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Biomedical subjects

P C Lai

Publications and source records attributed to P C Lai.

At least 19 recordsLinked to original sources
PubMed2005

Interleukin-11 reduces renal injury and glomerular NF-kappa B activity in murine experimental glomerulonephritis.

BACKGROUND/AIMS: There is now considerable evidence implicating T cells and macrophages in glomerular injury in crescentic glomerulonephritis. Recently, it has been shown that interleukin-11 (IL-11) has an immune modulatory function through its effect on both macrophages and T cells. We, therefore, examined the therapeutic effect of IL-11 in a murine model of experimental glomerulonephritis. METHOD: Accelerated nephrotoxic nephritis was induced in C57BL/6 mice. IL-11 at a dose of 0.5 mg/kg/day (n = 10) in vehicle was given daily subcutaneously from the day of sensitization until day 14 after initiation of glomerulonephritis. Control mice (n = 10) received injection of vehicle alone with the same schedule. RESULTS: IL-11 treatment markedly decreased albuminuria (6.2 +/- 1.9 vs. 18.2 +/- 4.5 mg/day, p < 0.05), the number of glomerular macrophages (1.1 +/- 0.2 vs. 1.7 +/- 0.3 cells/glomerular cross-section, p < 0.05) and glomerular fibrin deposition (fibrin score 0.9 +/- 0.3 vs. 2 +/- 0.3, p < 0.05). There was no difference in the glomerular T cell numbers between the IL-11-treated and the vehicle group. Glomerular NF-kappaB activity was markedly suppressed by 75% in the treated group (p = 0.0015). CONCLUSION: In this study, we provide the first in vivo evidence that IL-11 treatment decreases glomerular NF-kappaB activity and reduces renal injury in experimental glomerulonephritis.

Albuminuria↗
PubMed2004

Understanding the spatial clustering of severe acute respiratory syndrome (SARS) in Hong Kong.

We applied cartographic and geostatistical methods in analyzing the patterns of disease spread during the 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong using geographic information system (GIS) technology. We analyzed an integrated database that contained clinical and personal details on all 1,755 patients confirmed to have SARS from 15 February to 22 June 2003. Elementary mapping of disease occurrences in space and time simultaneously revealed the geographic extent of spread throughout the territory. Statistical surfaces created by the kernel method confirmed that SARS cases were highly clustered and identified distinct disease "hot spots." Contextual analysis of mean and standard deviation of different density classes indicated that the period from day 1 (18 February) through day 16 (6 March) was the prodrome of the epidemic, whereas days 86 (15 May) to 106 (4 June) marked the declining phase of the outbreak. Origin-and-destination plots showed the directional bias and radius of spread of superspreading events. Integration of GIS technology into routine field epidemiologic surveillance can offer a real-time quantitative method for identifying and tracking the geospatial spread of infectious diseases, as our experience with SARS has demonstrated.

Databases, Factual↗
PubMed1997

Glomerular transforming growth factor-beta1 mRNA as a marker of glomerulosclerosis-application in renal biopsies.

As transforming growth factor-beta1 (TGF-beta1) is implicated in the pathogenesis of glomerulosclerosis, the aim of the study was to demonstrate if levels of glomerular TGF-beta1 mRNA in renal biopsies correlated with glomerulosclerosis. Glomeruli were collected by microdissection from renal biopsies in patients with membranous nephropathy, lupus nephritis, diabetic nephropathy, minimal change disease and IgA nephropathy presented by proteinuria when serum creatinine was <3 mg%. Glomerular mRNAs were reverse transcribed and TGF-beta1, alpha2(IV) collagen, beta-actin cDNA quantitated by competitive polymerase chain reaction (PCR). By semiquantitative electron microscopy, a 3.5-fold increase of glomerular TGF-beta1/beta-actin mRNA ratio in the moderate sclerotic group (n = 23, p < 0.01) and a 1.5-fold increase in the mild sclerotic group (n = 22, p < 0.05) were observed when compared to the minimal sclerotic group (n = 12). A concordant increase of glomerular alpha2(IV) collagen mRNA was found with 2.2- and 1.3-fold in moderate and mild sclerotic groups, respectively. The TGF-beta1/beta-actin mRNA ratios were highest in membranous nephropathy (466.4 +/- 133.4, n = 11), followed by lupus nephritis (394.9 +/- 94.8, n = 12) and diabetic nephropathy (333.2 +/- 97.6, n = 10). Patients with minimal change disease(233.1 +/- 54.1, n = 15)and IgA nephropathy(185.3 +/- 39.6, n = 9) had low levels. The degree of glomerulosclerosis in each group followed the TGF-beta1/beta-actin mRNA ratios indicating that the level is the major determinant ofglomerulosclerosis but not the disease entities. Glomerular TGF-beta1/beta-actin mRNA ratio did not correlate with clinical parameters such as the urinary protein excretion and creatinine clearance. These results suggest that glomerular TGF-beta1/beta-actin mRNA ratio may be used as a marker of glomerulosclerosis in renal biopsy to reflect the local sclerotic process.

Actins↗
PubMed1996

Peritoneal nitric oxide is a marker of peritonitis in patients on continuous ambulatory peritoneal dialysis.

Nitric oxide plays an important role in mediating the inflammatory process. The aim of this study was to evaluate if nitric oxide production was increased during peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD), and the association with the prognosis. The study population comprised 21 patients with 22 episodes of peritonitis. Fifteen patients without peritonitis were controls. Nitrate was measured by HPLC and nitrite by the Griess method, to reflect nitric oxide production. Peritoneal dialysate effluent and plasma were collected from six patients during peritonitis and 1 week after treatment to study changes in dialysate:plasma ratio. In 15 patients, nitrite was measured during peritonitis and every 3 days for 2 weeks or until normalized for evolutional changes. The dialysate:plasma ratios of nitrate and nitrite during peritonitis were reduced 26% and 41.5%, respectively, after 1 week of treatment, indicating the peritoneal production of nitric oxide during peritonitis. In the evolutional study, a 5.1-fold increase of peak nitrite levels in bacterial peritonitis (n = 13) and a 2.5-fold increase in fungal peritonitis (n = 3) were observed compared to controls. Nitrite gradually declined to control levels (9.3 +/- 7.2 days) after effective antibiotic treatment, but took longer than to normalize leukocyte count in the peritoneal dialysate effluent (3.9 +/- 1.9 days). In four patients with refractory peritonitis (Candida infection in three, Acinetobacter infection in one), the nitrite levels remained elevated 2-fold despite treatment, and the catheters were removed. It is concluded that nitrite levels in peritoneal dialysate effluent may serve as a marker to assess treatment efficacy in CAPD patients with peritonitis.

Acinetobacter Infections↗
PubMed1994

Efficacy of intravenous and subcutaneous erythropoietin in patients on hemodialysis and continuous ambulatory peritoneal dialysis.

We carried out our study with 54 hemodialysis patients and 11 CAPD patients. The hemodialysis patients were divided into five groups. Group 1 & group 2 received intermediate doses of erythropoietin ranging from 150 U/Kg/wk to 180 U/Kg/wk. Group 3, group 4 and group 5 received low doses of erythropoietin ranging from 75 U/Kg/wk to 90 U/Kg/wk. While group 1 & group 4 received erythropoietin subcutaneously, group 2 & group 3 received erythropoietin intravenously. The CAPD patients all received subcutaneous erythropoietin. The efficacy of the erythropoietin therapy was evaluated by (1) the early response rate, (2) the late response rate, (3) the time to reach the target hematocrit, (4) the therapeutic cumulative dose, and (5) the maintenance dose. We concluded that: (1) dose is the prime factor determining the rate and ratio of patients response to erythropoietin. (2) subcutaneous administration is more effective than the intravenous route resulting in a 20% to 30% dose-reduction effect, and (3) CAPD patients had a better erythropoietin response than the hemodialysis patients. A larger study is necessary to confirm this finding.

Adult↗
PubMed1986

Fetal-maternal transfer of [H3]-6 beta-hydroxycortisol in the pregnant ewe.

Distribution and fetomaternal transfer of 6 beta-hydroxycortisol (6 beta-OHF) was studied using serial sampling following injection of tritium labelled 6 beta-OHF into various fluid compartments in the chronically cannulated unaesthesized pregnant ewe. There was a rapid transfer of 6 beta-OHF from the fetal circulation into amniotic fluid and maternal blood. In contrast, the maternal----fetal transfer of this steroid metabolite was considerably less. The sequence of appearance of 6 beta-OHF in fetal blood and amniotic fluid following injection into maternal blood suggests that this steroid is first transferred across the placenta to fetal blood before gaining entry into the amniotic fluid space. The half-lives of 6 beta-OHF after initial equilibration in maternal plasma, fetal plasma and amniotic fluid were 2.0 h, 5.1 h and 8.9 h respectively. The amniotic sac appears to contain a relatively static pool of 6 beta-OHF and may act as a "trap" for 6 beta-OHF in the ovine conceptus.

Amniotic Fluid↗
PubMed1984

Distribution of alpha-fetoprotein in fetal plasma and in amniotic and allantoic fluids of the pig.

The concentration of AFP in the plasma of fetal pigs was highest in early gestation (Days 15-30) and declined with advancing gestation. This pattern was comparable to those observed in other mammals with similar lengths of gestation. In contrast, allantoic and amniotic fluid AFP concentrations were highest during the middle third of gestation but these concentrations were much lower than those in fetal plasma throughout gestation. The allantois appears to be a significant distribution space for AFP in early gestation.

Allantois↗
PubMed1983

Distribution of acute-phase alpha 2-macroglobulin in rat fetomaternal compartments.

Rat acute-phase alpha 2-macroglobulin (AP alpha 2M) concentration was measured by radioimmunoassay in maternal serum, fetal plasma, maternal liver, fetal liver, and amniotic fluid as a function of gestational and neonatal age. The concentration profiles of AP alpha 2M in maternal serum and fetal plasma displayed two peaks, one in early gestation and another during late gestation. Synthesis of AP alpha 2M was confirmed by the immunoprecipitation of [35S]methionine incorporated into cultures of selected tissues. The following observations were made. 1) Maternal serum concentrations of AP alpha 2M were higher than those observed in fetal plasma in early gestation. This was attributable to a high level of maternal AP alpha 2M synthesis in metrial gland which was absent in liver and moderate in yolk sac. 2) In late gestation fetal plasma concentrations of AP alpha 2M greatly exceeded those observed in maternal serum. This could be explained by the pronounced synthesis of AP alpha 2M in fetal liver that was not apparent in maternal liver or yolk sac. 3) During labor, a transient increase in AP alpha 2M concentration was observed in maternal serum and fetal plasma. 4) During lactation a moderately elevated maternal serum concentration of AP alpha 2M was maintained. 5) Amniotic fluid concentration of AP alpha 2M was very low throughout gestation, which indicated that the fetal glomerulus was relatively impermeable to this large protein. It is concluded that in early gestation a principal maternal source of AP alpha 2M appears to be the metrial gland, whereas in late gestation fetal liver is a major source of AP alpha 2M appearing in fetal plasma from where some of this macroglobulin is speculated to be transported to the maternal circulation.

Aging↗
PubMed1982

Proteins in cerebrospinal fluid and plasma of fetal pigs during development.

The concentrations of total protein, alpha-fetoprotein, fetuin, transferrin and albumin have been measured in cerebrospinal fluid (CSF) and plasma of fetal pigs from 26 to 109 days gestation. Plasma total protein concentration was lowest in the youngest fetuses but thereafter it was between 1,500 and 2,200 mg/100 ml. alpha-Fetoprotein was the predominant plasma protein early in development but its concentration declined throughout the fetal period. alpha-Fetoprotein, fetuin and transferrin accounted for over 65% of the total protein concentration at all fetal ages. Albumin was not detectable in either plasma or CSF at 26 days and did not account for more than 10% of total plasma protein concentration at later stages of gestation; in contrast fetuin was the major protein in plasma (and CSF) later in fetal development. In CSF the concentration of fetuin was highest (178 +/- 8 mg/100 ml) at 26 days. The concentrations of total protein (961 +/- 95 mg/100 ml), alpha-fetoprotein (406 +/- 77 mg/100 ml) and transferrin (195 +/- 19 mg/100 ml) were highest at 31 days after which the concentration of all the main proteins fell very considerably. Albumin was first detected in CSF at 38 days and contributed less than 10% of total protein concentration at later fetal ages. Possible origins of plasma proteins in fetal CSF are discussed. Differences in CSF: plasma ratios for different proteins are consistent with a specific transfer mechanism between their two compartments; but synthesis by fetal choroid plexus or brain has not been excluded.

Animals↗
PubMed1981

Distribution of bovine fetuin and albumin in plasma, allantoic and amniotic fluids during development.

A radioimmunoassay for bovine fetuin was developed and its specificity and validity established. Albumin was measured by radial-immunodiffusion assay. Fetuin levels in fetal plasma increased from 10 to 15 mg/ml between 4 and 8 months of gestation; albumin levels remained higher than fetuin. Neonatal plasma fetuin levels rapidly declined during the first 14 days post partum, coincident with a marked reciprocal increase in albumin levels. In allantoic fluid fetuin and albumin concentrations reached a peak at 7 months but fetuin values were always higher. In amniotic fluid both proteins peaked at 8 months; albumin levels were similar to those in allantoic fluid but fetuin values remained consistently lower than those in allantoic fluid throughout gestation. Fetuin levels in maternal plasma declined from 0.7 to 0.4 mg/ml between 1 month and term. We conclude that (1) at term there is an abrupt change from fetuin synthesis to increased albumin synthesis by the neonatal liver; (2) fetuin appears to be preferentially accumulated in the allantois whereas albumin is equally concentrated in the allantois and amnion.

Allantois↗
PubMed1979

Distribution of alpha 1-fetoprotein in fetal plasma, allantoic fluid, amniotic fluid and maternal plasma of cows.

Maximal concentrations of AFP, measured by RIA, were obtained in fetal plasma and amniotic and allantoic fluid between the 3rd and 4th month of gestation, with levels declining thereafter until term. AFP values in maternal plasma were unchanged. Throughout gestation, AFP values were higher in allantoic than in amniotic fluid and the ratio of allantoic fluid/amniotic fluid AFP was significantly correlated with gestational age.

Allantois↗
PubMed1978

Bovine fetus-specific serum proteins. Purification and characterization of alpha1-fetoprotein and immunological identification of alpha2- and beta-fetoproteins.

Bovine alpha1-fetoprotein was isolated from fetal calf serum by successive procedures of concanavalin A-Sepharose chromatography, DEAE-Sephadex chromatography, SP-Sephadex chromatography and preparative disc polyacrylamide gel electrophoresis. The bovine alpha1-fetoprotein preparation was considered homogeneous by several physicochemical and immunochemical criteria. Bovine alpha1-fetoprotein has a molecular weight of 68 000 with an amino acid composiotn similar to that of other mammalian alhpa1-fetoprotein. In addition, bovine alpha1-fetoprotein was shown to exist as two distinct variants on the basis of carbohydrate heterogeneity. alpha2-Fetoprotein and a new beta-fetoprotein were immunologically identified in fetal calf serum. These fetoproteins, like alpha1-fetoprotein, were not detectable in non-pregnant cow serum by immunoelectrophoresis.

Amino Acids↗