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Biomedical subjects

K Yong

Publications and source records attributed to K Yong.

At least 19 recordsLinked to original sources
PubMed2005

Extramedullary myeloma representing as a pericardial effusion with tamponade: two case reports and a further review of 19 cases in the literature.

Two rare cases of extramedullary pericardial myeloma presenting after initial diagnosis of multiple myeloma are described. A systematic search using PubMed (National Library of Medicine) identified a further 19 cases in the literature. The characteristics of presentation, duration of survival and optimal management of patients with pericardial myelomatous involvement are discussed.

Aged↗
PubMed2005

Differential expression of CD 180 and IgM by B-cell chronic lymphocytic leukaemia cells using mutated and unmutated immunoglobulin VH genes.

We have studied the surface expression of the Toll-like receptor family member CD 180 on cells from 78 patients with B-chronic lymphocytic leukaemia (B-CLL). B-CLL cells had variable levels of CD 180 expression, but this was always less than that expressed by normal blood B cells and was stable for 24 months. Significantly higher levels of CD 180 were expressed by B-CLL cells with mutated IGVH genes compared with those using unmutated IGVH genes. This was in contrast to the higher levels of expression of surface immunoglobulin M by B-CLL cells using unmutated, rather than mutated IGVH genes. CD 180 was functional on B-CLL cells from some of the patients, as shown by the increased expression of CD 86 following incubation in vitro with anti-CD 180. The differential expression of CD 180 amongst B-CLL patients is one more marker that may define more precisely the different biological properties of this heterogeneous disease.

Aged↗
PubMed2002

Peripheral blood stem cell transplantation for POEMS syndrome.

In common with other plasma cell dyscrasias in which a small tumour burden is associated with severe clinical symptoms (notably systemic AL amyloidosis) the possible benefits of dose intensification are yet to be fully explored in POEMS syndrome. One important issue is whether the toxicity of the procedure is significantly increased in this group. We report two cases of POEMS syndrome with solitary asymptomatic bone lesions treated with high-dose melphalan (200 mg/m(2)) and peripheral blood stem cell (PBSC) rescue. In both cases there was minimal peri-transplant morbidity and a subsequent substantial and maintained improvement in the peripheral neuropathy.

Adult↗
PubMed2001

Dermatomyositis and sarcoid-like reaction associated with multiple myeloma treated effectively by high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

We report the case of a 46-year-old male who developed dermatomyositis and a sarcoid-like reaction in association with testicular relapse of multiple myeloma. The myositis progressed despite chemotherapy directed at the underlying malignant disorder and immunosuppressive treatment. There was, however, a dramatic and sustained response to high-dose chemotherapy and autologous peripheral blood stem cell transplantation which resulted in resolution of the myopathy and partial resolution of the sarcoid-like reaction. This case report highlights the potential of autologous stem cell transplantation as treatment for para-neoplastic disorders associated with haematological malignancies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Expansion of CD4+ T cells with a cytotoxic phenotype in patients with B-chronic lymphocytic leukaemia (B-CLL).

Abnormal CD4/CD8 ratios and T-cell function have previously been shown in patients with B-chronic lymphocytic leukaemia (B-CLL). We have demonstrated that CD4+ T cells containing both serine esterase and perforin (PF) are increased in the blood of these patients. Using flow cytometry, we have shown that the CD4+ PF+ cells were CD57+ but lacked expression of CD28, suggesting a mature population. The same phenotype in CD8+ T cells is characteristic of mature cytotoxic T cells. However, in contrast to the CD8+ T cells, the CD4+ T cells were more frequently CD45RO positive than CD45RA positive, indicating prior antigen experience. In contrast, this population lacked expression of either CD69 or HLA-DR, arguing that they were not activated or that they are an abnormal population of T cells. Their constitutive cytokine levels showed them mainly to contain IL4 and not IFNgamma, suggesting a Th2 phenotype. The role of the CD4+ PF+ T-cell population is at present uncertain. However, this potentially cytotoxic T-cell population could contribute both to enhancing survival of the B-CLL tumour cells through production of IL4, and to the immunodeficient state frequently seen in patients with this tumour, independent of drug treatment.

Aged↗
PubMed2001

An economic evaluation of universal infant vaccination against hepatitis B virus using a combination vaccine (Hib-HepB): a decision analytic approach to cost effectiveness.

OBJECTIVE: To evaluate the health impact and cost effectiveness of two infant vaccination strategies for protection against hepatitis B virus (HBV) infection in the Australian population. Vaccinating only high-risk infants, assuming 65% compliance, was compared with universal vaccination of infants using a combination Hib-HepB vaccine, with 87.4% compliance. METHOD: A Markov model simulated the natural history of HBV infection and disease in an Australian birth cohort. The cohort was divided into those at high risk of infection (infants born into high-risk families) and low-risk infants. Clinical and epidemiological data used were obtained from published reports and a survey of clinical experts. The model included the health costs associated with acute and chronic HBV infection, and the sequelae of chronic HBV infection. RESULTS: The model predicted that universal hepatitis B vaccination of an Australian birth cohort (260,000 births) would result in a 77% reduction in cases of HBV infection. The incremental cost per life year gained was $11,862, which is low compared with many other health care interventions. With no discounting of costs or consequences, universal vaccination with the combination vaccine was predicted to save lives and reduce costs. CONCLUSION: There is no socially accepted threshold value for cost per life year gained to guide decisions about funding Australian health care interventions. Nevertheless, based on these results, universal hepatitis B vaccination of Australian infants using a combination Hib-HepB vaccine would almost certainly be regarded as a worthwhile investment of public funds.

Australia↗
PubMed1999

Cord blood progenitor cells have greater transendothelial migratory activity and increased responses to SDF-1 and MIP-3beta compared with mobilized adult progenitor cells.

When cord blood is used as a source of haemopoietic stem cells for transplantation, fewer cells are required per kg of recipient. This greater engraftment efficiency of cord blood cells may relate to an increased ability to traverse sinusoidal endothelium, a crucial step in the homing of stem cells. We report that freshly isolated cord blood progenitors migrated more efficiently than mobilized adult cells. Cord blood progenitors responded rapidly to growth factor stimulation with an increase in migratory ability within 24 h whereas mobilized adult cells responded only after 72 h (P < 0.01). Cord blood cells also exited G0/G1 rapidly; after 24 h of growth factor exposure, 20.2 +/- 1.2% of cord blood CD34+ cells were in S + G2/M compared to 6.9 +/- 1.2% of adult CD34+ cells (P < 0.01). Proliferating CFC migrated more efficiently (13.3 +/- 3.4% for GM-CFC) than non-proliferating CFC (1.4 +/- 0.5%, P < 0.01) as determined using a 3H-thymidine suicide assay. Cord blood progenitor cells also demonstrated a greater transmigratory response to chemokine stimulation compared with adult cells; this was manifested as a differential response of freshly isolated cells to SDF-1, and of growth factor activated cells to MIP-3beta. Finally, cord blood CD34+ cells express higher levels of the chemokine receptor for SDF-1, CXCR4, when compared with mobilized adult CD34+ cells (P < 0. 05).

Adult↗
PubMed1998

Naphthazarin derivatives: synthesis, cytotoxic mechanism and evaluation of antitumor activity.

The rate of the GSH conjugate formation, the inhibition of DNA topoisomerase-I and the cytotoxic activity against L1210 cells of the naphthoquinones showed the same order; 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) > 6-(1-hydroxyethyl)-DMNQ > 2-(1-hydroxyethyl)-DMNQ; the steric hindrance of the substituents, particularly 2-substutuent, in reacting with cellular nucleophiles must be the main cause for lowering the bioactivities. Acetylation of 2-(1-hydroxyethyl)-DMNQ producing 2-(acetyloxyethyl)-DMNQ potentiated the bioactivities; 2-(1-hydroxyethyl)-DMNQ did not react with GSH and the enzyme, and showed ED50 of 0.680 microgram/ml, whereas the values of 2-(1-acetyloxyethyl)-DMNQ were the conjugate formation of 0.14 microM, IC50 value of 81 microM for the enzyme inhibition and ED50 of 0.146 microgram/ml for the cytotoxcity. Furthermore, the acetylation 2-(1-hydroxyethyl)-DMNQ (T/C, 119%) enhanced the T/C values for the mice bearing S-180 tumor [T/C of 2-(1-acetyloxyethyl)-DMNQ, 276%]. It was assumed that the difference in bioactivities ensued by acetylation was based on the mechanism of the so-called bioreductive alkylation.

Acetylation↗
PubMed1997

2-Substituted naphthazarins; synthesis and antitumor activity.

A series of 2-substituted naphthazarin derivatives, 5,8-dihydroxy-1,4-naphthoquinone (DHNQ) derivatives and 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) derivatives, were synthesized, and their cytotoxic activity against some cancer cell lines and antitumor action against S-180 tumor were evaluated. In general, 2-(1-hydroxyalkyl)-DHNQ derivatives showed a higher cytotoxicity than 2-(1-hydroxyalkyl)-DMNQ derivatives, implying a predominant role of redox cycling rather than electrophilicity in cytotoxicity. 2-(1-Alkoxy-4-methylpentyl) or 2-(1-acyloxy-4-methylpentyl) derivatives were produced by alkylation or acylation at the C-1' position of 2-(1-hydroxy-4-methylpentyl)-DHNQ or DMNQ derivatives. Although the cytotoxicity differed according to the size of the alkyl or acyl chain, alkylation or acylation at the C-1' position did not improve the cytotoxicity remarkably, and DHNQ derivatives were still more cytotoxic than DMNQ derivatives. Separately, in vivo testing showed that 2-(1-acyloxyalkyl)-DHNQ derivatives or 2-(1-alkoxyalkyl)-DHNQ derivatives expressed a higher antitumor action than 2-(1-hydroxyalkyl)-DMNQ or -DHNQ derivatives in contrast to the cytotoxicity observations. The total size of two side chains at C-1' seemed to govern the antitumor activity, with 9 to 11 carbon atoms being optimal. Thus, it is suggested that the physical properties as well as the chemical reactivity are to be considered in relation to the antitumor action of 2-substituted naphthazarin compounds.

Animals↗
PubMed1996

Impaired migration in vitro of neutrophils from patients with paroxysmal nocturnal haemoglobinuria.

Migration of neutrophils in patients with paroxysmal nocturnal haemoglobinuria (PNH) was studied using two different complement-free in vitro model systems, subagarose and transendothelial migration. In the subagarose migration assay the mean migration distance of PNH neutrophils was slightly, but significantly, reduced to 1236 microns (range 753-1586, n = 6) compared to a normal mean of 1476 microns (range 1076-1768, n = 6, P = 0.016). By immunocytochemical staining for the urokinase type plasminogen activator receptor (uPAR) which is a glycosyl-phosphatidyl-inositol (GPI) anchored protein expressed by normal, but not by PNH-affected, neutrophils, it was shown that the uPAR-positive subpopulation of normal neutrophils predominated among the faster migrating cells (60-80% normal cells at the front of migration) while uPAR-negative (i.e. PNH-affected neutrophils) were more numerous close to the application well (5-30% normal cells). When migration of neutrophils was tested across a monolayer of human umbilical vein endothelial cells (HUVEC) cultured on polycarbonate filters, there was a 3-4-fold impairment of the migration of the PNH-affected neutrophils both in the absence of stimulation and after stimulation with fMLP (P < 0.001 in both cases). After IL-1 stimulation of the endothelium the impairment was even more pronounced (8-fold difference, P < 0.001). When the endothelial cells were grown on collagen-coated filters the impairment of the migration of PNH neutrophils was less pronounced, but still significant after stimulation with fMLP and IL-1 (2-fold, P < 0.05 in both cases). These results demonstrate that there is a complement-independent impairment of migration of neutrophils from patients with PNH which may be related to their failure to express GPI-linked proteins involved in cell migration and/or adhesion such as the uPA receptor and the CD66b antigen.

Cell Movement↗
PubMed1994

Differentiation-linked changes in tyrosine phosphorylation, functional activity, and gene expression downstream from the granulocyte-macrophage colony-stimulating factor receptor.

The HL-60 model of myeloid maturation was used to test whether changes in signaling from the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor accompany maturation-related changes in cellular responses to GM-CSF. Receptor expression, tyrosine phosphorylation, functional activity, and c-fos gene expression were measured. Functional GM-CSF receptors were present throughout differentiation as both uninduced and dimethyl sulfoxide (DMSO)-induced HL-60 cells responded to GM-CSF, albeit in different ways. Uninduced promyelocytes proliferated in response to GM-CSF, whereas DMSO-induced cells lost the capacity to proliferate but did respond with increased expression of beta 2-integrins, enhanced respiratory burst activity, and metabolism of arachidonic acid. GM-CSF-stimulated upregulation of c-fos mRNA expression was not detected in immature cells but developed after 2 to 4 days with DMSO in line with a marked increase in responsiveness to stimulation with phorbol ester, showing that increased expression of c-fos is predominantly a feature of mature phagocytes. GM-CSF stimulated the tyrosine phosphorylation of a broadly similar range of proteins in both uninduced and DMSO-treated HL-60 cells, but protein bands were more heavily phosphorylated in DMSO-induced cells. Phosphorylation was rapid in onset and very transient in immature cells. Phosphorylation of several proteins, in particular a 130-kD band, was more sustained in DMSO-induced cells. These differences in signaling were not because of numerical differences in receptors, because reduction of GM-CSF concentration to trigger equivalent numbers of high-affinity receptors delayed the onset of phosphorylation in DMSO-induced cells. We conclude that there are maturation-related changes in signaling downstream from the GM-CSF receptor.

Arachidonic Acid↗
PubMed1994

Interleukin-3 administration enhances human monocyte function in vivo.

In addition to its haemopoietic effects, interleukin-3 (IL-3) enhances leucocyte function in vitro. In this study we examined the effects on haematological variables and monocyte function of a single IL-3 infusion in five haematologically normal individuals. There was a rapid fall in circulating monocyte (to 24 +/- 6% of pre-infusion value) and eosinophil numbers (to 3 +/- 2%) with a nadir at 30 min and gradual return to baseline over 6 h. No significant changes in monocyte expression of the adhesion molecules CD11b or L-selectin or of monocyte respiratory burst activity were detected. There was a significant increase in monocyte phagocytosis and killing of Candida after IL-3 infusion: the percentage of monocytes which had ingested Candida increased from 39 +/- 10% to 62 +/- 12% and the total number of Candida killed per 100 monocytes increased from 63 +/- 34 to 210 +/- 59 (P < 0.05 and P < 0.01 respectively). There was no inhibition of neutrophil migration into a 'skin window' site and monocyte migration was moderately enhanced (peak increase of 260 +/- 47%). These results show that IL-3 has significant effects on monocyte function in vivo and could be of use in augmenting host defence mechanisms in immunocompromised patients.

CD11 Antigens↗
PubMed1992

Human macrophage colony-stimulating factor levels are elevated in pregnancy and in immune thrombocytopenia.

Plasma macrophage colony-stimulating factor (M-CSF) levels were measured by enzyme immunosorbent assay (ELISA) using horse and rabbit polyvalent antibodies raised against human M-CSF purified from urine (hM-CSF). Plasma M-CSF levels in nonpregnant female controls were 364 +/- 69 U/mL (mean +/- SD, n = 20). Pregnancy results in significant elevation of circulating M-CSF levels (541 +/- 164 U/mL, n = 46, P < .0005). M-CSF levels were increased by 28 weeks' gestation and did not increase further in later pregnancy. M-CSF levels were also measured in 20 female controls before and after commencing on the oral contraceptive pill. There was no effect of the contraceptive pill on plasma M-CSF levels (364 +/- 69 U/mL before v 373 +/- 66 U/mL after commencing on the pill). In 28 nonpregnant patients with untreated immune thrombocytopenic purpura, (ITP), plasma M-CSF levels were significantly increased (797 +/- 402 U/mL, n = 28, v 364 +/- 69 U/mL in controls, N = 20, P < .0005). Pregnant ITP patients had higher levels of plasma M-CSF (929 +/- 327 U/mL, n = 25) than nonpregnant patients, but this difference was not significant. Elevated levels of M-CSF in ITP may reflect activation of the reticuloendothelial system (RES), which could result in positive feedback to increase the destruction of platelets. The increase in M-CSF associated with pregnancy could contribute to the exacerbation of latent ITP in pregnancy.

Adult↗
PubMed1992

The effect of macrophage colony-stimulating factor on haemopoietic recovery after autologous bone marrow transplantation.

Macrophage colony-stimulating factor (M-CSF) is active in the late stages of monocyte maturation, activates mature monocyte-macrophages and enhances their production of various other cytokines. We have examined the effects of a 21 d course of escalating doses of M-CSF purified from human urine (hM-CSF) on recovery following autologous bone marrow transplantation (ABMT) in 20 patients with malignant lymphomas. Four patients were treated at each dose level of 4, 8, 16, 32 and 64 x 10(6) U/m2/d and results compared to 46 concurrent controls. There was no significant difference in recovery to an absolute neutrophil count (ANC) of 0.5 x 10(9)/l (median 20 d in hM-CSF group versus 22 in controls) or in recovery of platelets to 50 x 10(9)/l (32 d versus 39 d, 0.05 less than P less than 0.1); hM-CSF patients received a median of 81 platelet units following ABMT (controls 112 units, P = NS). hM-CSF patients had a median of 5.5 d with fever greater than 37.5 degrees C (control 8, P = NS), received parenteral antibiotics for 14.5 d (control 17, P = NS) and had a 50% incidence of bacteraemia (control 48%). hM-CSF treated patients were discharged by a median of day 29 following transplantation (control 33, P less than 0.05). Platelet and neutrophil recovery correlated significantly with the number of marrow mononuclear cells (MNC) reinfused in the hM-CSF group (P = 0.05 and P = 0.014 respectively) but not in controls. Subgroup analysis showed that hM-CSF patients receiving greater than 2 x 10(8) MNC/kg body weight reached an ANC of 0.5 x 10(9)/l by a median of day 16.5 (control 18.5, NS), became platelet transfusion independent by day 17 (control 29, P less than 0.05) and reached a platelet count of 50 x 10(9)/l by day 21 (control 40, P less than 0.05). No significant toxicity attributable to hM-CSF treatment was seen. These results suggest that hM-CSF accelerates platelet recovery following ABMT and that relatively large marrow innocula are required to see this effect.

Adult↗
PubMed1991

Lack of effect of granulocyte-macrophage and granulocyte colony-stimulating factors on cultured human endothelial cells.

The hematopoietic growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), enhance the effector functions of mature myeloid cells, including the interaction with vascular endothelium. We examined the direct effect of recombinant human GM-CSF (rhGM-CSF) and recombinant human G-CSF (rhG-CSF) on the growth and function of cultured human umbilical vein endothelial cells (HUVEC). Endothelial cell growth supplement (ECGS) increased the proliferation of passaged and primary cells by 305% +/- 45% (mean +/- SEM, n = 5, P less than .01) over control cells at 4 days; GM-CSF and G-CSF had no effect. Endothelial cell procoagulant activity was increased after 4-hour incubation with recombinant interleukin-1 beta (IL-1 beta) 10 U/mL and recombinant tumor necrosis factor (TNF) 10 U/mL to 1,721% +/- 376% (n = 7, P less than .005) and 247% +/- 71% (n = 4) of control levels, respectively. gamma-Interferon (gamma-IFN) 50 U/mL had no direct effect of its own but was able to prime the response to IL-1 beta. There was no direct or priming effect of GM-CSF (1 ng to 1 microgram/mL) on the expression of procoagulant activity in endothelial cells. GM-CSF and G-CSF (1 ng/mL to 1 microgram/mL) had no effect on the expression of either tissue plasminogen activator (tPA) or plasminogen activator inhibitor-1 (PAI-1) by endothelial cells. The secretion of tPA by endothelial cells was increased, however, after 24-hour incubation with thrombin 4 U/mL (314% +/- 72% of control levels, n = 5, P less than .025). The production of PAI-1 was increased by TNF 200 U/mL (241% +/- 44% of control, n = 3, P less than .005), thrombin 4 U/mL (180% +/- 12% of control, n = 5, P less than .0005) and IL-1 beta 10 U/mL (275% +/- 44% of controls, n = 5, P less than .0005). In four experiments, endothelial cells showed no specific binding of 125I-GM-CSF, whereas peripheral blood (PB) neutrophils demonstrated the presence of 802 +/- 78 high-affinity receptors for GM-CSF. Thus, we found no effect of rhGM-CSF or rhG-CSF on the proliferation activities by these cells. These findings are in accordance with the lack of demonstrable receptors for GM-CSF on cultured HUVEC.

Cell Division↗
PubMed1991

In vivo effects of macrophage colony-stimulating factor on human monocyte function.

Macrophage colony-stimulating factor (M-CSF) is reported to enhance a variety of functions of mature monocyte/macrophages in vitro. We have examined the effects of a 2 h intravenous infusion of M-CSF obtained from human urine (hM-CSF) on haematological parameters and selected monocyte functions. There was a rapid, small, but consistent reduction in Hb concentration (mean 6.5 +/- 2.3%, P less than 0.0005 by paired t test) by the completion of the hM-CSF infusion and small, transient falls in platelet, monocyte and neutrophil counts were noted in the 2 h following the end of the infusion. No effect on monocyte or neutrophil CD11b cellular adhesion molecule expression was detected. Exposure to hM-CSF in vivo did not directly stimulate the monocyte respiratory burst, but increased the percentage of monocytes responding to f-met-leu-phe from 9.8 +/- 2.5 to 16.6 +/- 4.2 (P less than 0.01). The number of candida ingested and degraded per 100 monocytes increased from 101 +/- 14 pre-infusion to 160 +/- 22 post-infusion (P less than 0.01). There was a rapid increase in the numbers of monocytes entering a skin window membrane from a mean of 226 +/- 71 pre-infusion to 1064 +/- 404 at the end of the infusion, with no effect on neutrophil migration. These data show that the administration of hM-CSF enhances several of the functions of peripheral blood monocytes in vivo, and this may be of benefit in the treatment of selected infections.

Adult↗
PubMed1991

Role of leucocyte integrins in phagocyte responses to granulocyte-macrophage colony stimulating factor (GM-CSF): in vitro and in vivo studies on leucocyte adhesion deficiency neutrophils.

The role of leucocyte integrins in phagocyte function has been studied by comparing normal neutrophils with those from a patient with partial leucocyte adhesion deficiency (LAD), in whom the levels of CD11b and CD11c were 10% of controls, whereas CD11a levels were normal. Unstimulated LAD neutrophils exhibited defective adhesion to plastic (4.4 +/- 1.5% cf. 14.4 +/- 3.8% in controls), but not to human umbilical vein endothelial cells (HUVECs). The adhesion to HUVECs could be further upregulated by granulocyte-macrophage colony stimulating factor (GM-CSF), but not by 12-O-tetradecanoylphorbol 13-acetate (TPA) which, in normal cells, is a more potent 'pro-adhesive agonist'. The normal neutrophil-endothelial interaction induced by GM-CSF in LAD neutrophils was confirmed in vivo when administration of GM-CSF resulted in rapid phagocyte margination. Neutrophil migration and phagocytosis/killing were defective in LAD neutrophils, and some improvement in phagocytosis/killing was seen following in vivo administration of GM-CSF. These studies illustrate that the degree to which the leucocyte integrins mediate adherence-related phagocyte functions varies not only with the particular function, but also with the conditions of stimulation. High levels of CD11b and CD11c expression appear not to be required for unstimulated or GM-CSF-stimulated neutrophil-endothelial interactions, either in vitro or in vivo. Other neutrophil functions, on the other hand, such as migration and phagocytosis/killing are much more dependent on the leucocyte integrins.

Antigens, CD↗