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Biomedical subjects

L Pan

Publications and source records attributed to L Pan.

At least 127 records · Page 7Linked to original sources
PubMed1996

Ongoing mutation in MALT lymphoma immunoglobulin gene suggests that antigen stimulation plays a role in the clonal expansion.

Indirect antigenic stimulation by H. pylori-specific T cells is implicated in the development of low-grade gastric lymphoma of mucosa-associated lymphoid tissue (MALT), however, the role of direct antigen stimulation is unknown. To study the role of direct antigen stimulation in MALT lymphomagenesis and its relationship with the pathogenesis of distinct pathological lesions, which represent different stages of the tumour progression, we cloned and sequenced the rearranged immunoglobulin (Ig) heavy chain gene in three low-grade (two from the lung, one from the stomach) and one high-grade (from the stomach) cases. In the low-grade gastric case, we studied the Ig sequence in primary as well as its disseminated and recurrent tumours. In the high-grade gastric case, we analysed the Ig sequence in tumour cell populations microdissected from the residual diffuse low-grade lesions, diffuse high-grade areas from follicles colonized by high-grade blasts. Compared with the published germline sequences, the heavy chain variable (VH) genes of three MALT lymphomas, in which the putative germline was identified, contained frequent somatic mutations, showing a much higher ratio of replacement/silent mutations in the complementarity determining regions (CDRs) than the framework regions (FRs). Ongoing mutation as indicated by intraclonal variation of the Ig sequence clearly existed in low-grade tumour including its dissemination and recurrence, but was not evident in high-grade tumour cell populations including those microdissected from independent colonized follicles. In addition, the germlines of VH genes used by the three MALT lymphomas are frequently found in autoreactive antibodies. Our results suggest that MALT lymphoma derives from postgerminal centre memory B cells, possibly autoreactive B cell clones, and that direct antigen stimulation may play an important role in the clonal expansion of low-grade MALT lymphoma.

Animals↗
PubMed1996

[Cardiotoxicity of 5-fluorouracil].

OBJECTIVE: To determine the possibility and magnitude of cardiotoxicity following high dose intravenous infusion of fluorouracil (5-FU). METHODS: A prospective clinical study was performed on 104 patients with choriocarcinoma and invasive mole. 5-FU was administered by slow intravenous infusion in 5% glucose 500 ml for 8 hours at doses of 28-30 mg.kg-1.day-1 when used as a single agent treatment or 24-26 mg.kg-1.day-1 when used in combination with kengshengmycin (KSM). The total cycles of treatment with 5-FU + KSM were 109 and those of 5-FU or KSM each used as a single agent were 71 and 12 respectively. The cardiac functions were monitored by cardiac symptoms, ECG and serum cardiac enzymes before and after 5-FU infusion. RESULTS: Among the 192 treatment cycles tachycardia, palpitation or cardiac distress were observed in 14 cycles. ECG showed changes of ST or T waves in 8 cycles, sinus tachycardia in 3 cycles. The results of serum cardiac enzyme determinations were variable. The diagnostic criteria of cardiotoxicity were appearances of abnormalities manifested in any two of the three monitor items. The incidence of cardiotoxicity was 4.2% in 5-FU group, 4.6% in 5-FU + KSM group and 0% in KSM group. All episodes were mild, reversible spontaneously after cessation of chemotherapy and did not reappear in subsequent chemotherapeutic cycles. Seven patients with definite cardiac diseases before chemotherapy were given 5-FU treatment, but no obvious aggravation of cardiotoxicities were observed even with repeated 5-FU treatments. CONCLUSION: Only occasional cardiotoxicities were observed in 5-FU treatments. They were rather mild and reversible. The incidence of cardiotoxicity might be reduced with emphasis on strict observance of the treatment regimen in regard to the dosage used, the speed of the infusion and attention to the treatment of any side-effects.

Adult↗
PubMed1996

Long-term engraftment, graft-vs.-host disease, and immunologic reconstitution after experimental transplantation of allogeneic peripheral blood cells from G-CSF-treated donors.

Peripheral blood cells (PBPC) are an alternative source of bone marrow for allogeneic transplantation. Reports from recent clinical trials granulocyte colony-stimulating factor (G-CSF)-mobilized PBPC for allogeneic transplantation show incidence and severity of graft-vs.-host disease (GVHD) similar to those observed in conventional bone marrow transplantation (BMT), despite the presence of 10- to 20-fold more T cell in the PBPC inoculum. In the present study, we examined the effects of pretreatment of donors with G-CSF on GVHD, long-term engraftment, and lymphocyte reconstitution in a murine parent-->F1 model (B6.Ly-5a-->B6d2F1) using splenocytes as a source of peripheral progenitor cells. Recipients of splenocytes from G-CSF-treated donors experienced less mortality from acute GVHD and showed sustained weight gain by day 100 after transplantation. At that time, there was no histological evidence od GVHD in either liver or gut. Recipients of splenocytes from G-CSF-treated donors showed complete donor engraftment within 1 month, which was sustained until the end of the observation period. In contrast, recipients of T cell-depleted splenocytes showed slower donor engraftment and persistent donor/host chimerism. In addition, lymphocyte phenotype and function in mice receiving splenocytes from G-CSF-treated donors was significantly restored by day 100 after transplantation. Thus, the use of G-CSF-mobilized PBPC may provide significant advantages to conventional BMT by reducing GVHD without impairing long-term engraftment and immunologic reconstruction.

Animals↗
PubMed1996

[Study on small intestinal lumenal and membrane flora of 30 healthy Chinese].

Lumenal and membrane flora were investigated using ileum and jejunum samples obtained through endoscopy. 10 kinds of representative anaerobic or aerobic bacteria were cultured for quantitative and qualitative analysis. The result showed there were significant differences between lumenal and membrane flora on Clostridium of ileum, Lactobacillus and Bacillus bifudus in jejunum (P < 0.05). Enterococci were not found in all of these 30 patients. In jenumum, E. Coli was found in 53.3% (16/30) of lumenal flora and 33.3% (10/30) of membrane flora, Bacteroides were found in 40.0% (12/30) of lumenal flora and 33.3% (10/30) of membrane flora respectively.

Adolescent↗
PubMed1995

Pretreatment of donor mice with granulocyte colony-stimulating factor polarizes donor T lymphocytes toward type-2 cytokine production and reduces severity of experimental graft-versus-host disease.

The incidence and severity of acute graft-versus-host disease (GVHD) after allogeneic transplantation using peripheral blood progenitor cells mobilized by granulocyte colony-stimulating factor (G-CSF) appear to be no worse than those after bone marrow transplantation, despite the presence of large numbers of T cells in the donor infusion. Experimental studies have shown that type-1 T cells (secreting interleukin-2 [IL-2] and interferon-gamma) mediate acute GVHD, whereas type-2 T cells (secreting IL-4 and IL-10) can prevent acute GVHD. We tested the hypothesis that G-CSF modulates T-cell function toward a type-2 response and thus reduces the severity of acute GVHD. B6 mice were injected with G-CSF or diluent for 4 days, and their splenic T cells were stimulated in vitro with alloantigen or mitogen in the absence of G-CSF. T cells from G-CSF-treated mice showed a significant increase in IL-4 production, with a simultaneous decrease in IL-2 and interferon-gamma production in response to both stimuli. We also examined the effect of G-CSF pretreatment of donors in a GVHD model (B6-->B6D2F1). Survival was significantly improved in recipients of G-CSF-treated donors. Concanavalin-A-induced cytokine production at day 13 after transplantation also showed an increase in IL-4 along with a decrease in IL-2 and IFN-gamma production by splenocytes from recipients of G-CSF-treated bone marrow and T cells. These data show that pretreatment of donors with G-CSF polarizes donor T cells toward the production of type-2 cytokines, which is associated with reduced type-1 cytokine production and reduced severity of acute GVHD.

Acute Disease↗
PubMed1995

The accumulation of p53 abnormalities is associated with progression of mucosa-associated lymphoid tissue lymphoma.

The genetic mechanisms underlying the genesis of low-grade mucosa-associated lymphoid tissue (MALT) lymphomas and their transformation into high-grade lymphoma are poorly understood. p53 inactivation, commonly caused by mutation and allele loss, has been shown to play an important role in the early development and/or the late disease progression of many human tumors including lymphoid malignancies and, thus, may also be important in MALT lymphomagenesis. We examined 75 cases (48 low grade and 27 high grade) of MALT lymphoma for p53 allele loss and mutation as well as protein accumulation. DNA samples prepared from microdissected cell populations were used for the detection of p53 gene abnormalities. Loss of heterozygosity (LOH) of the gene was detected by polymerase chain reaction-based analysis of p53 CA repeat polymorphism, whereas p53 mutation was studied by single-strand conformation polymorphism analysis and direct sequencing. p53 expression was assessed by immunostaining with CM1 polyclonal antibody. p53 allele loss and mutation, which resulted in the alteration in the amino acid sequence, were found in both low-grade (LOH, 3 of 44 [6.8%]; mutation, 9 of 48 [18.8%]) and high-grade (LOH, 6 of 21 [28.6%]; mutation, 9 of 27 [33.3%]) MALT lymphomas, particularly in the latter group. p53 staining was not observed in any low-grade tumors but in 6 high-grade cases that harbored missense mutations. There were also differences in the extent of p53 abnormalities, between low- and high-grade tumors. Of the 11 low-grade tumors showing p53 abnormalities, only 1 tumor showed the concomitance of p53 mutation and allele loss, whereas in high-grade tumors, 6 of 9 affected cases displayed both p53 mutation and allele loss. Our results suggest that p53 partial inactivation may play an important role in the development of low-grade MALT lymphomas, whereas complete inactivation may be associated with high-grade transformation.

Alleles↗
PubMed1995

On the role of ligand in retinoid signaling: positive cooperativity in the interactions of 9-cis retinoic acid with tetramers of the retinoid X receptor.

Previously, we have shown that the retinoid X receptor (RXR) forms tetramers with a high affinity and that interactions of the receptor with its ligand, 9-cis retinoic acid (9cRA), result in dissociation of protein tetramers. Here it is shown by fluorescence anisotropy studies that ligand-induced tetramer dissociation displays a pronounced positive cooperativity. The binding affinity of RXR for 9cRA at low saturation levels of the receptor with ligand was found to be significantly weaker than the affinity observed at higher levels of saturation. In addition, the rate of dissociation of 9cRA from RXR was found to be faster at low vs. high saturation levels of the receptor. These data suggest that the observed positive cooperativity of the ligand-induced dissociation of RXR tetramers stems from positive cooperativity in binding of 9cRA by the receptor. Kinetic studies showed that dissociation of RXR tetramers upon ligand binding is a rapid reaction characterized by a t1/2 of 80 ms, which is about 5 orders of magnitude faster than the rate of dissociation in the absence of ligand. The data indicate that the oligomeric state of RXR is tightly regulated by the precise concentrations of 9cRA and that it rapidly responds to changes in the ligand's concentrations. These findings further substantiate the hypothesis that modulation of the oligomeric state of RXR by 9cRA is an important regulatory step in the pathway by which retinoids affect gene transcription.

Fluorescence Polarization↗
PubMed1995

Role of ligand in retinoid signaling. 9-cis-retinoic acid modulates the oligomeric state of the retinoid X receptor.

Many of the effects of retinoids on cells are mediated by the transcription factors known as retinoid nuclear receptors, but the mechanisms by which retinoids regulate the activity of the receptors are not known. It was previously shown that the retinoid X receptor (RXR) forms tetramers with a high affinity. In the present work it is demonstrated that binding of 9-cis-retinoic acid to RXR leads to rapid dissociation of receptor tetramers. In addition, fluorescence anisotropy studies indicate that ligand-binding results in a significant conformational change such that holo-RXR is more compactly folded as compared to the apo-protein. These findings suggest that the initial event in signaling by 9-cis-retinoic acid is a change in the oligomeric state of RXR. The data also imply that tetramer formation is a regulatory feature of the pathway by which RXR mediates the effects of retinoids on gene transcription.

Binding Sites↗
PubMed1995

Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4.

Nerve growth factor and other neurotrophins signal to neurons through the Trk family of receptor tyrosine kinases. TrkB is relatively promiscuous in vitro, acting as a receptor for brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT4) and, to a lesser extent, NT3 (refs 3-5). Mice lacking TrkB show a more severe phenotype than mice lacking BDNF, suggesting that TrkB may act as a receptor for additional ligands in vivo. To explore this possibility, we generated mice lacking NT4 or BDNF as well as mice lacking both neurotrophins. Unlike mice lacking other Trks or neurotrophins, NT4-deficient mice are long-lived and show no obvious neurological defects. Analysis of mutant phenotypes revealed distinct neuronal populations with different neurotrophin requirements. Thus vestibular and trigeminal sensory neurons require BDNF but not NT4, whereas nodose-petrosal sensory neurons require both BDNF and NT4. Motor neurons, whose numbers are drastically reduced in mice lacking TrkB, are not affected even in mice lacking both BDNF and NT4. These results suggest that another ligand, perhaps NT3, does indeed act on TrkB in vivo.

Animals↗
PubMed1995

Insulin enhances glucocorticoid receptor-mediated induction of gene expression independent of a specific insulin response element.

We have established a system in which we observe a synergistic interaction between insulin and glucocorticoids. This includes chimeric genes constructed to contain synthetic glucocorticoid-responsive elements, 5' of the HSV thymidine kinase promoter and the chloramphenicol acetyltransferase reporter gene. The magnitude of induction of gene expression by glucocorticoid was dependent on the number of GREs. Insulin alone had virtually no effect on the expression of any of these genes but together with dexamethasone acted in a synergistic manner. This synergy diminished as the number of GREs in the promoter increased. The synergy is independent of promoter sequences other than the GREs and a functional TATAA box. Three different approaches demonstrate that the effect of insulin is not directly on the glucocorticoid signal transduction pathway. Insulin does not change the dose-response relationship for dexamethasone. The effect of insulin is independent of the intracellular concentration of glucocorticoid receptor. The effect is independent of any specific domain of the glucocorticoid receptor. The target of insulin action is likely to be part of the normal host cell transcriptional initiation complex or a putative adaptor molecule.

Animals↗
PubMed1995

Time course of ciliary neurotrophic factor mRNA expression is coincident with the presence of protoplasmic astrocytes in traumatized rat striatum.

Adrenal grafting for Parkinson's disease has led to modest functional improvement despite poor graft survival. One explanation is a neurotrophic response within the traumatized striatum. This study was undertaken to investigate the time course of the astrocytic response in vivo and in vitro, and the expression of ciliary neurotrophic factor (CNTF) mRNA following striatal injury. Unilateral stereotaxic biopsy of the rat striatum was performed and gelatin sponge (gel-foam) was immediately placed into the biopsy cavity. Rats were sacrificed on days 1, 3, 5, 7, 14, and 28 post biopsy. Immunohistochemical staining of the traumatized striatum with antibodies to glial fibrillary acidic protein (GFAP) was carried out. The reactive astrocytes which appeared within 7 days after trauma were mostly protoplasmic on the basis of morphology, and maximal on day 7, being 30 times the level in the normal striatum. After day 7, fibrous astrocytes appeared and increased up to day 28, while protoplasmic astrocytes decreased. In addition, immunocytochemical double staining of short term cultured astrocytes from the traumatized striatum with anti-A2B5 and anti-GFAP antibodies revealed that 84% and 90% of astrocytes were type 1 astrocytes on days 3 and 7, respectively; however, by day 28 47% of astrocytes were type 2. Northern blot analysis revealed that CNTF mRNA expression was up-regulated and peaked on day 7, coincident with a predominance of protoplasmic astrocytes in vivo and type 1 astrocytes in vitro, respectively. These findings suggest that the expression of CNTF mRNA is part of the early astrocytic response to trauma, particularly associated with protoplasmic astrocytes in vivo and type 1 astrocytes in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Suppression of collagenase gene expression by all-trans and 9-cis retinoic acid is ligand dependent and requires both RARs and RXRs.

Retinoic acids (RA) are active metabolites of vitamin A which affect the expression of many genes involved in embryonic development, cell differentiation, and homeostasis. One important target gene for RA is matrix metalloproteinase (MMP-1, collagenase), the only enzyme active at neutral pH that can degrade interstitial collagen, a major component of extracellular matrix. Using a cell line of normal rabbit synovial fibroblasts, HIG82 cells, as a model, we report that both all-trans- and 9-cis-RA inhibit collagenase synthesis. This inhibition occurs at a transcriptional level and is ligand-dependent. Constitutive levels of retinoic acid receptor (RAR) mRNA levels are low, but are increased by all-trans and by 9-cis RA. In contrast, constitutive levels of retinoid X receptor (RXR) mRNA are higher and are not affected by RA. To measure DNA/protein interactions, we used a gel mobility shift assay with oligonucleotides containing either an AP-1 site or a 40 bp region between -182/-141, nuclear extracts from RT-treated cells, and antibodies to RARs and RXRs. We found that both RARs and RXRs interact with these regions of the collagenase promoter, perhaps as part of a complex with other proteins. Our results suggest that heterodimers between RARs and RXRs mediate suppression of the collagenase gene by RA, and that RAR is a limiting factor in this negative regulation.

Animals↗
PubMed1995

Mature polymorphonuclear leukocytes express high-affinity receptors for IgG (Fc gamma RI) after stimulation with granulocyte colony-stimulating factor (G-CSF).

The high-affinity receptor for the constant region of immunoglobulin G IgG (Fc gamma RI; CD64) is virtually undetectable on mature polymorphonuclear neutrophils (PMNs) in healthy individuals but is expressed on PMNs in patients with certain infections and in patients treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF). The induction of Fc gamma RI by rhG-CSF has previously been reported to result from effects on immature granulocyte progenitors. To evaluate the G-CSF effect on mature PMNs, we studied the correlation between G-CSF plasma concentration and expression of Fc gamma RI on PMNs in vivo as well as the effect of G-CSF on Fc gamma RI expression on mature PMNs in vitro. Fc gamma RI expression on PMNs correlated (R = 0.79; p < .001) with plasma concentrations of endogenous or recombinant G-CSF in healthy volunteers and in patients undergoing high-dose chemotherapy and autologous bone marrow transplantation. PMNs exhibited a unimodal distribution for elevated Fc gamma RI expression, suggesting that G-CSF induced increased expression of Fc gamma RI on mature as well as on immature PMNs. In vitro, incubation of mature PMNs with G-CSF induced mRNA for Fc gamma RI. Significant Fc gamma RI surface expression was induced in a time- and dose-dependent manner. Thus, G-CSF can act on mature PMNs to increase Fc gamma RI expression and may be useful for stimulating antibody mediated immune functions of PMNs in vivo.

Bone Marrow Transplantation↗
PubMed1995

B-cell monoclonality, Epstein Barr virus, and t(14;18) in myoepithelial sialadenitis and low-grade B-cell MALT lymphoma of the parotid gland.

Low-grade mucosa-associated lymphoid tissue (MALT) type B-cell lymphomas of the salivary gland arise in a background of myoepithelial sialadenitis (MESA), usually in association with Sjögren's syndrome. The distinction between benign MESA and early lymphoma has proved difficult using histological criteria alone and the significance of B-cell monoclonality in this respect is controversial. We have used immunohistochemistry and polymerase chain reaction (PCR) amplification of immunoglobulin heavy-chain VDJ regions to assess clonality in biopsies from 45 patients with lymphoid infiltration of the parotid. Sequential biopsies spanning 3-18 years were available from seven patients, three of whom had developed disseminated nodal B-cell lymphoma. In light of previous studies, each biopsy was additionally analyzed for the presence of t(14;18) and Epstein Barr Virus (EBV) DNA using PCR. Monoclonality was detected in 34/45 cases. Comparison of histology with clonality confirmed earlier suggestions that the emergence of an identifiable population of centrocyte-like B cells around ducts or epithelial islands correlated with monoclonality. In six of seven patients with sequential biopsies PCR fragments of identical size were amplified from each biopsy, suggesting that demonstrable monoclonality in "lymphoepithelial" lymphoproliferative lesions of the salivary gland is indicative of lymphoma. No t(14;18) chromosome translocations were identified; EBV sequences were detected in three of 45 cases.

Adult↗
PubMed1995

High-resolution SSCP analysis using polyacrylamide agarose composite gel and a background-free silver staining method.

We describe here an improved methodology for single-strand conformation polymorphism (SSCP) analysis of PCR products. The method utilizes a polyacrylamide agarose composite gel and background-free silver staining. In comparison with conventional pure polyacrylamide gel for PCR-SSCP analysis, the composite gels have a much greater mechanical strength and improved resolution. The background staining commonly seen in many silver staining protocols has been eliminated by incorporation of thiosulfate, which can prevent nonspecific deposits of silver salts. As shown in our titration tests, the composite gel and background-free silver staining together have allowed clear identification of point mutations in samples containing as little as 5% of the target sequences, the same sensitivity achieved by radioactive labeling methods.

DNA↗
PubMed1995

[Personal characteristics as risk factors of endometriosis].

203 patients with pelvic endometriosis, all Beijing resident, were collected from the Peking Union Medical College Hospital and the Beijing Obstetrical and Gynecological Hospital. The diagnosis of endometriosis was confirmed by pathological examination of surgical specimens in 186 patients and by aspiration of chocolate substance under laparoscopy in 17. Two population controls, age matched +/- 1 year, were randomly selected for each patient from the same residential area, after careful pelvic examinations and ultrasonographies. A questionnaire for any possible risk factors to endometriosis was developed and with this questionnaire a face to face interview for each subject was carried out by the trained interviewers. All interviews were tape recorded and calculated in a AST 386 computer. The continuous logistic regression for matched sites was used to obtain a maximum likelihood point and to control the potential confounding effects of selected variables. Relative risk (RR) substituted for odds ratio together with the 95% confidence intervals was estimated. All the results were adjusted for the variables of the model including some relevant factors of menstruation, pregnancy and contraception. An increased risk for endometriosis was found to be related to women who had a higher level of education. Even it was adjusted for age of first marriage and pregnancy, gravidity, parity, contraception and all other variables of the model, the relative risk was 1.84 for endometriosis. Therefore, it is the education level itself that plays a true role in development of endometriosis. Although there was a trend in risk for endometriosis in height, it was statistically insignificant.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗
PubMed1995

[A clinical and experimental study of L-form bacteria in 66 cases].

In order to study the relationship between the time for establishing the diagnosis of infectious diseases and L-form bacteria, a series of clinical specimens taken from 321 cases of patients suspected to have infection were collected. Besides routine bacterial culture, special culture for L-form bacteria was also performed. The results were as follows: the rate of positive routine bacterial culture was 10.90% (35/321); the rate of negative routine bacterial culture but positive L-form bacterial culture was 20.56% (66/321). In this study, L-form bacteria infection was treated with sensitive antibiotics and a satisfactory result was obtained. It is shown that L-form bacterial culture is very useful in detection of pathogenic bacteria and helpful to the therapy of infectious diseases. Ultrastructure organization of these bacteria was studied by using transmission electron microscope.

Adult↗