Biomedical subjects

Y F Li

Publications and source records attributed to Y F Li.

At least 91 records · Page 5Linked to original sources

PubMed1997

Machado-Joseph disease in four Chinese pedigrees: molecular analysis of 15 patients including two juvenile cases and clinical correlations.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder associated with the expansion of a (CAG)n array in the MJD1 gene. We analyzed the sizes of the (CAG)n array using DNA samples from 61 members of four Chinese MJD families and 18 Chinese normal control subjects and confirmed that the (CAG)n array in 15 MJD chromosomes was expanded to 72-86 repeat units. There were no subjects with (CAG)n array sizes intermediate between those of normal and MJD affected groups. Meanwhile, we found a significant negative correlation between the age of onset of symptoms and (CAG)n array size. The largest (CAG)n array of 86 repeat units was in the youngest patient, whose age of onset was 5 years. The intergenerational increase in number of CAG repeat units was associated with the clinical phenomenon of anticipation.

Adolescent↗

PubMed1997

Oltipraz chemoprevention trial in Qidong, People's Republic of China: study design and clinical outcomes.

In 1995, 234 adults from Qidong, Jiangsu Province, People's Republic of China, where hepatocellular carcinoma is the leading cause of cancer deaths and exposure to dietary aflatoxins is widespread, were enrolled and followed in a Phase II chemoprevention trial. The goals of the study were to define a dose and schedule of oltipraz for reducing levels of validated aflatoxin biomarkers and to characterize dose-limiting toxicities. Healthy eligible individuals, including those infected with hepatitis B virus, were randomized to receive either 125 mg of oltipraz daily, 500 mg of oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor toxicities and evaluate biomarkers over the 8-week intervention period and subsequent 8-week follow-up period. Unique trial aspects included a synchronous follow-up schedule, daily observed administration of all medications, timely international data transference, and use of biomarkers as outcomes. One hundred thirty-two participants took their medications without interruptions, approximately 77% contributed all nine urine samples, and 78% contributed all seven blood samples. Fifty-one participants (21.8%) reported clinical adverse events. An extremity syndrome, developing soon after the start of treatment, was the only event that occurred more frequently (P = 0.002) among the active groups (18.4 and 14.1% of the daily 125 and weekly 500 mg arms, respectively) compared with placebo (2.5%). The oltipraz arms did not differ in symptom type or severity, and there were no indications of exacerbated drug intolerance among the few participants infected with hepatitis B virus. The good compliance with an intense follow-up schedule shows that chemoprevention trials with biomarker end points may be conducted in such populations.

Adult↗

PubMed1997

Oltipraz chemoprevention trial in Qidong, Jiangsu Province, People's Republic of China.

Oltipraz has been used clinically in many regions of the world as an antischistosomal agent and is an effective inhibitor of aflatoxin hepatocarcinogenesis in rats. This chemopreventive action of oltipraz results primarily from an altered balance in aflatoxin metabolic activation and detoxication. In 1995, a randomized, placebo-controlled, double-blind intervention was conducted in residents of Qidong, People's Republic of China, who are at high risk for exposure to aflatoxin and development of hepatocellular carcinoma. The major study objectives were to define a dose and schedule for oltipraz that would reduce levels of aflatoxin biomarkers in biofluids of the participants, and to further characterize dose-limiting side effects. Two hundred thirty-four healthy eligible individuals, including those infected with HBV, were randomized to receive either 125 mg oltipraz daily, 500 mg oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor potential toxicities and evaluate biomarkers over the 8-week intervention and subsequent 8-week follow-up periods. Overall, compliance in the intervention was excellent; approximately 85% of the participants completed the study. Objective evaluation of adverse events was greatly facilitated by inclusion of a placebo arm in the study design. A syndrome involving numbness, tingling, and pain in the fingertips was the only event that occurred more frequently among the active groups (18 and 14% of the daily 125 mg and weekly 500 mg arms, respectively) compared to placebo (3%). These symptoms were reversible and could be relieved with non-steroidal antiinflammatory agents. A more complete understanding of the chemopreventive utility of oltipraz awaits completion of an assessment of the efficacy of oltipraz in modulating levels of aflatoxin biomarkers.

Animals↗

PubMed1997

[Alteration of cardiac beta-adrenoceptors and subtypes with increasing age].

The alteration of cardiac beta-adrenoceptor (beta-AR) and subtypes in Wistar rats of 48 and 10 weeks old were investigated by radioligand binding assay and functional determination of isolated perfused left atria. The results indicated that: (1) The density of cardiac total beta-AR was downregulated about 28% in 48 weeks old rats as compared with rats of 10 weeks old for both beta 1- and beta 2-AR; (2) The sensitivity of beta-AR and subtypes to isoproterenol in isolated perfused atria was significantly lowered in rats of 48 weeks old; (3) The beta-AR mediated contractile effect of 10 weeks old rat hearts was mainly attributed to beta 1 type, but equally to both beta 1 and beta 2 types in 48 weeks old rat hearts; (4) The two receptor subtypes showed mutually potentiation effect in 10 weeks old rat hearts when stimulated simultaneously, but only additive in 48 weeks old rat hearts.

Aging↗

PubMed1997

[Different susceptibilities to desensitization of three alpha 1-adrenoceptor subtypes induced by sustained norepinephrine stimulation].

cDNAs for the bovine alpha 1A-, hamster alpha 1B- and rat alpha 1D-adrenoceptors (AR) were transfected into human embryonic kidney 293 (HEK293) cells by calcium phosphate precipitation and stably expressed at high levels. The inositol phosphates (InsPs) accumulation was measured by the method of 3H-inositol incorporation and column chromatography. Susceptibilities to the desensitization of alpha 1-AR subtypes-mediated InsPs accumulation were determined in HEK 293 cells stimulated sustainedly by norepinephrine (NE). The NE-induced InsPs accumulation showed progressive decrease by NE pretreatment with increasing time of preincubation and concentration of NE in the cells transfected with all the alpha 1-AR subtypes. However, susceptibilities to the desensitization were different among the three subtypes. The desensitization of alpha 1A-AR took place earliest and needed lowest concentration of NE. The desensitization of alpha 1D-AR appeared to be the latest and needed hightest concentration of NE, while alpha 1B-AR stood in between.

Adrenergic alpha-Agonists↗

PubMed1996

Reversed-phase high-performance liquid chromatography method for the simultaneous quantitation of the lactone and carboxylate forms of the novel natural product anticancer agent 10-hydroxycamptothecin in biological fluids and tissues.

Camptothecins are indole alkaloids isolated from a Chinese tree, Camptotheca acuminata, and have a wide spectrum of anticancer activity in vitro and in vivo. A novel camptothecin congener 10-hydroxycamptothecin (HCPT) has been shown to be more active and less toxic than camptothecin, and the lactone HCPT is believed to be responsible for its anticancer activity. In the present study, a reversed-phase high-performance liquid chromatography, (HPLC) with fluorescence detection was developed and validated for the simultaneous analysis of HCPT for lactone from (I) and carboxylate form (II) in plasma, urine and feces and tissues. Biological samples were prepared by a liquid-liquid extraction method using ice-cold methanol-acetonitrile (1:1, v/v). This method was shown to be reproducible and reliable, with intra- and inter-day variations being less than 7%, and accuracy being 94.3%-102.7%. The limits of determination were 2 ng/ml, 2 ng/ml, 2 ng/g, and 10 ng/ml for HCPT forms I and II in rat plasma, urine, feces, and tissues, respectively. The assay was liner over the range 2-2000 ng/ml (r = 0.999, P < 0.001) with recoveries of greater than 90% for plasma and urine and approximately 70-80% for feces and tissue homogenates through the extraction procedure. This analytic procedure has been successfully applied to a pharmacokinetic study of HCPT in experimental animals and should be useful in the future human studies.

Animals↗

PubMed1996

Melanoma-specific CD4+ T cells recognize nonmutated HLA-DR-restricted tyrosinase epitopes.

Tyrosinase was the first melanoma-associated antigen shown to be recognized by CD4+ T cells. In this study, we have identified two HLA-DRB1*0401-restricted peptides recognized by these T cells: Ty 56-70 and Ty 448-462. As with many of the MHC class I-restricted melanoma epitopes, both are nonmutated self peptides that have intermediate and weak MHC binding affinities, respectively. Mutated and truncated versions of these peptides were used to define their MHC binding anchor residues. Anchor residues were then modified to derive peptides with increased MHC binding affinities and T cell stimulatory properties. Ty 56-70 and Ty 448-462 enhance the list of immunogenic HLA-A2-, A24-, and B44-restricted tyrosinase peptides already described. Thus, tyrosinase provides a model for anti-melanoma vaccines in which a single molecule can generate multivalent immunization incorporating both CD4+ and CD8+ T cell responses.

Amino Acid Sequence↗

PubMed1996

A mutated beta-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes.

A number of antigens recognized by tumor-reactive T cells have recently been identified. The antigens identified in mouse model systems appear, with one exception, to represent the products of mutated genes. In contrast, most of the antigens recognized by human tumor-reactive T cells reported to date appear to represent the products of non-mutated genes. Here we report the isolation of a cDNA clone encoding beta-catenin, which was shown to be recognized by the tumor-infiltrating lymphocyte (TIL) 1290, a HLA-A24 restricted melanoma-specific CTL line from patient 888. The cDNA clone, which was isolated from the autologous melanoma cDNA library, differed by a single base pair from the published beta-catenin sequence, resulting in a change from a serine to a phenylalanine residue at position 37. Normal tissues from this patient did not express the altered sequence, nor did 12 allogeneic melanomas, indicating that this represented a unique mutation in this patient's melanoma. A peptide corresponding to the sequence between amino acids 29 and 37 of the mutant gene product was identified as the T cell epitope recognized by TIL 1290. The observation that HLA-A24 binding peptides contain an aromatic or hydrophobic residue at position 9 suggested that the change at position 37 may have generated a peptide (SYLDSGIHF) which was capable of binding to HLA-A24, and a competitive binding assay confirmed this hypothesis. The beta-catenin protein has been shown previously to be involved in cell adhesion mediated through the cadherin family of cell surface adhesion molecules. The high frequency of mutations found in members of cellular adhesion complexes in a variety of cancers suggests that these molecules may play a role in development of the malignant phenotype.

Amino Acid Sequence↗

PubMed1996

Further progress towards a catalogue of all Arabidopsis genes: analysis of a set of 5000 non-redundant ESTs.

Nearly 7000 Arabidopsis thaliana-expressed sequence tags (ESTs) from 10 cDNA libraries have been sequenced, of which almost 5000 non-redundant tags have been submitted to the EMBL data bank. The quality of the cDNA libraries used is analysed. Similarity searches in international protein data banks have allowed the detection of significant similarities to a wide range of proteins from many organisms. Alignment with ESTs from the rice systematic sequencing project has allowed the detection of amino acid motifs which are conserved between the two organisms, thus identifying tags to genes encoding highly conserved proteins. These genes are candidates for a common framework in genome mapping projects in different plants.

Amino Acid Sequence↗

PubMed1996

Decreased ileal muscle contractility and increased NOS II expression induced by lipopolysaccharide.

This study was designed to determine if an increase in nitric oxide synthase (NOS) activity induced by lipopolysaccharide (LPS) is associated with increases in NOS II protein and mRNA abundance and with altered ileal longitudinal muscle contractility. Strips of muscle taken from LPS-treated, but not control, animals exhibited reduced in vitro contractility when L-arginine was a component of the physiological salt solution. This reduction was reversed by N omega-nitro-L-arginine (L-NNA), a competitive inhibitor of NOS. Full-thickness segments of jejunum, ileum, and colon taken 5 h after LPS injection exhibited increased NOS activity, NOS II immunoreactivity, and NOS II mRNA abundance. Increased NOS II immunoreactivity and mRNA abundance also were detected in ileal muscle strips taken from LPS-treated animals. These data confirm the reported effects of LPS on intestinal NOS activity and indicate that it can be attributed, at least in part, to an increase in NOS II mRNA and protein abundance. Furthermore, the data suggest that an LPS-induced increase in NOS II may lead to a decrease in ileal muscle contractility.

Animals↗

PubMed1996

Endothelium-dependent effect of perindopril and enalaprilat in rat thoracic aorta.

AIM: To study the effect of the angiotensin-converting enzyme (ACE) inhibitors perindopril (Per) and enalaprilat (Ena) on the reactivity of the endothelium in normal rats. METHODS: Male rats were treated intragastrically with Per (2 mg.kg-1.d-1) or placebo (n = 18) for 6 wk. Aorta was isolated for experiment. Another set of isolated aortic rings with and without endothelium were incubated with Ena (0.1 mumol.L-1) for 30 min. Responses to acetylcholine, serotonin, phenylephrine, sodium nitroprusside (SN), and nitroglycerin (Nit) were observed. RESULTS: Endothelium-dependent relaxation to acetylcholine was augmented in aortic rings from rats treated with Per in comparison with control. The IC50 value (95% confidence limits) decreased from 3.8 (0.56-26.1) mumol.L-1 (control group) to 0.98 (0.28-3.41) mumol.L-1 (Per-treated group). The maximal relaxation was augmented from 62 +/- 9% to 78 +/- 10% (P < 0.01). However, the responses to the endothelium-independent vasodilators, SN and Nit, were similar. Serotonin- and phenylephrine-induced contractions were decreased, which were influenced by basal release of endothelium-derived relaxing factor (EDRF). EC50 values was 6.1 (2.6-14.4) nmol.L-1 vs 8.3 (3.6-18.8) nmol.L-1 in comparison with control group and Per-treated group. The maximal contraction was decreased from 2.42 +/- 0.29 g (control group) to 1.96 +/- 0.25 g (treated group) (P < 0.01). Similar results were found in incubation with Ena. CONCLUSION: Ena and Per enhanced the basic release of EDRF from vascular endothelium.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

[Electroanalytical characteristics of ofloxacin in micellar solution].

In a pH 6.30 buffer solution containing 0.001% Tween-80, ofloxacin (OFX) gives a sensitive polarographic wave at -1.46 V (vs SCE), which can be used for the determination of OFX down to 10(-8) mol.L-1. The linear range is from 1.39 x 10(-7) to 1.39 x 10(-5) mol.L-1. The proposed method was applied to determination of OFX in urine and serum samples with relative standard deviation less than 7.0%.

Humans↗

PubMed1995

Cloning of a new gene encoding an antigen recognized by melanoma-specific HLA-A24-restricted tumor-infiltrating lymphocytes.

The role of tumor-specific T cells in mediating the regression of metastatic melanoma has been suggested by the clinical response of patients to treatment with tumor-infiltrating lymphocytes (TIL). A number of Ags recognized by class I-restricted melanoma-specific T cells have recently been isolated, raising the hope that this will lead to the development of improved therapies. In this study, we report the cloning of a tumor Ag recognized by T cells from melanoma patient 888. Previously, we reported that TIL 888, grown from the tumor of this patient, recognized tyrosinase in an HLA-A24-restricted fashion. This line, when infused into the autologous patient, resulted in complete regression of multiple metastases. Three years later, a second TIL line, TIL 1290, was isolated from a recurrent pelvic tumor. Infusion of a mixture of TIL 888 and TIL 1290 cell lines into the patient resulted in complete regression of a residual abdominal mass and the patient remains disease-free 2 yr later. The TIL 1290 cell line, which recognized melanoma in an HLA-A24-restricted manner, failed to recognize tyrosinase. TIL 1290 was then used to screen an 888 melanoma cDNA library, and an Ag was isolated that did not correspond to any found in sequence databases. This gene, termed p15, was found to be expressed in a variety of normal tissues, and a peptide epitope recognized by TIL 1290 was found to represent the product of an nonmutated gene. Screening of additional cDNA pools resulted in the isolation of a second clone which stimulated TIL 1290. This clone also appeared to represent a transcript of the p15 gene, indicating that this gene may encode the predominant Ag recognized by TIL 1290.

Amino Acid Sequence↗

PubMed1995

Cis-acting elements and expression pattern of the spinach rps22 gene coding for a plastid-specific ribosomal protein.

In order to study the regulation of nuclear genes coding for plastid ribosomal proteins, we have analysed the promoter region of spinach rps22 using both in vitro and in vivo approaches. By footprinting analyses, we have identified eight DNA elements interacting with spinach leaf nuclear factors in the 300 bp promoter region upstream of the transcription start site. Among these elements, four are short AT-rich sequences and one is identical to the Hex motif characterized initially in wheat histone genes. In transgenic tobacco plants, the reporter gene coding for the beta-glucuronidase (GUS) directed by a 1.2 kb upstream region of rps22 was expressed in several plant organs, with high levels in leaf mesophyll, embryo cotyledons and root meristematic cells and very low levels in other cell types. Interestingly, when deleted to -295, the promoter, which contained all the foot-printed elements, was still able to confer the same expression pattern, although the activity was relatively lower than with the 1.2 kb promoter. When deleted further to -154, the promoter, from which the AT-rich elements were eliminated, loses its activity almost completely, suggesting that these AT-rich elements are important for the rps22 promoter activity. Altogether, our results show that rps22 gene expression is controlled by specific cis elements not present in other nuclear-encoded plastid ribosomal protein genes studied so far.

Base Sequence↗

PubMed1995

The growth of meta-analytic literature from 1980 to 1993.

A search of the literature was undertaken to estimate the number of meta-analytic studies that have been published in the social and health sciences to date. Altogether, 1,874 published quantitative reviews were located by the end of 1994: 892 in the health sciences, 982 in the social sciences. Trends from 1980 to 1993 indicate that, while the social sciences embraced the technique earlier, health researchers are now publishing almost twice as many meta-analyses as their social science colleagues.

Data Collection↗

PubMed1995

Realizing the meta-analytic potential--a survey of experts.

A survey of 99 authors of meta-analyses conducted between 1988 and 1993 was undertaken to identify policies and products that might be helpful in the realization of the procedure's ultimate potential. Although a number of differences were found between medical and social/nonmedically related health scientists, the greatest degree of overall enthusiasm for both groups was observed for the need to educate journal editors and primary researchers regarding information that needs to be reported in an empirical study. The respondents were also in general agreement that a consensus should be developed and disseminated on minimum standards for published meta-analyses. A number of the other proposals were less popular, although an argument is made that some of these have actually come to fruition since the original survey was conducted.

Data Collection↗

PubMed1995

[Effect of intracerebroventricular injection of IL-1 beta on generation of immuno-suppressive factor in lymphocytes in stressed mice].

Our previous work showed that a suppressive factor (a protein with large molecular weight) in serum was induced by restraint stress in mice and rats, which suppressed Con A induced lymphocyte proliferation. It was also found that the generation of serum suppressive factor was under control of the central nervous system. Our further study showed that intracerebroventricular (icv) injection of interleukin 1 receptor antagonist (IL-1Ra) antagonised the generation of serum suppressive factor induced by restraint stress and icv injection of interleukin-1 beta (IL-1 beta) increased the generation of the suppressive factor. Our experiment also showed that the serum suppressive factor induced by restraint stress was first made in lymph tissue and then released into blood. The present work was designed to investigate the role of IL-1 in the brain in generation of the suppressive factor in lymph node in mice. Icv injection of IL-1 beta (1 pg/mouse) was shown to significantly increase the generation of the suppressive factor in lymph node. Icv injection of IL-1Ra, however, antagonised generation of the suppressive factor. In mice without restraint stress, both the suppressive factor in serum and in lymph node were found to be induced in dose-dependent manner by icv injection of IL-1 beta. Taken together, these results suggest that IL-1 beta in brain played a very important role in generation of the suppressive factor in lymph node. The positive correlation between the suppressive action of lymph node and of serum added to the evidence that lymph tissue is probably the source of the serum suppressive factor.

Animals↗

PubMed1995

[Intracerebroventricular injection of interleukin 1 receptor antagonist antagonises on the generation of immuno-suppressive factor in restraint mice].

Our previous work showed that a lymphocyte proliferation suppressing factor could be found in the serum of restraint mice. In the present work, it was found that intracerebroventricular (icv) injection of IL-1 receptor antagonist (IL-1Ra) was found capable of suppressing the production of such a serum protein under restraint stress. Nearly complete suppression could be achieved by 5.0 micrograms IL-1Ra. Intracerebroventricular injection of IL-1 beta (1 pg), however, increased the generation of the supressive protein. Neither intraperitoneal (ip) injection of IL-1Ra or IL-1 beta had any effect on the generation of the protein. The fact that icv. injection of a very small dose of IL-1 beta (0.06 fmol) was effective on the generation of the supressive protein led us to suggest that IL-1 in brain might act as an important mediator between CNS and the immune system.

Animals↗