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Biomedical subjects

G Cheng

Publications and source records attributed to G Cheng.

At least 217 records · Page 12Linked to original sources

Alpha subunit of calcium/calmodulin-dependent protein kinase enhances excitatory amino acid and synaptic responses of rat spinal dorsal horn neurons.

1. Here we report that in acutely isolated rat spinal dorsal horn (DH) neurons, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate and N-methyl-D-aspartate (NMDA) receptors can be regulated by endogenous and exogenous calcium/calmodulin-dependent protein kinase II (CaM-KII). Intracellularly applied, the alpha-subunit of CaM-KII enhanced AMPA/kainate and NMDA currents recorded with the use of the whole cell patch-clamp technique. 2. Microcystin, a nonselective phosphatases inhibitor, also enhances AMPA and NMDA responses. 3. Conventional intracellular recordings were made from substantia gelatinosa neurons in spinal cord slices to determine the effect of intracellular application of CaM-KII on excitatory synaptic potentials evoked by electrical stimulation of primary afferent fibers. Excitatory synaptic transmission was enhanced by CaM-KII, which is consistent with the importance of phosphorylation of the postsynaptic AMPA/kainate and NMDA receptor-ion complexes in the short- and long-term changes in synaptic transmission.

Animals↗

Evaluation of a recombinant parasite antigen for the diagnosis of lymphatic filariasis.

We evaluated the usefulness of a recombinant parasite antigen (recSXP1) for the serologic diagnosis of lymphatic filariasis. A large proportion of sera from microfilaremic donors living in five different endemic countries (356 of 446 [80%]) contained IgG antibodies to recSXP1, as do sera from approximately 33% of amicrofilaremic patients with acute filarial disease and/or indirect evidence of active filarial infection. Exposure to filarial worms per se does not appear sufficient to elicit an anti-SXP1 antibody response. Thus, this serologic test identifies a large proportion of persons with active lymphatic filariasis among residents of endemic areas.

Animals↗

Induction of H3.3 replacement histone mRNAs during the precommitment period of murine erythroleukemia cell differentiation.

Differential hybridization to a cDNA library made from the mRNA of differentiating mouse erythroleukemia (MEL) cells has been used to identify sequences that are induced during the early stages of MEL cell differentiation. One of the differentially expressed genes identified encodes the H3.3 histone subtype. We show here that the three polyadenylated mRNAs produced from the H3.3B gene, as well as the single mRNA produced from the related H3.3A gene, are coordinately induced during the first few hours of MEL cell differentiation and subsequently down regulated as cells undergo terminal differentiation. Nuclear run-on transcription experiments indicate that the accumulation and decay of these mRNAs are controlled at the post-transcriptional level. Unlike the polyadenylated mRNAs of two H1 histone genes that exhibit similar kinetics of induction and decay controlled by c-myc, induction of the H3.3 mRNAs is unaffected by deregulated expression of c-myc.

Animals↗

Childhood acute lymphoblastic leukaemia presenting with relapsing hypoplastic anaemia: progression of the same abnormal clone.

A 13-year-old girl presented with two spontaneously reversible episodes of marrow hypoplasia. She subsequently developed acute lymphoblastic leukaemia (ALL) 8 months later. Southern analysis showed identical clonal immunoglobulin heavy chain gene rearrangement bands in the leukaemic cells as well as the marrow cells obtained at the two hypoplastic episodes. Hypoxanthine phosphoribosyl transferase polymorphism studies showed that the ALL blast cells, bone marrow and peripheral blood cells during the two hypoplastic episodes all exhibited clonal haematopoiesis with the same X-chromosome inactivated. This case provides strong evidence that aplastic anaemia and ALL may represent evolution of the same abnormal clone.

Adolescent↗

[Retinal hemorrhage in newborn infants].

The fundi of the 527 infants born within one week were investigated. The results showed that 54 cases (78 eyes) had retinal hemorrhage. Among them, 23 cases (28 eyes) accompanied macular hemorrhage. The retinal hemorrhage in newborn infants was higher in vaginal delivery than in cesarean section, and the incidence of the fetal distress was higher in the newborn infants with macular hemorrhage. The essential causes of the retinal hemorrhage in newborn infants, development of infant macular and the mechanism of amblyopia induced by macular hemorrhage were discussed.

Adult↗

Transient myeloproliferative disorder in a Down's neonate with rearranged T-cell receptor beta gene and evidence of in vivo maturation demonstrated by dual-colour flow cytometric DNA ploidy analysis.

Neonates with Down's syndrome may develop a transient myeloproliferative disorder (TMPD) which on presentation is indistinguishable from acute leukemia, with the difference manifest only on follow-up. The clinical course is one of spontaneous remission in TMPD and relentless progression in leukemia. We describe a Down's neonate presenting with hyperleucocytosis and circulating blasts which were positive for CD34, myeloid (CD33), megakaryocytic (CD41, CD42b, CD61), and T-lineage (CD3, CD7), but not B-lineage, associated antigens. Clonal rearrangement of the T-cell receptor beta (TCR beta) gene was found, with the immunoglobulin heavy chain gene in germline configuration, showing the disease to be a clonal proliferation of a multipotential stem cell involving the myeloid and T lineages. Dual-colour flow cytometric DNA ploidy analysis of CD41 positive blasts showed initially a predominant 2N population, but polyploidization to 6N and 8N cells was found on follow-up, concomitant with a progressive decrease in circulating blasts, suggesting maturation of the abnormal clone and a provisional diagnosis of TMPD. This was shown by the eventual resumption of normal haemopoiesis with the disappearance of blasts and the clonally rearranged TCR beta gene.

Bone Marrow↗

Intra-hepatic-arterial infusion of misonidazole--an experimental study of regional radiosensitisation by intraarterial embolisation.

The purpose of this study was to generate a selective radiosensitising effect by the intra-hepatic-arterial infusion of misonidazole (MISO). MISO (10 mg) was infused after transcatheter hepatic-arterial embolisation into the livers of rabbits bearing VX2 liver cancer. This procedure was followed by 15 Gy electron irradiation. Evaluation of tumour volume and histological examination was carried out on the 7th day after treatment. The greatest tumour response was obtained in the group which received MISO followed by radiation and was characterised by extensive fibrosis around the tumour and nearly complete tumour necrosis. Liver cell regeneration was also noted in adjacent liver tissue. The advantages of regional infusion of MISO following hepatic-arterial embolisation are: (1) Selectivity increased radiosensitivity of liver cancer alongside very low drug concentration in the plasma. (2) Reduced or absent deleterious side effects of MISO with higher tumour/normal tissue ratios of drug concentration. (3) Reduced cost due to the lower dosage of MISO required for regional infusion.

Animals↗

Anti-hepatitis C virus (HCV) screening at a Canadian Red Cross center: significance of a positive c100 HCV enzyme-linked immunosorbent assay.

The c100 hepatitis C virus (HCV) enzyme-linked immunosorbent assay (ELISA) has been used to screen blood donors to prevent transfusion-associated non-A,non-B hepatitis. This test is not specific, and only about 25 percent of c100 HCV ELISA-positive blood samples appear to transmit hepatitis C. However, the intensity of the ELISA (sample/cutoff ratio [S/C], greater than 2) could identify a subpopulation of donors that are at high risk for transmitting hepatitis. Blood samples from 20,186 volunteer blood donors at a Canadian Red Cross blood transfusion center were screened for antibodies to HCV using the c100 HCV ELISA. Fifty-nine (0.3%) of these donors were repeatably reactive on ELISA. When their samples were tested with the c100 recombinant immunoblot assay (RIBA) and second-generation RIBA (RIBA-2), 26 (44%) and 31 (52%) samples, respectively, were found to be positive. Thirty-three of the 59 ELISA-reactive donors had an S/C greater than 2. Of these 33 donors, 30 (91%) had elevated alanine aminotransferase (ALT), 27 (82%) were RIBA-2 positive, and 22 (67%) had risk factors for hepatitis. In contrast, of the 26 ELISA-reactive donors with S/C less than 2, only 7 (27%) had elevated ALT, and 4 (15%) were RIBA-2 positive and also had high risk factors for hepatitis. Thus, while the HCV ELISA may lack specificity, its intensity can serve to identify a subgroup of donors that are at high risk for transmitting hepatitis.

Adult↗

Widespread differentiation stage-specific expression of the gene encoding phosphoprotein p19 (metablastin) in mammalian cells.

p19 is a highly conserved 19 kD cytosolic protein that undergoes phosphorylation in response to diverse extracellular factors in mammalian cells. Its expression is abundant in brain and testis and is developmentally regulated. To gain insights regarding its function, we analyzed the expression of p19 mRNA in a variety of cell types during induction of differentiation. Murine erythroleukemia cells showed a moderate increase followed by a marked decrease in the abundance of p19 mRNA during induction of differentiation. In murine C2 myoblasts and primary fetal rat osteoblasts, p19 mRNA was abundant in replicating cells and decreased to undetectable levels during differentiation. In resting human peripheral blood lymphocytes, p19 mRNA was virtually undetectable but was strongly induced during blast transformation of both B and T cells. In rat liver, p19 mRNA was abundant on embryonic day 17 and decreased during early postnatal development. Upon fractionation of adult rat liver cells by centrifugal elutriation, p19 mRNA was not detected in hepatocytes while a low level was observed in a fraction enriched in non-parenchymal epithelial cells. CCl4-induced liver regeneration resulted in induction of p19 mRNA in hepatocytes. Primary cultures of embryonic and neonatal rat brain were analyzed by indirect immunofluorescence using co-staining with stage-specific markers. p19 expression was restricted to immature neurons and oligodendrocyte precursors. In contrast to the other cell types examined, the neuronal and glial precursors that express p19 were shown, using BrdU labeling, to be postmitotic both in primary culture and in vivo. The data demonstrate widespread, stage-specific expression of p19 and suggest that the protein exerts a general, lineage-independent function during induction of differentiation of mammalian cells. In view of the available evidence on the stimulation of serine phosphorylation of p19 by several growth factors, our working hypothesis is that phosphorylation of p19 may be involved in the mechanism by which growth factors control cell differentiation.

Animals↗

[Pharmacological activities of musk. IV. Effects of musk on arachidonic acid metabolism in leukocytes from rat inflammatory exudate].

The present work was designed to further study the mechanism of the anti-inflammatory action of musk from the viewpoint of arachidonic acid (AA) metabolism: 1) effect on AA release; 2) action on leukotriene B4 (LTB4) and 5-HETE biosyntheses. Leukocytes obtained from rat inflammatory exudate by i.p. injection of 1% carrageenan were labelled with 14C-AA at 37 degrees C for 2 h. The 14C-AA labelled cells were incubated with the water soluble fraction of musk (MWF) and stimulated with calcium ionophore A23187 to release AA. The radioactivity released from the labelled leukocytes was determined as a criterion of AA release. In order to observe the influence of musk on the biosyntheses of LTB4 and 5-HETE, leukocytes were incubated with MWF and AA, and then stimulated with A23187. The LTB4 and 5-HETE produced were determined by RP-HPLC. The results showed that AA release decreased to 50-70% of the control at MWF concentration of 6.25-37.5 micrograms/ml. The biosyntheses of LTB4 and 5-HETE were not affected. However, AA release increased to 1.5-fold at the MWF concentration of 400 micrograms/ml. At the same time, biosyntheses of LTB4 and 5-HETE decreased by 66.7 and 90%, respectively, as compared with controls. This result indicates that MWF not only inhibited phospholipase A2 (PLA2) activity, but also prevented AA peroxidation and inhibited LTB4 biosynthesis. These results suggest that inhibition of the AA metabolic pathway may play a major role in the mechanism of the anti-inflammatory action of musk.

Animals↗

Expression of stem cell factor and c-kit mRNA in cultured endothelial cells, monocytes and cloned human bone marrow stromal cells (CFU-RF).

Previously, we have shown that conditioned medium from a subpopulation of human marrow stromal cells (CFU-RF) contain an activity able to stimulate the growth of macroscopic epo-dependent erythroid colonies. The ligand for the product of the c-kit proto-oncogene (also known as stem cell factor or SCF), among other activities, has been reported to have similar effects on erythroid colony growth. We have also presented data showing that SCF together with phytohemagglutinin-stimulated leukocyte conditioned medium can stimulate erythroid colony growth in the presence of antibodies to erythropoietin. Using the human SCF cDNA probe (K. Zsebo, Amgen Inc.) we now show that cells derived from CFU-RF colonies express SCF but not c-kit. Human umbilical vein endothelial cells were also found to express SCF and this expression was increased by addition of monocyte supernatant, IL-1 beta or thrombin. Cells of the human erythroleukemia cell line HEL were found to express c-kit but not SCF. Neither c-kit nor SCF mRNA were detected in phytohemagglutinin-stimulated lymphocytes. Together, these data support the view that the behaviour of proliferating erythroid stem cells in the marrow, which may express c-kit, could be regulated by membrane-bound SCF present on surrounding stromal cells.

Base Sequence↗

Rearrangement of BCR genes in malignant lymphoma.

The Philadelphia chromosome, originally thought to be associated solely with chronic myelogenous leukemia (CML), has since been identified in acute leukemias and in some cases of lymphoma. The Philadelphia chromosome results from reciprocal translocation of genetic material between chromosome 9 and 22 involving the c-abl and BCR genes respectively. Southern blot analysis of the BCR genes was carried out on biopsy specimens from 49 patients presenting with malignant lymphoma without a previously documented CML phase. In two patients, BCR gene rearrangements were detected in the malignant lymph nodes but not in the bone marrow samples. A third patient showed BCR gene rearrangements in the bone marrow but not in the lymph node. From this limited study, it seems that the overall incidence of BCR gene rearrangement in malignant lymphoma is similar to that observed in adult AML.

Blotting, Southern↗