Biomedical subjects

L Pan

Publications and source records attributed to L Pan.

At least 55 records · Page 3Linked to original sources

PubMed2000

Mechanistic studies of a linear trisazoalkane, a new azimine, and a bicyclic triaziridine. Azoalkane homolysis into seven fragments

An aliphatic azo compound containing three azo groups (1) has been prepared by IF(5) oxidation of beta-azoamine 3. The thermolysis kinetics of this vicinal trisazoalkane were investigated above 155 degrees C, leading to a rate constant only 5.5 times faster than that of the simple model, azo-tert-butane. Because thermolysis to form seven stable products proceeds stepwise, the rate is hardly affected by the high exothermicity of the overall reaction (-93.4 kcal/mol). Oxidation of amine 3 also afforded a cyclic azimine 5 that underwent photolysis to yield a highly strained triaziridine 9 plus an unusual triazane 10, whose structures were elucidated by detailed NMR studies. On standing at ambient temperature, 9 reverted to 5 with a half-life of about an hour.

Journal Article↗

PubMed2000

Clonality analysis of defined cell populations in paraffin-embedded tissue sections by RT-PCR amplification of X-linked G6PD gene.

This paper establishes a method of clonality analysis using the reverse transcription-polymerase chain reaction (RT-PCR) to amplify X-linked G6PD transcripts on defined cell populations microdissected from archival, paraffin-embedded tissue sections. Four known monoclonal low-grade B-cell lymphomas from females who were heterozygous (informative) at the 1131 exonic polymorphic locus of the G6PD gene were used to validate the method. Lymphoma and reactive lesions in each case were separated by microdissection. In order to preserve the intact RNA species in the lesion, sections were digested on the slides before microdissection. A one-step RT-PCR was performed with a single pair of primers, one of which contained a mismatched base adjacent to the polymorphic site, to generate a PvuI cutting site. Successful amplification and allele identification by PvuI digestion were achieved from all RNA samples studied. Three of four samples from non-neoplastic reactive lesions showed two bands with equal intensity, representing transcription of the two alleles of the G6PD gene, while the corresponding tumour samples demonstrated a biased intensity in one allele, indicating monoclonality. To assess the method further, the clonal nature of in situ and invasive breast cancers was examined, along with adjacent normal breast tissue and hyperplastic lesions from three informative females from our archives. Apart from the clusters of normal terminal duct-lobular units, all lesions were monoclonal. This result is in agreement with data derived from other X-linked gene studies and loss of heterozygosity (LOH) analyses of pre-invasive breast disease. The results suggest that the clonality analysis method presented here is simple and reliable, and is therefore potentially applicable in a wide range of pathological conditions.

Breast↗

PubMed2000

Increased sensitivity of multidrug-resistant myeloid leukemia cell lines to lovastatin.

Lovastatin, a competitive inhibitor of HMG-CoA reductase, reportedly inhibits proliferation and induces apoptosis of tumor cells with MDR-1 coded P-glycoprotein (Pgp) expression. In this study we investigated the sensitivity to lovastatin of eight myeloid leukemia cell lines: K562, NOMO-1, NB4 and its retinoic acid (RA) resistant subline NB4/RA, and their multidrug-resistant (MDR) sublines: K562/ADR, NOMO-1/ADR, NB4/MDR and NB4/RA/MDR. MTT and apoptosis assays revealed that K562/ADR, NOMO-1/ADR and NB4/RA/MDR were more sensitive to lovastatin than their parental cell lines, while NB4/MDR showed the same level of sensitivity as parental NB4 cells, which already were very sensitive to lovastatin. Significant elevation of transcript levels of HMG-CoA reductase was observed by semiquantitative RT-PCR analysis in more than three lovastatin-sensitive MDR sublines, but not in NB4/MDR compared with the parental cell lines. HMG-CoA reductase mRNA levels were up-regulated more than two-fold by the exposure to lovastatin in all of the parental non-Pgp-expressing cell lines. In NB4/MDR, HMG-CoA reductase mRNA level was elevated to a similar extent as in parental NB4, whereas in three other MDR sublines which showed preferential sensitivity to lovastatin, their HMG-CoA reductase mRNA levels were not significantly elevated after 24- and 48-h treatment with lovastatin. These results indicate a connection between drug resistance and regulation of the mevalonate pathway, and further strengthen the clinical possibility that drug resistant leukemias would be susceptible to treatment with lovastatin.

Apoptosis↗

PubMed2000

In vitro IL-12 treatment of peripheral blood mononuclear cells from patients with leukemia or myelodysplastic syndromes: increase in cytotoxicity and reduction in WT1 gene expression.

Interleukin-12 (IL-12) has potent antitumor activities. We examined whether IL-12 enhanced the cytotoxicity of peripheral blood mononuclear cells (PBMNC) and decreased leukemia cells in 30 patients with leukemia or myelodysplastic syndromes (MDS): 12 acute myeloid leukemia (AML) (five in complete remission (CR) and seven in non-CR); six chronic myeloid leukemia (CML); and 12 MDS (three refractory anemia (RA), eight RA with excess of blasts and one chronic myelomonocytic leukemia). PBMNC from patients and five healthy volunteers were cultured at 5 x 10(5)/ml parallel with or without 100 units/ml of IL-12 for 3 days. Cytotoxicity of PBMNC against K562 cells was assessed by flow cytometry. To quantify the amount of leukemia cells, WT1 mRNA was measured by competitive reverse transcription polymerase chain reaction (RT-PCR), since WT1 mRNA is considered as a marker of minimal residual disease (MRD) in leukemia or MDS. The cytotoxicity of non-IL-12-treated PBMNC of 30 patients was 13.4+/-9.3% at the effector to target (E:T) ratio of 20:1, and significantly lower than that of normal subjects (25.7+/-8.4%). The cytotoxicity increased to 30.6+/-17.9% in the IL-12-treated PBMNC. WT1 mRNA in PBMNC of five healthy volunteers was less than 10(3) copies/microg of total RNA. Following the 3-day IL-12 treatment, mean WT1 mRNA of PBMNC was reduced from 10(4.8) to 10(4.2) copies/microg of total RNA in six CML patients, from 10(5.4) to 10(4.8) copies/microg in 12 MDS patients and from 10(5.0) to 10(4.2) copies/microg in five AML patients in CR, but not reduced in five of seven AML in non-CR. These results showed that IL-12 significantly enhanced PBMNC cytotoxicity and decreased the quantity of leukemia cells in PBMNC of most patients with MDS, CML and AML in CR. IL-12 might be of considerable benefit in the elimination of MRD in patients with hematological malignancies.

Adult↗

PubMed2000

Nucleoside diphosphate kinase required for coleoptile elongation in rice.

Although several nucleoside diphosphate (NDP) kinase genes have been cloned in plants, little is known about the functional significance of this enzyme during plant growth and development. We introduced a chimeric gene encoding an antisense RNA of NDP kinase under the control of the Arabidopsis heat shock protein HSP81-1 promoter into rice (Oryza sativa L.) plants using the Agrobacterium tumefaciens transformation system. The expression of antisense RNA down-regulated the accumulation of mRNA, resulting in reduced enzyme activity even under the standard growth temperature (25 degrees C) in transgenic plants. Following heat shock treatment (37 degrees C), NDP kinase activities in some transgenic rice plants were more reduced than those grown under 25 degrees C. The comparison of the coleoptile growth under submersion showed that cell elongation process was inhibited in antisense NDP kinase transgenic plants, suggesting that an altered guanine nucleotide level may be responsible for the processes.

Nucleoside-Diphosphate Kinase↗

PubMed2000

3,5-Pyrazoledicarboxylic acid monohydrate

In the title compound, C(5)H(4)N(2)O(4).H(2)O, the 3, 5-pyrazoledicarboxylic acid (H(3)pdc) molecules are joined into one-dimensional chains by O-H.O and N-H.O hydrogen bonds, with distances of 2.671 (2) and 2.776 (2) A, respectively. The one-dimensional chains form a three-dimensional structure via O-H.OW and OW-HW.N hydrogen bonds, with distances of 2.597 (3) and 2.780 (3) A, respectively. In addition to the potential for forming open-channel frameworks, access to the six coordination atoms of H(3)pdc can be directly controlled by varying the pH of the reaction environment, allowing further control over the design and synthesis of novel coordination polymers using various metal centers.

Journal Article↗

PubMed2000

Spicamycin and KRN5500 induce apoptosis in myeloid and lymphoid cell lines with down-regulation of bcl-2 expression and modulation of promyelocytic leukemia protein.

Spicamycin is a potent inducer of differentiation of human myeloid leukemia cells (HL-60) and murine myeloid leukemia cells (M1). One of the spicamycin derivatives, KRN5500, shows a broad spectrum of antitumor activity against human tumor xenografts in nude mice. In this study, we first investigated the differentiation efficacy of spicamycin and KRN5500 in HL-60 and acute promyelocytic leukemia cell line, NB4, and found that low concentrations of both compounds induced differentiation to a small extent in both cell lines, but markedly induced apoptosis in NB4 cells. Further investigation in a myeloid leukemia cell line, NKM-1, a lymphoma cell line, Daudi, and a multiple myeloma cell line, NOP-1, showed that high concentrations of both compounds also induced apoptosis in these cells. The 50% inhibitory concentration (IC(50)) determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that myeloid cells were more sensitive to both compounds than lymphoid cells, and spicamycin was more potent than KRN5500. Western blot analysis of Bcl-2, Bcl-xL and Bax expression and immunofluorescence analysis of promyelocytic leukemia (PML) protein indicated that apoptosis induced by spicamycin and KRN5500 was associated with down-regulation of Bcl-2 expression and modulation of PML protein. Thus, spicamycin and KRN5500 may be useful for the treatment of myeloid and lymphoid neoplasms.

Antibiotics, Antineoplastic↗

PubMed2000

Gamma Knife radiosurgery as a primary surgical treatment for hypersecreting pituitary adenomas.

OBJECT: To estimate the efficacy of Gamma Knife radiosurgery (GKR) especially as a primary surgical treatment for hypersecreting pituitary adenomas. METHODS: 274 patients were treated with GKR. The mean tumor volume was 1.86 cm(3). The mean peripheral dose was 28.7 Gy. RESULTS: 223 patients were followed up for an average of 31.6 months. The dose related to the tumor growth control and endocrinological normalization was detailed and statistical analysis of the data was performed. CONCLUSION: GKR as a primary surgical treatment for hypersecreting pituitary adenomas may be safe and effective.

Adenoma↗

PubMed2000

A genetic investigation of E2A function in lymphocyte development.

Lymphocytes are derived from hematopoietic stem cells (HSC) following a series of regulated differentiation events. Multipotent HSCs become committed to the B cell lineage in bone marrow and the T cell lineage in the thymus after receiving appropriate signals from the corresponding microenvironment. These committed lymphoid cells must then undergo V(D)J recombination at the immunoglobulin gene or T cell receptor gene locus resulting in clonal production of functional B or T lymphocytes, respectively. Lymphocyte commitment and differentiation are accompanied by programmed gene expression or repression events which are driven by lineage and stage specific transcription factors. The basic-helix-loop-helix (bHLH) transcription factors encoded by the E2A gene are involved in several differentiation events during B and T cell development, including lineage commitment, initiation of V(D)J recombination, and antigen receptor mediated proliferation and differentiation. Several recent reviews have provided a comprehensive discussion of biochemical, cellular, and genetic research on E2A function in lymphocyte development (1,2). Here, we only discuss some of the genetic approaches our laboratory (except where it is noted) has undertaken to investigate the molecular pathways mediated by E2A transcription factors in lymphocyte development.

Animals↗

PubMed2000

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗

PubMed2000

Novel Single- and Double-Layer and Three-Dimensional Structures of Rare-Earth Metal Coordination Polymers: The Effect of Lanthanide Contraction and Acidity Control in Crystal Structure Formation.

Lanthanide atom sizes (the lanthanide contraction) directly control the type of structure formed by the coordination of a single multidentate ligand, 3,5-pyrazoledicarboxylic acid (H(3)pdc). Single-layer, double-layer ([Eu(2)(Hpdc)(3)(H(2)O)(6)], see picture), and three-dimensional networks were found. Control of the reaction pH plays a key role in the structure formation in this system.

Journal Article↗

PubMed2000

[Study of mdr1 antisense oligodeoxynucleotides on reversal of multidrug resistance in ovarian carcinoma cell line SKOV3].

OBJECTIVE: To investigate the effect of mdr1 antisense oligodeoxynucleotides (ASON) on reversal of multidrug resistance in ovarian carcinoma cells. METHODS: Drug resistance ovarian carcinoma cells SKOV3/mdr1 transducted with human multidrug resistance gene (mdr1) were served as models. The positive rate and function of the mdr1 gene product P-glycoprotein (P-gp) in SKOV3/mdr1 cells after mdr1-ASON (250 micrograms/ml) treatment were determined by flow cytometry and rhodamine 123 efflux trial. Drug resistance of SKOV3/mdr1 cells was also observed by cell colony culture. RESULTS: P-gp positive rate of SKOV3/mdr1 cells after mdr1-ASON treatment was decreased from 38.9% to 21.3% (P < 0.01). Intracellular rhodamine retension in SKOV3/mdr1 cells after mdr1-ASON treatment was increased from 32.1% to 50.7% (P < 0.01). Under effect of Taxol 5 ng/ml, the relative percents of drug-resistant colony in mdr1-ASON treated SKOV3/mdr1 cells and in SKOV3/mdr1 cells was 8% and 63%, respectively, (P < 0.01). Under effect of Doxorubicin 100 ng/ml, the relative percents of drug-resistant colony in mdr1-ASON treated SKOV3/mdr1 cells and in SKOV3/mdr1 cells was 34% and 79%, respectively, (P < 0.01). CONCLUSION: mdr1-ASON can reverse multidrug resistance of ovarian carcinoma cell in a certain extent so as to increase chemotherapeutic sensitivity of ovarian carcinoma cells.

Drug Resistance, Neoplasm↗

PubMed2000

[Determination of fructose-1,6-diphosphate with aldolase-DNPH by the colorimetric method].

This paper presents a modified method of enzymatic assay for Fructose-1,6-diphosphate(FDP). FDP is split to dihydroxyacetone phosphate (DAP) and glyceraldehyde-3-phosphate (GAP) by the action of aldolase. DAP is hydrolyzed at room temperature to free triose. Under alkaline conditions, the free triose is reacted with 2,4-dinitrophenylhydrazine (DNPH), yielding a 2,4-dinitrophenylhydrazine derivative which dissolve in alkali forming a purple color mixture, with maximum absorption at 540.nm. It is proportional to the contents of FDP. Because the method depends on the colorimetric determination of triose formed from fructose-1,6-diphosphate only by aldolase, glycerophosphate dehydrogenase/triosephosphate isomerase (GDH/TIM) and reduced nicotinamide adenine dinucleotide (NADH) which usually applied in multienzymatic method, are omitted in the modified method. The method is specific, convenient and accuracy for the determination of FDP.

Colorimetry↗

PubMed2000

[Chemoprotection of transfer of multidrug resistance gene into human hematopoietic progenitor cell].

OBJECTIVE: To observe the effect of the transfer of multidrug resistance gene (mdr1) into human hematopoietic progenitor cells (HPC) on the chemoprotection. METHODS: Human CD34+ cells served as a target of mdr1 gene transfer. Retroviral vector SF-mdr containing human total length mdr1cDNA was introduced into packing cells GP-envAM12 by liposome-mediated transfection. The mdr1 gene was transduced into human CD34+ cells by retroviral supernatants of packing cells. The integration and expression of the mdr1 gene and its protein (P170) in transduced cells were determined by PCR, RT-PCR, and flow cytometry. The drug resistance of chemotherapy in transduced HPC was determined by culturing colonies. RESULTS: The mdr1 gene was integrated and expressed in transduced CD34+ cells. The efficiency of mdr1 gene transfer was 10%-14%. Compared with untransduced controls, within a certain range of drug concentration, the number of drug-resistant colony in transduced HPC for taxol, doxorubicin, VCR and VP16 were increased by 3.6 +/- 2.1 fold, 2.9 +/- 0.3 fold, 1.9 +/- 0.4 fold, and 3.5 +/- 0.5 fold, respectively. CONCLUSION: The transfer of the mdr1 gene into human HPC can increase the drug resistance of the transduced cells to corresponding chemotherapeutic drugs that may provide some degree of chemoprotection for HPC.

Antigens, CD34↗

PubMed2000

[High-dose chemotherapy with peripheral-blood stem cells transplantation in patients with advanced gynecological malignant tumors].

OBJECTIVE: To evaluate the clinical effectiveness of high dose chemotherapy(HDC) with peripheral-blood stem cells transplantation(PBSCT) in the patients with advanced malignant tumors. METHODS: Four patients with advanced or refractory ovarian carcinoma and 1 patient with recurrent fallopian tube carcinoma received the HDC with PBSCT after optimal tumor debulking. Of whom 4 patients were with the recurrent or progressive tumors, 1 patient received HDC as primary chemotherapy. The response and toxicity were assessed after treatment. RESULTS: Among 5 patients, four patients are survival. One case died from the recurrence of juvenile granulosa cell tumor. The average survival periods were 21 months. The tumors were all recurrent among the 4 survival patients. The average periods of recurrence after HDC treatment was 9 months. The main toxicity of HDC was severe marrow suppression. The lowest value of the neutrophil count and platelet count was 0.05-0.2 x 10(9)/L and 7 x 10(9)/L-8 x 10(9)/L respectively. The median time to recover a neutrophil count greater than 0.5 x 10(9)/L was 14 days and a platelet count greater than 50 x 10(9)/L was 17 days. None of the patients was complicated with severe complications. CONCLUSIONS: HDC and PBSCT used for ovarian carcinoma was flexibility and security if the patient was selected strictly though its toxicity was severe. Further study among the chemorefactory recurrent patients need to try in the future.

Adult↗

PubMed2000

[Effects of arsenic trioxide on K562 cells stably expressing two promyelocytic leukemia-specific fusion proteins].

OBJECTIVE: To illustrate the possible roles of acute promyelocytic leukemia-specific chimeric proteins PML-RARalpha and PLZF-RARalpha in the effects of arsenic trioxide (As(2)O(3)). METHODS: K562 sublines stably expressing PML-RARalpha (K(PML() and PLZF-RARalpha (K(PLZF)) were established by retrovirus transfection with K(V) transfected empty vectors as controls. Effects of As(2)O(3) and all-trans retinoic acid (ATRA) on these sublines were analyzed through cell count, morphology, measurement of cellular DNA contents and differentiation antigens on flow cytometry. Subcellular distributions of PML-RARalpha proteins were observed with immunofluorescence. RESULTS: 1.0 micromol/L of As(2)O(3) did not induce cell apoptosis and differentiation, but it significantly inhibited the growth of K(V) sublines. As(2)O(3) showed the similar but more potent effects in K(PML) and K(PLZF) sublines. 1.0 micromol/L As(2)O(3) treatment for 3 days induced growth inhibition by 32% +/- 3%, 57% +/- 4% and 54% +/- 6%, respectively in K(V), K(PML) and K(PLZF) sublines. 1.0 micromol/L ATRA also exerted, to a less extent than As(2)O(3), growth-inhibitory effects in K(V) sublines, which became more obvious in K(PML) but not in K(PLZF) sublines. In addition, PML/PML-RARalpha proteins were decreased and even disappeared in K(V) and K(PML) sublines with the treatment of 1.0 micromol/L As(2)O(3) for 48 hours. CONCLUSION: PML-RARalpha and PLZF-RARalpha markedly enhance growth-inhibitory effects of As2)O3) on K562 cells.

Antineoplastic Agents↗

PubMed2000

[Dural arterovenous fistula involving cavernous sinus].

OBJECTIVE: To study the pathogenesis and treatment of dural arteriovenous fistulas (DAVFS) involving the cavernous sinus. METHODS: 32 cases were embolized with particle by microcatheterization via endovascular approach and ervation by digital substraction angiography. Of the 32 cases, 14 were embolized by microsoils through superior petrosal sinus approach into the cavernous sinus. RESULTS: In 28 of the 32 cases the fistulas were completely embolized angiographically. The fistulas were partly embolized in 4 of the 32 cases. The carotid artery was compressed for 6 months. One week later, the fistula disappeared angiographically. No fistulas were found during the follow-up for 6 months to 8 years. CONCLUSION: Endovascular treatment of DAVFS involving the cavernous sinus is effective.

Adolescent↗

PubMed2000

[Radiographic studies of cervical spine motion range in normal Chinese subjects with computer-assisted image analysis: full flexion and extension].

OBJECTIVES: To study the degenerative regularity of normal Chinese cervical spine by observing the motion range of full cervical flexion and extension, and to provide evidences for further investigation of cervical segmental instability. METHODS: 764 X-ray plain films of full cervical flexion and extension in 382 normal Chinese subjects (214 were male and 168 female) were investigated using self-designed cervical X-ray image analysis system. The subjects within the same sex group were divided into three groups according to the age: group A (20 years to 39 years), group B (40 years to 59 years) and group C (60 years to 76 years). During the full cervical flexion and extension motion, total intervertebral motion range (from C(2) - C(3) to C(6) - C(7)) and intervertebral motion range at each level were major parameters. RESULTS: The range of total intervertebral motion showed much greater mobility in group A than in group B and group C (P < 0.01) but no statistically significant difference between group B and group C (P > 0.05). The range of intervertebral motion was maximal at C(5) - C(6) in group A. The place of maximal motion shifted to the C(4) - C(5) in both group B and group C. C(2) - C(3) showed minimal mobility in all three groups. There was no statistically significant difference (P > 0.05) between male and female. CONCLUSIONS: The motion range and degenerative regularity of normal Chinese cervical spine were similar in either sex. The range of total intervertebral motion (from C(2) - C(3) to C(6) - C(7)) had a tendency to decrease rapidly and then became steady with age. For the range of intervertebral motion, the place of maximal motion shifted to the higher level with age from C(5) - C(6) in group A to C(4) - C(5) in group B and group C.

Adult↗