubMed2004

Refining in vitro digestibility assays: fractionation of digestible and indigestible peptides.

Typically, in vitro methods used for estimating the amount of ileal digestible AA do not exhaustively digest samples, and arbitrary methods for separating digestible from indigestible protein are used. This may lead to over- or underestimation of digestibility coefficients. A method that exhaustively digests proteins using pepsin and pancreatin was developed, and the first objective of this research was to confirm that exhaustive digestion was indeed appropriate and to determine the fractionation method for separating digestible from indigestible proteins. For this, three homoarginine-labeled animal proteins were prepared. Samples were subsequently digested in vivo and in vitro to determine which fraction should be considered indigestible, and in vitro followed by in vivo to determine whether the extent of digestion in vivo was improved by predigestion. In vivo, soluble but unabsorbed peptides were smaller than 1 kDa, suggesting that the size of soluble peptides is not what prevents their absorption. Thus, all in vitro-soluble proteins should be considered digestible. In vitro, 88 +/- 3% of the soluble peptides were smaller than 1 kDa, with the remainder between 1 and 5 kDa, suggesting that in vitro digestion is less complete. Predigested samples were digested in vivo to the same size distribution as the nonpredigested samples. The second objective was to test whether in vitro digestibility assays based on these principles equaled in vivo digestibility. For this, digestibility data for 25 animal proteins were compared. Results showed a lack of correlation between lysine digestibility coefficients; however, across samples, the extent of digestion did not differ for lysine (P = 0.71), threonine (P = 0.26), methionine (P = 0.18), or valine (P = 0.66), whereas in vitro digestibility coefficients were lower for (the less water-soluble) histidine (P = 0.05), isoleucine (P < 0.01), leucine (P < 0.01), and phenylalanine (P = 0.05). In conclusion, in vitro digestibility assays should exhaustively digest proteins to mimic in vivo digestibility. All in vitro-soluble peptides could be considered digestible, because in vivo, no large soluble peptides were observed whose size prevented them from being absorbed. However, an in vitro assay based on these principles lacked precision for highly water-soluble AA, and underestimated digestibility for other AA. Better solubilization of the digesta and more replicates may improve the in vitro assay further.

Amino Acids↗
PubMed2003

The relationship of brain and cervical cord volume to disability in clinical subtypes of multiple sclerosis: a three-dimensional MRI study.

OBJECTIVES: Brain and cervical cord volume is a potentially valuable index marker of irreversible pathological processes in multiple sclerosis (MS). Volume in both brain and cervical cord regions in the same patients has only been investigated in a small number of subjects. We aimed at measuring volume in different parts of the central nervous system, and its relationship with clinical measures, in relapsing-remitting (RR) and secondary progressive (SP) MS patients. MATERIAL AND METHODS: Conventional dual echo and three-dimensional (3-D) magnetization prepared rapid acquisition gradient echo imaging was performed on 97 (49 RR and 48 SP) MS patients, and on 31 age- and gender-matched healthy controls. The volumes of the supratentorial brain, lateral ventricles, brainstem, cerebellum and upper cervical cord (UCC) were determined on 3-D magnetic resonance imaging. RESULTS: RR MS patients had significantly smaller supratentorial brain (P=0.002) and larger lateral ventricles (P=0.047) compared with controls, but no differences were found for cerebellum, brainstem and UCC volumes. Significantly smaller supratentorial brain (P<0.0001), cerebellum (P=0.007), brainstem (P=0.0004) and UCC (P<0.0001) volumes, and larger lateral ventricles (P<0.0001) were observed in SP MS patients than in controls. In RR MS, T2-lesion volume correlated with supratentorial (r=-0.46, P=0.0009), lateral ventricular (r=0.65, P<0.0001), cerebellar (r=-0.42, P=0.003) and brainstem (r=-0.35, P=0.01) volumes, but not with UCC volume (r=-0.18, P=0.22). In SP MS, apart from lateral ventricular volume (r=0.52, P=0.0002), none of the estimated structural volumes correlated with T2-lesion volume. The UCC volume correlated with brainstem volume in both RR MS (r=0.35, P=0.016) and SP MS (r=0.38, P=0.007). Multiple regression analysis showed that supratentorial brain volume in RR group, and UCC volume in SP group, were single significant contributors (P=0.01 and 0.04, respectively) to the Expanded Disability Status Scale of all factors entered into the regression model. CONCLUSION: Atrophy is confined to the supratentorial compartment early in the disease course corresponding to the RR stage, but becomes more pronounced in the brain and cervical spinal cord in the SP phase. The estimate of cervical cord volume for SP MS is relevant to functional disability and may be helpful in monitoring MS evolution in the progressive form of disease.

Adult↗
PubMed2003

T-bet expression is upregulated in active Behçet's disease.

AIM: To investigate T-bet mRNA and protein expression on peripheral blood mononuclear cells (PBMC) in patients with Behçet's disease with active uveitis. METHODS: Blood samples were taken from 24 patients with Behçet's disease who had active uveitis and 16 healthy individuals. PBMC were subjected to analysis of T-bet mRNA and protein expression using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot, respectively. The products from PCR were sequenced. In order to determine the influence of activation on T-bet expression, the phytohaemagglutinin (PHA) stimulated PBMC from each sample were also evaluated for expression of T-bet mRNA and protein. RESULTS: A significantly increased T-bet mRNA accumulation was detected in the samples from patients with active Behçet's disease compared with that in controls. A 62 kDa band was detectable in patients with active Behçet's disease, but not in controls. No difference was found between patients with Behçet's disease who had active uveitis and normal controls concerning the expression of either T-bet mRNA or its protein after stimulation with PHA for 72 hours. CONCLUSION: Behçet's disease is associated with an upregulation of T-bet expression, which supports a role for the Th1 subset of T cells in the pathogenesis of this disease.

Adult↗
PubMed2003

Spinal cord atrophy and disability in multiple sclerosis over four years: application of a reproducible automated technique in monitoring disease progression in a cohort of the interferon beta-1a (Rebif) treatment trial.

BACKGROUND: Pathology in the cervical spinal cord is considered an important cause of disability in multiple sclerosis. However, the majority of serial studies have failed to find a correlation between spinal cord atrophy and disability. OBJECTIVES: To use a highly reproducible and accurate method to quantify spinal cord area change on three dimensional magnetic resonance imaging and relate this to disability change in patients with multiple sclerosis. METHODS: 38 patients with multiple sclerosis (20 with the relapsing-remitting (RRMS) form and 18 with the secondary progressive (SPMS) form) were imaged at baseline and at months 6, 12, 18, and 48 during two treatment trials of the high dose subcutaneous thrice weekly interferon beta-1a (IFNbeta, Rebif). Thirty one healthy subjects were also imaged at baseline. Upper cervical cord area (UCCA) was measured using Sobel edge detection. RESULTS: The intraobserver coefficient of variation of the method was 0.42%. A significant reduction in UCCA was detected at month 6 in the placebo group (p = 0.04) and at month 12 for INFbeta (p = 0.03). The mean reduction of UCCA at month 48 was 5.7% for patients initially on placebo who received treatment at 24 months (RRMS) or at 36 months (SPMS), and 4.5% for those on IFNbeta throughout the study (p = 0.35). The change in UCCA was significantly correlated with change in the expanded disability status scale at month 12 (r = 0.4, p = 0.016), month 18 (r = 0.32, p = 0.05), and month 48 (r = 0.4, p = 0.016) in the total cohort. CONCLUSIONS: Despite the small number of patients studied and the possible confounding effects of interferon treatment, this study showed that edge detection is reproducible and sensitive to changes in spinal cord area, and that this change is related to changes in clinical disability. This suggests a role for measurement of spinal cord atrophy in monitoring disease progression and possible treatment effects in clinical trails.

Adult↗
PubMed2003

Exploiting new potential targets for anti-hepatitis B virus drugs.

Based on the recent studies of HBV strains with different replication efficiency, several new potential targets for anti-HBV replication have been presented. These include the viral and cellular regulatory factors associated with HBV replication and the process for encapsidation of viral genome and budding into endoplasmic reticulum (ER). A putative regulatory domain has been reported at the carboxyl-end of reverse transcriptase (RT) and when serine is substituted for proline at residue 652 of RT, replication efficiency of HBV is decreased. Substitution of proline for threonine at the 2798 nucleotide of the terminal protein (TP) gene, renders the mutant completely replication deficient. Expression of TP blocks the interferon (IFN) pathway and inhibits the responsive state of cells to interferons ( IFN) alpha and gamma. Interference of HBV capsid assembly drastically affects the encapsidation of viral genome, a crucial process for reverse transcription and viral DNA synthesis. Small molecules (bis-ANS) have been reported to act as a "wedge" to misdirect the polymerization of capsid, resulting in inhibition of virus replication. Another new group of compounds (HAP) has been shown to inhibit virus replication and also inhibit the assembly of viral capsid (core particle). Finally the capsids containing HBV genome are enveloped by budding into endoplasmic reticulum and release from virus infected cells, and this morphogenesis and secretion of HBV is dependent on glucosidases in the ER of host cells. Competitive inhibition of these glucosidases has been suggested as strategy against HBV replication.

Antiviral Agents↗
PubMed2002

Natural history of bone loss over 6 years among premenopausal and early postmenopausal women.

The aims of this prospective cohort study were to determine rates of premenopausal and early postmenopausal bone loss, age at onset of bone loss, and whether rates of bone loss depend on baseline bone mineral density (BMD). The cohort of 614 women aged 24-44 years at baseline from the longitudinal Michigan Bone Health Study was followed for 6 years beginning in 1992-1993. Up to five BMD measurements of the lumbar spine (L(2-4)) and the femoral neck were obtained through 1998-1999 by using dual x-ray absorptiometry and were standardized (as z scores) relative to a young adult, female BMD distribution. Regression models were used to estimate rates of BMD change and to examine BMD as a function of age. At the lumbar spine, the rate of BMD change for premenopausal women varied with time. At the femoral neck, the rate of change was -1.6% (95% confidence interval: -0.9%, -2.3%) of a z score annually (annual loss of 0.3% of baseline BMD (g/cm(2))). Evidence for age at onset of bone loss at the lumbar spine was inconclusive. Bone loss began by the midtwenties at the femoral neck. Additional annual change of -0.7% (95% confidence interval: -0.2%, -1.2%) of a z score was observed at the femoral neck for each unit increase in BMD z score at baseline.

Absorptiometry, Photon↗
PubMed2002

Measurement of hypocretin/orexin content in the mouse brain using an enzyme immunoassay: the effect of circadian time, age and genetic background.

The hypocretins (1 and 2) have emerged as key regulators of sleep and wakefulness. We developed a high-throughput enzyme immunoassay (EIA) to measure total brain hypocretin levels from large numbers of mice. Hypocretin levels were not altered by circadian time or age. However, significant differences in one or both hypocretin peptides were observed between different mouse strains. We studied hypocretin levels in knockout and transgenic mouse models with obesity, circadian gene mutations or monoaminergic defects. Compared to controls, only histamine receptor knockouts had lower hypocretin levels. This was most pronounced in H1 receptor knockouts suggesting the existence of a positive feedback loop between hypocretin and histaminergic neurons.

Aging↗
PubMed2002

The cellular pharmacology of oxaliplatin resistance.

Oxaliplatin is a third generation platinum compound that differs from cisplatin and carboplatin in having a broader spectrum of antitumour activity. Molecular studies suggest that oxaliplatin adducts are recognised and processed differently than those produced by the earlier generation Pt-containing drugs. We report here studies on the kinetics of the development of oxaliplatin resistance, and the changes in the cellular pharmacology of oxaliplatin that accompany the emergence of the resistant phenotype in five parental human tumour cell lines and their sub-lines selected for acquired oxaliplatin resistance in vitro. During selection, resistance did not substantially increase until after at least six cycles of oxaliplatin treatment. Oxaliplatin demonstrated schedule-dependency with a 1-h exposure being substantially less cytotoxic than a continuous exposure. Whole cell uptake was linear with concentration, but uptake in the resistant cells averaged only 27+/-10 S.D.% of that in the sensitive cells. Pt accumulation in DNA was markedly reduced in four of the five resistant cell lines, but this did not correlate with either IC(50) or total cellular accumulation. Four of the five resistant sub-lines also demonstrated increased tolerance to adducts in DNA that ranged from 3.1 to 7.6-fold. We conclude that development of acquired resistance to oxaliplatin is accompanied by independent defects in both whole cell uptake and in adduct formation.

Antineoplastic Agents↗