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Biomedical subjects

L Li

Publications and source records attributed to L Li.

At least 901 records · Page 50Linked to original sources
PubMed1999

Egg-laying hormone peptides in the aplysiidae family.

The neuropeptidergic bag cells of the marine mollusc Aplysia californica are involved in the egg-laying behavior of the animal. These neurosecretory cells synthesize an egg-laying hormone (ELH) precursor protein, yielding multiple bioactive peptides, including ELH, several bag cell peptides (BCP) and acidic peptide (AP). While immunohistochemical studies have involved a number of species, homologous peptides have been biochemically characterized in relatively few Aplysiidae species. In this study, a combination of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) and electrospray ionization Fourier transform ion cyclotron resonance MS is used to characterize and compare the ELH peptides from related opisthobranch molluscs including Aplysia vaccaria and Phyllaplysia taylori. The peptide profiles of bag cells from these two Aplysiidae species are similar to that of A. californica bag cells. In an effort to characterize further several of these peptides, peptides from multiple groups of cells of each species were extracted, and microbore liquid chromatography was used to separate and isolate them. Several MS-based sequencing approaches are applied to obtain the primary structures of bag cell peptides and ELH. Our studies reveal that (&agr;)-BCPs are 100 % conserved across all species studied. In addition, the complete sequences of (&egr;)-BCP and ELH of A. vaccaria were determined. They show a high degree of homology to their counterparts in A. californica, with only a few amino acid residue substitutions.

Amino Acid Sequence↗
PubMed1999

Troglitazone improves insulin-stimulated glucose utilization associated with an increased muscle glycogen content in obese Zucker rats.

Recent studies have demonstrated that troglitazone has the capacity to improve insulin resistance. The present study was undertaken to determine the effect of troglitazone on in vivo insulin action, the activities of the pyruvate dehydrogenase (PDH) complex and 3-hydroxyacyl-CoA dehydrogenase (3-HADH) in muscle, and muscle GLUT-4 and glycogen content in obese and lean Zucker rats. Rats were fed a normal chow diet with and without troglitazone as a food admixture (0.2%) for 3 weeks. In vivo insulin action was measured by the sequential euglycemic clamp technique at two different insulin infusion rates (6 and 30 mU/kg BW/min). At the basal (fasting) state and after the clamp studies, the activities of PDH complex and 3-HADH, and the amounts of GLUT-4 and glycogen contained in the red gastrocnemius muscles were determined. Troglitazone treatment produced a significant rise in the metabolic clearance rate of glucose (MCR) during the 6-mU/kg BW/min insulin clamp study (19.5+/-3.9 vs 9.9+/-1.5 ml/kg BW/min, mean+/-SE, P<0.05) in obese rats, but not in lean rats. Troglitazone significantly increased the muscle glycogen content after the clamp study, compared to non-treated rats, in obese rats (9.9+/-0.5 vs 6.5+/-0.4 mg/g tissue, P<0.05) and has the tendency to increase the activity state of PDH complex in obese and lean rats at the fasting state. However, no effect of the drug on muscle GLUT-4 content was found. These results indicate that troglitazone may improve insulin sensitivity associated with increased muscle glycogen content.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1999

Aberrant splicing in the PKD2 gene as a cause of polycystic kidney disease.

It is estimated that approximately 15% of families with autosomal dominant polycystic kidney disease (ADPKD) have mutations in PKD2. Identification of these mutations is central to identifying functionally important regions of gene and to understanding the mechanisms underlying the pathogenesis of the disorder. The current study describes mutations in six type 2 ADPKD families. Two single base substitution mutations discovered in the ORF in exon 14 constitute the most COOH-terminal pathogenic variants described to date. One of these mutations is a nonsense change and the other encodes an apparent missense variant. Reverse transcription-PCR from patient lymphoblast RNA showed that, in addition, both mutations resulted in out-of-frame splice variants by activating cryptic splice sites via different mechanisms. The apparent missense variant produced such a strong splicing signal that the processed transcript from the mutant chromosome did not contain any of the normally spliced, missense product. A third mutation, a nonconservative missense change effecting a negatively charged residue in the third transmembrane span, is likely pathogenic and defines a highly conserved residue consistent with a potential channel subunit function for polycystin-2. The remaining three mutations included two frame shifts resulting from deletion of one or two bases in exons 6 and 10, respectively, and a nonsense mutation due to a single base substitution in exon 4. The study also defined a novel intragenic polymorphism in exon 1 that will be useful in analyzing "second hits" in PKD2. Finally, the study demonstrates that there are reduced levels of normal polycystin-2 protein in lymphoblast lines from PKD2-affected individuals and that truncated mutant polycystin-2 cannot be detected in patient lymphoblasts, suggesting that the latter may be unstable in at least some tissues. The mutations described will serve as critical reagents for future functional studies in PKD2.

Humans↗
PubMed1999

Analysis of mouse intron 7 DNA sequence of the APP gene: comparison with the human homologue.

Mutations in the beta-amyloid precursor protein gene (APP) cause Alzheimer disease (AD) in certain families. The mature protein (APP) exists in several different isoforms resulting from alternative splicing of the primary transcript. Several lines of evidence indicate that particular isoform(s) of APP may contribute to the etiology of AD. One of the isoforms, APP695, lacks the Kunitz protease inhibitor (KPI) domain encoded by exon 7. APP695 is expressed predominantly in neurons, whereas the KPI domain containing isoforms, APP751 and APP770, are expressed ubiquitously. The ratio of APP751/APP695 mRNA tends to increase in the brain of AD patients. Furthermore, this ratio in mouse brain is much lower than that in human brain, and mice are resistant to the spontaneous development of beta-amyloidosis. In addition, transgenic mice that develop pathological changes similar to those of AD expressed more KPI-domain containing APP mRNA than transgenic mice without the changes. Previous studies imply that the controlling elements exist in the flanking sequences of the alternatively-spliced exons. Therefore, we have determined the DNA sequences of intron 7 and made a comparison between mouse and human DNA sequences of intron 7. Mouse intron 7 shares about 50% sequence identity with the human homologue, with higher sequence identity (approximately 85%) mainly in the 5' end (approximately 250 bp) of the intron. A palindromic sequence was found in both human and mouse intron 7 and showed subtle differences in their structure between the two species. Whether this sequence plays any roles in regulating alternative splicing of exon 7 remains to be determined. Human intron 7 contains a Alu element, which possesses potential retinoic acid and thyroid hormone responsive elements that might be involved in the regulation of alternative splicing. Mouse intron 7 sequence also contains a few repeat sequences which are specific to the genome of mice and rats. Homologies shared between human and mouse intron 7 sequences may contribute to the common characteristics of neuron-specific splicing of APP in both species. The unique features of the intron may account for differences between human and mouse brain in fine tuning of alternative splicing of the APP transcript, which may lead to their different susceptibilities to beta-amyloidosis.

Alternative Splicing↗
PubMed1999

Design and preparation of cyclopeptamine antifungal agents.

The lack of agents for infections caused by pathogenic fungi has demanded further investigation of a key lead structure which has shown promise, echinocandin B. In recent years, two analogs of this cyclic hexapeptide are proceeding through the clinic exhibiting proof of concept for the target of these drugs. This target, the ss-1,3-glucan synthesis complex, produces the majority of fungal cell wall glucan in many of the most pathogenic fungi such as Candida. A methodical structure-activity relationship review of several major fragments of these highly functionalized molecules is described. This information is useful for determination of the minimum functional/structural requirements for design of an optimal compound in this series. Analogs are presented with their accompanying whole cell antifungal activities.

Antifungal Agents↗
PubMed1999

[A gene analysis of familial lipoprotein lipase deficiency in China].

OBJECTIVE: To investigate the gene mutation of lipoprotein lipase(LPL) of familial LPL deficiency in China. METHODS: The DNA sequencing of LPL gene of the patients was performed with the dideoxy method based on the polymerase chain reaction amplification using the genomic DNA as a template. RESULTS: It was identified that a missense mutation in exon 6 of LPL gene (6G(979)-->A) resulted in the substitution of Glu(242) by Lys in a heterozygous state. CONCLUSION: The missense mutation of LPL may play a key role in the decrease of LPL activity. This is the first report about the gene mutation of LPL at this site in familial LPL deficiency. Moreover, it contributes to the elucidation of the pathophysiological mechanisms of atherosclerosis and some metabolic diseases.

Adult↗
PubMed1999

Expression in normal human tissues of five nucleotide excision repair genes measured simultaneously by multiplex reverse transcription-polymerase chain reaction.

DNA repair is central to the integrity of the human genome. Reduced DNA repair capacity has been linked to genetic susceptibility to cancer. An adequate expression level of DNA repair genes is essential for normal DNA repair activities. Although there is tissue specificity in the expression, searching for a surrogate tissue is needed for molecular epidemiological studies. In this study, the relative expression levels of five selected human nucleotide excision repair (NER) genes (ERCC1, XPB/ERCC3, XPG/ERCC5, CSB/ERCC6, and XPC) in 20 different types of human normal tissue were simultaneously measured by a new multiplex reverse transcription (RT)-PCR assay using the expression level of the beta-actin gene as an internal control. Transcripts of each of the five NER genes were detectable, but the levels varied in these normal tissues. Both mitogen (phytohemagglutinin)-stimulated and unstimulated human peripheral lymphocytes showed similar expression patterns for the five NER genes. In general, the expression levels of stimulated lymphocytes were also similar to most of the rapidly proliferating tissues, such as the skin, breast, intestine, liver, testis, ovary, placenta, or prostate, but was relatively higher than that of the slowly proliferating or nonproliferating tissues such as adipose, brain, hippocampus, muscle, spleen, or lung. The data suggested that although the five NER genes were expressed at different levels in the normal tissues examined, PHA-stimulated peripheral lymphocytes may be used as a surrogate tissue for estimating expression levels of these genes in proliferating tissues. This new multiplex RT-PCR assay may help detect aberrant expression of these NER genes in both normal and tumor tissues.

Cell Line↗
PubMed1999

Modeling empiric antibiotic therapy evaluation of QID.

At AMIA 1997, we reported on the design and development of a new computer-based tool, called QID, for empiric antibiotic decision support. QID was designed to help physicians identify the antibiotic regimens with the highest probability of covering the pathogens that are most likely to be present in individual patients. QID creates a list of antibiotics, ordered by potential benefit in treatment, for a patient with a suspected infection before culture results are available. Since our initial publication, a "before and after" study has been done using 20 internal medicine residents and the same number of internal medicine attendings. In order to test the hypothesis that physician's would make more appropriate empiric antibiotic choices with the aid of QID, we chose University of Utah physicians and had each evaluate four infectious disease cases that were abstracted from medical record infectious disease cases. Immediately following their initial review and determination of antibiotic therapy for each case, the study participants were presented with QID's antibiotic recommendations on the same case to see if this information would change their initial drug regimen. The tool was shown to have a greater impact on the most difficult cases but statistically improved scores overall (p < .001). Details of our study design and results are presented.

Anti-Bacterial Agents↗
PubMed1999

Genetically fluorescent melanoma bone and organ metastasis models.

We report here the establishment and metastatic properties of bright, highly stable, green fluorescent protein (GFP) expression transductants of the B16 mouse malignant melanoma cell line and the LOX human melanoma line. The highly fluorescent malignant melanoma cell lines allowed the visualization of skeletal and multiorgan metastases after i.v. injection of B16 cells in C57BL/6 mice and intradermal injection of LOX cells in nude mice. The melanoma cell lines were transduced with the pLEIN expression retroviral vector containing the GFP and neomycin resistance genes. Stable B16F0 and LOX clones expressing high levels of GFP were selected stepwise in vitro in levels of G418 of up to 800 microg/ml. Extensive bone and bone marrow metastases of B16F0 were visualized by GFP expression when the animals were sacrificed 3 weeks after cell implantation. Metastases for both cell lines were visualized in many organs, including the brain, lung, pleural membrane, liver, kidney, adrenal gland, lymph nodes, skeleton, muscle, and skin by GFP fluorescence. This is the first observation of experimental skeletal metastases of melanoma, which was made possible by GFP expression. These models should facilitate future studies of the mechanism and therapy of bone and multiorgan metastasis of melanoma.

Animals↗
PubMed1999

Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members.

In a series of 111 patients with squamous cell carcinoma (SCC), we used immunohistochemistry to examine the expression levels of four epidermal growth factor receptor (EGFR) family members (EGFR, HER-2/neu, HER-3, and HER-4). Expression of the EGFR members was not significantly associated with tumor size. However, their expressions (except for HER-4) were significantly associated with the presence of lymph node metastasis, and all of them were significantly associated with distant metastasis. We further examined the association between the expression levels of the EGFR members and the survival rates in 47 oral SCC patients whose detailed clinical follow-ups were available. The expression of all EGFR members was significantly associated with shortened patient survival, and the association was strongest for HER-2/neu. Furthermore, the combination of HER-2, HER-3, and EGFR but not HER-4 significantly improved the predicting power. The expression level of HER-2/neu was significantly correlated with that of EGFR or HER-3. Similar coexpression patterns were also observed in three oral SCC cell lines studied, but not in four other head and neck SCC cell lines. Taken together, these results indicated that expression levels of EGFR, HER-2/ neu, and HER-3 may help predict the outcome of patients with oral SCC.

Adolescent↗
PubMed1999

Cardiac afferents to the nucleus of the tractus solitarius: A WGA-HRP study in the rat.

Central distribution of the sensory fibers of the heart was investigated in the rat by the use of transganglionic transport of horseradish peroxidase (HRP). After the left intercostal thoracotomy was done under deep anesthesia and artificial respiration, wheat germ agglutinin-conjugated HRP (WGA-HRP) was injected into the left and right ventricular walls and the apex of the heart. HRP-labeled fibers were observed to be distributed to the dorsomedial portion of the medulla oblongata through the vagal nerve. The labeled fibers were present in various subnuclei of the nucleus of the tractus solitarius (NTS) bilaterally at the level of +0.36 to -1.74 mm to the obex. However, the most conspicuous feature in the present study was that the labeled fibers were exclusively confined to the medial, ventrolateral and commissural NTS with some distribution to the dorsolateral NTS. Although the labeling in the medial and ventrolateral NTS was observed to extend rostrocaudally, it was of interest that the labeling in the medial NTS was divided into the ventral and dorsal parts at the level around the obex. Accumulation of the labeled fibers in the commissural NTS was found at the level caudal to the obex and these fibers were traced to the caudal portion of its subnucleus with a gradual decrease in number. This pattern of distribution of cardiac afferents in the NTS was considered to be peculiar to the rat, because it was quite different from that reported previously in the cat.

Afferent Pathways↗
PubMed1999

[A prevalence study on injuries among 2,553 children 7-16 years old].

OBJECTIVE: In order to find out the present situation and cause of injuries among children. METHODS: A cluster sampling study on the conditions of injuries was conducted among 2,553 children 7-16 years old during the period of October 1996 to September 1997 in Shantou City, Guangdong Province. RESULTS: There was a trend that the incidence of injuries increased with age among children. The overall incidence of injuries was 37.96% with schoolboys higher than schoolgirls (P < 0.05). There were 38.1% children who had more than two episodes. Falls took the leading type of incidence among both sexes and all age groups. Among the causes of injuries, playing, motion, riding and walking ranked the consecutive leading 4 places. The places where injuries occurred were mainly at home and then on campus. Self injured was mostly seen followed with hurt by others (classmate, sibling, et al). Medium and serious injuries took up 8% with a disability rate of 121.4/100,000. CONCLUSION: Some preventive measures were preliminarily suggested.

Adolescent↗
PubMed1999

[Cellular immunity and epidemiologic analysis of pediatric patients with Mycoplasma pneumonia].

OBJECTIVE: To understand the of immuno-reactions of pediatrics patients with Mycoplasma pneumonia. METHODS: 90 patients suffered from M. pneumonia were administered and divided into three groups: mild group, severe group, and normal control group. T cell subset parameters, natural killer cell and the serumsoluble interleukin-2 recepter of all of above were determined. RESULTS: Data showed:CD4 decreased at both acute and recovery stage of M. pneumonia, while CD8 remarkably increased (t = 2.63, 66, 2.77, 3.36, P < 0.05). SIL-2R level of all patients also greatly increased (t = 5.26, 3.19, P < 0.01), especially in the serious group. CONCLUSION: There are disturbances of cell-immune in M. pneumonia. The level of SIL-2R can serve as monitor on the degree of severeness of M. pneumonia. The incidence M. pneumonia appeared highest in the 10-14 year-old group.

Adolescent↗
PubMed1999

[The changes of plasma endothelin-1 and calcitonin gene-related peptide levels in patients with pregnancy induced hypertension].

OBJECTIVE: To study the changes and clinical significance of plasma endothelin (ET-1) and calcitonin gene-related peptide (CGRP) levels in patients with pregnancy induced hypertension (PIH). METHODS: Plasma ET-1 and CGRP were studied by immunoradiological method in 60 patients with pregnancy induced hypertension (PIH) and 23 normal pregnant women and 20 normal non-pregnant women. RESULTS: The levels of plasma ET-1 in patients with PIH were significantly higher than those in healthy pregnancies (P < 0.01). There was a positive correlation between the plasma ET-1 level and degree of PIH; the higher the ET-1 level, the severer the PIH. The levels of plasma CGRP in patients with moderate and severe PIH decreased significantly than those in healthy pregnancy. There was a negative correlation between the plasma CGRP level and ET-1 level. CONCLUSION: The results suggest that plasma ET-1 and CGRP concentration could be used as indicators for the severity of PIH. CGRP may be one of the antagonists of ET-1 in the pathogenesis of PIH.

Adult↗
PubMed1999

[Influences of gestational hyperglycemia on the function of fetal rat pancreatic islets].

OBJECTIVE: To investigate the influences of gestational hyperglycemia on the function of fetal rat pancreatic islets. METHODS: Twenty-eight pregnant SD rats were randomly allocated into two groups. The study group was continually infused with 30% glucose at the rate of 2 ml/min, while the controls with sterilized distilled water in the same time and at the same rate. The infusion began on day 16.5 post-coitus and lasted for 5 days until the removal of the fetuses. The functions of the beta-cells in fetal rat islets were studied by determining the content of insulin, using the tests of extracting, releasing and perfusing. RESULTS: The data showed that the insulin content of study group (3,329.81 +/- 163.39) ng was significantly higher than that of controls (2,390.04 +/- 151.39) ng (P < 0.05); After 2 hours' incubation in Hanks solution which contained different concentration of glucose, increased insulin secretion was found in the study group (P < 0.05); When the islets were perfused, the insulin peak value of study group was higher and appeared earlier than that of controls. CONCLUSION: Insulin synthesis and secretion function of beta-cells of fetal pancreas from hyperglycemia rats were enhanced and the pancreas had a hypersensitive response to glucose challenge.

Animals↗