Clinical outcome of HBsAg(+) renal allograft recipients.
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Publications and source records attributed to D S Han.
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To investigate the factors affecting low values of serum albumin (SA) in continuous ambulatory peritoneal dialysis (CAPD) patients, we undertook a cross-sectional study of 106 CAPD patients, with a mean age of 49.0 years and dialysis duration of 43.4 months, with respect to demographic, clinical, and biochemical parameters. In group I (n = 28, SA < or = 3.5 g/dL), diabetics were more common, patients were significantly older, and more patients were malnourished, according to the subjective global assessment (SGA), compared to group II (n = 78, SA > 3.5 g/dL). Serum C-reactive protein (CRP), lipoprotein (a), and 24-hour dialysate-to-plasma creatinine concentration ratio (D/P) were significantly higher, and 24-hour dialysate albumin was greater in group I. Compared to group II, group I had significantly lower serum creatinine and urea nitrogen appearance (UNA). Blood urea nitrogen (BUN), lean body mass (LBM), % of body weight (%BW), and normalized protein equivalent of nitrogen appearance (nPNA) tended to be lower in the low SA group, without statistical significance. There were no differences in the duration of CAPD, peritonitis rate, serum insulin-like growth factor-I (IGF-I), anthropometric data, dietary assessment, dialysis adequacy, and residual renal function (RRF) between the two groups. SA was positively correlated with serum creatinine, IGF-I, LBM, UNA, BUN, nPNA, and CAPD duration, and was negatively correlated with 24-hour D/P, 24-hour dialysate albumin, age, CRP, and bicarbonate (HCO3-). By stepwise multiple logistic regression analysis, 24-hour D/P, age, CRP, and SGA were independent risk factors for low SA level. In conclusion, SA seems to be influenced not only by nutritional factors but also by nonnutritional factors such as peritoneal membrane transport characteristics, age, and presence of acute phase protein response manifested by CRP elevation.
The aetiology and the pathophysiological mechanisms underlying the development of dry skin in uraemia are still unclear, but the hydration status of stratum corneum clearly influences the appearance of skin. The xerotic skin texture is often referred to as 'dry skin' and has been suggested as a cause of uraemic pruritus. To understand the aetiology of dry skin in uraemia we measured the status of skin surface hydration of uraemic patients with the corneometer and skin surface hydrometer, the functional capacity and the urea concentration of stratum corneum and the response of eccrine sweat gland to sudorific agent (0.05% pilocarpine HCL) in 18 age-matched haemodialysis patients and 10 healthy volunteers. We also performed the water sorption-desorption test to uraemic and control subjects after application of urea in various concentrations. Uraemic patient's skin showed decreased water content compared to control subjects. However, we found no correlation between dry skin and pruritus. Although the urea concentration of the horny layer in uraemic patients was elevated compared to control subjects (28.2 microgram/cm2 vs 5.04 micrograms/cm2, P < 0.05), its moisturizing effect to relieve pruritus is questionable because its artificial application revealed no improvement of the functional capacity of horny layer in concentration 5 times higher than the physiological concentration. Uraemic patients showed decreased sweating response to sudorific agent. In conclusion, the functional abnormalities of eccrine sweat glands may be account for dry skin in uraemic patients at least in part, but there is no correlation between xerosis and pruritus.
OBJECTIVE: During HIV-1 infection, CD4+ T lymphocytes migrate to immune-reactive lymphoid organs where they are infected by the virus and/or killed by apoptosis on immunoregulatory stimuli--a potential mechanism underlying fatal CD4+ T-cell depletion observed in AIDS. This study seeks to determine the effects of glucocorticoids (GCC) on the activation-induced T-cell apoptosis triggered by HIV-1. METHODS: CD4+ and CD8+ T cells were purified from HIV-negative donor peripheral blood mononuclear cells (PBMC) by positive selection and exposed to HIV-1 (primary isolates). HIV-1-exposed CD4+ and CD8+ T cells as well as PBMC derived from HIV-1-infected patients were cultured with medium alone or anti-CD3 monoclonal antibodies (MAb)/mitogens in the presence or absence of hydrocortisone or prednisolone. Viral infection kinetics were assessed by polymerase chain reaction and viral replication was measured by p24 enzyme-linked immunosorbent assay. Cell survival, apoptosis, T-cell proliferation, blast cell transformation, and interleukin (IL)-2 receptor (CD25) expression were monitored in parallel for each cell population. RESULTS: Fractionated CD4+ T cells acutely infected by HIV-1 underwent apoptotic death on anti-CD3 MAb/mitogen stimulation. This activation-induced apoptotic cell killing was antagonized by pharmacological doses of prednisolone or hydrocortisone added up to 6 h after stimulation. GCC were also found to be capable of inhibiting the accelerated apoptosis in PBMC (including both CD4+ and CD8+ T-cell fractions) from HIV-1-infected patients. This anti-apoptotic action of GCC overbalanced their downregulatory effect on T-cell proliferation, resulting in an overall improvement of CD4+ T-cell survival in patient PBMC. These effects of GCC were abrogated by the anti-GCC RU 486 and were not associated with significant suppression of CD25 expression and IL-2-dependent T-cell blast transformation; moreover, GCC had no impact on viral infection and replication. CONCLUSION: GCC exert a receptor-mediated anti-apoptotic activity in mature T cells through both activation-induced and HIV-1-triggered pathways and could be potent inhibitors of T-cell apoptosis in HIV-1-infected patients.
NS3 of hepatitis C virus (HCV) is a serine protease that carries out the proteolytic processing of the nonstructural proteins of the HCV polyprotein. Deletion analysis of the N terminus of NS2,3,4 fusion protein revealed that the N-terminal boundary of the active protease resides between amino acids 1050 and 1083. The processing patterns of internal deletion mutants of NS2,3,4 indicated that the C terminus of the enzymically active protease resides between amino acids 1115 and 1218. The N- and C-terminal boundaries of the protease were also confirmed by determining the trans-cleavage activity of internally deleted NS3,4. NS3 protease activity was inhibited by Cu2+ but was slightly enhanced by Zn2+. This report provides a possible approach for development of antiviral agents based on protease inhibitors.
The polyprotein encoded by a single open reading frame of hepatitis C virus (HCV) is processed by host- and virus-encoded proteases. The viral protease NS3 is responsible for the cleavage of at least four sites (NS3/4A, NS4A/4B, NS4B/5A, and NS5A/5B junctions) in the nonstructural protein region. To characterize the protease function of NS3 and NS4 on various target sites, efficient cis- and trans-cleavage assay systems were developed by using in vitro transcription and translation. Deletion of the C-terminal two-thirds from NS3 in an NS3-NS4A-4B polypeptide (NS3 delta C-4A-4B) hampered cleavage of the NS3/4A junction but not that of the NS4A/4B junction. As a consequence, expression of NS3 delta C-4A-4B containing an internal deletion of NS3 results in an NS3 delta C-4A fusion protein. NS3 delta C-4A shows very efficient and specific trans-cleavage activity at NS4A/4B, NS4B/5A, and NS5A/5B junctions. In addition, the biochemical properties of HCV NS3 delta C-4A were further elucidated by adding known protease inhibitors in trans-cleavage reactions. The HCV protease NS3-4A is inhibited by chymotrypsin-specific inhibitors N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), chymostatin, and Pefabloc SC but not by trypsin-like protease inhibitors antipain, leupeptin, and N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) or by the protease inhibitors E-64, bestatin, pepstatin, and phosphoramidon. This finding strongly suggests that HCV protease NS3-4A is a chymotrypsin-like serine protease.
A retrospective study of 223 patients with IgA nephropathy (IgAN) was performed to clarify the prognostic factors and the renal survival rates of the disease. One hundred twenty-two patients were followed-up for more than 6 months after their renal biopsy (mean follow-up duration: 43.0 months), and 20 of them (16.4%) had progressed to end-stage renal disease (ESRD). Using univariate analysis, 8 risk factors (2 clinical and 6 histopathological findings) for developing ESRD were identified: renal insufficiency at initial presentation (serum creatinine > or = 1.5 mg/dl); heavy proteinuria (> or = 3.5 gm/day); moderate to severe histopathologic findings such as class IV/V lesions by W.H.O. classification, mesangial hypercellularity, glomerular sclerosis, interstitial infiltration, interstitial fibrosis, and tubular atrophy. In multivariate regression analysis, class IV/V lesions and renal insufficiency at initial presentation were the independent prognostic factors of IgAN. The renal survival rates were 100% at 1 year, 97.0% at 3 years, and 78.9% at 5 years. In conclusion, it seems that about 20% of IgAN patients have a risk to progress to ESRD within 5 years, and a careful follow-up is recommended especially in patients who have either renal insufficiency at the time of presentation or severe renal pathology (class IV/V lesions).
In order to investigate the anti-proliferative effect of 3-hydroxy-3-methylglutaryl coenzyme. A reductase inhibitor, we evaluated the effects of lovastatin on DNA replication and the proliferation of rat mesangial and aortic smooth muscle cells, both of which were mesenchymal origin cells. Proliferations were determined by measuring [3H]thymidine uptake, and counting the number of cells. Growth-arrested mesangial and aortic smooth muscle cells were exposed to platelet-derived growth factor (PDGF), endothelin (ET) and angiotensin II (Ang II) to stimulate mitogenesis. All agents exhibited dose-dependent stimulation of [3H] thymidine uptake. PDGF was more potent than the others. Ang II increased [3H] thymidine uptake without demonstrable mitogenic activity. Lovastatin inhibited PDGF (10 ng/ml in mesangial cell, 25 ng/ml in smooth muscle cell)-, ET (10(-7)M)- and Ang II (10(-7)M)-induced [3H] thymidine uptake significantly in a dose-dependent manner in both cells. The increase of cell number in response to PDGF and ET treatment were also inhibited at 10 microM of lovastatin. The inhibitory effect of lovastatin was largely overcome in the presence of exogenous mevalonate at 200 microM, with 75.5% restoration from lovastatin-induced inhibition on PDGF-induced [3H] thymidine uptake in mesangial cells (77.8% in aortic smooth muscle cells). However, the addition of cholesterol did not prevent inhibition by lovastatin. In conclusion, lovastatin had an inhibitory effect on mesangial and aortic smooth muscle cell proliferation, and mevalonate was essential for DNA replication in both types of cells. Lovastatin may reduce glomerular and atherosclerotic injury through an anti-proliferative effect on mesangial and vascular smooth muscle cells, in addition to lowering circulating lipids.
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Quantitative analysis of polymerase chain reaction (PCR) amplified HIV-1 DNA or cDNA fragments is attained using an automated system that combines capillary-gel electrophoresis (CGE) for high-efficiency separation and laser-induced fluorescence (LIF) for high-sensitivity detection. This system enables the detection of PCR-amplified multiple target DNA or cDNA in the same tube by a single injection with high precision.
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Flow cytometric analysis reveals that 5 human melanoma cell lines (M14, IGR3, ME1477, JUSO, GLL19) express both alpha and beta chain of the interleukin 2 receptor (IL-2R alpha and IL-2R beta). These chains are able to specifically bind IL-2 and to form high-affinity heterodimers (IL-2R alpha beta). Analysis of poly A+ RNAs by Northern blot reveals the presence of typical transcripts for both the IL-2R alpha gene (3.6 kb) and the IL-2R beta gene (4 kb). Reverse transcription/polymerase chain reaction analysis allowed transcripts for the IL2R gamma (p64) gene to be detected in 3 of these melanoma cell lines (M14, IGR3, ME 1477). Incubation with human recombinant IL-2 modifies in IL-2R alpha+beta+gamma+ (M14) the expression of several surface molecules: down-regulation of ICAM-1, HLA class I and HLA-DR and up-regulation of CD44. IL-2 is also active on IL-2 alpha+beta+gamma- cell lines since it decreases ICAM-1 and HLA class-II expression at the surface of JUSO cells. Down-regulation of ICAM-1, whose expression in melanoma cells is a marker of tumor progression, is detectable within 3 hr in M14 cells and is maximal after 48 hr incubation, at IL-2 concentrations corresponding to the high-affinity heterodimers. This feature is specific since it is partially inhibited by MAbs directed against the IL-2 binding site of the IL-2R alpha (MAR93, 10T14) and IL-2R beta (MiK beta 1, TU27) chains. Our data support the notion of a direct effect of IL-2 on human melanoma cells. Modulation of the expression of surface molecules which is important for the interaction with immunocompetent cells or for tumor progression, could have a role to play during in vivo IL-2 treatment of human melanomas.
We have done cross sectional and prospective studies to determine the prevalence and the clinical significance of antibodies to the hepatitis C virus (Anti-HCV) in 54 hemodialysis (HD) patients and 227 continuous ambulatory peritoneal dialysis (CAPD) patients. Fifteen patients (27.8%) were anti-HCV (+) among the HD group, and twelve patients (5.3%) were anti-HCV (+) among the CAPD group. In the HD group, the positivity of anti-HCV correlated with the duration of HD, but there was no significant correlation with the history of transfusion, the amount of transfusion and abnormal alanine aminotransferase (ALT). At the follow-up study in 164 cases (HD 50 cases, CAPD 114 cases) after 6 months, one of 14 anti-HCV (+) CAPD patients was converted to anti-HCV (-) and two of 35 anti-HCV (-) HD patients were converted to anti-HCV (+). In conclusion, the prevalence of anti-HCV was significantly higher in HD patients compared to CAPD patients, and the positivity for anti-HCV in HD patients correlated with the duration of HD. A regular follow-up of anti-HCV and isolation of anti-HCV (+) HD patients with a separate machine may be needed to prevent the transmission of the hepatitis C virus during hemodialysis.
To elucidate the nature of altered cellular immunity seen in patients with chronic renal failure, the values of interleukin-2 (IL-2), a kind of lymphokine, and T-cell colony forming units were measured in controls (N = 10), predialysis uremic patients (N = 14), patients undergoing chronic hemodialysis (HD, N = 11) and patients on continuous ambulatory peritoneal dialysis (CAPD, N = 9). Dialytic patients were selected as relatively stable cases receiving dialysis for more than 3 months. The duration of dialysis was 25.5 +/- 5.5 months in HD and 14.7 +/- 3.0 months in CAPD groups. The mean age was 30.3 years in the control, 36.1 years in the predialysis, 32.9 years in the HD and 41.1 years in the CAPD groups; all 4 groups showed male predominance. The serum creatinine concentration of each group was 1.2 +/- 0.1 mg/dl in the control, 14.1 +/- 0.9 mg/dl in predialysis, 13.5 +/- 1.3 mg/dl in HD and 14.7 +/- 0.9 mg/dl in CAPD groups. The level of IL-2 in the predialysis group was markedly lower compared to the control, HD and CAPD groups (as 3.1 +/- 0.8 unit vs. 8.8 +/- 2.2 unit, 11.8 +/- 3.0 unit and 14.9 +/- 3.4 unit, respectively, p < 0.05); the difference between the control and dialytic groups was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Interleukin 2 (IL2) is an important regulator of the immune system. In this report, we have analysed five human melanoma cell lines expressing the IL2R for their ability to secrete IL2. In the M14 melanoma cell line, we observed the appearance of the 0.9 kb transcript specific for the IL2 gene, 72 h after subculture, and the secretion of a biologically active IL2 which specifically sustains the proliferation of the IL2 dependent murine lymphoid cell line CTLL2. In M14 cells, IL2 gene activation is transient as in lymphoid cells but is not inhibited by the immunosuppressive drugs cyclosporine-A and FK506 which are effective on PHA-blasts. In M14 cells, recombinant IL2 (36 pM) induces the down modulation of ICAM-1 expression at the surface of M14 cells. Overnight incubation of these cells with polyclonal anti-IL2 antibodies leads to an increased expression of ICAM-1 and a decreased membrane detection of the IL2R alpha, suggesting the existence of an autocrine/paracrine loop involved in the surface expression of these antigens. A decreased expression of the ICAM-1 protein could help some melanoma cells to escape from cytolytic recognition and therefore favour their metastasis.
A new acylated glycoside isolated from the roots of Aristolochia contorta (Aristolochiaceae), has been characterized as aristolactam N-(6'-trans-p-coumaroyl)-beta-D-glucopyranoside [2]. Aristolactam-N-beta-D-glucopyanoside [1] was also isolated from the same source. Compound 2 showed relatively significant antibacterial activity against Gram-positive bacteria, based on disc diffusion and dilution methods.