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Biomedical subjects

E Li

Publications and source records attributed to E Li.

At least 91 records · Page 5Linked to original sources
PubMed1998

[Clinical significance of P-glycoprotein expression in breast cancer].

OBJECTIVE: To study the clinical significance of P-glycoprotein (P-gp) in breast cancer. METHODS: Expression of P-gp in 60 cases of breast cancer was examined by immunohistochemistry. P-gp expression and response to chemotherapy were comparatively investigated in 19 patients with metastatic breast cancer. RESULTS: The P-gp was positive in 48.3% of the 60 cases of breast cancer. P-gp expression was not related to patients' age, menstruation status, number of axillary lymph nodes involved, clinical stage, histological type, and hormonal receptor status(P > 0.05). The frequency of metastasis (62.1%) and mortality (51.7%) were higher in P-gp positive cases than those in negative cases (16.1% vs 12.9%, P < 0.005). The 5-year survival rate of P-gp positive cases (48.3%) was significantly lower than that of negative cases (87.1%) (P < 0.05). In patients received adjuvant chemotherapy distant metastasis occurred more frequently in P-gp positive cases (94.7%) than in P-gp negative cases (57.1%) (P = 0.0468). More P-gp negative patients (7/9) than positive patients (1/10) were responsive to chemotherapy (P = 0.0055). CONCLUSION: Immunohistochemical examination of P-gp expression is useful in predicting response to chemotherapy and prognosis in breast cancer patients. P-gp positivity is associated with poor prognosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

[Neuroendocrine differentiation in ovarian mucinous tumors].

OBJECTIVE: To investigate the relationship between neuroendocrine differentiation of ovarian mucinous tumors and its genesis. METHODS: A morphologic study on 73 cases of ovarian mucinous tumors (32 benign, 20 borderline, 21 malignant) using immunohistochemical and immunohistochemical/histochemical double staining techniques. RESULTS: The incidences of CgA positive cell in tumors of benign, borderline and malignant were 62.5%, 75%, 76% and that of 5-HT positive cells were 31.3%, 40%, 39% respectively. But these NEC were not evenly distributed. The interesting point was that in four cases of the benign tumors the number of CgA positive cell was more than 30 per cent localizing between the glandular basement membrane and the mucinous epithelial cells. There were also many intermediate cells containing both CgA and PAS positive granules. CONCLUSIONS: The positive rate of CgA was increased corresponding to the lowering down of differentiation grades. The four cases of the benign tumors might be originating from a common stem cell, such as so-called amphocrine cell. The relationship between these four tumors and neuroendocrine differentiation in ovarian mucinous tumors remain further clarified.

Cell Differentiation↗
PubMed1998

[Treating portal hypertension by subtotal splenectomy with retroperitoneal splenic transposition and devascularization: clinical study].

OBJECTIVE: To devise a new surgical procedure for improving the operative effect of portal hypertension caused by hepatic cirrhosis. METHOD: In treatment group, subtotal splenectomy with retroperitoneal transposition was performed in 36 patients of cirrhotic hypertensives. In control group, 36 patients were treated by devascularization. The follow-up period ranged from 3 months to 5.5 years (average 26 months). RESULT: In the treatment group, the rates of disappearance, improvement and absence of changes of esophageal varices were 11.5%, 61.5% and 26.9%, respectively, and in the control group those of improvement were 50.0%, absence of change 45.8% and aggravation 4.2%. There was a significant difference between them (P < 0.05). In the treatment group, hypersplenism disappeared in all. There was also significant difference between the two groups in immunological indexes (P < 0.05). DSA showed abundant collateral circulation in the residual spleen and retroperitoneal wall, which enabled the portal blood flow diverting to retroperitoneal tissues. CONCLUSION: This method possesses the advantages of devascularization and decompression shunt. It is of value in retaining part of spleen in surgical treatment of portal hypertension.

Female↗
PubMed1998

[The habit of flowering and fruiting of Scaphium lychnophorum].

The flowering and fruiting are much different between the trees of Scaphium lychnophorum which were introduced in Jinghong. The trees have on-year of fruiting once 3-4 years and off-year continue 2-3 years. In Jinghong, the low temperature in the early flowering period is one factor among the main factors effecting flowering and fruiting of trees. The trees which vegetative grow flush and which grow on the place in a poor sunlight are effected their flowering and fruiting, too.

Flowers↗
PubMed1997

Disruption of alpha3 connexin gene leads to proteolysis and cataractogenesis in mice.

Gap junction channels formed by alpha3 (Cx46) and alpha8 (Cx50) connexin provide pathways for communication between the fiber cells in the normal transparent lens. To determine the specific role of alpha3 connexin in vivo, the alpha3 connexin gene was disrupted in mice. Although the absence of alpha3 connexin had no obvious influence on the early stages of lens formation and the differentiation of lens fibers, mice homozygous for the disrupted alpha3 gene developed nuclear cataracts that were associated with the proteolysis of crystallins. This study establishes the importance of gap junctions in maintaining normal lens transparency by providing a cell-cell signaling pathway or structural component for the proper organization of lens membrane and cytoplasmic proteins.

Aging↗
PubMed1997

Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2.

Phospholipase A2 (PLA2) enzymes are critical regulators of prostaglandin and leukotriene synthesis and can directly modify the composition of cellular membranes. PLA2 enzymes release fatty acids and lysophospholipids, including the precursor of platelet-activating factor, PAF, from phospholipids. Free fatty acids, eicosanoids, lysophospholipids and PAF are potent regulators of inflammation, reproduction and neurotoxicity. The physiological roles of the various forms of PLA2 are not well defined. The cytosolic form, cPLA2, preferentially releases arachidonic acid from phospholipids and is regulated by changes in intracellular calcium concentration. We have now created 'knockout' (cPLA2-/-) mice that lack this enzyme, in order to evaluate its physiological importance. We find that cPLA2-/- mice develop normally, but that the females produce only small litters in which the pups are usually dead. Stimulated peritoneal macrophages from cPLA2-/- animals did not produce prostaglandin E2 or leukotriene B4 or C4. After transient middle cerebral artery occlusion, cPLA2-/- mice had smaller infarcts and developed less brain oedema and fewer neurological deficits. Thus cPLA2 is important for macrophage production of inflammatory mediators, fertility, and in the pathophysiology of neuronal death after transient focal cerebral ischaemia.

Animals↗
PubMed1997

Baculovirus-mediated expression and characterization of the full-length murine DNA methyltransferase.

The original cDNA sequence reported for the murine DNA methyltransferase (MTase) was not full length. Recently, additional cDNA sequences have been reported that lie upstream of the original and contain an extended open reading frame with three additional ATGs in frame with the coding region [Tucker et al . (1996) Proc. Natl. Acad. Sci. USA , 93, 12920-12925; Yoder et al . (1996) J. Biol. Chem . 271, 31092-31097]. Genomic DNA upstream of this ATG contains two more ATGs in frame and no obvious splice site. We have constructed, and expressed in baculovirus, MTase clones that begin at each of these four ATGs and examined their properties. Constructs beginning with any of the first three ATGs as their initiator methionines give a predominant DNA MTase band of approximately 185 kDa on SDS-PAGE corresponding to translational initiation at the third ATG. The fourth ATG construct gives a much smaller protein band of 173 kDa. The 185 kDa protein was purified by HPLC, characterized by mass spectrometry and has a measured molecular mass of 184 +/- 0.5 kDa. All of these MTases were functional in vitro and steady state kinetic analysis showed that the recombinant proteins exhibit similar kinetic properties irrespective of their length. The homogeneous recombinant enzyme from the fourth ATG construct shows a 2.5-fold preference for a hemi-methylated DNA substrate as compared to an unmethylated substrate, whereas the 185 kDa protein is equally active on both substrates. The kinetic properties of the recombinant enzyme are similar to those reported for the native MTase derived from murine erythroleukemia cells. The new clones are capable of yielding large quantities of intact MTases for further structural and functional studies.

Amino Acid Sequence↗
PubMed1997

The signaling pathway mediated by the type IIB activin receptor controls axial patterning and lateral asymmetry in the mouse.

Vertebrate animals exhibit segmented axial skeletons and lateral asymmetry of the visceral organs. The segment identity of individual vertebrae is believed to be determined by a combination of functionally active Hox genes that have defined expression boundaries along the anteroposterior axis (known as the axial Hox code). Disturbance of the Hox code by ectopic expression or mutation of Hox genes often leads to homeotic transformation of the vertebrae. Largely unknown, however, are the signaling molecules that provide the positional cues for the precise establishment and maintenance of the Hox code. In this study we show that disruption of the type IIB activin receptor (ActRIIB) by gene targeting results in altered expression of multiple Hox genes and abnormal patterning of the vertebrae, similar to but severer than retinoic acid (RA)-induced anterior transformation. We further show that RA and ActRIIB mutation have synergistic effects on vertebral patterning. Activin, Vg-1 and, type II activin receptors have been implicated in regulation of lateral asymmetry during chick and Xenopus development. We show here that the ActRIIB-/- mice die after birth with complicated cardiac defects including randomized heart position, malposition of the great arteries, and ventricular and atrial septal defects. In addition, the heart anomalies are associated with right pulmonary isomerism and splenic abnormalities, recapitulating the clinical symptoms of the human asplenia syndrome. These findings provide genetic evidence that the ActRIIB-mediated signaling pathway plays a critical role in patterning both anteroposterior and left-right axes in vertebrate animals.

Activin Receptors↗
PubMed1997

The isolation and characterization of purified heterocomplexes of recombinant retinoic acid receptor and retinoid X receptor ligand binding domains.

Retinoic acid exerts many of its biological effects by interaction with heterocomplexes of nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). To further examine this interaction, a glutathione S-transferase (GST) fusion protein containing the ligand binding domain of human RXR alpha has been used to copurify the ligand binding domain of human RAR gamma by affinity chromatography over glutathione-agarose. Complexes of recombinant RAR-RXR ligand binding domains retaining full ligand binding capacity were purified, and their interactions with various retinoids were characterized by fluorometric titration and photoaffinity labeling. Analyses of the distribution of limiting amounts of [3H]-all-trans-retinoic acid between cytoplasmic retinoic acid binding proteins, CRABP-I and CRABP-II, and the purified heterocomplexes indicate that all-trans-retinoic acid binds with comparable affinity to CRABP-I and the heterocomplexes, but with approximately 10-fold less affinity to CRABP-II. The aromatic retinoid acitretin, which is used in the treatment of psoriasis, binds relatively poorly to the purified heterocomplexes, although it binds with high affinity to the CRABPs. Acitretin displaces [3H]-all-trans-retinoic acid from the CRABPs and increases retinoic acid occupancy of the heterocomplexes. These results suggest that certain retinoids could potentially perturb the distribution of endogenous retinoic acid between the CRABPs and the nuclear receptors and thus affect retinoid signaling. The purified recombinant complexes should provide a useful model system for further structural analysis of the dimerization interface between the RAR and RXR ligand binding domains.

Acitretin↗
PubMed1997

Female infertility in mice lacking connexin 37.

The signals regulating ovarian follicle development and the mechanisms by which they are communicated are largely undefined. At birth, the ovary contains primordial follicles consisting of meiotically arrested oocytes surrounded by a single layer of supporting (granulosa) cells. Periodically, subsets of primordial follicles undergo further development during which the oocyte increases in size and the granulosa cells proliferate, stratify and develop a fluid-filled antrum. After ovulation, oocytes resume meiosis and granulosa cells retained in the follicle differentiate into steroidogenic cells, forming the corpus luteum. It has been proposed that intercellular signalling through gap junction channels may influence aspects of follicular development. Gap junctions are aggregations of intercellular channels composed of connexins, a family of at least 13 related proteins that directly connect adjacent cells allowing the diffusional movement of ions, metabolites, and other potential signalling molecules. Here we show that connexin 37 is present in gap junctions between oocyte and granulosa cells and that connexin 37-deficient mice lack mature (Graafian) follicles, fail to ovulate and develop numerous inappropriate corpora lutea. In addition, oocyte development arrests before meiotic competence is achieved. Thus, cell-cell signalling through intercellular channels critically regulates the highly coordinated set of cellular interactions required for successful oogenesis and ovulation.

Animals↗
PubMed1997

19F-NMR studies of retinol transfer between cellular retinol binding proteins and phospholipid vesicles.

The cellular retinol binding proteins, CRBP and CRBP II, are implicated in the cellular uptake of retinol and intracellular trafficking of retinol between sites of metabolic processing. 19F-NMR studies of retinol transfer between CRBP and CRBP II and phospholipid vesicles, using either fluorine-labeled ligand or protein, demonstrated that there was significantly more transfer of retinol from CRBP II to lipid vesicles than from CRBP. Differences in how readily protein-bound retinol is released to lipid bilayers may lead to differences in how these two proteins modulate intracellular retinol metabolism.

Animals↗
PubMed1997

Lamivudine is effective in suppressing hepatitis B virus DNA in Chinese hepatitis B surface antigen carriers: a placebo-controlled trial.

Lamivudine is a novel 2',3'-dideoxy cytosine analogue that has potent inhibitory effects on hepatitis B virus replication in vitro and in vivo. We performed a single-blind, placebo-controlled study to assess its effectiveness and safety in Chinese hepatitis B surface antigen (HBsAg) carriers. Forty-two Chinese HBsAg carriers were randomized to receive placebo (6 patients) or lamivudine orally in dosages of 25 mg, 100 mg, or 300 mg daily (12 patients for each dosage). The drug was given for 4 weeks. The patients were closely monitored clinically, biochemically, and serologically up to 4 weeks after drug treatment. All 36 patients receiving lamivudine had a decrease in hepatitis B virus (HBV) DNA values of >90% (P < .001 compared with placebo). Although 25 mg of lamivudine was slightly less effective than 100 mg (P = .011) and 300 mg (P = .005), it still induced 94% suppression of HBV DNA after the fourth week of therapy. HBV DNA values returned to pretreatment levels within 4 weeks of cessation of therapy. There was no change in the hepatitis B e antigen status or in aminotransferase levels. No serious adverse events were observed. In conclusion, a 4-week course of lamivudine was safe and effective in suppression of HBV DNA in Chinese HBsAg carriers. The suppression was >90% but reversible. Studies with long-term lamivudine administration should be performed to determine if prolonged suppression of HBV DNA can be achieved.

Adolescent↗
PubMed1997

Treatment participation and outcome among problem drinkers in a managed care alcohol outpatient treatment program.

This article uses Markov analysis to investigate patterns of treatment participation of 361 patients treated in the alcohol and drug abuse programs of a large group model Health Maintenance Organization (HMO) to examine how participation is related to abstinence. Findings indicate that 82% of the patients in treatment one month after intake were in treatment three months later, and treatment retention dropped to 46% by month 6. Findings also indicate that 74% of patients abstinent and in treatment at month 1 remained so at month 3. Abstinence at the first three-month interval was a strong predictor of abstinence at later time periods. A multivariate analysis showed that an expressed desire to stop alcohol use upon entry into treatment was the most consistent predictor of both treatment participation and abstinence at most time points. Treatment participation was also a significant predictor of abstinence.

Adolescent↗
PubMed1997

Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality.

The adult mammalian cortex is characterized by a distinct laminar structure generated through a well-defined pattern of neuronal migration. Successively generated neurons are layered in an "inside-out" manner to produce six cortical laminae. We demonstrate here that p35, the neuronal-specific activator of cyclin-dependent kinase 5, plays a key role in proper neuronal migration. Mice lacking p35, and thus p35/cdk5 kinase activity, display severe cortical lamination defects and suffer from sporadic adult lethality and seizures. Histological examination reveals that the mutant mice lack the characteristic laminated structure of the cortex. Neuronal birth-dating experiments indicate a reversed packing order of cortical neurons such that earlier born neurons reside in superficial layers and later generated neurons occupy deep layers. The phenotype of p35 mutant mice thus demonstrates that the formation of cortical laminar structure depends on the action of the p35/cdk5 kinase.

Animals↗
PubMed1997

Chromosome 3p14 homozygous deletions and sequence analysis of FRA3B.

Loss of heterozygosity (LOH) involving 3p occurs in many carcinomas but is complicated by the identification of four distinct homozygous deletion regions. One putative target, 3p14.2, contains the common fragile site, FRA3B, a hereditary renal carcinoma-associated 3;8 translocation and the candidate tumor suppressor gene, FHIT. Using a approximately 300 kb comsid/lambda contig, we identified homozygous deletions in cervix, breast, lung and colorectal carcinoma cell lines. The smallest deletion (CC19) was shown not to involve FHIT coding exons and no DNA sequence alterations were present in the transcript. We also detected discontinuous deletions as well as deletions in non-tumor DNAs, suggesting that FHIT is not a selective target. Further, we demonstrate that some reported FHIT aberrations represent normal splicing variation. DNA sequence analysis of 110 kb demonstrated that the region is high in A-T content, LINEs and MER repeats, whereas Alu elements are reduced. We note an intriguing similarity in repeat sequence composition between FRA3B and a 152 kb segment from the Fragile-X region. We also identified similarity between a FRA3B segment and a small polydispersed circular DNA. In contrast to the selective loss of a tumor suppressor gene, we propose an alternative hypothesis, that some putative targets including FRA3B may undergo loss as a consequence of genomic instability. This instability is not due to DNA mismatch repair deficiency, but may correlate in part with p53 inactivation.

Acid Anhydride Hydrolases↗
PubMed1997

Mammalian cell expression of dimeric small immune proteins (SIP).

We have designed and expressed bivalent small immune proteins (SIP) based on scFv fragments connected through a short linker of four amino acids to the CH3 domain of the human immunoglobulin gamma 1 H-chain. Three different versions have been designed and expressed in mammalian cells. In one construct a cysteine residue was included in the last amino acid of the flexible 15-amino acid long linker connecting the V(L) and V(H) domains, thus creating a disulphide bond stabilized molecule. A version with a shorter (five amino acids) V(L)/V(H) linker was also produced and shown to be efficiently assembled and secreted. All three SIPs form dimers retaining their antigenic specificity in Western blotting and having a comparable functional affinity (avidity) as determined by ELISA.

Animals↗
PubMed1997

Human intestinal epithelial cells produce proinflammatory cytokines in response to infection in a SCID mouse-human intestinal xenograft model of amebiasis.

The protozoan parasite Entamoeba histolytica causes amebic dysentery and amebic liver abscess, diseases associated with significant morbidity and mortality worldwide. E. histolytica infection appears to involve the initial attachment of amebic trophozoites to intestinal epithelial cells, followed by lysis of these cells and subsequent invasion into the submucosa. A recent in vitro study (L. Eckmann, S. L. Reed, J. R. Smith, and M. F. Kagnoff, J. Clin. Invest. 96:1269-1279, 1995) demonstrated that incubation of E. histolytica trophozoites with epithelial cell lines results in epithelial cell production of inflammatory cytokines, including interleukin-1 (IL-1) and IL-8, suggesting that intestinal epithelial cell production of cytokines might play a role in the inflammatory response and tissue damage seen in intestinal amebiasis. To determine whether intestinal epithelial cell production of IL-1 and IL-8 occurs in response to E. histolytica infection in vivo and as an approach to studying the specific interactions between amebic trophozoites and human intestine, we used a SCID mouse-human intestinal xenograft (SCID-HU-INT) model of disease, where human intestinal xenografts were infected with virulent E. histolytica trophozoites. Infection of xenografts with E. histolytica trophozoites resulted in extensive tissue damage, which was associated with the development of an early inflammatory response composed primarily of neutrophils. Using oligonucleotide primers that specifically amplify human IL-1beta and IL-8, we could demonstrate by reverse transcription PCR that mRNA for both IL-1beta and IL-8 is produced by human intestinal xenografts in response to amebic infection. The increase in human intestinal IL-1beta and IL-8 in response to invasive amebiasis was confirmed by enzyme-linked immunosorbent assays specific for human IL-1beta and IL-8. Using immunohistochemistry, we confirmed that human intestinal epithelial cells were the source of IL-8 in infected xenografts and established that IL-8 production can occur at sites distal to areas of intestinal mucosal damage. These results demonstrate that human intestinal epithelial cells can produce inflammatory cytokines in response to infection in vivo and establish the SCID-HU-INT model as a system for studying the interactions between E. histolytica and human intestine.

Animals↗