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Biomedical subjects

L Qian

Publications and source records attributed to L Qian.

At least 37 records · Page 2Linked to original sources

[Sequential intensified immunosuppressive therapy combining with hematopoietic growth factors in the treatment of severe aplastic anemia].

OBJECTIVE: To explore more effective regimen for reducing early mortality of severe aplastic anemia (SAA) and improving therapeutic effectiveness. METHODS: Antilymphocyte globulin/antithymocyte globulin (ALG/ATG) and cyclosporine A (CsA) (sequential intensified immunosuppressive therapy, SIIST), with or without hematopoietic growth factors (HGFs) were administered to 73 SAA patients in a prospective randomized clinical trial to test the effectiveness of the addition of HGFs for the patients. RESULTS: The response rate of SIIST with HGFs group was significantly higher than that of SIIST alone group (89.2% vs 63.9%), with lower rates of early infection (24.3% vs 55.3%) and mortality (4.0% vs 16.7%), shorter duration of cytopenia and blood transfusion dependence and faster recovery of bone marrow hematopoiesis. The addition of HGFs to SIIST was tolerated well in all patients. There was no difference in the treatment outcome of the two groups with GM-CSF plus Epo or G-CSF plus Epo. CONCLUSION: The use of HGFs in combination with SIIST could reduce early infection and mortality rates and, therefore, improve the response rates in SAA patients.

Adolescent↗

Thio- and oxoflavopiridols, cyclin-dependent kinase 1-selective inhibitors: synthesis and biological effects.

Flavopiridol analogues, thio- and oxoflavopiridols which contain a sulfur (16) or oxygen (18) atom linker between a chromone ring and the hydrophobic side chain, are selective cyclin-dependent kinase 1 (CDK1) inhibitors with an IC(50) of 110 and 130 nM. These analogues were prepared from key intermediate 7 by substituting the ethyl sulfoxide. Enantio pure intermediate piperidone 10 was obtained from the racemic piperidone 8 via a very efficient "dynamic kinetic resolution" in 76% yield. Hydrophobic side chains such as chlorophenyl or tert-butyl produced potent CDK1 inhibitory activity, while hydrophilic side chains such as pyrimidine or aniline caused a severe reduction in CDK inhibitory activity. These analogues are competitive inhibitors with respect to ATP, and therefore activity was dependent upon the CDK subunit without being affected by the cyclin subunit or protein substrate. Thio- and oxoflavopiridols 16 and 18 are not only selective within the CDK family but also discriminated between unrelated serine/threonine and tyrosine protein kinases. CDK1 selective thio- and oxoflavopiridol analogues inhibit the colony-forming ability of multiple human tumor cell lines and possess a unique antiproliferative profile in comparison to flavopiridol.

Antineoplastic Agents↗

[Detection of apoptosis by in situ labeling and study on the expression of PCNA in hypertrophic scars and keloids].

To investigate the involvement of apoptosis and proliferation in the lesions of hypertrophic scars and keloids, eighteen samples of hypertrophic scar and five samples of keloid were collected. The apoptosis was detected with terminal deoxynucleatidyl transferase mediated d-UTP biotin nick end labeling(TUNEL) and the expression of PCNA was assessed with immunohistochemical technique in scar lesions and normal skin. Results showed that in hypertrophic scar and keloid samples the rate of proliferating cells in dermis was higher than that of normal skin(P < 0.05), whereas the apoptosis index between scars and normal skin shows no statistical significance. It indicates that excessive proliferation and the lack of apoptosis of cells in dermis may cause the formation and development of hypertrophic scars and keloids.

Adolescent↗

Distension-induced myoelectrical dysrhythmia and effect of intestinal pacing in dogs.

The aims of this study were to investigate the effect of duodenal distension on intestinal myoelectrical activity and to investigate whether intestinal pacing was able to reverse the effects of distension. Six female hound dogs with four pairs of electrodes on the proximal jejunum were involved in this study. The protocol consisted of 30 min of recording of jejunal myoelectrical activity as baseline and 90 min of recording during distension. Intestinal pacing was performed during the second 30 min of distension. Duodenal distension severely impaired intestinal myoelectrical activity. The percentage of normal slow waves was reduced from 90.8+/-8.4% at baseline to 73.8+/-10.2%, 57.2+/-11.4%, and 53.7+/-16.0% during the first, second and third 30 min of distension (P<0.05, ANOVA). The dominant power was similarly decreased and the minute-by-minute variation of dominant frequency was significantly increased after distension. Intestinal pacing reversed distension-induced dysrhythmia. The percentage of normal slow waves during the 30 min of distension with pacing was significantly higher than the corresponding 30 min of distension without pacing (88.5+/-6.6% vs. 57.2+/-11.4%, P<0.03). It was concluded that intestinal pacing can normalize distension-induced dysrhythmia and has a potential as a future therapeutic modality for intestinal motor disorders.

Animals↗

Folate deficiency reduces the GPI-anchored folate-binding protein in rat renal tubules.

A folate-binding protein (FBP) anchored to cell membranes by a glycosyl phosphatidylinositol (GPI) adduct is constitutively expressed in some transformed and cultured cell lines. Its expression is upregulated when these cells are grown in medium containing low folate, but whether this occurs in vivo with nutritional folate deficiency is unknown. To address this question, the GPI-FBP in the liver, kidney, and brain of rats on control and folate-deficient (FD) diets was measured. The GPI-FBP in the kidney of FD rats decreased significantly in contrast to the upregulation of this protein in cultured cells. Northern blot analysis and nuclear run-on assays indicated that transcription of the GPI-FBP gene in the kidney was not reduced by folate deficiency. This decrease of the GPI-FBP appears to result from its proteolysis, similar to the enzymatic degradation of the apoprotein that occurs in vitro. Because the GPI-FBP is on the brush borders of the proximal renal tubules and provides for the reabsorption of folate, this function diminishes when the protein decreases in folate deficiency.

Animals↗

Changes in local cerebral blood flow, glucose utilization, and mitochondrial function following traumatic brain injury in rats.

The pathophysiology of secondary brain damage following experimental traumatic brain injury was investigated by measuring local cerebral blood flow (lCBF), local cerebral glucose utilization (lCGU), and activity of succinate dehydrogenase (SDH), which is a mitochondrial enzyme of the tricarboxylic acid cycle, in the rat brain after moderate lateral fluid percussion injury. Measurements used autoradiography for lCBF and lCGU with [14C]iodoantipyrine and [14C]2-deoxyglucose, respectively. Regional SDH activity was determined using quantitative imaging of formazan produced from 2,3,5-triphenyl tetrazolium chloride by SDH. lCBF decreased at 1 hour after injury and was significantly lower than the preinjury level in almost all regions of both hemispheres at 6 and 24 hours, and remained low at 2 weeks. lCGU increased 1 hour after injury but was significantly decreased at 6 and 24 hours, and at 2 weeks in most regions of both hemispheres. The ipsilateral hemisphere showed a significant decrease in the activity of SDH in the cortices, hippocampus, thalamus, and caudate/putamen, most conspicuously 72 hours after injury, whereas no significant decrease was observed in the contralateral hemisphere at any time. Necrosis in the injured cortex and reduction of the number of neurons in the ipsilateral hippocampus were observed 2 weeks after injury. The present study showed that a decrease in lCBF and mitochondrial dysfunction occur with glucose hypermetabolism around 1 hour after lateral fluid percussion injury, and that lCBF, lCGU, and mitochondrial function all deteriorate after 6 hours. This suggests that lCBF and cellular metabolism may change dynamically during the several hours following traumatic brain injury, and afterwards neuronal damage may result in an irreversible change in the areas with depressed glucose hypermetabolism in the early period after injury in combination with mitochondrial dysfunction.

Animals↗

[Clinicopathological studies on bone marrow involvement of non-Hodgkin's lymphoma].

OBJECTIVE: To investigate the relationship between pathomorphological features and clinical manifestations of non-Hodgkin's lymphoma (NHL) with bone marrow involvement (BMI). METHODS: Plastic-embedded section of bone marrow biopsy was stained with H-Giemsa-E. Immunotyping of NHL was performed immunohistochemically. RESULTS: A total of 70 patients with NHLBMI(male: 52, female: 18; median age: 49 years) was studied. There were 20 patients with T cell-lymphoma and 50 patients with B cell-lymphoma. The extent of bone marrow involvement was minimal in 15 cases, moderate in 16 cases and severe in 39 cases. Bone marrow involvement was of interstitial type in 23 cases, nodular type in 7 cases, and mixed type in 18 cases and diffuse type in 22 cases. The frequency of splenomegaly in nodular type NHLBMI was significantly higher than that in any other type. Nodular type NHLBMI occurred mainly in B cell-lymphoma. Lymphoma cell leukemia (LCL) developed in 14 of 39 (35.9%) cases of NHL with severe bone marrow involvement which was significantly more frequent than that in NHL with mild and moderate bone marrow involvement. CONCLUSION: Difference in the extent and pattern of bone marrow involvement in NHL is related to clinical manifestations. Bone marrow biopsy helps evaluate response to treatment.

Adolescent↗

[The genetic instability of mismatch repair gene linked microsatellite and the evolution of CML].

OBJECTIVE: To explore the relationship between the genetic instability of microsatellite linked with mismatch repair gene and the evolution of CML to blast crisis. METHODS: The loss of heterozygosity (LOH) and microsatellite instability (MSI) of two polymorphic microsatellite markers, D2s123 and D3s1298, linked with mismatch repair gene hMSH2 and hMLH1 respectively, were detected by PCR-silver staining method on the bone marrow cells of 18 CML patients, who clinically progressed from the chronic phase to accelerated phase or blast crisis. RESULTS: Differences in microsatellite D2s123 and D3s1298 at the CML accelerated phase or blast crisis in 5 (27.8%) of the 18 patients were demonstrated compared with chronic phase. For D2s123, MSI and LOH were observed in 1 of 8 patients with accelerated phase (12.5%) and 2 of 10 patients in blast crisis (20%). For D3s1298, MSI and LOH were observed in 2 of 10 patients in blast crisis (20%). CONCLUSION: The genetic alteration of microsatellite D2s123 and D3s1298 may play a role in the progress of some CML cases.

Adolescent↗

[In vitro induction of autologous T cell killing by heat treated human chronic myelogenous leukemia cells].

OBJECTIVE: To investigate the potential of autologous T cell killing of heat treated chronic myelogenous leukemia (CML) cells (autologous tumor killing, ATK). METHODS: (51)Cr release assay was used to measure the ATK activity of autologous T cells against CML cells treated with 42 degrees C for 30 minutes (heat) or 37 degrees C for 30 minutes (non-heat). The phenotypes of T cells and heat shock protein 70 (HSP70) expression of CML cells were measured by flow cytometry (FCM). T cells from the CML patients were stimulated and expanded by autologous mixed lymphocyte/tumor cell cultures (MLTC). RESULTS: ATK activity of autologous T cells to the non-heated and heated CML cells were found in 4 (19.05%) and 10 (47.62%) of the 21 cases, respectively. The ATK activity of interleukin-2 (IL-2) stimulated autologous T cells against heated CML cells was markedly higher than that of unstimulated autologous T cells against non-heated CML cells (P < 0.001). FCM analysis showed that no HSP70 was expressed on the CML cell membranes whether heated or non-heated, but intracellular HSP70 expressions were (83.42 +/- 5.65)% and (78.34 +/- 6.32)% pre- and post-heated, respectively. The phenotypes of T cells stimulated and expanded in MLTC were TCRgammadelta - CD(3)(+), mostly CD(8)(+), with some activation markers (CD(25) and HLA-DR) expression. The ATK activities of these T cells against the heated and non-heated CML cells and K562 cells were (51.25 +/- 4.26)%, (36.52 +/- 3.83)% and (2.92 +/- 1.19)%, respectively. CONCLUSIONS: ATK activity of autologous T cells against CML cells could be induced or enhanced by heat treatment of the CML cells particularly of T cells stimulated with IL-2. This ATK activity was not associated with gammadelta T cells or HSP70 expression of CML cells.

Adolescent↗

[Study on the clinical characteristics of biphenotypic acute leukemia].

OBJECTIVE: To analyze the biological characteristics and the treatment outcome of adult biphenotypic acute leukemia. METHODS: Immunophenotypes were examined using indirect immunofluorescence method. Biphenotypic acute leukemia (BAL) was diagnosed according to EGIL scoring system. RESULTS: (1) The incidence of BAL in acute leukemia was 3.4%. Percentage for coexpression of B lymphoid and myeloid antigens was 68.4%, for T lymphoid and myeloid antigens 21.1%, for B, T lymphoid and myeloid antigens 10.5%. (2) CD(34) was expressed in 43.75% of the BAL cases. (3) Cytogenetic analysis revealed normal and abnormal karyotypes in 41.7% and 58.3% of the BAL cases, respectively. (4) Six of 19 patients achieved completed remission (CR), but the disease free survivals were all less than 6 months. Treatment outcomes were negatively related to the expression of CD(34) antigen and cytogenetic findings. The BAL patients were poorly responded to therapeutic regimens directed to AML. CONCLUSION: Coexpression of B/M antigens is the commonest subtype in BAL. BAL had a poor prognosis, especially treated with induction regimen directed to AML.

Acute Disease↗

Regulation of MCL1 through a serum response factor/Elk-1-mediated mechanism links expression of a viability-promoting member of the BCL2 family to the induction of hematopoietic cell differentiation.

Proliferation, differentiation, and apoptosis are tightly regulated during hematopoiesis, allowing amplification along specific lineages while preventing excessive proliferation of immature cells. The MCL1 member of the BCL2 family is up-regulated during the induction of monocytic differentiation (approximately 10-fold with 12-O-tetradecanoylphorbol 13-acetate (TPA)). MCL1 has effects similar to those of BCL2, up-regulation promoting viability, but differs from BCL2 in its rapid inducibility and its pattern of expression. Nuclear factors that regulate MCL1 transcription have now been identified, extending the previous demonstration of signal transduction through mitogen-activated protein kinase. A 162-base pair segment of the human MCL1 5'-flank was found to direct luciferase reporter activity, allowing approximately 10-fold induction with TPA that was suppressible upon inhibition of the extracellular signal-regulated kinase (ERK) pathway. Serum response factor (SRF), Elk-1, and Sp1 bound to cognate sites within this segment, SRF and Elk-1 acting coordinately to affect both basal activity and TPA inducibility, whereas Sp1 affected basal activity only. Thus, the mechanism of the TPA-induced increase in MCL1 expression seen in myelomonocytic cells at early stages of differentiation involves signal transduction through ERKs and transcriptional activation through SRF/Elk-1. This finding provides a parallel to early response genes (e.g. c-FOS and EGR1) that affect maturation commitment in these cells and therefore suggests a means through which enhancement of cell viability may be linked to the induction of differentiation.

Base Sequence↗

The stability and fate of a spliced intron from vertebrate cells.

Introns constitute most of the length of typical pre-mRNAs in vertebrate cells. Thus, the turnover rate of introns may significantly influence the availability of ribonucleotides and splicing factors for further rounds of transcription and RNA splicing, respectively. Given the importance of intron turnover, it is surprising that there have been no reports on the half-life of introns from higher eukaryotic cells. Here, we determined the stability of IVS1Cbeta1, the first intron from the constant region of the mouse T-cell receptor-beta, (TCR-beta) gene. Using a tetracycline (tet)-regulated promoter, we demonstrate that spliced IVS1Cbeta1 and its pre-mRNA had half-lives of 6.0+/-1.4 min and 3.7+/-1.0 min, respectively. We also examined the half-lives of these transcripts by using actinomycin D (Act.D). Act.D significantly stabilized IVS1Cbeta1 and its pre-mRNA, suggesting that Act.D not only blocks transcription but exerts rapid and direct posttranscriptional effects in the nucleus. We observed that in vivo spliced IVS1Cbeta1 accumulated predominantly as lariat molecules that use a consensus branchpoint nucleotide. The accumulation of IVS1Cbeta1 as a lariat did not result from an intrinsic inability to be debranched, as it could be debranched in vitro, albeit somewhat less efficiently than an adenovirus intron. Subcellular-fractionation and sucrose-gradient analyses showed that most spliced IVS1Cbeta1 lariats cofractionated with pre-mRNA, but not always with mRNA in the nucleus. Some IVS1Cbeta1 also appeared to be selectively exported to the cytoplasm, whereas TCR-beta pre-mRNA remained in the nucleus. This study constitutes the first detailed analysis of the stability and fate of a spliced nuclear intron in vivo.

Animals↗

Effects of electroacupuncture on gastric migrating myoelectrical complex in dogs.

The aim-of this study was to investigate the characteristics of the gastric slow wave during different phases of the migrating myoelectrical complex (MMC) and the effect of electroacupuncture on the MMC. The experiment was performed in eight hound dogs implanted with one pair of bipolar serosal electrodes 2 cm proximal to the pylorus. Gastric myoelectrical activity was recorded for three complete cycles of the MMC in two sessions, one with electroacupuncture at points ST36 and PC6 and the other at sham points. The acupuncture was performed for 30 min in phase I of the second cycle of the MMC. Spectral analysis was performed to compute the frequency and power (amplitude) of the gastric slow wave, whereas blind visual analysis was applied to compute the appearance of spike potentials and the length of each phase of the MMC. It was found that there was a significant difference in the frequency and power of the gastric slow wave during different phases of the MMC (P < 0.05). Phase I was characterized with the highest frequency and lowest power of the gastric slow wave, whereas phase III exhibited the highest power in the slow wave. It was also found that in comparison with the sham points, electroacupuncture at the acupoints increased the number of spike bursts. This increase was not significant during the MMC cycle with electroacupuncture (34.4+/-4.1 vs 27.5+/-2.5%, P > 0.05) but became significant during the cycle after electroacupuncture (39.8+/-3.3% vs 27.5+/-2.5%, P < 0.0005). Similarly, during the MMC cycle after electroacupuncture at the acupoints, there was a significant decrease in the length of phase I (14.8+/-2.2 vs 46.9+/-6.1 min, P < 0.003) and a significant increase in the length of phase II (75.6+/-9.9 vs 30.6+/-4.1 min, P < 0.003) and phase III (25.8+/-0.6 vs 22.1+/-0.7 min, P < 0.003). A similar increase was observed during the MMC cycle with electroacupuncture but was not statistically significant. In conclusion, the gastric slow wave has the highest power during phase III of the MMC, indicating that the antral contraction is characterized not only by the appearance of spikes, but also by the increased power of the slow wave. Electroacupuncture at acupoints of ST36 and PC6 enhances the gastric MMC by reducing the length of phase I and increasing the length of phases II and III.

Acupuncture Points↗

Cyclin D2 promoter disrupted by t(12;22)(p13;q11.2) during transformation of chronic lymphocytic leukaemia to non-Hodgkin's lymphoma.

In a unique case of chronic lymphocytic leukaemia (CLL) we performed a longitudinal cytogenetic and molecular genetic study of tumour cells from diagnosis through progression and transformation to non-Hodgkin's lymphoma (NHL) and lymphomatous meningitis. CLL cells at diagnosis had trisomy 12 and a t(14;19)(q32;q13.3). At relapse, the leukaemic cells had a subclone carrying a t(12;22)(p13;q11.2) in addition to the initial changes. We cloned reciprocal translocation junctions at the 22q11.2- chromosome and the 12p13+ chromosome and the corresponding germline DNA fragments. Restriction map analysis and nucleotide sequence analysis of the cloned DNA fragment from the 22q11.2- chromosome mapped the translocation break within the immunoglobulin (Ig)-lambda-C complex at the nt3889; nts 3890, 3891 were lost from the translocation site. A probe from the 3'-end of the clone derived from the 22q11.2- chromosome showed single copy hybridization which was different from the Ig-lambda probe. Nucleotide sequence analysis of the exact junction region and the corresponding germline DNA showed that the translocation at 12p13 occurred in the negative regulatory region of the cyclin D2 gene at the nt -1602, and a pentamer consisting of nts -1603 to -1599 was lost at the break site. We sequenced another 227 bp upstream of the known 5'-end of the promoter and did not find any open reading frame. From these results we hypothesize that, in this patient, the t(12;22) disrupted the negative regulator in the promoter of cyclin D2 which in turn might have deregulated cyclin D2.

Base Sequence↗

Retrospective analysis of the Beijing family of Mycobacterium tuberculosis in preserved lung tissues.

Direct repeat spoligotyping of 85 paraffin-embedded lung biopsies was used to investigated the occurrence around Beijing of the Beijing family of Mycobacterium tuberculosis. Samples ranged in time from 1956 to 1990. Hybridization patterns were found with 49 (58%) samples, and 45 (92%) produced typical Beijing family patterns extending over the 34-year period.

Bacterial Typing Techniques↗

Normalization of atropine-induced postprandial dysrhythmias with gastric pacing.

Gastric pacing has received increasing attention recently. However, few studies have systematically assessed the effect of pacing on gastric dysrhythmias. The aims of this study were to investigate the effect of gastric pacing on gastric dysrhythmia and to explore whether the effect of gastric pacing was mediated via cholinergic nerves. Eight hound dogs implanted with three pairs of serosal electrodes were studied. Three study sessions were performed on each dog. The experiment was conducted sequentially as follows: a 30-min myoelectrical recording immediately after a meal, intravenous injection of atropine or saline, and three sequential 20-min myoelectrical recordings with or without gastric pacing during the second 20-min recording. The percentage of regular slow waves (3.5-7. 0 cycles/min) was calculated using spectral analysis. The percentage of the regular slow waves was progressively reduced from 96.7 +/- 1. 7% at baseline to 29.6 +/- 9.0 (P < 0.001), 23.1 +/- 7.1 (P < 0.001), and 27.3 +/- 4.3% (P < 0.001), respectively, during the first, second, and third 20 min after atropine injection. Normalization of the gastric slow wave was achieved with gastric pacing 2.3 +/- 1.0 min after the initiation of pacing. The percentage of regular slow waves was significantly increased both during pacing (93.6 +/- 2.4 vs. 23.1 +/- 7.1%, P < 0.002) and after pacing (70.9 +/- 6.8 vs. 27. 3 +/- 4.3%, P < 0.003) in comparison with the session without pacing. We conclude that 1) atropine induces gastric myoelectric dysrhythmia in the fed state, 2) gastric pacing is able to normalize gastric postprandial dysrhythmia induced by atropine, and 3) the effect of gastric pacing is not mediated by vagal cholinergic mechanism.

Animals↗

[Reversion of HBV-related liver fibrosis and early cirrhosis by baicao rougan capsule].

OBJECTIVE: To observe the therapeutic effect of herbal compound, Baicao Rougan Capsule on human liver fibrosis and early cirrhosis associated with chronic hepatitis B. METHODS: Forty-two patients with liver fibrosis and 10 cases early cirrhosis were treated with a herbal compound for six months. Two liver biopsies were performed before and after treatment, their serum samples were collected before, in the middle of and after the treatment, all samples were measured at the same time. RESULTS: Improvement of clinical symptoms and signs occurred in 75% to 91% of the patients, serum ALT lowered to normal level in 68%. The serum level of type IV collagen, laminin and hyaluronic acid were significantly reduced by the end of treatment (P < 0.05). Grading score was reduced from 7.79 +/- 6.15 to 5.36 +/- 3.95 after treatment (P < 0.05), while staging score was reduced from 7.39 +/- 5.55 to 5.26 +/- 4.36 (P < 0.05). CONCLUSION: Chinese herbal compound Baicao Rougan Capsule is effective in the treatment, and in the reversal of HBV related liver fibrosis and early cirrhosis.

Adolescent↗