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Biomedical subjects

J Luo

Publications and source records attributed to J Luo.

At least 109 records · Page 6Linked to original sources
PubMed2000

Cloning and characterization of DIP1, a novel protein that is related to the Id family of proteins.

Using human cyclin D1 as the "bait" in a yeast two-hybrid system, together with a HL60 cDNA library, we identified a novel human nuclear protein designated DIP1. This protein is expressed in a variety of cell types, and in fibroblasts its level remains constant throughout the cell cycle. However, the level of this protein increases severalfold during the differentiation of HL60 cells. The DIP1 protein can be phosphorylated in vitro by a cellular kinase and this activity reaches its maximum in extracts obtained from cells in the G1 phase of the cell cycle. DIP1 contains a helix-loop-helix motif but lacks an adjacent basic DNA-binding domain, thus resembling the Id family of proteins. The dip1 gene is located on human chromosome 16p11.2-12, a locus that is amplified in several types of human cancer. These results suggest that DIP1 may be involved in the control of gene expression and differentiation, but its precise function remains to be determined.

Amino Acid Sequence↗
PubMed2000

Growth of Spanish, BoerxAngora and BoerxSpanish goat kids fed milk replacer.

Seventy-seven male kids were used to compare growth performance of Spanish (S, n=26), BoerxAngora (BA, n=21) and BoerxSpanish (BS, n=30) kids during the preweaning period. All kids were removed from does 3 days postpartum, moved indoors and randomly allocated to individual cages. Kids received goat milk fortified with milk replacer for approximately 1 week followed by 600ml of milk replacer (23% CP, 30% crude fat) twice daily until weaning at 8 week. At 3 week of age, all kids had ad libitum access to a commercial goat starter diet (20% CP). Feed intake was measured daily and BW gain at 2-week intervals. There were interactions (P<0.05) between breed and time or 2-week period in BW, BW gain and feed efficiency. Boer crosses (i.e., BA and BS) were heavier than S kids at 2, 6 and 8 weeks of age (P<0.05), but there were no BW differences between Boer crosses (P0.10). From Week 3-8, Boer crosses gained BW more rapidly (P=0.001) than did S kids (60, 71 and 77g/day for S, BA and BS, respectively), although BW gain of S in Week 3-4 was greater (P<0.05) than that of Boer crosses (60, 50 and 54g/day for S, BA and BS, respectively). Starter diet DM intake in Week 3-8 was greatest for BS (S versus BA and BS, P=0.05; BA versus BS, P<0.01) (23, 24 and 37g/day for S, BA and BS, respectively). The ratio of BW gain to total DM intake in Week 3-8 was greater (P=0.03) for BA and BS than for S (0.52, 0.59 and 0.58 for S, BA and BS, respectively). The incidence of scours was 17, 21 and 31% for S, BA and BS kids, respectively (P0.10). These results reflect that crossbreeding with Boer goats can improve growth of young kids and, thus, potentially increase economic returns for goat producers.

Journal Article↗
PubMed2000

Secondary lymphoid tissue chemokine mediates T cell-dependent antitumor responses in vivo.

Secondary lymphoid tissue chemokine (SLC, also referred to as Exodus 2 or 6Ckine) is a recently identified high endothelial-derived CC chemokine. The ability of SLC to chemoattract both Th1 lymphocytes and dendritic cells formed the rationale to evaluate this chemokine in cancer immunotherapy. Intratumoral injection of recombinant SLC evidenced potent antitumor responses and led to complete tumor eradication in 40% of treated mice. SLC-mediated antitumor responses were lymphocyte dependent as evidenced by the fact that this therapy did not alter tumor growth in SCID mice. Studies performed in CD4 and CD8 knockout mice also revealed a requirement for both CD4 and CD8 lymphocyte subsets for SLC-mediated tumor regression. In immunocompetent mice, intratumoral SLC injection led to a significant increase in CD4 and CD8 T lymphocytes and dendritic cells, infiltrating both the tumor and the draining lymph nodes. These cell infiltrates were accompanied by the enhanced elaboration of Th1 cytokines and chemokines monokine induced by IFN-gamma and IFN-gamma-inducible protein 10 but a concomitant decrease in immunosuppressive cytokines at the tumor site. In response to irradiated autologous tumor, splenic and lymph node-derived cells from SLC-treated tumor-bearing mice secreted significantly more IFN-gamma, GM-CSF, and IL-12 and reduced levels of IL-10 than did diluent-treated tumor-bearing mice. After stimulation with irradiated autologous tumor, lymph node-derived lymphocytes from SLC-treated tumor-bearing mice demonstrated enhanced cytolytic capacity, suggesting the generation of systemic immune responses. These findings provide a strong rationale for further evaluation of SLC in tumor immunity and its use in cancer immunotherapy.

Animals↗
PubMed2000

Isolation and characterization of protoporphyrin glycoconjugates from rat harderian gland by HPLC, capillary electrophoresis and HPLC/electrospray ionization MS.

It has been widely reported that the Harderian gland, present in most vertebrates, accumulates high levels of porphyrins, particularly protoporphyrin. The present study describes the extraction, identification and characterization of a group of hitherto unreported protoporphyrin glycoconjugates in the rat Harderian gland using HPLC, capillary electrophoresis, on-line HPLC/electrospray ionization MS and tandem MS. The major glycoconjugate was identified as protoporphyrin-1-O-acyl beta-xyloside with a smaller amount of protoporphyrin-1-O-acyl beta-glucoside also detected. In the Harderian glands studied, 50-70% of the porphyrins present were in the form of protoporphyrin glycoconjugates. This is the first reported occurrence of glycoconjugates of porphyrins in Nature and suggests that previous studies have wrongly identified the major porphyrin in the Harderian gland as the unconjugated protoporphyrin.

Animals↗
PubMed2000

A novel peptide antagonist of CXCR4 derived from the N-terminus of viral chemokine vMIP-II.

The viral macrophage inflammatory protein-II (vMIP-II) encoded by Kaposi's sarcoma-associated herpesvirus is unique among all known chemokines in that vMIP-II shows a broad-spectrum interaction with both CC and CXC chemokine receptors including CCR5 and CXCR4, two principal coreceptors for the cell entry of human immunodeficiency virus type 1 (HIV-1). To elucidate the mechanism of the promiscuous receptor interaction of vMIP-II, synthetic peptides derived from the N-terminus of vMIP-II were studied. In contrast to the full-length protein that recognizes both CXCR4 and CCR5, a peptide corresponding to residues 1-21 of vMIP-II (LGASWHRPDKCCLGYQKRPLP) was shown to strongly bind CXCR4, but not CCR5. The IC(50) of this peptide in competing with CXCR4 binding of (125)I-SDF-1alpha is 190 nM as compared to the IC(50) of 14.8 nM of native vMIP-II in the same assay. The peptide selectively prevented CXCR4 signal transduction and coreceptor function in mediating the entry of T- and dual-tropic HIV-1 isolates, but not those of CCR5. Further analysis of truncated peptide analogues revealed the importance of the first five residues for the activity with CXCR4. These results suggest that the N-terminus of vMIP-II is essential for its function via CXCR4. In addition, they reveal a possible mechanism for the distinctive interactions of vMIP-II with different chemokine receptors, a notion that may be further exploited to dissect the structural basis of its promiscuous biological function. Finally, the potent CXCR4 peptide antagonist shown here could serve as a lead for the development of new therapeutic agents for HIV infection and other immune system diseases.

Amino Acid Sequence↗
PubMed2000

Neural tube defects and the 13q deletion syndrome: evidence for a critical region in 13q33-34.

Neural tube defects (NTD) are common findings in the 13q deletion syndrome, but the relationship between the 13q- syndrome and NTDs is poorly understood. We present a child with a 13q deletion and lumbosacral myelomeningocele. This was a boy with microcephaly, telecanthus, minor facial anomalies, and ambiguous genitalia. Cytogenetic and fluorescence in situ hybridization analysis showed a de novo 46,XY,del(13)(q33.2-->qter) with no visible translocation. By using microsatellite markers, the deletion breakpoint was mapped to a 350-kb region between D13S274 and D13S1311 and was paternal in origin. An analysis of 13q deletions with NTDs, including the present case, suggests that a deletion in 13q33-34 is sufficient to cause an NTD. The deletions associated with NTDs are distal to and nonoverlapping with the previously defined critical region in 13q32 for the major malformation syndrome [Brown et al., 1999: Am J Hum Genet 57: 859-866]. Our analysis also suggests that one or more genes in 13q33-34 produces NTDs by haploinsufficiency.

Abnormalities, Multiple↗
PubMed2000

Inhibition of Grb2 SH2 domain binding by non-phosphate-containing ligands. 2. 4-(2-Malonyl)phenylalanine as a potent phosphotyrosyl mimetic.

Nonhydrolyzable phosphotyrosyl (pTyr) mimetics serve as important components of many competitive Grb2 SH2 domain inhibitors. To date, the most potent of these inhibitors have relied on phosphonate-based structures to replace the 4-phosphoryl group of the parent pTyr residue. Reported herein is the design and evaluation of a new pTyr mimetic, p-malonylphenylalanine (Pmf), which does not contain phosphorus yet, in Grb2 SH2 domain binding systems, approaches the potency of phosphonate-based pTyr mimetics. When incorporated into high affinity Grb2 SH2 domain-directed platforms, Pmf is 15-20 times more potent than the closely related previously reported pTyr mimetic, O-malonyltyrosine (OMT). Pmf-containing inhibitors show inhibition constants as low as 8 nM in extracellular Grb2 binding assays and in whole cell systems, effective blockade of both endogenous Grb2 binding to cognate erbB-2, and downstream MAP kinase activation. Evidence is provided that use of an N(alpha)()-oxalyl auxiliary enhances effectiveness of Pmf and other inhibitors in both extracellular and intracellular contexts. As one of the most potent Grb2 SH2 domain-directed pTyr mimetics yet disclosed, Pmf may potentially have utility in the design of new chemotherapeutics for the treatment of various proliferative diseases, including breast cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Mechanistic and kinetic studies of crystallization of birnessite.

Kinetic and mechanistic features have been studied for the crystallization of birnessite in aqueous systems via different synthesis methods: the oxidation of Mn2+, reduction of MnO4-, and redox reaction between Mn2+ and MnO4-. For oxidation methods, a topotactical conversion from Mn(OH)2 to birnessite via feitknechtite (beta-MnOOH) is observed. In reduction methods, birnessite evolves from the initially produced amorphous manganese oxide (AMO gel). For redox methods, both mechanisms exist, with the latter prevailing. A liquid mechanism is proposed to describe the reduction and redox synthesis, which comprises three stages: an induction period, a fast crystallization period, and a steady-state period. The redox method is accompanied by the formation and phase transformation of feitknechtite to birnessite. A method combining IR and XRD quantitation is proposed to detect nuclei in the induction period. Crystallization rates and apparent energies of activation of crystallization for reduction and redox methods are determined.

Journal Article↗
PubMed2000

Tumors promote altered maturation and early apoptosis of monocyte-derived dendritic cells.

Tumors produce a number of immunosuppressive factors that block the maturation of CD34+ stem cells into dendritic cells (DC). We hypothesized that tumors might also interfere with the maturation and/or function of human monocyte-derived DC. In contrast to stem cells, we found that CD14+ cells responded to tumor culture supernatant (TSN) by increasing expression of APC surface markers, up-regulating nuclear translocation of RelB, and developing allostimulatory activity. Although displaying these characteristics of mature DC, TSN-exposed DC lacked the capacity to produce IL-12, did not acquire full allostimulatory activity, and rapidly underwent apoptosis. The effects of TSN appeared to be specific for maturing DC, and were not reversed by Abs against known DC regulatory factors including IL-10, vascular endothelial growth factor, TGF-beta, or PGE2. Supernatants collected from nonmalignant cell sources had no effect on DC maturation. The altered maturation and early apoptosis of monocyte-derived DC may represent another mechanism by which tumors evade immune detection.

Apoptosis↗
PubMed2000

Intratumoral administration of adenoviral interleukin 7 gene-modified dendritic cells augments specific antitumor immunity and achieves tumor eradication.

In two murine lung cancer models adenoviral interleukin 7-transduced dendritic cells (DC-AdIL-7) were administered intratumorally, resulting in complete tumor regression. Intratumoral DC-AdIL-7 therapy was as effective as DCs pulsed with specific tumor peptide antigens. Comparison with other intratumoral therapies including recombinant IL-7, AdIL-7 vector alone, unmodified DCs, IL-7-transduced fibroblasts, or DCs pulsed with tumor lysates revealed DC-AdIL-7 therapy to be superior in achieving antitumor responses and augmenting immunogenicity. Mice with complete tumor eradication as a result of either DC-AdIL-7 or AdIL-7 therapy were rechallenged with parental tumor cells 30 days or more after complete tumor eradication. All the DC-AdIL-7-treated mice completely rejected a secondary rechallenge, whereas the AdIL-7-treated mice had sustained antitumor effects in only 20-25% of the mice. DC-AdIL-7 therapy was more effective than AdIL-7 in achieving systemic antitumor responses and enhancing immunogenicity. After complete tumor eradication, those mice treated with DC-AdIL-7 evidenced significantly greater release of splenocyte GM-CSF and IFN-gamma than did controls or AdIL-7-treated mice. After intratumoral injection, gene-modified DCs trafficked from the tumor to lymph node sites and spleen. DCs were detected in nodal tissues for up to 7 days after intratumoral injection. We report that intratumoral DC-AdIL-7 leads to significant systemic immune responses and potent antitumor effects in murine lung cancer models.

Adenoviridae↗
PubMed2000

Specific inhibition of cyclooxygenase 2 restores antitumor reactivity by altering the balance of IL-10 and IL-12 synthesis.

Cyclooxygenase-2 (COX-2), the enzyme at the rate-limiting step of prostanoid production, has been found to be overexpressed in human lung cancer. To evaluate lung tumor COX-2 modulation of antitumor immunity, we studied the antitumor effect of specific genetic or pharmacological inhibition of COX-2 in a murine Lewis lung carcinoma (3LL) model. Inhibition of COX-2 led to marked lymphocytic infiltration of the tumor and reduced tumor growth. Treatment of mice with anti-PGE2 mAb replicated the growth reduction seen in tumor-bearing mice treated with COX-2 inhibitors. COX-2 inhibition was accompanied by a significant decrement in IL-10 and a concomitant restoration of IL-12 production by APCs. Because the COX-2 metabolite PGE2 is a potent inducer of IL-10, it was hypothesized that COX-2 inhibition led to antitumor responses by down-regulating production of this potent immunosuppressive cytokine. In support of this concept, transfer of IL-10 transgenic T lymphocytes that overexpress IL-10 under control of the IL-2 promoter reversed the COX-2 inhibitor-induced antitumor response. We conclude that abrogation of COX-2 expression promotes antitumor reactivity by restoring the balance of IL-10 and IL-12 in vivo.

Adjuvants, Immunologic↗
PubMed2000

Molecular modeling and site-directed mutagenesis of CCR5 reveal residues critical for chemokine binding and signal transduction.

The CC chemokine receptor CCR5 is the receptor for several chemokines and coreceptor for the entry of HIV-1. Whereas many studies focus on CCR5 interaction with HIV-1, residues in CCR5 important for chemokine binding and subsequent signal transduction remain poorly understood. Here we use an approach combining protein structure modeling and site-directed mutagenesis to probe the structure of CCR5 and its interactions with chemokine ligands and HIV-1. Structural models of CCR5 rationalize extensive biological data about the role of CCR5 in HIV-1 envelope glycoprotein gp120 binding and HIV-1 entry. Furthermore, we carry out site-directed mutagenesis guided by structural analysis of the complex of CCR5 and a chemokine. This leads to the novel observation that certain residues, such as Tyr10 and Lys26, in the N terminus of CCR5 play a critical structural role for ligand binding and signaling. Single glycine substitution of these residues significantly decreases chemokine binding and signal transduction. These results provide new insight into the structural basis for CCR5 receptor-ligand interaction and may guide the design of novel inhibitors.

Chemokines↗
PubMed2000

Effects of aprotinin on serum interleukin-2 and soluble interleukin-2 receptor during cardiopulmonary bypass.

Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve(s) replacement were randomly divided into two groups: control group (n = 10) and aprotinin group (n = 10). In aprotinin group, 1,000,000 KIU aprotinin was given by vein injection and then 2,000,000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and sIL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.

Aprotinin↗
PubMed2000

Effect of vibration magnitude and repetitive exposure on finger blood flow in healthy subjects.

In order to study the effect of the magnitude of vibrations and repetitive exposure on finger blood flow, we exposed ten healthy subjects to three experimental conditions: (1) vibration of 3.16 m/s2 at 60 Hz, (2) vibration of 31.6 m/s2 at 60 Hz, and (3) no vibration, as a control. Under the experimental conditions, the right hand was exposed to 5-min vibration three times, with intervening 5-min rests. Meanwhile, the blood flows of both middle fingers were continuously measured with a blood flow meter based on the thermal diffusion method. Finger blood flow was significantly decreased in both hands with exposure to vibrations of 3.16 m/s2 and 31.6 m/s2. Increased magnitude of vibration tended to enhance the decrease in finger blood flow in both hands, and repeated exposure to vibration had cumulative effects on the decrease in finger blood flow in the unexposed left hand.

Adult↗
PubMed2000

Antihyperglycemic activity of Teramnus labialis (Fabaceae).

In vivo bioassay-guided fractionation of the aqueous alcohol extract of the aerial parts of Teramnus labialis (Roxb.) Benth. (Fabaceae), using C57BL/Ks-db/db mice as a model for type 2 diabetes, yielded an active fraction containing a mixture of coumarins. The major coumarin present in the active fraction was identified as fraxidin.

Animals↗
PubMed2000

Counting nouns and verbs in the input: differential frequencies, different kinds of learning?

Previous research has focused on evaluating the nouns and verbs in parents' input through type/token ratios. This research offers an additional means of evaluating parent speech by first examining the frequencies of individual nouns, verbs and descriptors and second examining the learning task presented to children. Study 1 examines 25 transcripts from the CHILDES database of English-speaking parents' speech to children at five developmental levels ranging from 0;11 to 2;11 in age. Study 2 examines 50 transcripts from the CHILDES database of Mandarin-speaking caregivers' speech to children ranging from 1;9 to 2;3 in age. The results suggest that the patterns of frequency for individual nouns and individual verbs are different, but that the frequency patterns for nouns and the frequency patterns for verbs are similar in English and Mandarin. Further, this research suggests that in both languages the nouns in parents' input are similarly organized: the most frequent nouns spoken to children tend to name solid objects that share a similar shape. In contrast verbs' meanings in both languages tend to include more variable conceptual relations.

Child Language↗
PubMed2000

Ethanol enhances erbB-mediated migration of human breast cancer cells in culture.

Growth factor systems (ligands and their receptors) are targets of ethanol toxicity. Inasmuch as alcohol consumption may increase the risk and development of breast cancer, we hypothesize that ethanol enhances cell migration by up-regulating the activities of erbB receptors. Of the three tested breast cancer cell lines that exhibit low invasion capacity (BT-20, MCF-7, and T47D cells), erbB receptors were specifically affected by ethanol only in the T47D cells. Ethanol increased erbB2, erbB3, and erbB4 expression in T47D human breast cancer cells in a concentration-dependent manner. ErbB1 (epidermal growth factor receptor) was unaffected. Heregulin beta 1 (ligand for erbB3 and erbB4) induced a modest increase in the invasion potential of the T47D cells. Ethanol alone also promoted modest invasion by the T47D cells, however, ethanol dramatically increased their heregulin-mediated invasion. Knocking-out erbB2 with an anti-sense oligonucleotide eliminated heregulin beta 1-promoted migration and blocked ethanol-induced chemo-migration. Thus, these data suggest that alcohol may enhance metastasis by altering an erbB system, and pivotally, erbB2.

Breast Neoplasms↗