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Biomedical subjects

G Lin

Publications and source records attributed to G Lin.

At least 109 records · Page 6Linked to original sources
PubMed1998

Postantibiotic effect and postantibiotic sub-MIC effect of levofloxacin compared to those of ofloxacin, ciprofloxacin, erythromycin, azithromycin, and clarithromycin against 20 pneumococci.

The postantibiotic effect (PAE) (10 times the MIC of quinolones, 5 times the MIC of macrolides) and postantibiotic sub-MIC effect (PAE-SME) at 0.125, 0.25, and 0.5 times the MIC were determined for levofloxacin, ciprofloxacin, ofloxacin, erythromycin, azithromycin, and clarithromycin against 20 pneumococci. Quinolone PAEs ranged between 0.5 and 6.5 h, and macrolide PAEs ranged between 1 and 6 h. Measurable PAE-SMEs (in hours) at the three concentrations were 1 to 5, 1 to 8, and 1 to 8, respectively, for quinolones and 1 to 8, 1 to 8, and 1 to 6, respectively, for macrolides.

Anti-Bacterial Agents↗
PubMed1998

Activity of 5-alpha-reductase and 17-beta-hydroxysteroid dehydrogenase in the infrainfundibulum of subjects with and without acne vulgaris.

Linoleic acid deficiency, interleukin 1, retinoids and androgens have been implicated as causative factors in the follicular hyperkeratinization seen in acne. The goal of this study was to test the hypothesis that more androgens are produced in follicles of acne subjects compared to subjects without acne. Thirty-four subjects (males and females with and without acne) were studied. The activity of 5 alpha-reductase (5 alpha-R) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) was determined in keratinocytes cultured from the infrainfundibulum and epidermis. Mean enzyme activities were slightly higher in the acne groups compared to the groups without acne, but differences were not statistically significant, perhaps due to limitations of this in vitro model. The activity of both 5 alpha-R and 17 beta-HSD was significantly greater in infrainfundibular keratinocytes compared to epidermal keratinocytes in all subject groups. 17 beta-HSD activity was 2.5- to 7-fold greater than the activity of 5 alpha-R in infrainfundibular keratinocytes. The regulation of 17 beta-HSD by endogenous factors may be important in determining the directional activity of 17 beta-HSD and hence the local concentration of testosterone within the infrainfundibulum. Additional studies of the effects of androgens on follicular keratinization are needed.

17-Hydroxysteroid Dehydrogenases↗
PubMed1998

Prevention of vasospasm after subarachnoid hemorrhage in dogs by continuous intravenous infusion of PD156707.

This randomized, blinded study tested the prophylactic effect of PD156707, a nonpeptide competitive antagonist of endothelin A receptors, against vasospasm after subarachnoid hemorrhage in dogs. Twenty-two dogs were allocated on day 0 to undergo cerebral angiography followed by injection of arterial blood (0.5 ml/kg) into the cisterna magna. Dogs had central venous catheters implanted for continuous infusion of drug vehicle (n = 10) or PD156707 (n = 12). Cisternal blood injection was repeated on day 2. Drug levels were measured in plasma on days 2, 4, 6, and 7 and in cerebrospinal fluid (CSF) on days 2 and 7. Angiography was repeated on day 7 to assess vasospasm. After angiography on day 7, acute effects of infusion of PD156707, 100 mg, or drug vehicle on established vasospasm were assessed. Analysis of physiological variables within (analysis of variance) groups across time and between (unpaired t-test) groups at each time showed that drug-treated animals had significantly increased heart rate on day 7 compared to day 0 (p < 0.005). Comparison of basilar artery diameters at day 7 showed that PD156707 significantly decreased the degree of basilar artery vasospasm (placebo: -47 +/- 5% reduction [mean +/- SE] versus PD156707: -28 +/- 7%, p < 0.05, unpaired t-test). There was, however, significant vasospasm when comparing within groups (paired t-test, placebo: p < 0.0001, PD156707: p < 0.005). Mean plasma PD156707 levels (322 +/- 123 ng/ml) were adequate to block responses of endothelin-1 on endothelin A receptors in vitro although CSF levels (11 +/- 7 ng/ml) were substantially lower. Infusion of PD156707 into the basilar artery on day 7 caused a small but significant 10 +/- 3% (paired t-test, p < 0.01) increase in diameter compared to placebo (3 +/- 3% increase, p = 0.32). This infusion also was associated with a substantial increase in CSF drug levels to 19 +/- 9 mg/ml. These results suggest that endothelin A receptors mediate some of the vasospasm that occurs after SAH in dogs and that blockade of these receptors may be a beneficial treatment for vasospasm.

Animals↗
PubMed1998

[A study of the GSH contents, GST activity and the expression of GST isoenzyme and MRP in drug-resistant leukemic cell lines].

OBJECTIVE: To understand the non-mdr1 mechanism in multidrug-resistant leukemic cell lines. METHODS: GSH contents and GST activity were measured by biochemical methods, the expression of GST isoenzyme alpha, pi, mu and MRP mRNAs were examined by Northern blot, and the expression of GST alpha, pi, mu proteins were examined by Western blot in sensitive HL-60, K562 and resistant K562/H20, HL-60/Adr, K562/VCR leukemic cell lines, respectively. RESULTS: Compared with K562/S, GSH contents and GST activities were increased in K562/H20 and K562/VCR, and GST alpha, pi or GST mu, pi were overexpressed in K562/H20 or K562/VCR, while there was no difference of GSH contents, GST activities or GST isoenzyme expressions between HL-60/Adr and HL-60/S. The increased expressions of MRP mRNA were revealed in the three resistant cell lines. CONCLUSION: GSH, GST and MRP involved in the drug resistance of K562/H20 and K562/VCR, while only MRP associated with drug resistance of HL-60/Adr.

ATP-Binding Cassette Transporters↗
PubMed1998

[Clinical study on Shuanghuanglian powder in treating children viral myocarditis].

OBJECTIVE: To study immune function of children viral myocarditis and to evaluate the clinical effect of Shuanghuanglian Powder (SHLP). METHODS: The authors determined serum COXB-IgM and the numbers of lymphocyte subsets CD3+, CD4+, CD8+, CD4+/CD8+ with viral myocarditis patients by ELISA and indirect immunofluorescent assay. Sixty-two cases were divided randomly into two groups. Thirty-two cases treated by conventional therapy with SHLP and the other 30 cases treated with conventional therapy alone were taken as control group. RESULTS: COXB-IgM was positive in 39 of 62 patients, which were significantly different with those of normal controls (P < 0.001). In addition, the level of CD4+ cells and the ratio of CD4+/CD8+ were decreased while CD8+ increased. After treatment with SHLP, the recovery of symptoms, signs and immune function in patients were better than that of controls. These changes were significantly different (P < 0.01). CONCLUSIONS: There were disturbance of immune regulatory function with children viral myocarditis patients and SHLP is an effective drug in treating children viral myocarditis.

Adenosine Triphosphate↗
PubMed1998

Microsomal formation of a pyrrolic alcohol glutathione conjugate of clivorine. Firm evidence for the formation of a pyrrolic metabolite of an otonecine-type pyrrolizidine alkaloid.

The formation of the pyrrolic alcohol glutathione (GSH) conjugates of two different types of pyrrolizidine alkaloids (PAs), i.e. clivorine (an otonecine-type PA) and retrorsine (a retronecine-type PA), was investigated with rat microsomes in the presence of GSH. Two GSH conjugates identified as metabolites of retrorsine were the pyrrolic alcohol conjugated with one [7-GSH-dehydroretronecine (DHP)] or two (7,9-diGSH-DHP) molecules of GSH. diGSH-DHP, the less abundant of the two conjugates, had not been previously identified as a metabolite of PAs. In the case of clivorine, 7-GSH-DHP was identified. This is the first unequivocal identification of a pyrrolic metabolite of an otonecine-type PA. Consequently, this study provides the strongest evidence obtained to date to support the hypothesis, suggested >25 years ago, that the mechanism of hepatotoxicity induced by otonecine-type PAs involves key metabolic steps similar to those for retronecine-type PAs.

Alcohols↗
PubMed1997

Simultaneous analysis of 2-methoxyphenylmetyrapone and its seven potential metabolites by high-performance liquid chromatography.

A sensitive and specific high-performance liquid chromatographic (HPLC) assay has been developed for the quantification of 2-methoxyphenylmetyrapone (2-MPMP) and its seven potential metabolites in rat urine and whole blood. 2-MPMP, 2-hydroxyphenylmetyrapone and their N-oxides, together with 2-methoxyphenylmetyrapol, 2-hydroxyphenylmetyrapol and their N-oxides were separated on an Isco Spherisorb ODS-2 reversed-phase column (250 x 4.6 mm, I.D., 5 microm), with an Isco Spherisorb ODS-2 guard cartridge (10 x 4.6 mm I.D.). A gradient elution was employed using solvent system A (acetonitrile-water-triethylamine-acetic acid, 27.3:69.1:0.9:2.7%, v/v) and solvent system B (methanol), the gradient program being as follows: initial 0-4 min A:B=74:26; 4-10 min linear change to A:B=50:50; 10-16 min maintain A:B=50:50; 16 min return to initial conditions (A:B=74:26). Flow-rate was maintained at 1.25 ml/min, and the eluent monitored using a diode array multiple wavelength UV detector set at 260 nm. Most of the analytes were baseline resolved, and analysis of samples recovered from blood or urine (pH 12, 3 x 5 ml of dichloromethane, recovery approximately 20-95%) revealed no interference from any co-extracted endogenous compounds in the biological matrices, except for 2-hydroxyphenylmetyrapol N-oxide (2-OHPMPOL-NO) at low concentrations. The calibrations (n=6) were linear (r > or = 0.996) for all analytes (approximately 0.5-100 microg/ml), with acceptable inter- and intra-day variability. Subsequent validation of the assay revealed acceptable precision, as measured by coefficient of variation (C.V.) at the low (0.5 mg/ml), medium (50 microg/ml) and high (100 microg/ml) concentrations. The limits of detection for 2-MPMP and their available potential metabolites, except 2-OHPMPOL-NO, in rat urine and blood were both 0.5 microg/ml, respectively.

Animals↗
PubMed1997

Refocusing neutralizing antibody response by targeted dampening of an immunodominant epitope.

Immunodominant epitopes are known to suppress a primary immune response to other antigenic determinants by a number of mechanisms. Many pathogens have used this strategy to subvert the immune response and may be a mechanism responsible for limited vaccine efficacies. HIV-1 vaccine efficacy appears to be complicated similarly by a limited, immunodominant, isolate-restricted immune response generally directed toward determinants in the third variable domain (V3) of the major envelope glycoprotein, gp120. To overcome this problem, we have investigated an approach based on masking the V3 domain through addition of N-linked carbohydrate and reduction in net positive charge. N-linked modified gp120s were expressed by recombinant vaccinia virus and used to immunize guinea pigs by infection and protein boosting. This modification resulted in variable site-specific glycosylation and antigenic dampening, without loss of gp120/CD4 binding or virus neutralization. Most importantly, V3 epitope dampening shifted the dominant type-specific neutralizing Ab response away from V3 to an epitope in the first variable domain (V1) of gp120. Interestingly, in the presence of V3 dampening V1 changes from an immunodominant non-neutralizing epitope to a primary neutralizing epitope with broader neutralizing properties. In addition, Ab responses were also observed to conserved domains in C1 and C5. These results suggest that selective epitope dampening can lead to qualitative shifts in the immune response resulting in second order neutralizing responses that may prove useful in the fine manipulation of the immune response and in the development of more broadly protective vaccines and therapeutic strategies.

AIDS Vaccines↗
PubMed1997

High-level secretion of two antibody single chain Fv fragments by Pichia pastoris.

The diagnostic and therapeutic applications of antibody single-chain Fv (sFv) fragments often require large amounts of protein that can be problematic and expensive to obtain. Here we report the secretion of two sFv fragments by the yeast Pichia pastoris at levels up to 250 mg/l. Soluble sFv fragments were purified from culture supernatants in one step by affinity or metal-chelating chromatography, and were indistinguishable from their bacterially expressed counterparts in terms of affinity. Secretion of functional sFv fragments by Pichia pastoris provides a low cost, high yield alternative to current sFv expression systems.

Animals↗
PubMed1997

Expression cloning of a mammalian amino acid transporter or modifier by complementation of a yeast transport mutant.

A cDNA clone named L21 was isolated from L6 rat muscle cells by complementation of a yeast proline transport mutant. L21 cDNA has 2,268 bp and codes for a peptide of 228 amino acids with four potential transmembrane domains. The amino acid sequence of L21 shows no homology to any known proteins. Expression of L21 cDNA enables the mutant yeast to grow in proline as the sole nitrogen source and to transport proline, alpha-aminoisobutyric acid (AIB) and leucine. The Km for proline is about 1.0 mM. The substrate specificity of L21 expressed in yeast shows no striking similarity to known mammalian amino acid transporters.

Amino Acid Sequence↗
PubMed1997

The role of endoscopic retrograde cholangiopancreatography in management of patients recovering from acute biliary pancreatitis in the laparoscopic era.

BACKGROUND: Traditionally an episode of acute biliary pancreatitis (ABP) is an indication for direct imaging of the biliary tree. The optimal approach may vary according to local expertise, and endoscopic retrograde cholangiopancreatography (ERCP) is the most common. The fact that the incidence of choledocholithiasis in patients recovering from ABP varies between 3 and 33% raises a question about the necessity of visualizing the biliary tree in all patients recovering from ABP. METHODS: In order to evaluate this policy, we reviewed 48 ERCPs performed on patients recovering from ABP who were scheduled for laparoscopic cholecystectomy (LC). We checked the correlations between ERCP findings and the severity of pancreatitis, biochemistry values (which were sampled during the acute phase), and ultrasonographic (US) findings. RESULTS: The ERCP demonstrated common bile duct (CBD) stones in 11 (22.9%) patients. US finding of a dilated CBD and maximal aspartate transaminase (AST) values higher than 90 units/l were significantly correlated with CBD stones (a relative risk [RR] of 2.95 with a 95% confidence interval [CI] for a dilated CBD and RR of 3.89 with a 95% CI of 1.18-12.80 for an AST value higher than 90 units/l). No other parameters were significantly correlated with CBD stones. CONCLUSION: We, therefore, recommend performing a preoperative ERCP only on patients who present with an ultrasonographic finding of CBD dilatation. The correlation to high AST is still to be proven.

Acute Disease↗
PubMed1997

Pulse oxymetry evaluation of oxygen saturation in the upper extremity with an arteriovenous fistula before and during hemodialysis.

We noticed that some patients with arteriovenous (AV) fistula on chronic hemodialysis experience pain in the limb with the fistula a short time after being connected to the dialysis machine. We postulated that the pain is caused by relative ischemia and therefore performed this study to determine whether oxygen saturation (SaO2) of the extremities with AV fistula decreases during hemodialysis. Seventy-two patients with a side-to-side primary AV fistula were evaluated by pulse oxymetry. SaO2 was measured before hemodialysis and 20 minutes after initiation of dialysis. The contralateral arm served as a control. In 48 patients, SaO2 difference between the arms of each patient before hemodialysis was less than 4%. SaO2 values of this group of patients did not change significantly 20 minutes after initiation of dialysis. In 24 patients, SaO2 differences between the hands of each patient before hemodialysis were 4% or more. In this group of patients, SaO2 values of the hands with the AV fistula decreased significantly 20 minutes after hemodialysis from a mean of 90.85 +/- 2.84% to 81.60 +/- 3.94 (P < 0.001). SaO2 remained unchanged in the contralateral arm. Nine patients in this group complained of pain and change in sensation in the arm with the fistula during hemodialysis. One patient complained of severe pain in the arm with the fistula before hemodialysis, and SaO2 was unmeasurable. We conclude that, in some patients, SaO2 of the arm with the AV fistula decreases only during hemodialysis. This phenomenon may be symptomatic. A predialysis SaO2 difference of 4% or more between the arms predicts decreased SaO2 of the arm with the AV fistula during hemodialysis.

Arm↗
PubMed1997

Spectral and chromatographic properties of 2-methoxyphenylmetyrapone and its potential metabolites.

In the search for new metyrapone derivatives as radioligands for the functional diagnosis of adrenal pathology, 2-methoxyphenylmetyrapone [2-MPMP, 1-(2-methoxyphenyl)-2-methyl-2-(3-pyridyl)-1-propanone] (1), and related 2-substituted phenylmetyrapone derivatives, have been separated as potent inhibitors of adrenal 11 beta-hydroxylase, with high affinity for adrenal mitochondrial binding sites. Surprisingly, 2-[11C]MPMP showed a rapid loss of the radioactive label, which prompted investigation of its metabolism. Synthetic 2-MPMP (1) and its seven potential metabolites (2-8) have been identified spectroscopically (1H- and 13C-NMR and mass spectrometry) and further characterised by chromatography (TLC and gradient reversed-phase HPLC). Chromatographic and mass analysis of urinary extracts from rats dosed with 2-MPMP have confirmed the major metabolites as 2-hydroxyphenylmetyrapone (2-OHPMP), 2) and its N-oxide (2-OHPMP-NO, 6), which are present predominantly as conjugates.

Animals↗
PubMed1997

Elderly migration: household versus individual approaches.

"This paper employs a household approach to elderly migration analyses and compares it with the traditional individual approach. The first part of the paper develops some concepts about household mobility and relates them to individual mobility. It then compares the two mobility measurements in a case study using the Public Use Microdata Sample (PUMS) from the 1990 [U.S.] Census. The results show that the mean household size for the elderly moving together tends to be smaller than that for elderly stayers. It also demonstrates the utility of the household approach on profiling elderly movers' living arrangement choices. The second part of the paper calibrates a set of discrete choice models based on the household and individual approaches."

Adult↗
PubMed1997

Postantibiotic effect of sanfetrinem compared with those of six other agents against 12 penicillin-susceptible and -resistant pneumococci.

The postantibiotic effect (PAE) and postantibiotic sub-MIC effect (PAE-SME) of sanfetrinem were compared to those of penicillin G, amoxicillin, cefpodoxime, ceftriaxone, imipenem, and clarithromycin against four penicillin-susceptible, four intermediately susceptible, and four resistant pneumococci. The MICs of imipenem were the lowest against all of the strains (0.03 to 0.5 microg/ml), followed by those of sanfetrinem (0.016 to 1.0 microg/ml), amoxicillin and ceftriaxone (0.016 to 2.0 microg/ml), and cefpodoxime (0.03 to 8.0 microg/ml). High-level resistance to clarithromycin (MIC, >64.0 microg/ml) was seen in three selected strains. The PAEs of all of the oral beta-lactams tested were similar for all of the strains, ranging from 1 to 6.5 h. The PAEs of ceftriaxone and imipenem ranged from 1 to 8 h, and those of clarithromycin ranged from 1 to 7 h. The mean PAEs of all of the beta-lactams and clarithromycin were 2.8 to 4.3 and 2.5 h, respectively. PAE-SMEs could not be determined for all of the strains due to complete killing, especially at high subinhibitory concentrations. However, the overall pattern with all of the compounds tested was that PAE-SMEs were longer than PAEs. Measurable PAE-SMEs of sanfetrinem at the three subinhibitory concentrations (0.125, 0.25, and 0.5 times the MIC) were 2 to 7, 2 to 7, and 3 to 6 h, while those of amoxicillin and cefpodoxime were 1 to 7.5, 2 to 4, and 4 to 9 and 2 to 7, 4 to 7, and 4 to 6 h, respectively. Measurable PAE-SMEs of ceftriaxone and imipenem were 1 to 6.5, 2 to 9, and 2 to 9 and 1.5 to 6, 2 to 5.8, and 4 to 7.7 h, respectively. Measurable clarithromycin PAE-SMEs were 1 to 5, 1 to 5, and 1 to 6 h at the three concentrations.

Anti-Bacterial Agents↗
PubMed1997

Mechanisms for the coordination of intercellular calcium signaling in insulin-secreting cells.

Insulin-mediated increases in cytosolic calcium are synchronized among the cells in a pancreatic islet, and result in pulsatile secretion of insulin. Pancreatic beta cells express the gap junction protein connexin43 and are functionally coupled, making gap junctional communication a likely mechanism for the synchronization of calcium transients among islet cells. To define the mechanism by which pancreatic islet cells coordinate calcium responses, we studied mechanically-induced intercellular calcium waves in the communication-deficient rat insulinoma cell line RINm5f, and in RINm5f cells transfected with the gap junction protein connexin43. Both RINm5f and RINm5f cells transfected with connexin43 propagated calcium waves that required release of calcium from intracellular stores, did not involve gap junctional communication, and appeared to be mediated by autocrine activity of secreted ATP acting on P2U purinergic receptors. Connexin43 transfectants also propagated calcium waves that required gap junctional communication and influx of extracellular calcium through voltage-gated calcium channels. Gap junction-dependent intercellular calcium waves were inhibited by preventing plasma membrane depolarization. These studies demonstrate two distinct pathways by which insulin-secreting cells can coordinate cytosolic calcium rises, and show that it is by ionic traffic that gap junctions synchronize calcium-dependent events in these cells.

Animals↗
PubMed1997

[Endovascular treatment of brain arteriovenous malformation].

Eighteen patients with arteriovenous malformations (AVMs) of the brain were treated with endovascular techniques between 1993 and 1996. The following angiograms showed complete obliteration of the nidus in 2 patients, 70%-90% reduction in nidus volume in 5, 50%-70% reduction in 3, and < 50% in the remaining 3. Two patients suffered from moderate neurologic deficits after embolization. One week after the treatment, 4 patients with superficial AVMs underwent surgery, and 2 with deep-situated AVMs received gamma-knife therapy. 14 patients were followed up, suffered from more frequent epilepsy, and 1 had intracranial haemorrhage 6 months after embolization. A few AVMs can be cured by endovascular embolization. In regard to some large AVMs or AVMs situated at important functional areas, embolization can facilitate surgery and radiotherapy afterwards.

Adolescent↗