Biomedical subjects

S Li

Publications and source records attributed to S Li.

At least 1,423 records · Page 79Linked to original sources

PubMed1994

Cloning and expression of a prostaglandin E receptor EP3 subtype from human erythroleukaemia cells.

Prostaglandins inhibit platelet activation by stimulating intracellular cyclic AMP formation. We have postulated that intracellular cyclic AMP levels in platelets are buffered by a distinct prostaglandin receptor that mediates inhibition of cyclic AMP formation. In order to provide evidence for the model, we have cloned the cDNA coding for a prostaglandin receptor EP3 subtype, which is coupled to inhibition of adenylate cyclase, from the megakaryocytic cell line human erythroleukaemia (HEL) cells. A PCR-generated hybridization probe, produced using primers based on the sequence of the mouse prostaglandin EP3 receptor published by Sugimoto, Namba, Honda, Hayashi, Negishi, Ichikawa and Narumiya [(1992) J. Biol. Chem. 267, 6463-6466], was used to screen a lambda gt11 HEL cell cDNA library. The composite full-length cDNA clone HEP3, generated from the two partial clones pHEP3-7 and pHEP3-5, is 1.6 kb long with an open reading frame coding for 390 amino acids. This clone is 83% identical to the alpha subtype of the mouse EP3 receptor. The full-length construct was transfected into COS-1 cells. The cloned receptor exhibited the properties of a prostaglandin EP3 subtype, inhibiting forskolin-stimulated cyclic AMP formation in response to prostaglandin E2 (PGE2) and binding PGE2 with high specificity and a Kd of 3.2 nM. Radiolabelled PGE2 could be displaced by prostaglandins in the order PGE2 = PGE1 > iloprost = PGD2. Northern blot analysis revealed that the receptor is also present in human kidney.

Amino Acid Sequence↗

PubMed1994

Insight into E-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/EGF domains.

The three-dimensional structure of the ligand-binding region of human E-selectin has been determined at 2.0 A resolution. The structure reveals limited contact between the two domains and a coordination of Ca2+ not predicted from other C-type lectins. Structure/function analysis indicates a defined region and specific amino-acid side chains that may be involved in ligand binding. These features of the E-selectin/ligand interaction have important implications for understanding the recruitment of leukocytes to sites of inflammation.

Amino Acid Sequence↗

PubMed1994

Cross-competition between vasoactive intestinal peptide and somatostatin for binding to tumor cell membrane receptors.

Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide with a wide range of biological activities. Recent data suggest that functional VIP receptors are expressed on various tumor cells. Somatostatin (SST) and its long-acting analogue octreotide (OCT) are potent inhibitors of tumor cell growth and secretion. In the present study, the interactions between VIP and SST/OCT on primary tumors (insulinomas, n = 3; VIPomas, n = 2; intestinal adenocarcinomas, n = 5; neuroblastomas, n = 5; papillary thyroid cancers, n = 7; carcinoids, n = 5; ductal breast cancers, n = 8; small cell lung cancers, n = 3; ACTH-producing hypophyseal adenomas, n = 5; pheochromocytomas, n = 5) as well as on tumor cell lines (A431, HT29, PANC1, COLO320, HMC1, and KU812 cells) were analyzed by use of 123I-labeled VIP and 123I-labeled Tyr-3-OCT. Cross-competition between VIP and SST/OCT for binding to tumor cells was observed. The rank-order of potency for displacement of 123I-labeled VIP binding to intact A431 cells was VIP [concentration causing half-maximal inhibition (IC50) = 2.9 +/- 1.9 (SD) nM] > OCT (IC50 = 9.3 +/- 1.7 nM) = SST > substance P = secretin (IC50 = 1 microM). Binding of 123I-labeled Tyr-3-OCT to A431 cells, in turn, was inhibited by OCT = Tyr-3-OCT (IC50 = 1.5 +/- 0.3 nM) = SST > VIP (IC50 = 4.9 +/- 1.1 nM). This rank-order of potency was also obtained for primary tumors and tumor cell lines. Furthermore, SST and OCT inhibited VIP-induced [3H]thymidine incorporation, cyclic AMP formation, and tyrosine kinase activity with IC50 values < 10 nM. Together, these data provide evidence for functional interactions between SST and VIP on various tumor cells. These interactions may involve peptide cross-competition at cellular binding sites and may have implications for the biology and pathophysiology of respective cells and disease states.

Adenosine Triphosphate↗

PubMed1994

A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer.

BACKGROUND: The efficacy of surgery for patients with non-small-cell lung cancer is limited, although recent studies suggest that preoperative chemotherapy may improve survival. We conducted a randomized trial to examine the possible benefit of preoperative chemotherapy and surgery for the treatment of patients with non-small-cell lung cancer. METHODS: We studied 60 patients (59 men and 1 woman) with stage IIIA non-small-cell lung cancer. The patients were randomly assigned to receive either surgery alone or three courses of chemotherapy (6 mg of mitomycin per square meter of body-surface area, 3 g of ifosfamide per square meter, and 50 mg of cisplatin per square meter) given intravenously at three-week intervals and followed by surgery. All patients received mediastinal radiation after surgery. The resected tumors were evaluated by means of K-ras oncogene analysis and flow cytometry. RESULTS: The median period of survival was 26 months in the patients treated with chemotherapy plus surgery, as compared with 8 months in the patients treated with surgery alone (P < 0.001); the median period of disease-free survival was 20 months in the former group, as compared with 5 months in the latter (P < 0.001). The rate of recurrence was 56 percent in the group treated with chemotherapy plus surgery and 74 percent in the group treated with surgery alone. The prevalence of mutated K-ras oncogenes was 15 percent among the patients receiving preoperative chemotherapy and 42 percent among those treated with surgery alone (P = 0.05). Most of the patients treated with chemotherapy plus surgery had tumors that consisted of diploid cells, whereas the patients treated with surgery alone had tumors with aneuploid cells. CONCLUSIONS: Preoperative chemotherapy increases the median survival in patients with non-small-cell lung cancer.

Adult↗

PubMed1994

Interconversion of bilayer phase transition temperatures between phosphatidylethanolamines and phosphatidylcholines.

High-resolution differential scanning calorimetric studies were performed to investigate the thermotropic phase behavior of 31 molecular species of phosphatidylethanolamines in excess water. Upon reheating, the aqueous dispersions of these lipids undergo the gel to liquid-crystalline phase transitions at well defined temperatures (Tm). These Tm values were shown to relate to the structural parameters of the underlying lipid molecules in a characteristic manner. Based on these observations, an interconversion of the Tm values between saturated phosphatidylethanolamines and phosphatidylcholines is established quantitatively for the first time.

Calorimetry, Differential Scanning↗

PubMed1994

The magnitude of HIV replication in monocytes and macrophages is influenced by environmental conditions, viral strain, and host cells.

It has been difficult to standardize the effects of various stimuli on HIV replication in monocytes and macrophages in different laboratories. In this study we have shown that it is possible to standardize HIV inocula, culture conditions, and HIV antigen assay to achieve reproducibility with the same viral isolate and donor monocyte and macrophage. However, changes in serum concentration, in the strain of blood-derived isolate (even at low passage), in the donor source of the monocyte/macrophage, and in the state of cellular maturation all influenced HIV production by these cells. The donor source of monocytes contributed as much to variability in HIV production as the HIV strain and results were reproducible when the same source was used repeatedly. These in vitro data suggest that genetic differences may contribute to differences in HIV replication in macrophages and consequently to tissue virus load in vivo.

Antigens, Viral↗

PubMed1994

Sulfated polyanions prevent HIV infection of lymphocytes by disruption of the CD4-gp120 interaction, but do not inhibit monocyte infection.

Sulfated polyanions (SPs) bind variably to lymphocyte-expressed CD4 and inhibit binding of monoclonal antibodies to the first two domains of CD4. To further define this interaction, soluble recombinant CD4 (sCD4; four extracellular domains), its truncated amino-terminal two-domain derivative, and three linear peptide analogues spanning residues 6-60 (6-24, 20-40, 41-60) in the first domain were investigated for SP binding. Dextran sulfate (DXS) (500 kDa), polyvinyl sulfate, fucoidan, and carrageenan-kappa, each immobilized on carboxymethyl cellulose fibers, bound strongly to both the two-domain and four-domain recombinant CD4 molecules (similar to that observed with native CD4), whereas dextran sulfate (5 kDa), chondroitin 6-sulfate, and pentosan sulfate bound relatively poorly. No peptide binding to SPs was observed. Recombinant gp120 bound poorly (< 10%) to all of the immobilized polyanions, except pentosan sulfate (17%), for which some binding was noted. Binding of radiolabeled V3 loop peptide to SPs was slightly greater, with 20-30% binding to polyvinyl sulfate, dextran sulfate (500 kDa), and pentosan sulfate. Competitive binding studies demonstrated the predominance of sCD4 rather than rgp120 binding to SPs and supported previous data demonstrating a binding site for DXS (500 kDa) on the first domain of CD4 adjacent to the gp120 binding site and recognized by OKT4C and E monoclonal antibodies. Hence disruption of the CD4-gp120 interaction is probably responsible for most of the observed antiviral activity of SPs toward HIV infection of lymphocytes. However, HIV infection and gp120 binding to monocytes was unaffected by SPs, probably because SPs were unable to block the CD4-gp 120 interaction in monocytes.

Amino Acid Sequence↗

PubMed1994

Treatment of locally recurrent soft tissue sarcomas of the retroperitoneum: report of 30 cases.

To assess the results in treating locally recurrent soft tissue sarcomas of the retroperitoneum, we reviewed the clinical, therapeutic, and pathologic characteristics of 30 patients who underwent surgical exploration. Complete resection was achieved in 18 patients (60%), 6 with en bloc resection of adjacent organs involved by the tumors. Following the first operation for recurrent lesions, the median survival was 33 months for those undergoing complete resection and 14 months for those undergoing partial resection or biopsy (P = 0.04). Patients with a disease-free interval (DFI) of > 24 months were associated with better prognosis than those with DFI of < or = 24 months (median survival: 40 months vs. 17 months, P = 0.03). Patients with tumor size of < or = 20 cm had longer survival than those with tumor size of > 20 cm (median survival: 39 months vs. 23 months, P = 0.04). Among 14 patients who received adjuvant radiation therapy, four patients whose tumors had been considered unresectable at first exploration for recurrence underwent complete resection after preoperative radiation therapy. An aggressive surgery aimed at complete resection in treating recurrent retroperitoneal sarcomas is strongly recommended. We suggest that in large tumors preoperative radiation therapy should be used to reduce the tumor volume and therefore a higher rate of complete resection may be achieved.

Adult↗

PubMed1994

SRVX, a sex reversing locus in Xp21.2-->p22.11.

Duplication within Xp21 causes female or intersexual development in human embryos with an XY chromosome complement. We have mapped the responsible gene, SRVX (sex reversal X), in XY-sex-reversed maternal half siblings who had inherited the duplication from their mother. The limited size of the duplication in our cases, relative to its extent in other similar cases, allows assignment of the SRVX locus to Xp21.2-->p22.11. We infer that SRVX is part of a pathway of sex-determining genes that includes SRY and SRA1, the latter recently assigned to chromosome 17q. If mutation of SRA1 or SRVX can reverse the sex of the XY fetus, this would explain why mutation within SRY is found only sporadically in women with XY gonadal dysgenesis.

Adult↗

PubMed1994

Relationship between cellular DNA synthesis, PCNA expression and sex steroid hormone receptor status in the developing mouse ovary, uterus and oviduct.

The proliferative activities of the different cellular compartments of the developing mouse ovary, uterus, and oviduct were studied by radioautographic assessment of DNA synthesis with [3H]-thymidine labeling and by immunohistochemical staining of proliferating cell nuclear antigen (PCNA). The distributions of estrogen and progesterone receptors (ER and PR) were studied by immunohistochemical staining. The values of the PCNA positive staining indices were a little higher than that of the radioautographic labeling indices. However, linear relations were shown for the two indices. The proliferative activities were high from postnatal day 1-7 and decreased from day 14 in the different cellular compartments of the ovary. The proliferative activities were high on days 1, 3 and decreased from day 7 in the uterus and oviduct. Staining of ER and PR was very weak in the surface epithelium, stroma and large follicles of the ovary. Positive staining for ER occurred from day 14 in the uterine epithelium and from day 7 in oviductal epithelium. Positive staining for PR was observed from day 1 in both the uterine and oviductal epithelium. However, the positivity of both ER and PR occurred from postnatal day 1 in the stromal cells of the uterus and oviduct. These results suggest that the appearance of the steroid receptors differ between the different cellular compartment of the reproductive organs. The proliferative activities have an inverse relation with the expression of the steroid hormone receptors in the female reproductive organs during developmental stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Prevention by dehydroepiandrosterone of the development of mammary carcinoma induced by 7,12-dimethylbenz(a)anthracene (DMBA) in the rat.

The concentration of serum dehydroepiandrosterone sulfate (DHEA-S) and DHEA decreases markedly during aging, and low circulating levels of DHEA have been associated with a higher incidence of breast cancer in women. Using 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat as model, we have studied the effect of increasing serum levels of DHEA released from Silastic implants on the incidence of these tumors in the rat. Treatment with increasing doses of DHEA leading to serum DHEA levels comparable to those observed in normal adult women (7.1 +/- 0.6 nM and 17.5 +/- 1.1 nM) caused a progressive inhibition of tumor development from 68% bearing tumors in control animals to 22% and 11%, respectively. The average tumor area per rat decreased from 2.81 cm2 in intact control animals to 0.96 and 0.09 cm2 in the groups treated with the same doses of DHEA, respectively. The present data indicate that circulating levels of DHEA similar to those found in normal adult premenopausal women exert a potent inhibitory effect on the development of DMBA-induced mammary tumors in the rat, thus suggesting the possibility of a new and more physiological approach for the prevention of breast cancer in women.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1994

Suppression by isoproterenol of endothelial cell morphology and barrier function changes induced by platelet-activating factor.

Using a model to study vascular permeability on hydrostatically perfused bovine pulmonary artery endothelial cell (EC) monolayers and software to analyze cell morphological parameters automatically in a computer image workstation, we studied the effects of isoproterenol (IPN) on platelet-activating factor (PAF)-induced changes in EC monolayer permeability and cell morphological parameters. Albumin has fortifying effects on endothelial barrier function. As albumin concentration in the perfusate increased (0, 1, 5, 10, 20 mg/ml), EC monolayer hydraulic conductivity (Lp) decreased gradually while Lp of the filter membranes did not change. After treatment of the EC monolayer with PAF 10(-8) mol/liter for 30 min, transmonolayer fluid flow, protein clearance rate, and Lp value increased noticeably. At the same time, cell area decreased and intercellular distance and percentage of intercellular space area in total cell monolayer increased. Pretreatment with 10(-4) mol/liter IPN blocked PAF-induced EC permeability and morphological changes, suggesting that EC contraction and intercellular gap formation are important mechanisms for PAF-induced high vascular permeability. IPN inhibits the effects of PAF via stabilization of EC morphology, protection of intercellular junction, and blockade of intercellular gap formation.

Albumins↗

PubMed1994

Biodegradation of PLA/GA polymers: increasing complexity.

The degradation of aliphatic polyesters derived from lactic and glycolic acids (PLA/GA) depends on many factors. It has been found recently that the interior of large size devices degrades faster than the outer zone. A qualitative model has been proposed to account for this heterogeneous degradation. It is based on diffusion-reaction phenomena combined with the well-known autocatalytic effect of carboxylic chain ends. This contribution recalls the present understanding of the hydrolytic degradation of PLA/GA polymers and emphasizes its complexity on the basis of the influence of secondary factors such as the presence of a basic load, namely, gentamycin, in poly(lactic acid) matrices, and the presence of long stereoregular sequences in poly(DL-lactic acid) macromolecules.

Biocompatible Materials↗

PubMed1994

Selective effects of antipsychotic medications on eye-tracking performance in schizophrenia.

The potential impact of antipsychotic medications on eye-tracking impairments in schizophrenia has received little systematic attention. To address this issue, eye-tracking performance was studied in 19 neuroleptic-naive schizophrenic patients, 22 previously medicated schizophrenic patients who had not received antipsychotic drugs for at least 28 days, and 52 nonpsychiatric control subjects. Impairments were similar but generally more severe in previously treated than in neuroleptic-naive patients. An attention-facilitation manipulation improved eye-tracking performance in all groups. Ten neuroleptic-naive and 14 previously treated cases were retested after at least 3 weeks of treatment with antipsychotic medication. Short-term treatment with neuroleptics improved certain attention-related aspects of eye tracking involving saccadic eye movements such as anticipatory saccades, but it did not alter pursuit eye movements.

Adolescent↗

PubMed1994

Role of neuropeptide Y in the regulation of gonadotropin-releasing hormone gene expression in the rat preoptic area.

It is well documented that neuropeptide Y (NPY) is involved in the regulation of the hypothalamo-pituitary gonadal axis. In order to determine the influence of NPY on the biosynthesis of GnRH, we have studied the effects of NPY and some NPY analogs on GnRH gene expression in neurons in the male rat preoptic area (POA). The following peptides NPY, peptide YY (PYY), [Leu31,Pro34]NPY (a Y1 receptor agonist) and NPY13-36 (a Y2 receptor agonist) were injected into the left lateral ventricle of adult castrated male rats. In another series of experiments, the same peptides were administered intravenously (IV). All the animals were perfused with 4% paraformaldehyde 4 hours after injection. Cryostat sections through the POA were processed for quantitative in situ hybridization. The intracerebroventricular injection of PYY, NPY and [Leu31,Pro34]NPY induced a marked increase in the number of grains overlying the labelled neurons (20 to 45% over control). On the other hand, the Y2 receptor agonist NPY13-36 did not influence mRNA levels. Similar results were obtained following the i.v. administration although the magnitude of the stimulating effect was less important (12 to 20% over control). These data then strongly suggest that NPY positively regulates the genetic expression of GnRH in neurons via the Y1 NPY receptor subtype.

Animals↗

PubMed1994

A deficit in preprodynorphin mRNA expression in hippocampus of spontaneously hypertensive rats.

A significantly lower level of preprodynorphin mRNA hybridization signal was found in hippocampal dentate granule cells of spontaneously hypertensive rats at 4 and 16 weeks old, before and after hypertension development respectively, when compared with preprodynorphin (PPD) mRNA level in the hippocampus of age-matched Wistar-Kyoto rats. The possible implications of disturbed PPD mRNA and dynorphin expression in the hippocampus are discussed with regard to pathophysiology of hypertension and central control of cardiovascular function.

Analysis of Variance↗

PubMed1994

K-ras gene point mutation: a stable tumor marker in non-small cell lung carcinoma.

K-ras gene point mutation is a highly frequent event in human malignancy. About one third of non-small cell lung cancer (NSCLC) patients harbor K-ras gene point mutational activations. This study investigates the prevalence of K-ras mutation in autopsy tumors with NSCLC, and the correlation of K-ras gene point mutations between primary tumors and metastases in NSCLC. Formalin-fixed, paraffin-embedded tissue sections of 15 primary lung tumors and their metastases, (obtained from autopsy), were examined for the presence of point mutations in K-ras gene codon 12, 13 and 61 by oligodeoxynucleotide hybridization analysis of DNA fragments, amplified by polymerase chain reaction (PCR). K-ras gene point mutations were detected in five cases of lung carcinoma, of which four were adenocarcinomas and one was squamous cell carcinoma. In each of these cases, identical K-ras gene mutations were found in the DNA of both the primary tumor and its corresponding distant metastases. Activating K-ras base-substitutions correlate well between the primary tumor and its corresponding metastases in NSCLC. In the negative cases where no K-ras mutation was found in the primary tumors, no newly acquired K-ras mutation appeared in the metastases. Our study indicates that K-ras point mutation serves as a stable tumor marker in NSCLC.

Adenocarcinoma↗

PubMed1994

Role of serotonin in the regulation of prolactin gene expression in the male rat as evaluated by in situ hybridization.

It is well documented that serotonin (5-HT) is involved in the regulation of prolactin (PRL) release as a stimulator. To evaluate the role of 5-HT on PRL gene expression, we have investigated the effects of repeated administration (during 2 days) of 5-HT, the 5-HT1 + 2 receptor antagonist methysergide, the 5-HT2 receptor antagonist ketanserin, and a combination of 5-HT and methysergide on PRL mRNA levels as measured by in situ hybridization in the adult male rat. The treatment with 5-HT induced a 14% increase in the hybridization signal, although the administration of methysergide produced a small reduction (5%) in PRL mRNA levels. On the other hand, ketanserin had no effect on the hybridization signal. The stimulatory effect of 5-HT was completely prevented by the concomitant administration of methysergide. The present results, together with previous data, indicate that 5-HT exerts a positive tonic influence not only on the release of PRL but on the biosynthesis of the hormone as evaluated by mRNA level measurements. They also strongly suggest that the role of 5-HT in the regulation of PRL secretion is mediated via activation of 5-HT1 receptors, although a dopaminergic effect of methysergide on PRL secretion cannot be totally excluded.

Animals↗