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Biomedical subjects

C Li

Publications and source records attributed to C Li.

At least 559 records · Page 31Linked to original sources
PubMed1999

Characterization of the neuroanatomical distribution of agouti-related protein immunoreactivity in the rhesus monkey and the rat.

Agouti-related protein (AGRP) is a recently described homolog of the skin agouti protein. AGRP is transcribed primarily in the adrenal and hypothalamus and is a high affinity antagonist of the neural melanocortin-3 and melanocortin-4 receptors. The perikarya expressing AGRP messenger RNA are found in the arcuate nucleus of the rat and rhesus monkey. Using a polyclonal antibody against the pharmacologically active domain of AGRP (amino acids 83-132), we have also characterized the distribution of AGRP-immunoreactive neurons in both species. The major fiber tracts are conserved in both species, with dense projections originating in the arcuate nucleus and proceeding along the third ventricle. Dense fiber bundles are also visible in the paraventricular, dorsomedial, and posterior nuclei in the hypothalamus, in the bed nucleus of the stria terminalis, and in the lateral septal nucleus of the septal region. AGRP-containing neurons are not visualized in a number of areas, including portions of the amygdala, thalamus, and brain stem, that express MC3-R and MC4-R messenger RNA and receive innervation from POMC neurons that serve as the source of melanocortin agonists. Thus, AGRP is most likely to be involved in modulating a conserved subset of the physiological functions of central melanocortin peptides. Based on the particular distribution of AGRP neurons, those functions are likely to include the central control of energy homeostasis.

Animals↗
PubMed1999

Altered expression of agouti-related protein and its colocalization with neuropeptide Y in the arcuate nucleus of the hypothalamus during lactation.

During lactation, the levels of neuropeptide Y (NPY), which plays an important role in mediating food intake, are significantly elevated in a number of hypothalamic areas, including the arcuate nucleus (ARH). To identify additional hypothalamic systems that might be important in mediating the increase in food intake and alterations in energy homeostasis during lactation, the present studies examined the expression of agouti-related protein (AGRP), a recently described homologue of the skin agouti protein. AGRP is found in the hypothalamus and has been suggested to play an important role in the regulation of food intake. In the first experiment, animals were studied during diestrus of the estrous cycle, a stage of the cycle when estrogen levels are basal and similar to lactation, or during days 12-13 postpartum. Lactating animals had their litters adjusted to eight pups on day 2 postpartum. Brain tissue sections were used to measure AGRP messenger RNA (mRNA) levels by in situ hybridization. AGRP mRNA signal was found mostly in the ventromedial portion of the ARH, which has been shown to contain a high density of NPY neurons. A significant increase in AGRP mRNA content was observed in the mid- to caudal portion of the ARH of lactating animals compared with diestrous females. No difference was found in the rostral portion of the ARH. In the second experiment, double-label in situ hybridization for AGRP and NPY was performed in lactating animals to determine the extent of colocalization of the two peptides in the ARH, using 35S-labeled and digoxigenin-labeled antisense complementary RNA probes. It was found that almost all of the NPY-positive neurons throughout the ARH also expressed AGRP mRNA signal. Furthermore, AGRP expression was confined almost exclusively to NPY-positive neurons. Thus, the present study showed that during lactation, AGRP gene expression was significantly elevated in a subset of the AGRP neurons in the ARH. The high degree of colocalization of AGRP and NPY, coupled with previous reports from our laboratory demonstrating increased NPY expression in the ARH in response to suckling, suggests that AGRP and NPY are coordinately regulated and may be involved in the increase in food intake during lactation.

Agouti Signaling Protein↗
PubMed1999

Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5.

The transforming growth factor-beta (TGF-beta) signals are mediated by a family of at least nine SMAD proteins, of which SMAD5 is thought to relay signals of the bone morphogenetic protein (BMP) pathway. To investigate the role of SMAD5 during vertebrate development and tumorigenesis, we disrupted the Smad5 gene by homologous recombination. We showed that Smad5 was expressed predominantly in mesenchyme and somites during embryogenesis, and in many tissues of the adult. Mice homozygous for the mutation died between days 10.5 and 11.5 of gestation due to defects in angiogenesis. The mutant yolk sacs lacked normal vasculature and had irregularly distributed blood cells, although they contained hematopoietic precursors capable of erythroid differentiation. Smad5 mutant embryos had enlarged blood vessels surrounded by decreased numbers of vascular smooth muscle cells, suffered massive apoptosis of mesenchymal cells, and were unable to direct angiogenesis in vitro. These data suggest that SMAD5 may regulate endothelium-mesenchyme interactions during angiogenesis and that it is essential for mesenchymal survival.

Animals↗
PubMed1999

Education attainment as a predictor of HIV risk in rural Uganda: results from a population-based study.

We examined the association between education and prevalent HIV-1 infection in the Rakai district, rural Uganda based on a cross-sectional analysis of a population-based cohort. In 1990, 1397 men and 1705 women aged 13 years and older, were enrolled in 31 randomly selected communities. Strata were comprised of main road trading centres, secondary road trading villages and rural villages. Sociodemographic and behavioural data were obtained by interview and serum for HIV serostatus were obtained in the home. The analysis examines the association between sex-specific prevalent HIV infection and educational attainment, categorized as secondary, primary or none. The odds ratios (ORs) and 95% confidence intervals (95% CIs) of HIV infection were estimated, using no education as the referent group. Higher levels of education were associated with a higher HIV seroprevalence in bivariate analyses (OR 2.7 for primary and 4.1 for secondary education, relative to no education). The strength of the association was diminished but remained statistically significant after multivariate adjustment for sociodemographic and behavioural variables (adjusted OR of HIV infection 1.6 (95% CI: 1.2-2.1)) for primary education and 1.5 (95% CI: 1.0-2.2) for secondary education. Stratified multivariate analyses by place of residence indicated that the association between education and HIV prevalence was statistically significant in the rural villages, but not in the main road trading centres and intermediate trading villages. Educational attainment is a significant predictor of HIV risk in rural Uganda, in part because of risk behaviours and other characteristics among better educated individuals. Preventive interventions need to focus on better educated adults and on school-aged populations.

Adolescent↗
PubMed1999

Drug, meal and formulation interactions influencing drug absorption after oral administration. Clinical implications.

Drug-drug, drug-formulation and drug-meal interactions are of clinical concern for orally administered drugs that possess a narrow therapeutic index. This review presents the current status of information regarding interactions which may influence the gastrointestinal (GI) absorption of orally administered drugs. Absorption interactions have been classified on the basis of rate-limiting processes. These processes are put in the context of drug and formulation physicochemical properties and oral input influences on variable GI physiology. Interaction categorisation makes use of a biopharmaceutical classification system based on drug aqueous solubility and membrane permeability and their contributions towards absorption variability. Overlaying this classification it is important to be aware of the effect that the magnitudes of drug dosage and volume of fluid administration can have on interactions involving a solubility rate limits. GI regional differences in membrane permeability are fundamental to the rational development of extended release dosage forms as well as to predicting interaction effects on absorption from immediate release dosage forms. The effect of meals on the regional-dependent intestinal elimination of drugs and their involvement in drug absorption interactions is also discussed. Although the clinical significance of such interactions is certainly dependent on the narrowness of the drug therapeutic index, clinical aspects of absorption delays and therapeutic failures resulting from various interactions are also important.

Administration, Oral↗
PubMed1999

Writing Chinese characters and success on Mental Rotation Test.

Our recent study with Chinese and Chinese-American undergraduates indicated that writing Chinese characters was associated with better performance on the Piagetian Water-Level Task for Chinese-American men. The current study investigated whether the same effects would apply to the Vandenberg Mental Rotation Test. Two alternative hypotheses (bilingualism and birth place) were also tested. Participants were two groups of Chinese-American undergraduates: 48 writers of Chinese (21 men, 27 women) and 130 nonwriters of Chinese (58 men, 72 women). Analysis suggested that writing Chinese and birth in the USA contributed significantly to the success on Mental Rotation Test. Students who were born in the USA and able to write Chinese scored the highest on this test. Being bilingual was not associated with performance on the Mental Rotation Test. Men performed significantly better than women.

Analysis of Variance↗
PubMed1999

Implementation of substance use screening in prenatal clinics.

BACKGROUND AND OBJECTIVES: To reduce women's consumption of alcohol and other drugs during pregnancy, the Department of Epidemiology for the Aberdeen Area Indian Health Service (AAIHS) promoted a maternal substance use screening program for prenatal clinics in 1992. This report describes the adherence to the screening protocol at AAIHS facilities and barriers to such screening. METHODS: Prenatal clinic staff members at 20 AAIHS health care facilities were surveyed to determine the extent of prenatal substance use screening and the barriers to its implementation. The medical records of a random sample of 235 women who sought prenatal care at five hospitals were reviewed to determine whether prenatal clinic staff adhered to the screening protocol. RESULTS: Of the 20 health care facilities, 13 (65%) had implemented the screening. The major barriers to implementing screening were lack of training in prenatal substance use screening and lack of clinic staff designated to administer the screening protocol. Though not statistically significant, our data suggest that women not administered the screening questionnaire were more likely to be multiparous (prevalence ratio = 2.1; 95% confidence interval = 0.9, 4.5). CONCLUSIONS: To improve screening of pregnant women for substance use, prenatal clinic staff members should address administrative barriers and assess adherence of health care providers and patients to the screening protocol. Training of prenatal clinic personnel is essential to implement optimal maternal substance use screening in prenatal clinics.

Female↗
PubMed1999

Cimetidine transport in brush-border membrane vesicles from rat small intestine.

In previous studies, sulfoxide metabolite was observed in animal and human intestinal perfusions of cimetidine and other H2-antagonists. A sequence of follow-up studies is ongoing to assess the intestinal contributions of drug metabolism and drug and metabolite transport to variable drug absorption. An evaluation of these contributions to absorption variability is carried out in isolated fractions of the absorptive cells to uncouple the processes involved. In this report, data is presented on the drug entry step from a study on [3H]cimetidine uptake into isolated brush-border membrane vesicles from rat small intestine. A saturable component for cimetidine uptake was characterized with a Vmax and Km (mean +/- S.E.M.) of 6.1 +/- 1.5 nmol/30s/mg protein and 8.4 +/- 2.0 mM, respectively. Initial binding, and possibly intravesicular uptake, was inhibited by other cationic compounds including ranitidine, procainamide, imipramine, erythromycin, and cysteamine but not by TEA or by the organic anion, probenecid. Initial uptake was not inhibited by amino acids methionine, cysteine, or histidine, by the metabolite cimetidine sulfoxide, or by inhibitors of cimetidine sulfoxidation, methimazole, and diisothiocyanostilbene-2,2'-disulfonic acid. Equilibrium uptake was inhibited by ranitidine, procainamide, and cysteamine but not by erythromycin or imipramine. Initial cimetidine uptake was stimulated by an outwardly directed H+ gradient, and efflux was enhanced by an inwardly directed H+ gradient. Collapse of the H+ gradient as well as voltage-clamping potential difference to zero significantly reduced initial cimetidine uptake. The data is supportive of both a cimetidine/H+ exchange mechanism and a driving-force contribution from an inside negative proton or cation diffusion potential.

Animals↗
PubMed1999

Intestinal metabolism and transport of 5-aminosalicylate.

The purpose of this study was to determine the characteristics of intestinal absorption and metabolism of 5-aminosalicylic acid (5ASA). Regional perfusions of 5ASA in the anesthetized rat resulted in the appearance of N-acetyl-5-aminosalicylic acid in the intestinal lumen. Lumenal metabolite appearance was proportional to 5ASA permeability, which was 5-fold higher in the jejunum than in the ileum. Intestinal elimination significantly decreases 5ASA absorption at low lumenal drug concentrations and this process is saturated at high drug concentrations. Metabolite levels in intestinal tissue were higher than plasma levels at low perfusion drug concentrations, whereas the reverse was observed at high concentrations. Transport and metabolism of 5ASA was studied in Caco-2 monolayers. At low drug concentrations, 5ASA was preferentially transported in the basolateral (BL) to apical (AP) direction. With 5ASA incubation in either the AP or BL chamber, the N-acetyl metabolite appeared only in the AP compartment. Transport of N-acetyl-5-aminosalicylic acid was also exclusively observed in the BL to AP direction. Clinical data indicate that anti-inflammatory response to oral 5ASA correlates with the amount of 5ASA delivered to the intestinal tissue. This study shows that at lumenal levels below 200 microg/ml (concentrations that are typically achieved by controlled release dosage forms), intestinal secretion of 5ASA accounts for more than 50% of the total elimination and can significantly affect tissue levels and, therefore, may be an important factor in determining the response to 5ASA therapy.

Animals↗
PubMed1999

Antitumor activity of poly(L-glutamic acid)-paclitaxel on syngeneic and xenografted tumors.

Poly(L-glutamic acid)-paclitaxel (PG-TXL) is a new water-soluble paclitaxel derivative that has shown remarkable antitumor activity against both ovarian and breast tumors. The purpose of this study was to test whether the antitumor efficacy of PG-TXL depends on tumor type, as is the case for paclitaxel, and to test whether paclitaxel-resistant tumors could be responsive to PG-TXL. We evaluated the therapeutic activity of PG-TXL against four syngeneic murine tumors (MCa-4, MCa-35, HCa-1, and FSa-II) inoculated i.m. into C3Hf/Kam mice, a human SKOV3ip1 ovarian tumor injected i.p. into nude mice, and a human MDA-MB-435Lung2 breast tumor grown in the mammary fat pad of nude mice. Two paclitaxel-responsive murine tumors, MCa-4 and MCa-35, showed significant growth delay with PG-TXL given as a single i.v. injection at its maximum tolerated dose of 160 mg of equivalent paclitaxel/kg or even at a lower dose of 120 mg of equivalent paclitaxel/kg. The other two murine tumors, HCa-1 and FSa-II, did not respond particularly well to either of the two agents, although significant growth delay was observed for both tumors with PG-TXL. In mice with SKOV3ip1 tumors, the median survival times for mice treated with PG alone and PG-TXL at doses of 60 or 120 mg of equivalent paclitaxel/kg were 43, 61, and 75 days, respectively; no survival difference was found between paclitaxel-treated and Cremophor vehicle-treated mice. In mice with MDA-MB-435Lung2 tumor, PG-TXL at a dose of 120 mg of equivalent paclitaxel/kg produced regression of the tumor in 50% of the animals, and in the remaining mice, micrometastases in the lung were found only in 25% of the animals. In comparison, treatment with paclitaxel at 60 mg/kg did not result in tumor regression, and the rate of lung metastases was 42%. These results clearly demonstrate that PG-TXL has significant therapeutic activity against breast and ovarian tumors tested in this study. Future studies to elucidate the mechanism of action of PG-TXL and to assess its clinical applications are warranted.

Animals↗
PubMed1999

UV Resonance Raman Spectroscopic Identification of Titanium Atoms in the Framework of TS-1 Zeolite.

Framework titanium atoms in titanium-substituted silicalite (TS-1) can be identified by UV resonance Raman spectroscopy since the associated Raman bands at 1125, 530, and 490 cm(-1) (see figure) are observed only when the charge transfer transition associated with the framework Ti atoms is excited by a UV laser. Thus, framework Ti atoms can be distinguished from nonframework Ti atoms and other defect sites. This method can be applicable to identifying transition metal atoms in the frameworks of other molecular sieves.

Journal Article↗
PubMed1999

Distinct deleted regions on chromosome segment 16q23-24 associated with metastases in prostate cancer.

Cadherins (CDH) are cell adhesion molecules and their dysfunctions have been implicated in the development of cancer metastases. Several cadherin genes are tandemly located on 16q, which is frequently deleted in prostate cancer. We therefore used 22 markers on 16q to localize important deleted regions in metastases of this tumor. We found 16q deletions in 24/32 (75%) tumors. All lymph node and brain metastases showed extensive deletions, while 52% of primary tumors displayed limited deletions. Commonly deleted regions (CDRs) on 16q23-24, CDR2 (D16S515-D16S516) and CDR4 (D16S520-D13S3028), were strongly associated with metastases and increased Gleason score. Reduced CDH1 (E-cadherin) expression was seen in 16/32 (50%) tumors, but the CDH1 gene is not within either of these two regions. Sequencing analysis for all 16 exons of the CDH1 gene did not reveal any mutations in 10 tumors, including three brain metastases with both 16q22.1 deletion and absent E-cadherin expression. Our results implicate other, yet unidentified genes on 16q23-24 to be the frequent targets of mutations and deletions in prostate cancer metastases.

Aged↗
PubMed1999

Arginine methylation of a glycine and arginine rich peptide derived from sequences of human FMRP and fibrillarin.

N-methylation at the arginine residues in RNA binding proteins with the arginine and glycine rich RGG box has been identified. We show that a synthetic peptide R9 (GGRGRGGGF) with the RGG sequence present in human fibrillarin and fragile X mental retardation protein (FMRP) can be specifically methylated by rat brain extract. A control peptide K9 with all arginines replaced by lysines could not be methylated under the same conditions, indicating that the arginines in the peptide were the methylation sites. A novel missense mutation, which changes an arginine to a histidine in the RGG box region of FMRP in a typical fragile X patient, has been identified. A synthetic peptide with this Arg-->His (GGRGHGGGF) substitution was methylated by our in vitro methylation system to a much less extent. Amino acid analysis of the methylated R9 peptide identified the methylated amino acid as monomethylarginine. The R9 peptide may be useful for further studies on arginine methylation in RGG proteins.

Amino Acid Sequence↗
PubMed1999

The expression of p53 tumor suppressor gene in breast cancer cells is down-regulated by cytokine oncostatin M.

Previously (J. Liu, et al., Cell Growth Differ., 8: 667-676, 1997), we showed that oncostatin M (OM), a cytokine produced by activated T cells and macrophages, inhibited the proliferation of breast cancer cells derived from solid tumors and malignant effusions. OM-treated cells showed reduced growth rates and differentiated phenotypes. Because the p53 tumor suppressor protein plays an important role in cellular proliferation, we examined p53 protein expression in three OM-responsive breast cancer cell lines, MCF-7, MDA-MB231, and H3922. Western blot analysis showed that p53 protein levels in all three of the cell lines were decreased by OM treatment. Reduction of p53 protein was detected after 1 day of OM treatment and reached maximal suppression of 10-20% of control after 3 days in H3922 and 40% of control after 4 days in MCF-7 cells. A comparison of p53 mRNA in OM-treated cells versus untreated control cells showed that exposure to OM reduced the steady-state levels of p53 mRNA transcripts to an extent similar to that of the p53 protein levels. This observation suggests that the effect of OM on p53 protein expression does not occur at the posttranslational level. Nuclear run-on assays verified that OM decreased the number of actively transcribed p53 mRNAs, which suggests a transcriptional regulatory mechanism. The effect of OM on p53 expression seems to be mediated through the extracellular signal-regulated kinase (ERK) pathway, inasmuch as the inhibition of ERK activation with a specific inhibitor (PD98059) to the ERK upstream kinase mitogen/extracellular-regulated protein kinase kinase abrogated the OM inhibitory activity on p53 expression in a dose-dependent manner. In addition to OM, we showed that the p53 protein expression in MCF-7 cells was also decreased by phorbol 12-myristate 13-acetate treatment (PMA). Because both OM and PMA induce MCF-7 cells to differentiate, our data suggest that p53 expression in breast cancer cells is down-regulated during the differentiation process.

Blotting, Western↗
PubMed1999

A non-radioactive polymerase chain reaction method for diagnosis of Machado-Joseph disease.

Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) is caused by unstable CAG trinucleotide repeat expansion in the coding region of the MJD gene. In this study, we describe a non-radioactive polymerase chain reaction (PCR) method to detect the CAG repeat range of the MJD gene. This technique allows direct visualization of the PCR products on ethidium bromide-stained agarose gels within hours. In this study, genomic DNA samples isolated from peripheral lymphocytes, amniotic fluid cells, and chorionic villi were tested with two sets of commonly used MJD primers. PCR conditions were optimized, which resulted in clear visualization of both the primer sets on 3% agarose gels. Ten out of 25 candidate MJD patients have been identified with this method to date, with no false-positive or false-negative diagnoses. This simple, reliable, and cost-effective method can be used for patient diagnosis, pre-symptomatic diagnosis, and prenatal diagnosis.

Humans↗
PubMed1999

[An investigation of small marker chromosome in eight Turner syndrome patients by fluorescence in situ hybridization and DNA analysis].

OBJECTIVE: To direct genetic counseling and identify the origin of small marker chromosome in patients with Turner syndrome stigmata. METHODS: The specific primer on the sex determining region on Y (SRY) and biotin labeled X- and Y-chromosome DNA probes were utilized in the analysis of sex chromosome-derived markers. The PCR product from the amplification was detected on agarose gel, and fluorescence in situ hybridization (FISH) was conducted to metaphase chromosome. RESULTS: In 8 patients who had a small marker chromosome, five markers were derived from the X chromosome and three from the Y chromosome. Two patients with a Y-derived marker were determined by Y-chromosome probe as well as by SRY sequences amplification. One patient with a Y-derived marker was only demonstrated by FISH. CONCLUSION: The findings of this study demonstrate successfully the value and necessity of FISH utilizing DNA probes combined with specific amplification on SRY gene in the identification of sex chromosome marker. Such identification is important not only for clinical care, but also for understanding phenotype-karyotype correlations.

DNA-Binding Proteins↗
PubMed1999

Treatment of postapoplectic thalamic spontaneous pain by electroacupuncture at huatuojiaji points.

The authors have treated 30 cases of postapoplectic thalamic spontaneous pain (PTSP) by electro-acupuncture at Huatuojiaji points (Extra), with the other 30 cases of PTSP treated by oral administration of carbamazepine as the controls. The total effective rate was 90% in the acupuncture group, and 86.7% in the control group. The difference in the total effective rate between the two groups was not statistically significant (P > 0.05), suggesting that electroacupuncture at Huatuojiaji (Extra) is a better therapy for PTSP.

Acupuncture Points↗