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Biomedical subjects

S Lin

Publications and source records attributed to S Lin.

At least 289 records · Page 16Linked to original sources

Gene expression of receptor for advanced glycosylation end products and its modulation by aminoguanidine in diabetic kidney tissue.

OBJECTIVE: To explore the relationship between receptor for advanced glycosylation end products (RAGE) gene expression in the kidneys of diabetic rats and the role of aminoguanidine on it. METHODS: Among four groups of rats, 2 groups received streptozotocin (STZ) to induce diabetics (DM) and were followed by either aminoguanidine (AG) treatment for 12 weeks or no therapy. Two groups of normal rats in which one received AG and the other given water served as control (Con). Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the amount of receptor of advanced glycosylation and products (RAGE) messenger RNA (mRNA) expression. RESULTS: After 4 weeks of diabetes inducement, RAGE mRNA levels showed a continuous increase up to 12 weeks both in diabetic renal cortex and medulla compared with mRNA levels at the end of 2 weeks. The RAGE mRNA levels in renal cortex and medulla of control rats did not change significantly with age. AG as the prototype inhibitor of advanced glycosylation end products (AGEs) formation, when administered to diabetic rats for 4 weeks, had no visible effect on the alterations of renal RAGE mRNA in diabetes. By continuous administration up to 8 weeks, those alterations of RAGE mRNA both in diabetic renal cortex and medulla were all ameliorated [P < 0.05, (diabetes without AG) versus (diabetes with AG)]. In addition, diabetic animals had a progressive increase in urinary protein excretion compared to control rats from week 4 onwards. Similarly, after 8 weeks diabetic rats had significantly higher glycated Hb (GHb) (DM without AG vs Con: 7.71 +/- 0.22% vs 2.95 +/- 0.52% P < 0.001). AG treatment for 8 weeks decreased GHb by 24.78% and retarded the rate of rise in albuminuria in diabetic rats as compared with that in untreated diabetic rats (DM with AG vs DM without AG: 22.04 +/- 0.91 micrograms/24 h vs 70.25 +/- 13.05 micrograms/24 h, P < 0.001). CONCLUSIONS: Gene expression of RAGE in renal cortex and medulla was altered in diabetic rats and excessive gene expression of RAGE in kidney tissue may enhance the interactions between advanced glycosylation end products (AGEs) and its receptor (RAGE) which would contribute to the development of diabetic nephropathy. Cumulative AGEs play an important role in increasing RAGE gene expression in vivo. The decrease of AGEs level by AG therapy ameliorate the abnormal regulation of RAGE gene expression.

Animals↗

[Epidemiological characteristics of tuberculosis patients complicated with diabetes in Shanghai].

OBJECTIVE: To understand the epidemiological trends and characteristics of tuberculosis patients complicated with diabetes in Shanghai. METHOD: All the registered tuberculosis (TB) cases from 1992 to 1997 in Shanghai were included in the analysis. The new registration rates and percentages of TB cases complicated with diabetes were calculated. RESULT: The new registration rate of the cases increased from 0.70/100,000 in 1992 to 2.10/100,000 in 1997 with an annual increase rate of 24.57%. The cases with the complication accounted for 4.86% in 1997. Diabetes tends to be more prevalent among TB patients in urban area. The greater the age, the more diabetes were found in TB patients. A significant difference was also observed between sex. Bacillary positive rate and percentage of infiltration type were higher, and cavity was more common in cases with the complication. The percentage of cases with relapse was also higher. CONCLUSION: The complication of diabetes significantly affected the epidemiological trend of TB in Shanghai. The diagnosis of diabetes in TB patients should be enforced, and short-course chemotherapy targeting the cases should be investigated.

Age Factors↗

[Clinical study on active factors of vascular endothelial cells in acute cerebral infarction patients and therapeutical effect of activating blood stasis].

OBJECTIVE: To investigate the level of plasma tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), 6-keto-prostaglandin F1 alpha(PGF1 alpha), thromboxane B2(TXB2), factor VIII related antigen (VIII R:Ag) in acute cerebral infarction (ACI) patients with different TCM syndrome-type and the therapeutical effect of activating blood stasis (ABS). METHODS: Plasma fibrolysin system, prostaglandin system, and VIII R:Ag of 20 healthy subjects and 66 ACI patients were determined. The 45 of 66 cases were treated with ABS randomly and prospectively, 20 cases were treated by difibrase batroboxobin (DF-521), only 25 cases were treated by DF-521 together with Heart-Brain Mixture (HBM), on activating blood stasis mixture, concurrently. RESULTS: (1) The activity of tPA, ratio of tPA/(tPA + PAI) and level of PGF1 alpha decreased significantly, the level of VIII R:Ag increased remarkably in ACI patients than those of the controlled subjects. (2) Between Differentiation of Deficiency and Excess Syndromes, the level of above index changed more remarkably in the case with Excess Syndrome. Insignificant change of index shown in Deficiency cases except activity of tPA. (3) No more improvement of nerve impairment was shown between group of DF-521 together with HBM and DF-521 alone within 30 days. However, the improvement of index such as level of VIII R:Ag, ratio of tPA/(tPA + PAI) and TXB2/PGF1 alpha showed significant change between the beginning and end of treatment of DF-521 with HBM group. CONCLUSIONS: The vascular endothelial impairment was more serious in ACI patients with Excess than those with Deficiency Syndrome. DF-521 combining with HBM could protect vascular endothelial cells and improve the fibrolytic system and prostaglandin system.

6-Ketoprostaglandin F1 alpha↗

[Follow-up study on influence of Sini Decoction to living quality of patients after percutaneous transluminal coronary angioplasty].

OBJECTIVE: To determine the influence of Sini Decoction (SND) on living quality of patients after percutaneous transluminal coronary angioplasty (PTCA). METHODS: Randomized case-control clinical trail was conducted to evaluate the living quality of 40 post-PTCA patients before and after SND treatment by scoring. RESULTS: The scores in physical symptoms, sense of well-being, depression, satisfaction of life and work capacity of patients after PTCA were improved significantly as compared with before PTCA, P < 0.05-0.01. Scores of patients received SND treatment were higher than those untreated with SND in the first three criteria, P < 0.05, particularly on relieving palpitation and dyspnea. CONCLUSION: SND is helpful to improve the living quality of patients after PTCA.

Angioplasty, Balloon, Coronary↗

[Effect of hyperbaric oxygen on cerebral microcirculation and tissue cells in animals with cerebral ischemic injury].

Changes of cerebral microcirculation and tissue cells after Hyperbaric Oxygen (HBO) exposure were observed in 136 gerbils with cerebral ischemia by observation of meningeal microcirculation pathological study in cerebral tissues and determination of Na, K-ATPase. It is indicated that HBO may be helpful in improving microcirculatory dynamics and other microcirculatory functions, and enhancing cerebral tissue cell activity and cell function, as well as increasing oxygen content. It is suggested that HBO (250 approximately 300kPa) may play a role in protecting vessel endothelial cells and nerve cells.

Adenosine Triphosphatases↗

[Blepharospasm and hemifacial spasm treated with botulinum A toxin injection].

OBJECTIVE: To study the efficacy of botulinum A toxin (BTA) injections for the treatment of blepharospasm and hemifacial spasm (HFS). METHODS: Twelve patients with blepharospasm and thirty eight patients with HFS were treated with BTA local injections (2.5 U to 5 U for each injection). RESULTS: Of the fifty patients, ten (86.7%) in blepharospasm and thirty two (84.2%) in HFS were completely relieved, two (13.3%) and five (13.2%) were remarkably relieved respectively, zero and one (2.6%) were partial relieved respectively. All patients experienced relief from spasm. The duration of the effect in blepharospasm were 10 to 24 weeks (mean, 18 weeks) and in HFS 14 to 32 weeks (mean, 22 weeks). The local side effects were transient and mild, including minor facial paralysis in eight patients, ptosis in four patients and tearing in four patients. No systemic adverse and allergic reactions were noted. CONCLUSION: Botulinum A toxin local injection is a safe, effective and simple means for the treatment of blepharospasm and HFS.

Adult↗

[Simultaneous determination of the enantiomers of verapamil and norverapamil in plasma by high performance capillary electrophoresis].

An analytical method has been developed to determine simultaneously plasma concentration of the enantiomers of verapamil and its major metabolite, norverapamil, using capillary zone electrophoresis. Trimethyl-beta-cyclodextrin was selected as chiral selector. Good separation was achieved under the conditions as below: Running electrolyte was pH 2.5, 60 mmol.L-1 phosphate buffer containing 60 mmol.L-1 trimethyl-beta-cyclodextrin; capillary: 30 cm x 75 microns (ID), coated; setpoint of capillary temperature: 20 degrees C; detector: UV 200 nm; injection: electromigration at 12 kV for 7 s; running voltage: 14 kV. Solvent of sample was doubly deionized water. The migration times of enantiomers were less than 12 min. The good linear range was from 300.0 ng.ml-1 to 2.50 ng.ml-1. Relative standard deviations of assay accuracy and precision were less than 12%. It fits for routine therapeutic monitoring as it is highly efficient, rapid, sensitive, with less solvent and sample consumption and automation.

Electrophoresis, Capillary↗

[Protective and antioxidative effect of 2(3)tert-butyl-4-hydroxyanisole against cytotoxicity induced by doxorubicin in mice].

The protective and antioxidative effects of 2(3)tert-butyl-4-hydroxyanisole (BHA) against cardiotoxicity and hepatotoxicity induced by doxorubicin in mice were investigated. After pretreatment with different oral doses of BHA, doxorubicin 30 mg.kg-1 was given i.p. Serum GPT, GOT, LDH and CK were determined, and the mortality rate of animals was observed. Quinone reductase (QR), glutathione-S-transferases (GSTs) and glutathione reductase (GR) were determined on tissue cytosols with enzyme dynamic methods. Malondialdehyde (MDA) was measured by the method of thiobarbituric acid. Compared with the doxorubicin group, the serum GPT, GOT, LDH, CK and the mortality rate of mice were significantly decreased by BHA pretreatment, and BHA was shown to inhibit the increase of MDA induced by doxorubicin (P < 0.01 and P < 0.0001). Administration of BHA resulted in increased activities of QR, GSTs and GR in the myocardium and liver (P < 0.05 or P < 0.0001). These results suggest that BHA has protective effect against the toxicity induced by doxorubicin via the induction of QR, GSTs and GR activities and anti-lipid peroxidation.

Animals↗

[The design and clinical application of an apparatus for monitoring neuromuscular transmission function during operation under general anaesthesia].

This paper introduces a monitoring system of musle relaxant in action during the operation under general anaesthesia. The design of the monitor is based on measurement of acceleration. It consists of an acceleration transducer, a nerve stimulator and a microcomputer unit. The transducer can be fastened to the thumb, and the signal of the thumb movement in response to ulnar nerve stimulation is measured and registered in the computing unit. In clinical practice, it has been proved that this new apparatus can achieve reliable evaluation of nuromuscular transmission function and improve the quality of anesthesia in patients care during surgical operation.

Anesthesia, General↗

Identification and preliminary characterization of PCNA gene in the marine phytoplankton Dunaliella tertiolecta and Isochrysis galbana.

The gene coding for proliferating cell nuclear antigen (PCNA) was identified in Dunaliella tertiolecta (Chlorophyceae) and Isochrysis galbana (Prymnesiophyceae). Southern blot hybridization using a PstI fragment of rat PCNA gene (pCR-1) as a probe showed that there is apparently a single copy of this gene per haploid genome in both species. On the Northern blot pCR-1 probed a single messenger RNA for each species of a molecular size close to rat PCNA mRNA (1.1 kilobases [kb]). Polymerase chain reaction (PCR) with a set of degenerated primers produced a fragment of about 610 base pairs [bp] from genomic DNA of both species; the PCR products appeared close in size to the amplified from rat PCNA and hybridized to the pCR-1 probe. Further analysis with reverse transcription-PCR (RT-PCR), cloning, and sequencing revealed a complementary DNA of a similar size (616 and 576 bp) that possesses an open reading frame encoding 205 and 192 amino acids, respectively, for Dun (D. tertiolecta) and Iso (I. galbana). Surprisingly, the polypeptides deduced from the two cDNA shared no higher homology to each other (71%) than to animals such as Xenopus (Dun 72%; Iso 73%), rat (Dun 73%; Iso 74%), and human (Dun 73%; Iso 74%), and to higher plants such as soybean (Dun 78%; Iso 72%), Zea mays (Dun 77%; Iso 73%), and rice (Dunn 77%; Iso 72%), although D. tertiolecta has a higher homology (77%) to the Prasinophyceae alga Tetraselmis chiu than does I. galbana (71%). The homology to PCNA in budding and fision yeasts (63% and 53%, respectively) is also lower than to animals and higher plants. It is thus suggested that with regard to PCNA genes, the three algae are as different from each other as they are from higher plants and animals. In a partially synchronized exponential culture of D. tertiolecta grown with a photocycle of 12 h light and 12 h dark, the abundance of the transcript appeared to be low at hours 3 and 9 (hour 0 = the onset of light period), and increased about 2- to 3-fold at hours 15 and 21 (i.e., during the dark period). Western blotting and immunofluorescence analysis on concurrent diel samples showed an over 2-fold increase in PCNA protein abundance (in proportion to total cellular protein) and the percentage of cells labeled by PCNA antibody. A similar trend was found for I. galbana grown under the same conditions. The results suggest that the gene transcription was in pace with PCNA synthesis, which was lower in the light period when G1 phase was dominant and higher in the dark period when S (and probably G2 and early M) phase was dominant, and that the expression of this gene may be regulated at the transcriptional level in these two algae.

Amino Acid Sequence↗

Comparative pharmacokinetic and pharmacodynamic studies of human insulin and analogues in chronic diabetic Yucatan minipigs.

Pharmacokinetics and pharmacodynamics of insulin analogues were compared with human insulin in streptozotocin-induced chronic diabetic Yucatan minipigs. After overnight fasting, insulin or one of the insulin analogues (0.6 nmol/kg) in acid solutions (pH approximately 3.0) was administered to the minipigs s.c. The plasma insulin concentrations were then measured by radioimmunoassay at predetermined time intervals although blood glucose levels were monitored continuously. The mean (+/-S.E.) values of DeltaCmax (difference between peak and basal plasma insulin levels) were 598 (+/-21), 528 (+/-44), 176 (+/-21), 325 (+/-60) and 228 (+/-33) pM, respectively, for analogue AspB9GluB27, AspB9, GluB27, AspB28 and insulin. The differences in DeltaCmax values were statistically significant between AspB9GluB27 and insulin (P < .02), and between AspB9 and insulin (P < .01), but not between GluB27 or AspB28 and insulin. Moreover, the mean (+/-S.E.) values of DeltaAUC0-->6 (integrated area between plasma insulin concentration curve and basal level) were 1877 (+/-169), 1897 (+/-70), 485 (+/-36), 500 (+/-32) and 677 (+/-105) pM x hr, respectively, for AspB9GluB27, AspB9, GluB27, AspB28 and insulin. The differences in DeltaAUC0-->6 values were statistically significant between AspB9GluB27 and insulin (P < .05) and between AspB9 and insulin (P < .02), but not between GluB27 or AspB28 and insulin. However, there was no significant difference in the values of Deltanadir (difference between nadir and basal levels) and ABGC0-->12 (integrated area between blood glucose response curve and basal level) between insulin and various analogues. In conclusion, although the insulin analogues are different from human insulin in pharmacokinetics, they exhibit similar biological activity to human insulin in the streptozotocin-induced chronic diabetic minipigs.

Animals↗

Detection of non-covalent interaction of single and double stranded DNA with peptides by MALDI-TOF.

DNA-histone interaction facilitates packaging of huge amounts of DNA in the confined space of the nucleus. The importance of this interaction underscores the need for new analytical techniques to acquire a better understanding of nuclear dynamics. Electrospray-ionization mass spectrometry made it possible to investigate non-covalently-bound biopolymers. We are enlarging the scope of available analytical tools by studying non-covalent interaction between single and double stranded DNA and peptides with matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The interaction is an ionic one, between the negatively charged sugar-phosphate backbone of single stranded DNA and positively charged side chains of Arg- and Lys-rich peptides as demonstrated by Vertes' group with the dipeptides Arg-Lys and His-His. We replicated Lecchi and Pannell's work, which showed that double stranded DNA could be seen by MALDI using 6-aza-2-thiothymine (ATT) as matrix. We tried various peptides and found that as was demonstrated in DNA-histone interaction, a certain ratio and arrangement of basic residues was needed in order to generate ionic binding between DNA and peptide. We tested various single and double stranded DNA with the peptide of choice, and found that other variables such as pH value of solution, ionic strength, and matrix system did play a role.

DNA↗

Preliminary results from intensity-based CT-SPECT fusion in I-131 anti-B1 monoclonal-antibody therapy of lymphoma.

BACKGROUND: In treatment of non-Hodgkin's lymphoma patients with predose-plus-I-131-labeled anti-B1 (anti-CD20) monoclonal antibody, an intratherapy single photon emission computed tomography (SPECT) image is an important part of research estimates of tumor dosimetry. For that imaging, a computed tomography (CT)-SPECT fusion is used both to obtain an attenuation map for the space-alternating generalized expectation maximization reconstruction and to provide CT-based volumes of interest (VoI) to determine activity in tumors and organs. Fusion based on external, skin-surface markers has been used but may not correctly superimpose internal structures. METHODS: A new algorithm, developed and implemented in the Department of Radiology, University of Michigan, and based on the mutual information of grayscale values, was investigated. Results from four anti-B1 therapy patients are presented. RESULTS: In one patient, the new intensity-based fusion provided total reconstructed counts for kidneys that were higher than those produced by marker-based fusion; therefore, the VoI was probably located more accurately. In a second patient, after an acquisition that did not include any skin markers, the new algorithm produced counts/pixel that were similar for four of five tumors consistent with what is expected from an ideal therapy combined with accurate count density estimates. The fifth tumor was quite small and will have its final activity estimate moved toward consistency with the others after a recovery coefficient multiplication. For four tumors in two patients, direct comparison of the two algorithms yielded count totals that were different by no more than 7.2%. CONCLUSIONS: The use of CT-SPECT fusion and subsequent transfer of tumor VoI originally drawn in high-resolution CT space offers potential advantages for quantifying tumor uptake of radioactivity. A new, mutual-information-based fusion algorithm is usable without skin markers. Results indicate that the new fusion algorithm gives equal tumor count values within 7.2% compared with fusion based on external markers. It increases estimates of kidney activity by an average of 6.4%.

Algorithms↗

Determination of the dissociation constant of phosvitin-anti-phosphoserine interaction by affinity capillary electrophoresis.

We used affinity capillary electrophoresis (ACE) to study the interaction of a monoclonal anti-phosphoserine antibody (mAb) to a homopolyvalent antigen (hpAg), phosvitin. A model system, which allows the measurement of the true dissociation constant (Kd) in Ag excess based on measurement of migration shifts of mAb-hpAg complexes at different Ag concentrations in solution, is presented for the study of the interactions between a mAb and an Ag that has identical determinants. The experimental value of Kd (22.4 x 10(-6) M) obtained by ACE is shown to be in close agreement with the value (17.8 x 10(-6) M) obtained by the conventional immunoassay based on indirect competition enzyme-linked immunosorbent assay (ELISA). Moreover, the Kds of mAb-hpAg complexes were measured and shown to be independent of the applied electrical field strength. Thus, under conditions where the total Ag concentration is in large excess over the total Ab concentration and when certain requirements are fulfilled, this method offers the advantage of dealing with the determination of Kd for unlabeled mAb and homopolymeric Ag molecules in free solution rather than at the liquid-solid interface.

Antibodies, Monoclonal↗

Site-specific fluorescence labeling of the beta2 adrenergic receptor amino terminus.

A modified human beta2 receptor, designated 0K-beta2, was developed for site-specific labeling at the amino terminus with amine reactive fluorescent probes. 0K-beta2 has the following modifications: (1) all 16 lysines in the wild-type beta2 receptor were mutated to arginines, (2) a FLAG epitope preceded by a cleaved hemagglutinin signal sequence was fused to the amino terminus, and (3) a hexahistidine tail was added to the carboxyl terminus. The FLAG epitope and hexahistidine tail were added to facilitate purification while lysine to arginine mutations eliminate potential labeling sites for amine-reactive fluorescent probes. The remaining primary amines in the 0K-beta2 receptor, the amino terminal amine and the epsilon-amine of Lys3, both reside in the amino-terminal FLAG epitope. The 0K-beta2 receptor expressed in Sf9 insect cells exhibited ligand binding and G-protein coupling characteristics similar to the wild-type beta2 receptor. The modified receptor was labeled with fluorescamine, an amine-reactive fluorescent probe. Proteolysis with factor Xa showed that labeling was confined to the amino terminus of the 0K-beta2 receptor. Our results demonstrate site-specific fluorescamine labeling at the amino terminus of the 0K-beta2 receptor, a lysine-depleted beta2 receptor that retains functional characteristics of the wild-type receptor.

Adenylyl Cyclases↗