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Biomedical subjects

Y Hu

Publications and source records attributed to Y Hu.

At least 289 records · Page 16Linked to original sources
PubMed1999

Metabolism of antitumor hydroxymethylacylfulvene by rat liver cytosol.

Acylfulvenes are a potent class of antitumor agents derived from illudin S, a fungal sesquiterpene. Illudin S possesses antitumor activity but has a poor therapeutic index. Acylfulvene is 100-fold less toxic against human lung adenocarcinoma cells than illudin S, but inhibits tumor growth in human xenografts, opposite to illudin S. An analog of acylfulvene, MGI 114 (hydroxymethylacylfulvene), shows much greater efficacy, producing complete tumor regression in xenograft models. MGI 114 is currently in phase II clinical trials. Cytotoxicity of MGI 114, like that of illudin S, is believed to involve both chemical reaction and enzymatic reduction. Enzymatic reduction by a cytosolic NADPH-dependent enzyme (from rat liver) produced an aromatic metabolite similar to that formed from illudin S. However, the reaction occurred more slowly. In addition, four new metabolites were isolated, two hydroxylated derivatives and two in which the primary allylic hydroxyl was replaced by hydride. All retained the reactive centers of the parent MGI 114.

Animals↗
PubMed1999

Image analysis of p53 and cyclin D1 expression in premalignant lesions of the oral mucosa.

OBJECTIVE: The expression of p53 and cyclin D1 proteins was analyzed by image analysis in oral premalignant lesions and normal oral mucosa. STUDY DESIGN: Punch biopsies from the normal oral mucosa were obtained from 20 normal donors and 41 patients with oral dysplastic leukoplakias. After controlled formaldehyde fixation and paraffin embedding, immunohistochemistry was used to detect cyclin D1 and p53. Image analysis was performed using stain intensity levels established by determining color thresholds (nuclear score) in the basal and parabasal layers. RESULTS: Analysis of sections showed a similar pattern: only two normal donors had a few intensely positive p53 cells in the basal layer of the floor of the mouth and the tongue epithelia. Similarly, only three donors had intensely positive cyclin D1 cells in the normal epithelia of the same sites. Most cells fell in the range of negative or marginal stain (lower quartiles or terciles of nuclear score). These data on normal mucosa were compared with low grade oral leukoplakias (LGD) with mild to moderate dysplasia and with high grade leukoplakias (HGD) with severe dysplasia. Both markers were differentially expressed in precursor lesions versus normal epithelia. Statistical analysis of our data shows that the intensity of the immunohistochemical stain, as reflected in the nuclear scores of p53, is a reliable parameter that can differentiate between LGD and HGD of the oral mucosa. This was especially true when higher nuclear scores were compared. In contrast, low nuclear scores are more effective in differentiating normal epithelia from dysplastic epithelia. Although cyclin D1 immunohistochemistry does not stain as intensely as p53 stain, similar conclusions can be derived from those data. CONCLUSION: Image analysis of these two markers proved useful in distinguishing normal oral epithelia from low grade and high grade leukoplakias. With further developments in this field it is hoped that image analysis procedures could be used in different types of studies in which variations of protein expression in tissue sections could have prognostic implications or could be useful to determine subtle effects of curative or preventive treatment.

Adolescent↗
PubMed1999

[Cloning of mouse polycystic kidney disease 1 gene].

OBJECTIVE: To obtain mouse Polycystic kidney disease 1(PKD1) gene by plagues in situ hybridization from a genomic library. METHODS: With the use of partial mouse PKD1 genomic DNA fragments amplified by PCR as probes, a genomic library of 129SvTer mouse in bacteriophage vector was screened by plagues in situ hybridization. The inserts of genomic DNA fragments were analyzed by Southern blot, subclone and verified by sequencing. RESULTS: A positive phage clone was obtained after four-round screening. The sequence of the genomic DNA fragments inserted in the positive clone was in accordance with that of the Genebank. CONCLUSION: The authors found that the length and structure of mouse PKD1 genomic DNA fragments obtained from a genomic library were available to construct a replacement targeting vector.

Animals↗
PubMed1999

Stabilization and reactivation of the p53 tumor suppressor protein in nontumorigenic revertants of HeLa cervical cancer cells.

We demonstrated previously that loss of in vitro transformation and in vivo tumorigenicity in two independent revertant clones of HeLa cells (designated HA and HF) resulted from dominant-acting genetic changes. Analysis of the p53 tumor suppressor gene revealed stabilization and at least partial restoration of wild-type p53 transactivation properties pathways in both revertants of HPV-induced cell transformation. The half-lives of the p53 protein and both of the HA and HF clones were increased approximately 4 fold compared with the parental HeLa cells (16, 17, and 4 min, respectively). The levels of E6 viral protein expression were similar in the three cell lines, whereas the levels of the ubiquitin ligase protein, E6 associated protein (E6-AP), were elevated in the revertants. Western blot analysis of immunoaffinity-purified p53 demonstrated that stabilization of p53 in the revertants was correlated with a reduction in the in vivo formation of complexes involving the E6 oncoprotein and p53. Stabilization of p53 function in the revertants did not result from mutations in either the p53 or E6-AP genes. Despite the observed stabilization and restoration of p53 transactivation function in the revertants, exposure of the revertants to DNA-damaging agents did not result in elevated levels of p21(waf-1) protein and failed to induce growth arrest in the G1 phase of the cell cycle. However, p53-independent induction of p21(waf-1) protein also failed to induce the G1 phase of the cell cycle. Thus, restoration of wild-type p53 transactivation activity in the HA and HF revertants is insufficient to induce G1 arrest and reversion from HPV-induced cell transformation in our model system.

Cell Division↗
PubMed1999

Quality of life of patients with mild hypertension treated with captopril: a randomized double-blind placebo-controlled clinical trial.

OBJECTIVE: To determine the quality of life (QOL) of mild hypertensive patients treated with captopril as compared to placebo. METHODS: This is a randomized, double-blind, placebo-controlled clinical trial held in the out-patient clinic of Zhong Shan Hospital. Adult patients aged from 28 to 75 years with mild hypertension defined as diastolic blood pressure from 90 to 105 mm Hg were the inclusion criteria of the study. There were 278 patients who were eligible to enter the study. They were randomized to receive captopril or placebo 25 to 50 mg bid for 12 weeks. Change of QOL was compared both quantitatively and qualitatively between captopril and placebo groups. Change of blood pressure and side effects were also compared. RESULTS: With intention-to-treat analysis, significantly more improved QOL patients could be found qualitatively in patients with captopril treatment (45.3% vs 23.7%, P = 0.0002 for physical health domain; 48.9% vs 26.6%, P = 0.0002 for mental health domain; 33.8% vs 11.5%, P = 0.0001 for general function domain). Quantitatively, the change of score of mental health, general function and total QOL of captopril (3.18 +/- 5.90; 1.65 +/- 4.43; 7.84 +/- 11.03) were significantly higher than those of placebo (1.32 +/- 5.13, P = 0.00004; 0.64 +/- 3.45, P = 0.0008; 4.19 +/- 10.33, P = 0.0025 respectively), and the change of score of physical health domain (3.01 +/- 5.26 vs 2.23 +/- 4.79, P = 0.044) was of borderline statistical significant difference. Blood pressure was significantly lowered by captopril than by placebo (P = 0.000). CONCLUSION: Compared with the placebo, captopril is not only effective in lowering blood pressure, as has been established, but also effective in improving QOL in mild hypertensives.

Adult↗
PubMed1999

Corneal topographic analysis after excimer photorefractive keratectomy.

OBJECTIVE: To evaluate the corneal surface changes and visual quality after excimer photorefractive keratectomy (PRK) for myopia. METHODS: Corneal topographic analysis was performed on 23 patients (38 eyes) with myopia after PRK at the 1-, 3-, 6- month postoperative follow-up visits. RESULTS: The corneal sphericity was changed after excimer PRK. As time went on, the mean surface regularity index (SRI) and the surface asymmetry index (SAI) decreased gradually, and the corneal surface became more smooth; mean simulated keratoscope readings (SimK) showed a gradual restoration. At the 6-month postoperative examination, corneal topography showed four main patterns of ablation: round or oblong (50%), collar-button (23.68%), semicircular (18.42%) and central island (7.9%). Patterns of ablation were correlated with visual acuity. CONCLUSION: The quantitative analysis of corneal topography is essential for evaluating corneal surface changes after PRK and helpful in the surgical design of PRK and in predicting the refractive outcome with greater precision.

Adolescent↗
PubMed1999

[Cells culture of human lumbar disc and its morphological observation].

OBJECTIVE: To observe the continuous changes of disc cells, and explore the degeneration influenced by the cell effects. METHODS: Three discs were obtained from three human embryos and one was from a healthy adult. They were dissected and were digested with trypsin and collagenase. The isolated cells were cultured in HAM F-12 medium and 10% fetal bovine serum. The cultured cells were refrigerated and revived for observation under light microscope and TEM. RESULTS: The biological characteristics of the primary and the second generation of the disc cells were similar to those of the cells in vivo. After subculture, notochordal cells and chondrocytes were shown the characteristics of dedifferentiation. The metabolism of the revived cells after refrigeration was normal. The structures of the organellae in disc cells varied with the changes of cell biological characteristics. CONCLUSION: This successful model is useful for the study of biology and pharmacology of human disc cells.

Adult↗
PubMed1999

Modulation of in vivo granuloma formation related to regulation of in vitro IFN-gamma and IL-4 expressions in experimental schistosomiasis japonica.

OBJECTIVE: To find out relationship between the in vitro schistosome egg antigen (SEA) stimulated IFN-gamma and IL-4 mRNA expressions and the in vivo SEA elicited granulomatous responses, the transcriptions of IFN-gamma and IL-4 gene were investigated in the spleen of BALB/c mice infected with Schistosoma japonicum (S. japonicum). METHODS: Spleens were removed at 0, 3, 5, 8, and 10 and 12 weeks after infection and the spleen cells were incubated in the presence of SEA. The extracted RNA was analyzed for IFN-gamma and IL-4 mRNA by reverse transcription PCR (RT-PCR). Newly-formed liver granulomas were measured. RESULTS: The study revealed that no detectable IFN-gamma and IL-4 mRNA RT-PCR products were found in SEA treated spleen cells from uninfected, or 3-week infected mice, whereas IL-4 mRNA was found to be expressed in 5- and 8-week infected mice, and an appreciable enhanced expression of IL-4 mRNA was observed in SEA stimulated spleen cells at 8-week infection than at 5-week infections. However, SEA could not induce IFN-gamma and IL-4 mRNA transcription in 10- and 12-week infected mice, indicating the modulated expression of IFN-gamma and IL-4 mRNA. CONCLUSION: The significant changes of IL-4 mRNA expression in SEA stimulated spleen cells during S. japonicum infection were coincident with SEA elicited granuloma formation and modulation in vivo.

Animals↗
PubMed1999

Quantitative in vitro assessment of drug phototoxicity by a chemiluminescence method.

OBJECTIVE: To establish a test model for phototoxic agents using the method of chemiluminescence. METHODS: The phototoxicity of pipemidic acid, doxycycline, griseofuvin and chlorpromazine was detected. These agents and distilled water were irradiated with ultraviolet A (UVA) in the presence of nicotinamide adenine dinucleotide reduced (NADH), and the duplicated samples were incubated in the dark as dark controls. Then luminol was added to the test samples, and the chemiluminescent value was counted and calculated. RESULTS: Chemiluminescent values of pipemidic acid, doxycycline and griseofuvin were significantly higher than those in controls. The result of linear regression analysis showed that phototoxic intensity was linear correlated with UVA dosage. The regression coefficient for distilled water was 0.56, indicating that the luminescent value (LV) rose slightly after UVA irradiation. For pipemidic acid, griseofuvin and doxycycline, the regression coefficients reached 76.96, 254.33 and 92.61 respectively, significantly increased in comparison with those of negative controls (P < 0.01). CONCLUSION: Phototoxicity of pipemidic acid, doxycycline and griseofuvin can be detected with the method of chemiluminescence.

Dermatitis, Phototoxic↗
PubMed1999

Technology evaluation: ISIS-3521.

It is well known that the PKC family of enzymes is involved in the propagation of intracellular signals and is implicated in cancers, inflammatory processes, cardiovascular and endocrinological diseases. Relatively low isozyme specificity has largely limited the clinical use of PKC antagonists. The members of the PKC family differ from each other at the mRNA level and the selectivity of antisense compounds is distinguished by this feature. According to ISIS Pharmaceuticals Inc antisense compounds are highly selective inhibitors even within a family of closely-related genes [321211]. The use of these compounds could be invaluable as tools to discover the mechanisms and roles of specific PKC isozyme in normal and diseased tissues and could provide the information for better cancer treatments [226799]. The isozyme of PKC-alpha is believed to play an important role in the proliferation of several types of cancer cells [234471-323703]. Recently, ISIS Pharmaceuticals received a patent US-05885970, covering the antisense technique targeting human PKC-alpha for cancer therapy (US-0588970). In the past few years, several effective antisense oligonucleotides (AS ONs) targeting murine and human PKC-alpha isozymes have been developed and a series of positive results have been obtained in cell culture and in nude mice cancer transplantation [327453]. Phase I clinical trials have shown that relatively high doses were well tolerated with no obvious side-effects [226799]. Whether these AS ONs are beneficial to patients suffering from cancer, either alone or in combination with other chemotherapy drugs is still under evaluation in a clinical setting.

Animals↗
PubMed1999

[Identification of cDNA fragments related to alpha particles radiation induced neoplastic transformation of rat tracheal epithelial cells].

OBJECTIVE: To isolate genes involved in neoplastic transformation induced by alpha-particles. METHODS: The differential display technique was used to identify differentially expressed mRNA species between primary and neoplastic transformed rat tracheal epithelial (RTE) cells induced by alpha particles. RESULTS: 15 differentially displayed gene fragments were cloned and sequenced. Seven novel ESTs were submitted to GenBank. Homology searching revealed that clone ZG35 was highly homologous to rat Annexin I gene which was thought to be involved in mitogenic signal transduction as a substrate of epidermal growth factor receptor/kinase. Clone ZC52 was nearly identical to a novel rattus norvegicus gene for carboxylesterase precursor, clone ZG52 was 3' similar to human SRPK2 gene suggesting it may be a novel SRPK2 related gene involved in pre-mRNA splicing. Clone ZA73 was a novel gene fragments, and clone ZC66 was highly homologous to rat nucleoside diphosphate kinase gene or metastasis suppressor gene nm23, sequence analysis suggested that nm23 might be mutated in the transformed RTE cells. Northern hybridization confirmed the above gene or gene fragments to be up-regulated in the transformed RTE cells. CONCLUSION: These results provide clues to elucidate the mechanisms of radiation oncogenesis and suggest that Annexin I, carboxylesterase precursor gene, ZG52 and nm23 may be involved in the neoplastic transformation induced by alpha-particles radiation.

Alpha Particles↗
PubMed1999

[Biological mechanism of macrophage activation by wear particles at the bone-implant interface].

OBJECTIVE: To observe the response of membrane Ca(2+) channel of macrophage-like cells (MCs) to wear particles and analyze the cytoplasmic [Ca(2+)]i change in macrophage activation at the bone-implant interface. METHODS: The synoviocyte system of normal hip joint was established in vitro. Immunohistochemical technique (SABC) with CD68 Mab was used to differentiate MCs and fibroblast-like cells (FCs) in the system, and the time when MCs begin to perform phagocytosis was determined by SEM. 1.5 mg/ml (W/V) Ti alloy, Co-Cr alloy or UHMWPE particles suspension was added into the system to monitor the [Ca(2+)]i change in the MCs by confocal laser scanning microscope (CLSM). RESULTS: Phagocytosis of MCs happened after 6 hours, but within 1 hour the Ca(2+) channel of their cell membrane opened for 1 - 6 times and caused rapid and transient pulses of [Ca(2+)]i in cytoplasm after different period of incubation. There was no significant difference between times or range of the [Ca(2+)]i pulse (P > 0.05). The group of UHMWPE particles had the longest incubation period (P < 0.05), but the interval of pulses was shorter than that in the group of Co-Cr alloy particles (P < 0.05). [Ca(2+)]i pulses still appeared when MCs were incubated by indomethecin (P > 0.05), but the phenomenon could be blocked by nimodipin. CONCLUSIONS: Activation of macrophages at the bone-implant-interface could happen before they phagocytose wear particles. The primary switch-on mechanism of osteolysis mediated by cytokines at the bone-implant interface may be the opening of membrane Ca(2+) channel and pulse-like Ca(2+) influx of macrophages when stimulated by wear particles.

Biocompatible Materials↗
PubMed1999

[Transfection of articular chondrocytes with PcNDA3-hBMP3 and its stable expression].

OBJECTIVE: To explore the possibility of stable expression of PcDNA3-hBMP3 in cultured articular chondrocytes of rabbit. METHODS: PcDNA3-hBMP3 was constructed using gene clone technique and recombined DNA technique. With the help of profectamine, the cultured articular chondrocytes were transfected with PcDNA3-hBMP3, and the evidence of successfully stable transfection in these cells could be obtained by positive northern blot. RESULTS: The cultured articular chondrocytes of rabbits seemed to be polygonal, and its logarithmic growth phase was 2 - 4 days after cell inoculation. The two fragments cut from PcDNA3-hBMP3 by EcoR I and Xba I represented 5.4 kb and 1.4 kb by electrophoresis, which were confirmed to be the carrier and the fragment inserted originally, indicating that the construction of PcDNA3-hBMP3 was successful. The RNA extracted from cultured chondrocytes was screened for 4 weeks by G418 hibrided with the fragment cut from hBMP3 positively. CONCLUSIONS: With the help of profectamine, the cultured articular chondrocytes can be transfected by recombined gene of PcDNA3-hBMP3 successfully, and their stable expression at 4 weeks after transfection is obtained.

Animals↗
PubMed1999

[Effect of wear particles on cell-to-cell communication of synoviocyte system in vitro and its significance in aseptic loosening of prosthesis].

OBJECTIVE: To study the biological reason of abnormal fiber proliferation at bone-implant interface of aseptically loosened prosthesis by observing cell-to-cell communication of synoviocyte system in vitro under the stimulation of wear particles. METHODS: The synoviocyte system of normal human hip joint was established in vitro and the change of cell-to-cell communication was monitored by fluorescence redistribution after photobleaching technique (FRAP) and confocal laser scanning microscope (CLSM) after Ti alloy, CoCr alloy or UHMWPE particles suspension (1.5 mg/ml, W/V) was added into the system. RESULTS: Cell-to-cell communication of synoviocyte system significantly decreased under the stimulation of three kinds of particles (P < 0.01). he decreased degree was maximal in UHMWPE group and minimal in Ti alloy group (P < 0.01). The cell-to-cell communication level of fibroblast-like-cells (FCs) was significantly lower than that of macrophage-like-cells (MCs) (P < 0.05). CONCLUSIONS: Besides the effect of cytokines promoting fiber proliferation, the great amount of fibrous granuloma at bone-implant interface which has relations with aseptic loosening may be caused by the decrease of cell-to-cell communication of fibroblast under direct stimulation of wear particles.

Alloys↗
PubMed1999

[Acute rupture of anterior cruciate ligament: diagnosis and treatment by early arthroscopy].

OBJECTIVE: To early diagnose and treat acute rupture of anterior cruciate ligament (ACL). METHODS: 23 patients with acute rupture of ACL were examined and treated by early arthroscopy. RESULTS: The preoperative diagnosis of ACL rupture was similar to that of in 18 patients. Three patients were confirmed by early arthroscopy and 2 patients were found to have ACL rupture, 16 patients were combined with meniscus injuries and 6 patients with cartilaginous injuries. Patholanatomical type of ACL were rupture of parenchymal part (21 patients) and avulsion rupture of attachment point (2 patients). In 6 patients ACL was reconstructed under arthroscope. CONCLUSIONS: Early arthroscopy in the treatment of acute ACL rupture has advantages of minor injury, correct diagnosis, visible location of injury or combined injury and timely treatment. Early arthroscopy for acute ACL rupture is an important measure for diagnosis, treatment, and stabilization of the knee joint.

Acute Disease↗
PubMed1999

[Combined use of rhBMP2/BCB and free periosteum in repairing segmental defects in radii of rabbits].

OBJECTIVE: To study the efficacy of combined use of rhBMP2/BCBand free periosteal graft in repairing segmental bony defects. METHODS: A new grafting material (rhBMP2/BCB) was made by combining recombinant human BMP2 (rhBMP2) and an antigen-free bovine cancellous bone (BCB) as a carrier. rhBMP2/BCB was used alone in conjunction with free periosteal graft to repair a 1.5 cm defect in the radius of the rabbit. The defect-repairing capability for each of the treatment modalities was assessed radiographically, biomechanically, and by densitometry and histological studies. RESULTS: rhBMP2/BCB used alone was capable of healing the defect in large by 16 weeks, with a similar repair process and mechanism seen with RBX. Combined use of rhBMP2/BCB and free periosteal graft was superior in terms of increased amount and quality of the new bone formed at the early stage of the repair process (within 12 weeks) to rhBMP2/BCB used in isolation, with the defect basically healed by 12 weeks. CONCLUSIONS: Both methods are effective in repairing segmental bony defects, with rhBMP2/BCB used in conjunction with free periosteal graft being most preferred, considering the satisfactory osteogenesis, osteoconduction and osteoinduction.

Animals↗
PubMed1999

[Selective arterial embolization for the treatment of thoracolumbar spinal tumor].

OBJECTIVE: To decrease intraoperative blood loss during tumor resection. METHODS: Fifteen patients with primary thoraco-lumbar spinal tumor [giant cell tumor (5 patients), malignant nerinoma (2), chordoma (1), fibrous xanthosarcoma (1), malignant fibrohistocytoma (1), osteosarcoma (1), Ewing sarcoma (1), myeloma (1), leimyosarcoma (1), Non-Hodgkin diseases (1)] were treated by means of preoperative selective arterial embolization, tumor resection, and spinal reconstruction. Eight patients were subjected to total spondylectomy in one stage. RESULTS: Fourteen patients showed satisfactory results after embolization. The volume of intraoperative blood loss ranged from 3,000 ml to 400 ml (average 1,200 ml). Follow up of the patients varied from 8 months to 19 years (average 48.7 months). Local recurrence happened in 3 patients; 3 patients died from metastasis. Three of 4 patients recovered from complete bowel movement and urination. Seven of nine patients had musical strength improved. Six of 8 patients had recovery of the e sensation of the lower limbs. CONCLUSIONS: Selective arterial embolization before operation followed by operation within 24 hours can reduce intraoperative blood loss, shorten operative time, and provide a clear operative field for tumor resection.

Adolescent↗