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Biomedical subjects

C Y Li

Publications and source records attributed to C Y Li.

At least 73 records · Page 4Linked to original sources
PubMed2001

Bilateral diffuse uveal melanocytic proliferation in a woman with uterine leiomyoma: case report.

Bilateral diffuse uveal melanocytic proliferation (BDUMP) associated with systemic carcinoma is a rare paraneoplastic syndrome. It was reported to be associated with primary carcinomas of the lung, ovary, colon, gall bladder, esophagus, pancreas, uterus, and cervix. We report a case of BDUMP that occurred in a woman with cervical leiomyoma. The 79-year-old woman experienced bilateral progressive visual loss to hand motion within 2 weeks. Fundus examination showed bilateral exudative retinal detachment and multiple oval red patches. Echographic study showed diffuse thickening of the uveal tracts. Fluorescein angiography showed multiple patches of window defect without late leakage, which was correlated with the oval red patches. After screening for tumor markers and meticulous examinations, an elevated serum level of CA-125 was noted. The only neoplasm found in this patient was a cervical leiomyoma, which has never been reported to be associated with BDUMP. One month after the onset of symptoms, accidental head injury due to poor vision led to right parietal intracerebral hemorrhage and left hemiplegia. Prompt diagnosis of this paraneoplastic syndrome is important to discover the underlying malignancy in patients with no history of cancer. For those cases without malignant neoplasm, attention should be directed to the disability caused by the severe visual loss, which led to accidental head injury and intracerebral hemorrhage in this case.

Aged↗
PubMed2001

Systemic vector leakage and transgene expression by intratumorally injected recombinant adenovirus vectors.

Interleukin 12 is a heterodimeric cytokine that exhibits potent immunostimulatory effects. It has shown some promise in preclinical and clinical studies but was accompanied by serious systemic toxicity such as flu-like syndromes, a rapid transient leukopenia, elevated liver transaminases, gastrointestinal toxicity, and/or liver dysfunction. Gene therapy with intratumorally injected recombinant adenoviral vectors offers the potential to restrict therapeutic gene expression in the tumor. Here we show that a substantial amount of adenoviral vectors disseminates into the systemic circulation and infects parenchymal organs. We further show that this results in high systemic levels of potentially toxic transgene products. To reduce potential toxicity, we tested an inducible promoter based on the heat shock proteins (hsp70B) and present evidence that high intratumoral levels of a therapeutic transgene can be obtained while systemic expression is reduced to a minimum, increasing the safety of adenovirus-based tumor gene therapy.

Adenoviridae↗
PubMed2001

[A study on lyophilization injection of cucurbitacin polylactic acid nanoparticles].

OBJECTIVE: To prepare stable and redispersable Lyophilization injection of cucurbitacin polylactic acid nanoparticles(Cu-PLA-NP). METHOD: An optimal supporting agent was chosen to prepare the Cu-PLA-NP lyophilization injection. The physical and chemical properties of the injection were evaluated. RESULTS: The shape, diameters, association ratio, drug loading and pH of Cu-PLA-NP colloidal solution and lyophilization injection were not changed. The content of water consisted with the requirement of lyophilization injection. The critical relative humidity was 69.52%. The stability was good. CONCLUSION: It is practicable to prepare Cu-PLA-NP lyophilization injection with proper formulas and preparation processes.

Cucurbitacins↗
PubMed2001

[Poteintation of vincristine-induced apoptosis by tetrandrine, neferine and dauricine in the human mammary MCF-7 multidrug-resistant cells].

AIM: To investigate the poteintation of vincristine-induecd apoptosis by tetrandrine, neferine and dauricine isolated from Chinese medicinal plants in the human mammary MCF-7 multidrug resistant cells. METHODS: The apoptotic cells were detected by fluorescent staining of a combination of Hoechst 33342 and propidium iodide (PI), flow cytometry and agarose electrophoresis. RESULTS: The apoptotic cells induced by vincristine alone accounted for about 10% of all the cancer cells, while the percentage of apoptotic cells induced by a combination of vincristine with tetrandrine, neferine, or dauricine was found to be significantly higher than that by vincristine alone, and their reversal effects were positively correlated with the drug concentration and the exposure time. In addition, tetrandrine was shown to be the most potent in the reversal efficacy among the three compounds to be tested for apoptosis in vitro. CONCLUSION: Tetrandrine, neferine and dauricine showed obvious potenitiation of vincristine-induced apoptosis in the human mammary MCF-7 multidrug-resistant cells.

Alkaloids↗
PubMed2001

[Effects of leflunomide on immunological liver injury].

AIM: To study the effect of leflunomide (Lef) on immunological liver injury in mice. METHODS: Immunological liver injury was induced by tail vein injection of BCG + LPS (BCG 2.5 mg, 1 d, LPS 10 micrograms, 10 d). The ALT, AST, NO level in plasma and MDA, GSHpx in liver homogenate were assayed by spectroscopy. The serum content of TNF-alpha was determined by ELISA. IL-1, IL-2 and ConA-induced splenocyte proliferation response were determined by methods of 3H-infiltrated cell proliferation. RESULTS: Immunological liver injury induced by BCG + LPS was successfully duplicated. Lef (4, 12, 36 mg.kg-1) was found to significantly decrease the serum transaminase (ALT, AST) activity and MDA content in liver homogenate, and improved reduced GSHpx level of liver homogenate. Furthermore, Lef (4, 12, 36 mg.kg-1) significantly reduced TNF-alpha and NO level in serum, and IL-1 production by PM psi. Moreover, the decreased IL-2 production and ConA-induced splenocyte proliferation response were further inhibited. CONCLUSION: Lef showed significant protective action on immunological liver injury in mice.

Adjuvants, Immunologic↗
PubMed2001

[Inhibitory effect of artemin on endotoxin-induced nitric oxide synthesis].

OBJECTIVE: To investigate the effect of Artemin on LPS-induced nitric oxide synthesis in macrophages. METHOD: 1. Nitrite oxide (NO) production of RAW 264.7 cells was induced by LPS or LPS in combination with interferon-gamma (IFN gamma) in the presence or absence of Artemin. The amount of NO in the supernatant of RAW 264.7 cells was detected with Griess reagent. 2. Balb/c mice were injected with Artemin (i.m.) 50 mg.kg-1.d-1 x 3 d, and intraperitoneal macrophages were collected to detect the LPS-induced NO production. RESULT: LPS 1.0, 0.2 microgram.ml-1 or IFN-gamma 100u + LPS 1.0, 0.2, 0.04 microgram.ml-1 could induced a large amount of NO synthesis of RAW 264.7 cells. Artemin showed a significant inhibitory effect on LPS or IFN-gamma + LPS-induced NO production in a dose dependent manner. After treatment with Artemin, the response of Balb/c mice to LPS was reduced, which was showed by a decrease in NO production of intraperitoneal macrophages induced by LPS. CONCLUSION: Artemin could reduce LPS-induced production of inflammatory factors resulting in the inhibition of inflammatory effects.

Animals↗
PubMed2001

A novel method to 'exercise' rats: making rats rise to erect bipedal stance for feeding - raised cage model.

We employed a novel method to exercise rats: making them rise to bipedal stance for feeding using raised cages. We studied its effects on the skeletons of 6 and 10-month-old intact or orchidectomized (ORX) rats. Body and hindlimb muscle weights, tibial BMC and periosteal cortical bone formation increased after housing in raised cages, but more so in 6-month-old animals than in 10-month-old ones. In 6-month-old orchidectomized rats, raised cages partially prevented ORX-induced bone loss by stimulating periosteal cortical bone (TX) formation and decreased bone resorption next to marrow. In 10-month-old male orchidectomized rats, raised cages also decreased the endosteal and trabecular bone resorption, but not enough to prevent completely ORX-induced net bone losses. Because the osteogenic effects of raised cages alone were only partial, we also studied the interaction between raised cage and prostaglandin E(2) (PGE(2)) in 10-month-old retired female breeders. When treated with combined raised cage and PGE(2), both cortical (TX) and trabecular bone mass of the proximal tibial metaphysis and lumbar vertebral body increased over either raised cages or PGE(2) treatment alone, that was accompanied by dramatic increased bone formation at periosteal and endosteal surfaces. Thus making rats rise to erect bipedal stance for feeding helps to prevent bone loss after orchidectomy; it amplifies the anabolic effects of PGE(2), and it provides an inexpensive, non-invasive and reliable way to increase mechanical loading of certain bones of the rat skeleton.

Journal Article↗
PubMed2000

Enhancement of radiotherapy by hyperthermia-regulated gene therapy.

PURPOSE: Interleukin 12 (IL-12) has shown strong antitumoral effects in numerous pre-clinical studies and appears to act synergistically with radiation in murine tumors. The major impediment to its clinical use has been its systemic toxicity. While using intratumorally injected viral gene therapy vectors encoding IL-12 reduces systemic side effects substantially, elevated systemic transgene levels are still observed because adenovirus can reach the circulation. Further restricting IL-12 expression in the tumor is therefore desirable in a combined radiation and adenovirus mediated cancer gene therapy regimen. METHODS AND MATERILAS: Hyperthermia-regulated gene therapy was tested in a nonimmunogenic B16.F10 melanoma line that is syngeneic with C57BL/6 mice. For hyperthermic gene therapy, an adenoviral vector coding for IL-12 under the control of the promoter of the human heat shock protein 70B (hsp70B) was used. One week after transplantation (at a 5-7 mm diameter), tumors were irradiated with 3 x 11 Gy (mo-we-fri). Adenovirus was injected at 3 x 10(8) pfu/tumor 24 h before the last radiation fraction or 3 days afterwards. Hyperthermia was performed 24 h later at 42.5 degrees C. Growth delay to reaching 3 times initial tumor volume was chosen as the biologic endpoint. IL-12 levels in tumor and serum were determined by using the enzyme-linked immunosorbant assay (ELISA). RESULTS: Adenovirus mediated intratumoral expression of IL-12 under the control of a heat inducible promoter in combination with hyperthermia is almost as effective as that under the control of a constitutive cytomegaly virus (CMV) promoter while systemic transgene levels are substantially reduced with the heat inducible promoter. The response to radiotherapy is improved considerably when combined with heat inducible gene therapy without apparent systemic toxicity. When used as a single dose, applying IL-12 gene therapy after completion of radiotherapy appears to be beneficial. CONCLUSIONS: Hyperthermia-regulated gene therapy in combination with radiation is feasible and therapeutically effective in murine tumors with no apparent systemic toxicity.

Adenoviridae↗
PubMed2000

Lymphoproliferative disease of granular T lymphocytes presenting as aplastic anemia.

Lymphoproliferative disease of granular T lymphocyte (T-LDGL), also known as T-cell large granular lymphocyte leukemia, is a clonal disorder of cytotoxic T lymphocytes that is clinically manifested as chronic neutropenia and anemia. Association with autoimmune disorders is common. In 9 patients, T-LDGL is reported as presenting as aplastic anemia. The clinical characteristics were similar to acquired aplastic anemia. Morphologic evidence of increased granular lymphocytes in the peripheral blood and an excess of CD3(+)/CD8(+)/CD57(+) cells in the bone marrow were found in most cases. Cyclophosphamide was ineffective, but noncytotoxic immunosuppressive agents generally produced a good response. After a median follow-up of 49 months, 5 patients had died from the disease or related complications. Median survival was 40 months. Aplastic anemia can be a presenting manifestation of T-LDGL, and T-LDGL should be considered in the differential diagnosis of acquired aplastic anemia.

Adult↗
PubMed2000

Malignant lymphoma in southern Taiwan according to the revised European-American classification of lymphoid neoplasms.

BACKGROUND: The purpose of the current study was to determine the distribution and relative frequency of each subtype of malignant lymphoma in southern Taiwan according to the revised European-American classification of lymphoid neoplasms (REAL). METHODS: The pathology files of a regional hospital in southern Taiwan for 1989-1998 were searched for malignant lymphoma, lymphoproliferative disorder, and Hodgkin disease (HD). The results of light microscopy, immunohistochemistry, and in situ hybridization for Epstein-Barr virus-encoded RNA (EBER) were correlated with clinical findings, and all cases were classified according to REAL. RESULTS: A total of 205 cases were analyzed retrospectively. There were 197 cases (96.1%) of non-Hodgkin lymphoma (NHL) and 8 cases (3. 9%) of HD. Among the 197 NHL cases, 161 (81.7%) were of B-cell lineage and 36 (18.3%) were of T-/natural killer cell lineage. Diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, and follicular lymphoma were the most common B-cell subtypes and represented 47.2%, 19.3%, and 6.1%, respectively, of all NHL cases. Among the 36 cases of T-/natural killer cell lineage, unspecified peripheral T-cell lymphoma (8.6%), T-/natural killer cell lymphoma (angiocentric lymphoma) (4.1%), and anaplastic large cell lymphoma (3.6%) were the most common subtypes. Seven of eight T-/natural killer cell lymphoma cases were positive for EBER. The eight cases of HD were classified as lymphocyte-rich classic (two cases), nodular sclerosis (two cases), and mixed cellularity (four cases) subtypes. Three of these eight cases were positive for EBER. CONCLUSIONS: To the authors' knowledge this study is the first in Taiwan using the REAL classification and it again confirms the different geographic distribution of the various subtypes of malignant lymphoma. The frequency of T-/natural killer cell lineage NHL in Taiwan is higher than that in Western countries but not as high as reported previously.

Geography↗
PubMed2000

Heat shock protein 70 inhibits apoptosis downstream of cytochrome c release and upstream of caspase-3 activation.

Heat shock protein 70 (HSP70) has been shown to act as an inhibitor of apoptosis. We have also observed an inhibitory effect of HSP70 on apoptotic cell death both in preheated U937 and stably transfected HSP70-overexpressing U937 (U937/HSP70) cells. However, the molecular mechanism whereby HSP70 prevents apoptosis still remains to be solved. To address this issue, we investigated the effect of HSP70 on apoptotic processes in an in vitro system. Caspase-3 cleavage and DNA fragmentation were detected in cytosolic fractions from normal cells upon addition of dATP, but not from preheated U937 or U937/hsp70 cells. Moreover, the addition of purified recombinant HSP70 to normal cytosolic fractions prevented caspase-3 cleavage and DNA fragmentation, suggesting that HSP70 prevents apoptosis upstream of caspase-3 processing. Because cytochrome c was still released from mitochondria into the cytosol by lethal heat shock despite prevention of caspase-3 activation and cell death in both preheated U937 and U937/hsp70 cells, it was evident that HSP70 acts downstream of cytochrome c release. Results obtained in vitro with purified deletion mutants of HSP70 showed that the carboxyl one-third region (from amino acids 438 to 641) including the peptide-binding domain and the carboxyl-terminal EEVD sequence was essential to prevent caspase-3 processing. From these results, we conclude that HSP70 acts as a strong suppressor of apoptosis acting downstream of cytochrome c release and upstream of caspase-3 activation.

Animals↗
PubMed2000

Immunohistochemical staining for megakaryocyte c-mpl may complement morphologic distinction between polycythemia vera and secondary erythrocytosis.

Recent studies have shown decreased megakaryocyte expression of the thrombopoietin receptor (c-mpl) in patients with polycythemia vera (PV) but not in those with reactive erythrocytosis. We examined the diagnostic utility of this observation in 22 patients with PV, 7 patients with secondary erythrocytosis (SE), and 10 normal controls. Commercial antibodies against c-mpl were used with standard immunoperoxidase methods. Megakaryocyte c-mpl staining intensity was uniformly moderate-to-strong in the healthy controls and in all the patients with SE. In contrast, staining intensity in 9 patients with PV (41%) was uniformly weak. Furthermore, in 12 of the remaining 13 patients with PV, the c-mpl staining pattern in each case was heterogeneous and was associated with weak staining intensity in more than 20% of the megakaryocyte population. These preliminary data suggest that c-mpl immunostains may complement bone marrow histopathology in distinguishing PV from nonclonal causes of erythrocytosis. (Blood. 2000;96:771-772)

Bone Marrow↗
PubMed2000

Heat-induced gene expression as a novel targeted cancer gene therapy strategy.

One of the main advantages of gene therapy over traditional therapy is the potential to target the expression of therapeutic genes in desired cells or tissues. To achieve targeted gene expression, we experimented with a new approach based on the long-established phenomenon of the heat shock response. By using the green fluorescence protein as a reporter gene, it was demonstrated that expression of a heterologous gene with a heat shock protein 70 promoter could be elevated to 500-1000-fold over background by moderate hyperthermia (39 degrees C to 43 degrees C) in tissue cultured cells. The heat-induced green fluorescence protein expression was first detectable at 3 h after heating and reached a maximum at 18-24 h. The expression dropped back to baseline within 72 h. In addition, when cells were infected with adenovirus vectors containing the heat-inducible interleukin 12 or tumor necrosis factor alpha genes and then heated (42 degrees C, 30 min), expression was at least 13,600- or 6.8 x 10(5)-fold over background, respectively. Intralesion injection of the interleukin-12-carrying adenovirus vector in a mouse melanoma tumor model caused significant tumor growth delay only with hyperthermia treatment. Our results therefore support heat-induced gene expression as a feasible approach for targeted cancer gene therapy.

Adenoviridae↗
PubMed2000

Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models.

BACKGROUND: There is a paucity of information about events that follow immediately after tumor cells are triggered to initiate the process of angiogenesis (the formation of new blood vessels). Such information is relevant to the issue of when micrometastases vascularize and has implications for the accessibility of micrometastases to various treatments. In this study, we attempted to monitor events at the initiation of angiogenesis at the earliest possible stage of tumor growth in vivo. METHODS: Two different rodent mammary tumor cell lines, R3230Ac from the Fischer 344 rat and 4T1 from the BALB/c mouse, were stably transfected with a gene that encodes an enhanced version of green fluorescence protein (GFP). GFP-labeled R3230Ac or 4T1 cells (about 20-50 cells) were implanted into dorsal skinfold window chambers of Fischer 344 rats or BALB/c mice, respectively. Tumor angiogenesis was then monitored serially and noninvasively for up to 4 weeks. RESULTS: Clear evidence of modification of the host vasculature was observed when tumor mass reached approximately 60-80 cells, and functional new blood vessels were seen when tumor mass reached roughly 100-300 cells. Individual tumor cells exhibited a chemotaxis-like growth pattern toward the pre-existing host vasculature. When ex-flk1 (a soluble, truncated vascular endothelial cell growth factor receptor protein known to be antiangiogenic) was injected with the tumor cells, the initial angiogenic and tumor growth activities were inhibited considerably, indicating that angiogenesis inhibitors may halt tumor growth even before the onset of angiogenesis. CONCLUSION: Angiogenesis induced by tumor cells after implantation in the host begins at a very early stage, i.e., when the tumor mass contains roughly 100-300 cells. Identification of chemotactic signals that initiate tumor cell migration toward the existing vasculature may provide valuable targets for preventing tumor progression and/or metastases.

Animals↗
PubMed2000

Mechanism of inhibition of platelet aggregation by HCL-31D.

The antiplatelet effect of the pyridazinone analogue, 4, 5-dihydro-6-[4-[2-hydroxy-3-(3,4 dimethoxybenzylamino)propoxy]naphth-1-yl]-3(2H)-pyridazinone (HCL-31D), was investigated in vitro with rabbit platelets. HCL-31D dose-dependently inhibited the platelet aggregation and ATP release induced by collagen (10 microg/ml), arachidonic acid (100 microM) or thrombin (0.1 U/ml) with an IC(50) of about 0.95-5.41 microM. HCL-31D (0.5-5 microM) increased the platelet cyclic AMP level in a dose-dependent manner. Furthermore, HCL-31D potentiated cyclic AMP formation caused by prostaglandin E(1) but not that caused by 3-isobutyl-1-methylxanthine (IBMX). HCL-31D also attenuated phosphoinositide breakdown and intracellular Ca(2+) elevation induced by collagen, arachidonic acid or thrombin. HCL-31D inhibited the formation of thromboxane B(2) induced by collagen or thrombin but not by arachidonic acid. In addition, HCL-31D did not affect platelet cylooxygenase and thromboxane synthase activity. These data indicate that HCL-31D is an inhibitor of phosphodiesterase and that its antiplatelet effect is mainly mediated by elevation of cyclic AMP levels.

Adenosine Triphosphate↗
PubMed2000

Combination treatment of murine tumors by adenovirus-mediated local B7/IL12 immunotherapy and radiotherapy.

Failure of local tumor control still poses a problem for radiotherapy and translates into reduced survival. Combining radiation with chemotherapy or other newer modalities has shown promising results. Immunological approaches to tumor therapy have found renewed interest due to improved insight into mechanisms involved in the immune response to tumors. In this paper, we studied tumor growth delay after various combination regimens of locally injected adenovirus constitutively expressing IL12 and B7.1 (AdIL12/B7.1) and fractionated radiotherapy in two nonimmunogenic murine tumor models, 4T1 and B16.F10. Effects of radiation and virus infection on surface antigen expression in these tumor lines were assessed. Mechanisms of action of AdIL12/B7.1 were studied by conducting additional experiments with and without depletion of NK-cells and/or T-cells, and by cytotoxic T-lymphocyte assays, and immunohistochemical evaluation of tumor blood vessels. Both B7.1 and IL12 were effectively expressed in both irradiated and unirradiated 4T1 and B16.F10 tumor cells but did not add significantly to radiation-induced cell killing in vitro. However, local tumor infection by AdIL12/B7.1 after irradiation significantly increases the effectiveness of radiotherapy when applied after completion of radiotherapy. The mechanism appears to be complicated, involving a host of factors that included the ability of IL12 to activate T-cells and NK-cells and to inhibit angiogenesis and the ability of radiation to induce apoptosis or necrosis among tumor cells. These data support the combination of radiotherapy with adenovirus-mediated immunotherapy and suggest that the concept of adding genetic immunotherapy after radiotherapy in a combined regimen merits further study.

Adenoviridae↗
PubMed2000

Preincisional dextromethorphan treatment for postoperative pain management after upper abdominal surgery.

Previous studies showed that ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, provides a preemptive analgesic effect and preemptive analgesia improves postoperative pain management. The aim of this study was to examine whether premedication with dextromethorphan (DM) improves postoperative pain management after upper abdominal surgery. Sixty (American Society of Anesthesiologists class 1 and 2 of either gender) patients scheduled for upper abdominal surgery were included in the study. Patients were randomly assigned to one of four groups: control, DM-10, DM-20, and DM-40. In the control group, chlorpheniramine maleate (CPM, 20 mg) was injected immediately before induction of anesthesia intramuscularly (IM). In the DM-10, DM-20, and DM-40 groups, patients were premedicated with DM 10 mg, 20 mg, and 40 mg IM, respectively. After operation, patient-controlled analgesia (PCA) with morphine was given for pain relief. The time to the first PCA trigger, morphine consumption, pain scores, and analgesic-related side effects were recorded at 1, 2, 4, 24, 48, and 72 hours after surgery. The time to first PCA trigger for the control group was 17.8 +/- 1.4 minutes, for group DM-10 20.2 +/- 1.6 minutes, for group DM-20 32.4 +/- 1.9 minutes, and for DM-40 77.9 +/- 6.5 minutes. The morphine delivered and PCA triggering frequency were 5.5 +/- 0.5/11.3 +/- 0.8 times for the controls, 5.5 +/- 0.4/ 14.1 +/- 1.3 times for DM-10, 3.1 +/- 0.3/6.3 +/- 1.2 times for DM-20, and 0.2 +/- 0.1/0.3 +/- 0.2 times for DM-40 during the first hour after operation. For the first day, the figures are 19.9 +/- 1.2/23.9 +/- 1.4 for the controls, 15.6 +/- 1.2/17.3 +/- 2.4 for DM-10, 12.6 +/- 0.7/15.9 +/- 1.6 for DM-20, and 5.0 +/- 0.21/5.6 +/- 0.9 for DM-40. On the first day, the cough pain scores were 6.67 +/- 0.23, 6.53 +/- 0.16, 6.67 +/- 0.23, and 5.73 +/- 0.18 for the controls, DM-10, DM-20, and DM-40 groups, respectively. All data showed dose-dependent better pain relief in DM-premedicated patients. We conclude that DM premedication offers preemptive analgesia and reduces postoperative pain and morphine requirement.

Abdomen↗