Biomedical subjects

T Li

Publications and source records attributed to T Li.

At least 289 records · Page 16Linked to original sources

PubMed1998

Early-appearing tumor-infiltrating natural killer cells play an important role in the nitric oxide production of tumor-associated macrophages through their interferon production.

Both natural killer (NK) cells and macrophages are thought to be the main effectors responsible for early antitumor defense. In this study, we investigated the role of tumor-infiltrating NK cells in initiating nitric oxide (NO) production by tumor-associated macrophages (TAM). The in vivo depletion of NK cells prior to the i.p. inoculation of melanoma cells resulted in a significant decrease in the NO production of the TAM prepared from the peritoneal exudate cells (PEC). Such prior NK cell depletion also decreased the ability of TAM to show any antitumor activity in vitro. The addition of NG-monomethyl-L-arginine (Me-L-Arg) to the culture partially inhibited the ability of TAM to suppress the proliferation of melanoma cells and also decreased their cytolytic activity against melanoma cells. These results suggest that the TAM exhibited both cytostatic and cytolytic activities through their NO production. In an in vivo assay, the administration of Me-L-Arg permitted the more rapid growth of i.p. inoculated melanoma cells compared with the control. On the other hand, the decreased NO production of TAM, resulting from the prior NK cell depletion, was restored by the i.p. administration of interferon gamma (IFN gamma). In addition, the in vivo administration of anti-IFN gamma mAb into mice inoculated i.p. with melanoma cells also significantly decreased the NO production of TAM in peritoneal exudate cells. Furthermore, the tumor-infiltrating NK cells produced a considerable level of IFN gamma. Overall, these results indicate that early-appearing tumor-infiltrating NK cells play an important role in the NO production of TAM through their IFN gamma production.

Animals↗

PubMed1998

Antitumor vaccination effect of dendritic cells can be augmented by locally utilizing Th1-type cytokines from OK432-reactive CD4+ T cells.

In order to enhance the antitumor vaccination effect of dendritic cells (DC) pulsed with class I tumor peptide, we tried to utilize the local cytokine help of CD4+ T cells reactive to a streptococcal preparation OK432. DC were prepared from murine bone marrow cells by culture with both granulocyte/macrophage-colony-stimulating factor and interleukin(IL)-4. The peritumoral injections of OK432 induced OK432-reactive CD4+ T cells in the draining lymph nodes, and their in vitro production of interferon gamma was thus significantly enhanced by restimulation with OK432-pulsed DC. In addition, anti-P815 mastocytoma cytotoxic T lymphocytes were generated from the in vivo OK432-treated P815-draining lymph node cells only when the lymph node cells were restimulated in vitro with the DC pulsed with both P1A peptide and OK432. Moreover, the peritumoral injections of OK432 and the subsequent vaccination of the DC, pulsed with both OK432 and P1A peptide, significantly suppressed the growth of s.c. inoculated P815. Interestingly, a significant level of IL-12 was detected in the coculture supernatant of both OK432-pulsed DC and OK432-reactive CD4+ T cells. Collectively, our results suggest that the antitumor vaccination effect of DC pulsed with class I tumor peptide could thus be effectively augmented by locally utilizing the Th1-type cytokines from OK432-reactive CD4+ T cells.

Animals↗

PubMed1998

Characterization of B16 melanoma-specific cytotoxic T lymphocytes.

A B16 melanoma-specific CD8+ T cell line (AB1) was established from the spleen cells of C57BL/6 mice cured of B16 melanoma with interleukin (IL)-12 treatment. The AB1 line exclusively used T cell receptor Vbeta11. The AB1 cells exhibited a cytolytic activity against both syngeneic B16 melanoma and allogeneic P815 mastocytoma, whereas a cold inhibition assay revealed specificity of the AB1 cells against B16 melanoma. Their lostability to kill a class I loss variant of B16 melanoma was restored by the transfection of H-2Kb gene. In addition, their interferon (IFN)-gamma production was significantly suppressed by the addition of anti-H-2Kb monoclonal antibody, and RT-PCR analysis showed that the AB1 line expressed the mRNA encoding IFN-gamma, but not IL-4 or IL-10. The experiment using synthetic peptides of tyrosinase-related protein-2 (TRP-2) revealed that the AB1 cells could recognize TRP-2(181-188) peptide. Moreover, the AB1 cells showed an in vivo antitumor effect against established pulmonary metastases of B16 melanoma. Overall, these results indicate that the Tc1-type Vbeta11+ AB1 cells exert an antitumor activity against syngeneic B16 melanoma through recognition of TRP-2(181-188) peptide in an H-2Kb-restricted manner.

Animals↗

PubMed1998

Vaccination with activated B cells pulsed with tumor-lysates can induce tumor-specific CD4+ T cells in vivo.

Activated B cells, pulsed with tumor-lysates, were examined for their potential to induce tumor-specific CD4+ T cells in vivo, MH2 cells, which are CD4+ T cells and can also recognize purified protein derivative from mycobacterium tuberculosis (PPD), showed a proliferative response in the presence of both syngeneic activated B cells and PPD in a major histocompatibility complex class II-restricted manner. For B cells to function as efficient antigen presenting cells, they need to be activated. Both irradiation and several inhibitors for antigen-processing were observed to block the antigen-presenting ability of activated B cells. Based in these findings, the possibility of anti-tumor vaccination with activated B cells was thus investigated. The spleen cells from mice, which were immunized with activated B cells pulsed with B16 melanoma-lysates, produced a higher level of interferon (IFN)-gamma than those from mice, which were immunized with either non-pulsed activated B cells or the tumor-lysates alone, after in vitro restimulation. This IFN-gamma production was also dependent on the CD4+ T cells. Moreover, the splenic CD4+ T cells in such mice were suggested to increase their ability to generate B16 melanoma-specific cytotoxic T lymphocytes after in vitro restimulation. Even more importantly, immunization with B16 melanoma lysate-pulsed activated B cells elicited a protective immunity against B16 melanoma at rechallenge. Collectively, these results indicate that an anti-tumor effect could be induced by immunization with activated B cells, pulsed with the tumor-lysates, by eliciting tumor-specific IFN-gamma producing CD4+ T cells in vivo.

Animals↗

PubMed1998

Posterior maxillary anatomy: implications for Le Fort I osteotomy.

The most common site of haemorrhage in maxillary osteotomies is the posterior maxilla. Better understanding of the anatomy in this region may minimize possible vascular complications. The aim of the study was to study the osteology of the posterior maxillary region and establish clinical safety guidelines for the Le Fort I osteotomy Thirty human dry skulls were selected and assessed by a combination of direct inspection, computerized imaging and computed tomography (CT) scan analysis. Results showed that the presence of maxillary third molars influenced the transverse angulation of the posterior vertical cut. Synostosis of the pterygomaxillary junction was noted in 12% of samples. The mean length of the medial sinus wall from the piriform rim to the descending palatine canal at the Le Fort I level was 34 mm. The three-dimensional CT-reconstructed descending palatine canal ran at 60 degrees anteroinferiorly to the palatine plane and slightly medially to the exit through the greater palatine foramen.

Adult↗

PubMed1998

Synthesis and biological properties of C12,13-cyclopropyl-epothilone A and related epothilones.

BACKGROUND: The epothilones are natural substances that are potently cytotoxic, having an almost identical mode of action to Taxoltrade mark as tubulin-polymerization and microtubule-stabilizing agents. The development of detailed structure-activity relationships for these compounds and the further elucidation of their mechanism of action is of high priority. RESULTS: The chemical synthesis of the C12,13-cyclopropyl analog of epothilone A and its C12,13-trans-diastereoisomer has been accomplished. These compounds and several other epothilone analogs have been screened for their ability to induce tubulin polymerization and death of a number of tumor cells. Several interesting structure-activity trends within this family of compounds were identified. CONCLUSIONS: The results of the biological tests conducted in this study have demonstrated that, although a number of positions on the epothilone skeleton are amenable to modification without significant loss of biological activity, the replacement of the epoxide moiety of epothilone A with a cyclopropyl group leads to total loss of activity.

Animals↗

PubMed1998

Tissue reaction of hydroxyapatite sol to rat molar pulp.

Hydroxyapatite sol was prepared by dispersing unheated hydroxyapatite microcrystals into distilled water. A suspension of hydroxyapatite heated at 800 degrees C (HAp-800 degrees C) in distilled water was used as a comparative material. These were characterized by X-ray diffractometry, SEM and electroconductivity measurements. 0.001 ml of each material was injected into the upper first molar pulp of rats. After 7-14 days post-operatively, the group with hydroxyapatite sol showed slight inflammation in the pulp cavities and a highly calcified tubular dentine bridge was observed. Osteodentine had developed and adhered to the surface of the hydroxyapatite microcrystals. Matrix vesicles were observed in the extracellular matrix between collagen fibrils and electron-dense granules. After 28 days, the inflammation completely disappeared and tubular dentine was observed below the osteodentine. Acid phosphates (ACPase) activity was detected along all biosynthesizing pathways in odontoblast-like cells. Localized dehydrogenate (LDH) activity indicated phagocytosis of hydroxyapatite microcrystals by odontoblasts. In the group with HAp-800 degrees C after 7-14 days post-operatively, the inflammation was moderate. After 28 days, relatively fewer calcified dentine tubules were observed. ACPase activity was detected only along the membranes bounding cytoplasmatic vacuoles. It was concluded that hydroxyapatite sol is a safe biomaterial for use as dental pulp and induces early formation of dentine-bridge more so than HAp-800 degrees C.

Journal Article↗

PubMed1998

Fractal analysis of pharmaceutical particles by atomic force microscopy.

PURPOSE: Reliable methods are needed to characterize the surface roughness of pharmaceutical solid particles for quality control and for finding the correlations with other properties. In this study, we used fractal analysis to describe the surface roughness. METHODS: Atomic force microscopy (AFM) was used to obtain three-dimensional surface profiles. The variation method was used to calculate fractal dimensions. We have measured fractal dimensions of four granule samples, four powders, and two freeze-dried powders. RESULTS: A computer-program was written to implement the variation method. The implementation was verified using the model surfaces generated by fractional Brownian motion. The fractal dimensions of most particles and granules were between 2.1 and 2.2, and were independent of the scan size we measured. The freeze-dried samples, however showed wide variation in the values of fractal dimension, which were dependent on the scan size. As scan size increased, the fractal dimension also increased up to 2.5. CONCLUSIONS: Fractal analysis can be used to describe surface roughness of pharmaceutical particles. The variation method allows calculation of reliable fractal dimensions of surface profiles obtained by AFM. Careful analysis is required for the estimation of fractal dimension, since the estimates are dependent on the algorithm and the digitized model size (i.e., number of data points of the measured surface profile) used. The fractal dimension of pharmaceutical materials is also a function of the observation scale i.e., the scan size) used in the profile measurement. The multi-fractal features and the scale-dependency of fractal dimension result from the artificial processes controlling the surface morphology.

Algorithms↗

PubMed1998

Interactions between NFkappaB and its inhibitor ikappaB: biophysical characterization of a NFkappaB/ikappaB-alpha complex.

The N-terminal domain (1-318 amino acids) of mouse NFkappaB (p65) has been purified to homogeneity from the soluble fraction of Escherichia coli cells expressing this protein. Its complex with a full-length ikappaB-alpha (MAD3, 1-317 amino acids) molecule was generated by binding the E. coli-derived ikappaB-alpha to the purified NFkappaB and purifying the complex by sequential chromatography. The stoichiometry of NFkappaB to ikappaB in the complex was determined to be 2 to 1 by light scattering and SDS-polyacrylamide gel electrophoresis. The secondary structure of the NFkappaB (p65) determined by Fourier-transform infrared (FTIR) spectroscopy is in good agreement with that of the p50 in the crystal structure of the p50/DNA complex, indicating that no significant structural change in NFkappaB occurs upon binding of DNA. The FTIR spectrum of the NFkappaB/ikappaB complex indicates that its secondary structure is composed of 17% alpha-helix, 39% beta-strand, 18% irregular structures, and 26% beta-turns and loops. By comparing these data to the FTIR data for NFkappaB alone, it is concluded that the ikappaB (MAD3) in the complex contains 35% alpha-helix, 27% beta-strand, 22% irregular structures, and 16% beta-turns and loops. Circular dichroism (CD) analysis of a shorter form of ikappaB (pp40) indicates that it contains at least 20% alpha-helix and that the ikappaB subunit accounts for nearly all of the alpha-helix present in the NFkappaB/ikappaB complex, consistent with the FTIR results. The stabilities of NFkappaB, ikappaB, and their complex against heat-induced denaturation were investigated by following changes in CD signal. The results indicate that the thermal stability of ikappaB is enhanced upon the formation of the NFkappaB/ikappaB complex.

Animals↗

PubMed1998

Changes in conformation and stability upon SCF/sKit complex formation.

Stem cell factor (SCF) is thought to be a member of the four-helical bundle cytokine superfamily, and exists in solution as a noncovalent homodimer. It is the ligand for Kit, a tyrosine kinase type III receptor. The interaction of SCF and Kit affects early hematopoietic progenitors, as well as gametocytes, melanocytes, and mast cells. Upon binding of SCF the Kit undergoes dimerization and transphosphorylation. Circular dichroism (CD), intrinsic fluorescence, and Fourier transform infrared (FTIR) spectroscopy were used for conformational analyses of free SCF, soluble Kit (sKit), and the complex. The sKit consisted of the extracellular domain of Kit, contained five Ig-like domains, and was prepared from the conditioned media of transfected Chinese hamster ovary cells. With these techniques, a reproducible conformational change was seen upon ligand/receptor binding. The far-UV CD and FTIR spectroscopy indicated a slight increase in the alpha-helical content. The near-UV CD and fluorescence spectra showed changes in the environments of the aromatic amino acids. The thermal denaturation of SCF was not affected by complex formation, while the melting temperature of sKit increased only a few degrees when binding SCF. This indicates that binding is temperature dependent, consistent with titration calorimetry results published previously which demonstrated that there is a large enthalpy of binding. The conformational changes which accompany SCF/sKit binding could play a role in the receptor dimerization and signal transduction which follow.

Animals↗

PubMed1998

Perturbation of CD4+ and CD8+ T-cell repertoires during progression to AIDS and regulation of the CD4+ repertoire during antiviral therapy.

The T-cell antigen receptor (TCR) repertoire was studied longitudinally by analyzing the varying lengths of the beta chain CDR3 hypervariable region during the course of HIV-1 infection and following combination antiretroviral therapy. Drastic restrictions in CD8+ T-cell repertoire usage were found at all stages of natural progression and persisted during the first six months of treatment. In contrast, significant CD4+ T-cell repertoire perturbations were not found in early stages of infection but correlated with progression to AIDS. Out of ten patients presenting with pretreatment perturbations, normalization of the CD4+ repertoire was observed in eight good responders, but not in two cases of unsuccessful therapy. These results indicate that, besides CD4+ cell count rise, an efficient control of HIV replication may allow qualitative modifications of the CD4+ repertoire balance.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Involvement of both donor cytotoxic T lymphocytes and host NK1.1+ T cells in the thymic atrophy of mice suffering from acute graft-versus-host disease.

It has been reported that a dramatic decrease in the number of thymocytes (thymic atrophy) in mice suffering from acute graft-versus-host disease (GVHD) is ascribed to glucocorticoids. In this study, we examined the possibility that cellular immune responses may thus be involved in thymic atrophy. In contrast to chronic GVHD mice, acute GVHD (C57BL/6 X DBA/2) F1 (BDF1) hybrid mice, which were injected intravenously with both spleen and lymph node cells from C57BL/6 mice, showed a dramatic decrease in the number of CD4 CD8 double-positive thymocytes 2 or 3 weeks after the induction of GVHD. A flow cytometric analysis revealed the donor-derived T cells with either CD4 or CD8 molecules to infiltrate the thymus of the mice undergoing acute GVHD for 10 days. In a cytolytic assay, such thymus-containing cells exhibited a cytolytic activity specific to the host cells. In addition, anti-H-2d cytolytic T cells showed a high level of cytolytic activity against BDF1 (H-2bXd) thymocytes, whereas they also showed a low level of cytolytic activity against C57BL/6 (H-2b) thymocytes, thus suggesting that the thymus-infiltrating donor-derived T cells killed the host thymocytes through both anti-H-2d-specific and non-specific mechanisms. Interestingly, a flow cytometric analysis revealed both the percentage and the absolute cell number of host-derived NK1.1+ CD3+ cells to increase in the thymus of mice suffering from acute GVHD for 10 days. In addition, they also showed the cytolytic activity against YAC-1 cells and the mRNA expression of interleukin-12 (IL-12) in the thymus to be also significantly augmented on day 7 after the induction of acute GVHD. Collectively, our results indicate that the cellular immune responses such as donor cytotoxic T lymphocytes and host NK1.1+ T cells are therefore involved in the thymic atrophy of mice suffering from acute GVHD.

Acute Disease↗

PubMed1998

Comparative stereochemical analysis of glucose-binding proteins for rational design of glucose-specific agents.

There is a need for synthesizing glucose-sensitive molecules which can be used in glucose sensors and self-regulating insulin delivery devices. Currently, glucose-sensitive proteins, such as glucose oxidase and concanavalin A (Con-A), are used for detecting glucose molecules. For long-term in vivo applications, it is necessary to synthesize non-proteineous glucose-sensitive molecules which are biocompatible, nontoxic, cost-effective, and independent of environmental factors such as pH, ionic strength, or the presence of divalent cations. As a first step toward synthesizing glucose sensitive molecules, we have compared glucose-binding sites of four different types of glucose-binding proteins. They are human beta-cell glucokinase, D-xylose isomerase, lectins (Lathyrus ochrus isolectin I and Con-A), and glucose/galactose binding protein. Analysis of the glucose-binding sites of their 3-dimensional crystal structures showed that the hydrogen bonds between the hydroxyl groups of glucose and a few types of amino acid residues of proteins provided the main attraction. In some cases, the same atom was involved in multiple hydrogen bonds. Hydrophobic interactions between the pyranose ring of glucose and aromatic rings of hydrophobic amino acid residues also played an important role in the glucose specificity. A sandwich geometry was observed among the hydrophobic groups. This comparative stereochemical analysis suggests that a possible glucose binding site can be made by placing Asp and Asn around glucose for hydrogen bonding and Phe on both sides of glucose for hydrophobic interaction.

Binding Sites↗

PubMed1998

A novel method for selection of chymotrypsin inhibitors from a phage peptide library.

A novel screening strategy has been developed for the identification of alpha-chymotrypsin inhibitors from a phage peptide library. In this strategy, the standard affinity selection protocol was modified by adding a proteolytic cleavage period to avoid recovery of alpha-chymotrypsin substrates. After four cycles of selection and further activity assay, a group of related peptides were identified by DNA sequencing. These peptides share a consensus sequence motif as (S/T)RVPR(R/H). Then, a corresponding short peptide (Ac-ASRVPRRG-NH2) was synthesized chemically and proved to be an inhibitor of alpha-chymotrypsin. The present work provides a useful way for searching proteinase inhibitors without detailed knowledge of the molecular structure.

Bacteriophages↗

PubMed1998

Lack of association between a polymorphism in the promoter region of the dopamine-2 receptor gene and clozapine response.

Dopamine receptors are strong candidates for involvement in schizophrenia and are targeted by a wide variety of antipsychotics. We hypothesized that genetic variation in these neurotransmitter receptors may influence clinical response to clozapine, an antipsychotic which displays high affinity for dopamine D2 receptors in the limbic system. To test this hypothesis, we studied a functional polymorphism in the promoter region of the D2 receptor gene (-141C Ins/Del) in a sample of 151 clozapine treated patients of British origin. In addition, the influence of this polymorphism on antipsychotic response in general was investigated on a sample of 146 Han Chinese schizophrenic patients treated with a variety of antipsychotics. No association was found between this polymorphism and clinical response in either of the two samples suggesting that genetic variation in D2 receptors does not play a major role in determining clinical response to antipsychotic treatment.

Antipsychotic Agents↗

PubMed1998

Quality-adjusted time without symptoms or toxicity analysis of interferon maintenance in multiple myeloma.

PURPOSE: In a randomized trial conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), interferon alpha-2b (IFN) maintenance therapy (2 mU/m2 subcutaneously three times per week) after successful induction with melphalan and prednisone was found to prolong time to progression in patients with multiple myeloma. A favorable effect on survival was also present, but this difference was of borderline significance. However, IFN toxicity was a concern. To evaluate the trade-off between the clinical benefits of IFN and the associated toxicity, we applied the method of quality-adjusted time without symptoms or toxicity (Q-TWiST). MATERIALS AND METHODS: Three clinical health states were defined in this analysis: time with toxicity (TOX), time without disease relapse or toxicity (TWiST), and time following disease relapse (REL). Toxicity information for IFN had been collected using patient-completed diaries so the actual duration of each adverse event could be determined. The health states TOX and REL were weighted using utility scores to account for a possible decrement in quality of life, a weighted sum of the health state durations is used as a measure of quality-adjusted time. RESULTS: The health state durations were calculated at 72 months median follow-up. Patients in the IFN group gained an average of 9.8 months without disease relapse (P = .001) and 5.8 months of overall survival (P = .074) versus the control group. However, the IFN group suffered an average of 4.1 months of moderate or worse toxicity (P < .001). CONCLUSION: The clinical benefits of IFN outweigh the negative effects associated with treatment toxicity for a wide range of plausible utilities.

Antineoplastic Agents↗

PubMed1998

Childhood diabetes in China. Enormous variation by place and ethnic group.

OBJECTIVE: To investigate the incidence rate of IDDM in China. RESEARCH DESIGN AND METHODS: The Chinese IDDM registry was established in 1991 as part of the World Health Organization's Multinational Project for Childhood Diabetes (DiaMond) project. Twenty-two centers were developed to monitor the incidence of IDDM in children < 15 years of age. The population under investigation includes > 20 million individuals, representing approximately 7% of the children in China. Capture-recapture methods were used to estimate the ascertainment. RESULTS: The overall ascertainment-corrected IDDM incidence rate in China was 0.51 per 100,000, the lowest rate ever reported. There was a 12-fold geographic variation (0.13-1.61 per 100,000). In general, the incidence rate was higher in the north and the east. There was a sixfold difference among ethnic groups (highest: Mongol group, 1.82 per 100,000; lowest: Zhuang group, 0.32 per 100,000). CONCLUSIONS: China has an extremely low overall IDDM incidence rate. China also has the greatest geographic and ethnic variation seen for any country.

Adolescent↗

PubMed1998

[Study on the epidemiological characteristics of diabetes mellitus and IGT in China].

A community-based survey on diabetes mellitus (DM) and impaired glucose tolerance (IGT) was carried out in 11 provinces/autonomous regions/municipalities of China from July 1995 to June 1997, using stratified cluster sampling method and diagnostic criteria recommended by WHO. A total number of 42,751 persons aged 20-74 years having lived in the communities longer than 5 years, were selected as research subjects. Results showed that the prevalence rates of DM and IGT standardized by age were 3.21% (95% CI: 3.05%-3.37%) and 4.76% (95% CI: 4.56%-4.96%) respectively; with a ratio of DM to IGT 1:1.5. The prevalence rates of DM and IGT increased parallelly with the increase of age. Among the 20-39 years old, the prevalence rates of DM and IGT were 1.01% and 2.70% respectively, while both of them exceeded 7% and 11% among people aged 50-59 years and above 60 years.

Adult↗