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Biomedical subjects

K N Lai

Publications and source records attributed to K N Lai.

At least 19 recordsLinked to original sources
PubMed1999

Rates of nucleotide substitution in angiosperm mitochondrial DNA sequences and dates of divergence between Brassica and other angiosperm lineages.

We obtained 16 nucleotide sequences ( approximately 1400 bp each) of the first intron of the mitochondrial (mt) gene for NADH subunit 4 (nad4) from 10 species of Brassicaceae. Using these new sequences and five published sequences from GenBank, we constructed a phylogenetic tree of the Brassicaceae species under study and showed that the rate of nucleotide substitution in the first intron of nad4 is very low, about 0.16-0.23 x 10(-9) substitution per site per year, which is about half of the silent rate in exons of nad4. The ratios of substitution rates in this intron, ITS, and IGS are approximately 1:23:73, where ITS is the nuclear intergenic spacer between 18S and 25S rRNA genes and IGS is the intergenic spacer of 5S rRNA genes. A segment (335 bp) in the first intron of nad4 in Brassicaceae species that is absent in wheat was considered as a nonfunctional sequence and used to estimate the neutral rate (the rate of mutation) in mtDNA to be 0.5-0.7 x 10(-9) substitution per site per year, which is about three times higher than the substitution rate in the rest of the first intron of nad4. We estimated that the dates of divergence are 170-235 million years (Myr) for the monocot-dicot split, 112-156 Myr for the Brassicaceae-Lettuce split, 14.5-20.4 Myr for the Brassica-Arabidopsis split, and 14.5-20.4 Myr for the Arabidopsis-Arabideae split.

Base Sequence↗
PubMed1999

Increased sialylation of polymeric immunoglobulin A1: mechanism of selective glomerular deposition in immunoglobulin A nephropathy?

Immunoglobulin A nephropathy (IgAN) is characterized by raised serum IgA and predominant mesangial IgA deposits of polymeric nature. The abnormal glycosylation of the carbohydrate moieties in the hinge region of the IgA molecule has recently attracted much attention. In this study we investigated the galactosylation and sialylation of monomeric and polymeric IgA1 isolated from patients with IgAN. Total IgA1 in serum samples from patients with IgAN or from healthy controls was isolated with a jacalin-agarose column as jacalin-bound protein (JBP). Monomeric and polymeric IgA1 were distinctly separated by fast protein liquid chromatography. Lectin binding assays were designed to examine the sialylation and the expression of terminal galactose and N-acetyl galactosamine of the O-linked carbohydrate in the hinge region of the IgA molecule. Reduced terminal galactosylation was demonstrated in serum IgA and monomeric IgA1 isolated from patients with IgAN as compared with results in healthy control subjects. However, a reduction in terminal galactosylation was not found in polymeric IgA1 isolated from patients with IgAN. Instead, increased sialylation of IgA1 (alpha2-3 linked to galactose) was demonstrated in polymeric IgA1. This abnormality of IgA1 could bear considerable implication on the pathogenesis of IgAN, because the masking effect of sialic acid may hinder the clearance of polymeric IgA1 by the asialoglycoprotein receptor (ASGP-R) of the liver cells. An increase in the sialylated content would also render the polymeric IgA from patients with IgAN more anionic. These immunochemical properties may contribute to the selective glomerular deposition of polymeric IgA1 in IgAN.

Adult↗
PubMed1999

Comparison of double-bag and Y-set disconnect systems in continuous ambulatory peritoneal dialysis: a randomized prospective multicenter study.

We performed a multicenter, single-blinded, prospective randomized study on the use of a double-bag disconnect system (B) versus a Y-set disconnect system (Y). The peritonitis rate, exit site infection, clinical outcome, and patients' acceptance to the procedure were assessed. A total of 120 new end-stage renal failure patients of three regional hospitals were randomized: 60 each to the B and the Y systems. The results of 60 patients on the B system and 51 on the Y system were analyzable. They were followed up for a median of 16 months. Peritonitis rates for the B and the Y systems were 33.5 and 29.4 patient-months per episode, respectively. Exit site infection rates for the B and Y systems were 17.4 and 16.0 patient-months per episode, respectively. Four catheters were removed in each group. Patients on the B system were hospitalized for 2.1 days per patient per year related to peritonitis and exit site infection, and those on the Y system were hospitalized for 1.2 days. There was no significant difference between the B and Y systems in the incidences of peritonitis (all causes and those due to coagulase-negative staphylococci), exit site infection, and in hospitalization days. However, there was a higher percentage of gram-positive infections in the Y system (52%) than in the B system (32%) and a lower percentage of gram-negative infections in the Y system (16%) than in the B system (32%). Patients on the B system had a better acceptance of the procedure than patients on the Y system, as assessed by a six-item, 10-point questionnaire (total score, 43.1 +/- 10.2 v 37.6 +/- 9.4; P < 0.005 at 1 month; 44.6 +/- 9.1 v 39.8 +/- 8.6; P < 0.01 at 6 months). From this study, it is concluded that the B and Y systems are similar in the incidences of peritonitis and exit site infection, although the B system is better accepted by patients. This is probably the first multicenter randomized study comparing the double-bag and Y-set disconnect system using only new patients who had never used other systems of continuous ambulatory peritoneal dialysis.

Adult↗
PubMed1999

Increased production of hyaluronan by peritoneal cells and its significance in patients on CAPD.

Hyaluronan (HA) is a polysaccharide that forms a critical component of extracellular matrices. HA is present in high concentrations in tissues undergoing remodeling and morphogenesis, and it appears to have an important role in the early stages of wound healing. Here, we studied the level of HA in the peritoneal dialysate effluent (PDE) from 116 stable continuous ambulatory peritoneal dialysis (CAPD) patients. Longitudinal studies over a period of 6 weeks were performed in seven of these patients who developed peritonitis. The median HA level in PDE from these patients was 154.6 microg/L (range, 29.7 to 820.2 microg/L). Dialysate level of HA increased with age of the patients, but no such correlation was shown between HA level in PDE and duration of CAPD treatment or previous episodes of peritonitis. Patients with high or average peritoneal membrane transport of small solutes had a higher HA level in the PDE than those with a low peritoneal membrane transport (P = 0.046). A significant correlation was observed between PDE level of HA and interleukin-1beta (IL-1beta) or IL-6. The plasma level of HA in these patients was significantly greater than that of healthy controls (P < 0.0001), yet the plasma concentration of HA was only 85% that of the PDE concentration. In CAPD patients with peritonitis, there was a sharp increase in the PDE levels of HA, IL-1beta, and IL-6. These values decreased progressively with resolution of peritonitis. The changes in the PDE levels of HA closely followed those of IL-1beta or IL-6. In vitro [3H]-glucosamine incorporation studies suggest that the main bulk of HA is derived from synthesis by the peritoneal mesothelial cells, whereas the amount synthesized by macrophages is trivial. We conclude that elevated levels of HA found in the PDE of stable CAPD patients originate from increased synthesis by peritoneal mesothelial cells. This event may serve as a marker of regeneration and remodeling of the peritoneal lining.

Adult↗
PubMed1999

Lymphocyte subsets in renal allograft recipients with chronic hepatitis C virus infection.

BACKGROUND: The pathogenetic mechanisms of chronic hepatitis C virus (HCV) infection in renal allograft recipients are not well established. This study aimed to examine the relationship between altered immune status and HCV-related liver disease, by determining the changes in peripheral blood lymphocyte and natural killer (NK) cell subsets in these subjects. METHODS: Peripheral blood lymphocyte, NK cell and activation markers were detected by flow cytometry in renal allograft recipients with (TpC+) or without (TpC-) HCV infection, and compared with age- and sex-matched patients with post-transfusional chronic HCV infection (TfC+) and healthy controls. RESULTS: CD19+ cells were reduced in renal allograft recipients compared with controls. TpC+ subjects had increased CD3+CD8+ cells compared with controls, and increased CD3+DR+ cells but reduced CD4+ CD38+ and CD3-CD16/56+ cells compared with controls as well as TfC+ patients. TfC+ patients and controls had similar numbers and proportions for the lymphocyte subsets and NK cells. Chronic liver disease in HCV-infected renal allograft recipients was associated with increased CD3+CD16/56+ cells but reduced CD4+CD38+ cells. Reduction of CD3-CD16/56+ cells was noted in TpC+ subjects without liver disease. Yet among post-transfusional (TfC+) subjects this was associated with chronic hepatitis. CONCLUSIONS: Peripheral blood suppressor/cytotoxic T lymphocytes are increased, whereas activated helper/inducer T lymphocytes and NK cells are reduced, in renal allograft recipients with HCV infection. Increased non-MHC-restricted cytotoxic T cells and reduced NK cells are associated with the presence or absence of liver disease respectively. These data suggest that immune mechanisms are important in the pathogenesis of chronic hepatitis C after renal transplantation.

Adult↗
PubMed1998

Coexistence of Kaposi's sarcoma and tuberculosis in a renal transplant recipient.

BACKGROUND: We describe a case of Kaposi's sarcoma that developed in a renal transplant recipient as early as 5 months after the transplant. METHOD: The Kaposi's sarcoma evolved in an aggressive manner, involving the oral mucosa, the cervical and mediastinal lymph nodes, the gastrointestinal tract, and possibly the lung. Histological features of tuberculosis were also detected incidentally on an excisional biopsy of the lymph node. The patient was given 12 months of antituberculous chemotherapy. At the same time, immunosuppression was gradually tapered over a 2- to 3-week period. RESULTS: Despite the aggressive nature of the disease, the Kaposi's sarcoma regressed completely without the institution of chemotherapy. The patient remained disease-free after a follow-up period of 30 months. The kidney allograft, however, was rejected and the patient required dialysis again. CONCLUSION: Although lymphadenopathy is a well-recognized feature in organ transplant recipients who develop Kaposi's sarcoma, one has to watch out for other coexisting diseases, such as tuberculosis, lymphoma, and cytomegalovirus infection.

Adult↗
PubMed1998

Gene transcription and synthesis of adrenomedullin by cultured human renal cells.

Adrenomedullin (ADM) is a novel 52 amino acid peptide with a potent vasodilator effect. Gene expression of ADM is found in human kidney but the exact cell source in the kidney is uncertain. Its plasma level is raised in association with changes in sympathetic nervous activity and body fluid volume in hypertension and chronic renal failure. Herein, we examined the presence of mRNA encoding for ADM in cultured human glomerular cells. Adrenomedullin in cell culture supernatant was measured by a radio-immunoassay (with a detection level of 3.2 pmol/l). Adrenomedullin mRNA was found in cultured mesangial and glomerular epithelial cells as well as in vascular endothelial cells. Supernatant levels of ADM for cultured mesangial and glomerular epithelial cells were 21.2 and < 3.2 pmol/l respectively. Contrary to vascular smooth muscle cells, the gene expression for ADM in mesangial cells was up-regulated when incubated with increasing concentration of TNF-alpha or fetal bovine serum (FBS) but this effect was not observed with very high concentration. Parallel results were observed in adrenomedullin levels in supernatant from mesangial cell cultures. Forskolin, captopril, or TGF-beta had no effect on the transcription or synthesis of ADM in mesangial cells. The gene expression for ADM in glomerular epithelial cells was down-regulated when incubated with increasing concentration of TNF-alpha, forskolin or FBS. The ADM levels in all supernatant from resting glomerular epithelial cell cultures were < 3.2 pmol/l. Recent murine data show that ADM stimulates the release of cAMP but suppresses mitogenesis in cultured mesangial cells. Our results suggest ADM is synthesized by mesangial cells in an autocrine fashion and the peptide may potentially be involved in intra-renal blood pressure control.

Adrenomedullin↗
PubMed1998

Treatment of fibrosing cholestatic hepatitis with lamivudine.

Fibrosing cholestatic hepatitis is a histological variant of hepatitis B virus infection with a high rate of mortality. We describe a patient who acquired acute hepatitis B virus infection 8 months after renal transplantation. Clinical features of rapidly progressive liver failure, indicated by prolonged prothrombin time (57 seconds) and increased bilirubin (40.4 mg/dL) and ammonia (129 mumol/L) concentrations, were accompanied by an extremely high serum HBV DNA level (2.153 x 10(6) pg/mL). Liver biopsy specimen showed fibrosing cholestatic hepatitis with widespread balloon degeneration of hepatocytes, focal hepatocyte loss, bile stasis, periportal fibrosis, mild lymphocytic infiltration, and strongly positive immunohistochemical staining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen. Lamivudine therapy suppressed HBV DNA to < 10 pg/mL within 4 weeks, which was followed by gradual recovery of liver function from a state of hepatic precoma. Twenty-four months after the onset of hepatitis, the patient had normal prothrombin time and bilirubin, transaminase, and albumin levels. She remained HBsAg positive and hepatitis B e antigen negative. Renal allograft function was stable, with a creatinine level of 1.52 mg/dL. HBV DNA remained suppressed after 22 months of lamivudine therapy. Our experience shows that fibrosing cholestatic hepatitis and liver failure caused by HBV infection can be successfully treated with lamivudine.

Adult↗
PubMed1998

Increased ascitic level of hyaluronan in liver cirrhosis.

Hyaluronan (HA) is a polysaccharide that forms a critical component of extracellular matrixes. It is present in high concentrations in tissues undergoing remodeling and morphogenesis. Serum HA is elevated in patients with chronic liver disease, and this has been considered to be caused by impaired degradation by the liver endothelial cells. We studied the level of HA in the ascitic fluid and plasma from 27 patients with cirrhotic ascites. These values were compared with peritoneal dialysate effluent (PDE) and plasma from 33 patients with uremia who were undergoing continuous ambulatory peritoneal dialysis (CAPD). The median HA levels in ascitic fluid and plasma from our 26 patients with cirrhosis were significantly higher than corresponding PDE and plasma values from the 33 CAPD patients (p < 0.0001). The median peritoneal/plasma ratios of creatinine, albumin, and immunoglobulin G in either cirrhotic or CAPD patients were less than unity. In contrast, the median peritoneal/plasma ratios of HA in both groups of patients exceeded one with a higher peritoneal/plasma ratio of HA in patients with cirrhosis (p = 0.0035). A significant correlation was observed between the ascitic level of HA and interleukin-1beta, interleukin-6, or transforming growth factor-beta. Our in vitro cell culture studies revealed that HA is synthesized by both mesothelial cells and macrophages. We observed an additive effect in the synthesis of HA by mesothelial cells when the macrophage-conditioned medium was added to the RPMI culture medium. We conclude that a high level of HA is found in ascites from patients with cirrhosis. Our results strongly suggest that simultaneous increased synthesis of HA by the peritoneal cells and a reduction of degradation by liver endothelial cells occur in these patients with cirrhosis with ascites. This event of increased HA synthesis may be contributory to remodeling and regeneration of the peritoneal lining.

Adult↗
PubMed1998

The interleukin-5 messenger RNA expression in a patient with idiopathic hypereosinophilic syndrome.

Interleukin-5 has a specific role in various eosinophilic activities. It is the predominant cytokine produces by activated T-lymphocytes isolated from patients with idiopathic hypereosinophilic syndrome. We studied a young patient suffering from idiopathic hypereosinophilic syndrome who presented with Horner's syndrome, peripheral neuropathy and skin ulcers. The IL-5 gene expression by CD4+ T-lymphocytes and the peripheral eosinophil count were raised. The skin ulcers continued to deteriorate despite a swift reduction of the IL-5 gene expression and peripheral eosinophil count following systemic corticosteroid treatment. We suggest that peripheral eosinophilia may not be responsible for the damage in skin lesions and more aggressive treatment may be required.

Adrenal Cortex Hormones↗
PubMed1998

Association of HLA class-II genes and anti-neutrophil cytoplasmic antibodies in Chinese patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is common in the West but rare in China. The genetic factor predisposing to the disease is unclear. Ulcerative colitis (UC) is found to be associated with HLA DR2 alleles in the West. Subgroups of UC patients have been further defined by the presence of anti-neutrophil cytoplasmic antibodies (ANCA). METHODS: We attempted to define the HLA class-II genes (DRbeta, DQalpha, DQbeta) and their relationship with ANCA in southern Chinese patients with UC. Patients were tested for class-II genes by restriction fragment length polymorphism and polymerase chain reactions. The indirect immunofluorescence test was used to detect ANCA in the sera. Ethnically matched normal controls were used for comparison. RESULTS: In ANCA-positive UC patients (n = 18) there was a strong association with HLA-DQalpha1c allele (P < 0.0001) when compared with controls (n = 104). This association was not found in ANCA-negative UC patients (n = 10) (P = 0.21). CONCLUSIONS: In Chinese UC patients positive ANCA is associated with the HLA-DQalpha1c allele, which is not the case in Caucasian patients.

Adult↗
PubMed1998

Gene expression of the renin-angiotensin system in human kidney.

BACKGROUND: Immunocytochemical studies have revealed that all components of the renin-angiotensin system are widely distributed in human tissues yet the information on the gene expression of the renin-angiotensin system in various types of cell remains scarce. OBJECTIVE: We explored the presence of a local renin-angiotensin system in human kidney. METHODS: We sought to determine the presence of messenger RNA (mRNA) encoding for renin, angiotensinogen, and angiotensin converting enzyme (ACE) in cultured human glomerular cells and human umbilical vein endothelial cells using a two-step polymerase chain reaction. The gene expression of the renin-angiotensin system in normal human kidney and in diseased kidney was studied by in-situ hybridization using synthetic oligonucleotides. RESULTS: By using a two-step polymerase chain reaction, renin, angiotensinogen, and ACE mRNA were found in cultured mesangial and epithelial cells but only ACE mRNA was present in human umbilical vein endothelial cells. Renin mRNA was detected in juxtaglomerular granular cells and also in glomerular and tubular epithelia in normal kidney by in-situ hybridization. A similar tubular, but not mesangial, distribution was found with angiotensinogen and ACE mRNA. In contrast, stronger signals for renin, angiotensinogen and ACE mRNA were detected in mesangial and epithelial cells of kidney tissues from hypertensive patients and from patients with renal pathology characterized by mesangial proliferation (immunoglobulin A nephropathy, diabetes mellitus, or lupus nephritis). CONCLUSIONS: That gene expression of the renin-angiotensin system occurs in resident glomerular cells supports the hypothesis that there is a local renin-angiotensin system in human kidney. Our findings support the previous speculation that the renin-angiotensin system could be a local factor involved in the progression of chronic renal failure and consequent development of hypertension.

Angiotensinogen↗
PubMed1998

A simple assessment of peritoneal transport in stable continuous ambulatory peritoneal dialysis patients.

We studied the peritoneal transport properties in 175 stable continuous ambulatory peritoneal dialysis (CAPD) patients seeking a simple and handy assessment of peritoneal permeability to small solutes. Measurement of creatinine in biological fluid was known to suffer from interference by high glucose concentration in the sample. Furthermore, the interference is also affected by the creatinine concentration of the specimen. Peritoneal transport properties were studied by determining the dialysate to plasma ratio of creatinine concentration (D/P) at the fourth hour of the peritoneal equilibration test, and the mass transfer area coefficient of creatinine (MTACCr) or glucose (MTACGlu). The ratio of glucose concentration in peritoneal dialysate effluent (PDE) at 4 and 0 h (G4/G0) was examined and compared with various peritoneal parameters. There were significant logarithmic correlations between D/P or G4/G0 with MTACCr (r=0.96 and 0.79, respectively, p < 0.0001). The correlation between G4/G0 and D/P was linear (r=-0.82, p < 0.0001). A fairly good agreement was present between G4/G0 and D/P by Bland and Altman's method. The bias was -0.93% with 95% confidence interval -23.29% to 21.43% of the measured value. Systematic error was found when D/P or G4/G0 were compared with MTACCr. D/P under estimated MTACCr in the high range. The reverse happened for G4/G0. Net ultrafiltration (NUF) also correlated with MTACCr, D/P and G4/G0 (r=-0.32, p < 0.001; -0.26, p < 0.01; and 0.16, p < 0.05, respectively. In conclusion, the use of G4/G0 as a measure of peritoneal transport in CAPD is an acceptable alternative to D/P. It is highly reproducible and avoids correction of interference when creatinine transport parameters are measured. Because of the logarithmic relations of G4/G0 (or D/P) with MTACCr, the former should not be directly converted to MTACCr. Such a simple measure of peritoneal permeability is, however, most convenient for serial monitoring and can be useful to detect early loss of ultrafiltration or solute clearance.

Creatinine↗
PubMed1998

Treatment of pulmonary embolism by subcutaneous low-molecular-weight heparin in a hemodialysis patient.

Low-molecular-weight heparin (LMWH) has been used in the prophylaxis and treatment of deep vein thrombosis. Data regarding the efficacy of this drug without subsequent use of oral anticoagulant in the treatment of pulmonary embolism is limited. Pulmonary embolism may complicate the use of central venous catheter in hemodialysis. We report a case of acute submassive pulmonary embolism complicating a central venous hemodialysis catheter in a dialysis patient. After the catheter was removed, the patient was treated successfully with subcutaneous injection of LMWH for three months. We conclude that LMWH is safe and effective for treatment of pulmonary embolism in patient on hemodialysis.

Adult↗
PubMed1998

Treatment of Takayasu's aortitis with percutaneous transluminal angioplasty and wall stent--a case report.

The authors describe a young woman who developed severe toxemia during pregnancy, requiring emergency lower segment cesarian section at 27 weeks of gestation. Postpartum angiography showed a discrete stenotic lesion of the abdominal aorta proximal to the origin of the renal artery. Angioplasty was performed, followed by the insertion of a wall stent at the site of the stenosis. Her hypertension control improved dramatically after the stenting. This is, so far, the first reported case using a wall stent following angioplasty to relieve abdominal aortic stenosis due to Takayasu's arteritis.

Adult↗