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H H Cheng

Publications and source records attributed to H H Cheng.

At least 55 records · Page 3Linked to original sources
PubMed1999

Oligomerization state influences the degradation rate of 3-hydroxy-3-methylglutaryl-CoA reductase.

The steady-state level of the resident endoplasmic reticulum protein, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), is regulated, in part, by accelerated degradation in response to excess sterols or mevalonate. Previous studies of a chimeric protein (HM-Gal) composed of the membrane domain of HMGR fused to Escherichia coli beta-galactosidase, as a replacement of the normal HMGR cytosolic domain, have shown that the regulated degradation of this chimeric protein, HM-Gal, is identical to that of HMGR (Chun, K. T., Bar-Nun, S., and Simoni, R. D. (1990) J. Biol. Chem. 265, 22004-22010; Skalnik, D. G., Narita, H., Kent, C., and Simoni, R. D. (1988) J. Biol. Chem. 263, 6836-6841). Since the cytosolic domain can be replaced with beta-galactosidase without effect on regulated degradation, it has been assumed that the cytosolic domain was not important to this process and also that the membrane domain of HMGR was both necessary and sufficient for regulated degradation. In contrast to our previous results with HM-Gal, we observed in this study that replacement of the cytosolic domain of HMGR with various heterologous proteins can have an effect on the regulated degradation, and the effect correlates with the oligomeric state of the replacement cytosolic protein. Chimeric proteins that are oligomeric in structure are relatively stable, and those that are monomeric are unstable. To test the hypothesis that the oligomeric state of the cytosolic domain of HMGR influences degradation, we use an "inducible" system for altering the oligomeric state of a protein in vivo. Using a chimeric protein that contains the membrane domain of HMGR fused to three copies of FK506-binding protein 12, we were able to induce oligomerization by addition of a "double-headed" FK506-like "dimerizer" drug (AP1510) and to monitor the degradation rate of both the monomeric form and the drug-induced oligomeric form of the protein. We show that this chimeric protein, HM-3FKBP, is unstable in the monomeric state and is stabilized by AP1510-induced oligomerization. We also examined the degradation rate of HMGR as a function of concentrations within the cell. HMGR is a functional dimer; therefore, its oligomeric state and, we predict, its degradation rate should be concentration-dependent. We observed that it is degraded more rapidly at lower concentrations.

Dimerization↗
PubMed1999

Application of AFLP markers to genome mapping in poultry.

The amplified fragment length polymorphism (AFLP) technique has been used to enhance marker density in the East Lansing reference chicken genome map, using a backcross family derived from a Red Jungle Fowl by White Leghorn mating with White Leghorn as the recurrent parent. To date, 204 AFLP markers have been added, expanding overall map coverage by about 25%. To the limits of our resolution, AFLP markers are distributed relatively evenly across the EL reference map. AFLP are about 60% as frequent in a cross within White Leghorns (line 7(2) x 6(3)) in comparison to the more divergent reference map population. Based on apparent identity of size, about 40% of the 7(2) x 6(3) cross AFLP fragments were also polymorphic in the reference map cross. Primer pairs in which one primer contains 3' extensions of three selective nucleotides and the other has two selective nucleotides successfully generated AFLP from chicken DNA, but such pairs appeared to amplify only a subset of those fragments to which they have an exact sequence match. Three different restriction enzymes with 4 bp recognition sites (TaqI, HinP1I and MspI) were found to work well with EcoRI as the rarer of the two AFLP restriction enzymes used, with HinP1I being the most effective of the three. AFLP markers are likely to provide an economical method with which to enhance framework linkage maps of chicken and probably other avian genomes.

Animals↗
PubMed1999

High resolution mapping and identification of new quantitative trait loci (QTL) affecting susceptibility to Marek's disease.

Marek's disease (MD) is a lymphoproliferative disease of chickens that costs the poultry industry approximately $1 billion annually. Genetic resistance to MD is gaining increased attention to augment vaccinal control as disease outbreaks occur more frequently. Previously, analysis of a 272 F2 White Leghorn resource population measured for many MD traits and genotyped for 78 microsatellite markers revealed two and four quantitative trait loci (QTL) with significant and suggestive association, respectively, to one or more MD associated traits. Additional genetic markers have since been scored on the MD resource population to increase QTL resolution and genome coverage. Saturation of four of the QTL regions with 17 markers revealed five new QTL while 32 markers extended the genome coverage by 400 + CM and uncovered three more QTL. QTL analysis by single-point and interval mapping algorithms agreed well when marker saturation was approximately 20 CM or less. Currently 127 genetic markers cover approximately 68% of the genome that contain up to 14 MD QTL associated to one or more MD trait; seven at the significant level and seven at the suggestive level. Individually each QTL accounts for 2-10% of the variation and, in general, resistance was dominant although the resistant allele may come from either parental line. This study suggests that a limited number of genomic regions play a major role in the genetic control of MD resistance. Markers linked to these loci may be useful for selection of MD resistant stock by the poultry industry following verification of the association within their breeding populations.

Animals↗
PubMed1999

Hyaluronan decreases peritoneal fluid absorption: effect of molecular weight and concentration of hyaluronan.

BACKGROUND: We have recently shown that the addition of hyaluronan to peritoneal dialysis solution could decrease the peritoneal fluid absorption rate, possibly through decreasing peritoneal tissue hydraulic conductivity. The physical-chemical properties of hyaluronan were found to be both molecular weight and concentration dependent. In this study, we investigated the effects of different molecular weight as well as different concentrations of hyaluronan on the peritoneal fluid kinetics. METHODS: A four-hour dwell study was performed in 48 male Sprague-Dawley rats (6 rats in each group) with 131I albumin (RISA) as an intraperitoneal volume marker. Each rat was intraperitoneally injected with 25 ml of 1.36% glucose dialysate alone (control) or with 0.01% hyaluronan (HA) with different molecular weights [85,000 (HA85K group), 280,000 (HA280K group), 500,000 (HA500K group), and 4,000,000 (HA4M group) molecular wt] or with a different concentrations of hyaluronan [(molecular wt 500,000); 0.01% (0.01% HA group), 0.05% (0.05% HA group), 0.1% (0.1% HA group), and 0.5% (0.5% HA group) hyaluronan]. RESULTS: The peritoneal fluid absorption rate (as assessed by the RISA elimination rate, KE) was significantly decreased in the HA500K and H4M groups as well as in all the different concentration groups (with molecular wt 500,000) as compared with the control group, resulting in significantly higher net fluid removal in these groups (except for the H4M group) as compared with the control group. In the 0.5% HA group (but not in the other hyaluronan groups), the direct lymphatic absorption (KEB) was also significantly decreased. The transcapillary ultrafiltration rate (Qu) was significantly lower in the HA4M group as compared with the control group but significantly higher in the 0.05% HA (and tended to be higher in the 0.1% HA group) as compared with the other groups. No difference in Qu was found between the 0.5% HA group as compared with the control group, despite a more marked decrease in KE in this group as compared with the H4M group. There were no significant differences in KE, Qu, and net fluid removal between the HA85K and HA280K groups and the control group. CONCLUSIONS: Our results suggest that (a) the addition of hyaluronan to dialysate could decrease peritoneal fluid absorption and thus increase the net ultrafiltration; this effect appears to be both size dependent and concentration dependent. (b) High molecular weight fraction of hyaluronan may also decrease the transcapillary Qu by decreasing tissue hydraulic conductivity. (c) A higher concentration of hyaluronan in dialysate resulted in a more marked decrease in peritoneal fluid absorption (absorption to peritoneal tissues as well as direct lymphatic absorption), possibly through both decreasing tissue hydraulic conductivity and increasing fluid viscosity. (d) Decreasing tissue hydraulic conductivity by adding a high concentration of hyaluronan to dialysate does not decrease the transcapillary ultrafiltration, possibly because the osmotic effect of hyaluronan may counterbalance the decrease in transcapillary ultrafiltration because of the decrease in tissue hydraulic conductivity.

Absorption↗
PubMed1999

High peritoneal residual volume decreases the efficiency of peritoneal dialysis.

BACKGROUND: Wide variation in peritoneal residual volume (PRV) is a common clinical observation. High PRV has been used in both continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis to minimize the time of a dry peritoneal cavity and to achieve better dialysis. However, the impact of PRV on peritoneal transport is not well established. In this study, we investigated the effect of PRV on peritoneal transport characteristics. METHODS: Peritoneal effluents were collected in 32 male Sprague-Dawley rats after a five-hour dwell with 1.36% glucose solution. Forty-eight hours later, a four hour dwell using 25 ml of 3.86% glucose solution and frequent dialysate and blood sampling was done in each rat with 125I-albumin as a volume marker. Before the infusion of the 3.86% glucose solution, 0 (control), 3, 6, or 12 ml (8 rats in each group) of autologous effluent (serving as PRV) was infused to the peritoneal cavity. RESULTS: After subtracting the PRV, the net ultrafiltration was significantly lower in the PRV groups as compared with the control group: 13.4 +/- 0.5, 12.0 +/- 1.0, 11.7 +/- 1.7, and 8.9 +/- 0.4 ml for 0, 3, 6, and 12 ml PRV groups, respectively (P < 0.001). The lower net ultrafiltration associated with higher PRV was due to (a) a significantly lower transcapillary ultrafiltration rate (Qu) caused by a lower osmotic gradient, and (b) a significantly higher peritoneal fluid absorption rate (KE) caused by an increased intraperitoneal hydrostatic pressure. No significant differences were found in the diffusive mass transport coefficient for small solutes (glucose, urea, sodium, and potassium) and total protein, although the dialysate over plasma concentration ratios values were higher in the high-PRV groups. The sodium removal was significantly lower in the PRV groups as compared with the control group (P < 0.01). CONCLUSION: Our results suggest that a high PRV may decrease net ultrafiltration through decreasing the Qu, which is caused by a decreased dialysate osmolality, and increasing the KE caused by an increased intraperitoneal hydrostatic pressure. The high volume of PRV also decreased the solute diffusion gradient and decreased peritoneal small solute clearances, particularly for sodium. Therefore, a high PRV may compromise the efficiency of dialysis with a glucose solution.

Animals↗
PubMed1999

Epidemiological study of human salmonellosis during 1991-1996 in southern Taiwan.

Within a 6-year period from January 1991 to December 1996, 249 patients of salmonellosis admitted to Kaohsiung Medical College Hospital were enrolled for clinical and microbiological analysis. The number of patients increased by year from 1991 (14 patients) to 1996 (79 patients), especially in the case of nontyphoid salmonellosis. There were 57 different serotypes isolated during these period. Salmonella typhimurium was the most common clinical serotype of human origin in southern Taiwan, followed by S. choleraesuis, S. schwanzengrund, and S. derby. Fever (81.1%), diarrhea (68.9%), and anorexia (44.6%) were the most common manifestations of human salmonellosis. Relative bradycardia was a more important feature in S. typhi group (100%) than nontyphoid salmonellosis. Leukocytosis, especially lymphocytosis, was found especially in nontyphoid, but not in typhoid salmonellosis. Elevated liver function tests were found in the most severe patients, such as S. choleraesuis and S. typhi infections. Malignancy (8.8%), especially hematological malignancy (5.2%), gastrointestinal diseases (8.8%), and diabetes mellitus (6.4%) were the common underlying diseases. Case fatality rate of human salmonellosis was 8% (20/249), especially high in S. choleraesuis group. The severity of underlying diseases may be the major cause in S. choleraesuis group. There was no fatal case with typhoid fever. Very high resistance rate to commonly used antimicrobial agents in nontyphoid Salmonella was noted in southern Taiwan with overall rates of resistance to ampicillin, 67.9%, chloramphenicol, 66.7%, and TMP/SMZ, 42.2%. The emergence of ciprofloxacin-resistant and multiresistant strains was also a major therapeutic problem in this study.

Humans↗
PubMed1999

Salmonella choleraesuis bacteremia in southern Taiwan.

Within a 6-year period from January 1991 to December 1996, 19 patients with Salmonella choleraesuis bacteremia were enrolled for clinical and microbiological analysis. Young children, the elderly and patients with hematological malignancy (36.8%), liver cirrhosis (26.3%), systemic lupus erythematosus (10.5%), chronic renal impairment (10.5%), and peptic ulcer (10.5%) were at high risk of this infection. The ratio of male to female was 3:1. Three cases (15.8%) were nosocomially acquired. Fever (89.5%), chills (57.9%) and anorexia (52.6%) were the most common clinical manifestations. Seven patients (36.8%) presented no gastrointestinal manifestations. Normal white blood cell count was noted in seven patients (36.8%), and neutropenia caused by underlying diseases or severe infection was found in six cases (31.6%). Various types of metastatic focal infections were found, such as septic arthritis, cutaneous infection, spontaneous bacterial peritonitis, and pneumonia. The severe immunocompromised status of patients and the high virulence of this pathogen may contribute to the high case fatality rate (21%). Higher resistance rate to commonly used antimicrobial agents was noted in ampicillin (94.7%), chloramphenicol (89.5%), and TMP/SMZ (63.8%). All strains of S. choleraesuis were susceptible to third-generation cephalosporins and fluoroquinolones. Generally, S. choleraesuis bacteremia should be taken into account in the differential diagnosis of sepsis in immunocompromised patients, even without gastrointestinal manifestations. The third-generation cephalosporins and fluoroquinolones may be the first choice for treatment of this invasive infections.

Adolescent↗
PubMed1999

Intraperitoneal addition of hyaluronan improves peritoneal dialysis efficiency.

BACKGROUND: It has been shown that hyaluronan (HA) can decrease peritoneal fluid absorption. It is not known, however, how various molecular weights and various concentrations of hyaluronan affect peritoneal fluid absorption rate. METHODS: A study of 4-hour dwells, with frequent dialysate and blood sampling, was performed in male Sprague-Dawley rats (6-7 rats in each group) with 131I albumin as an intraperitoneal volume marker. Each rat was infused intraperitoneally with 25 mL of 1.5% glucose solution alone or 1.5% glucose solution containing hyaluronan at various molecular weights (MW-85 kD, 280 kD, 500 kD, and 4 MD) or containing hyaluronan of MW 500 kD at various concentrations (0.01%, 0.05%, 0.1%, 0.5%). Two additional groups were infused with 40 mL of 1.36% glucose dialysate alone or 1.36% glucose dialysate with 0.01% hyaluronan (MW 500 kD) to test the effect of hyaluronan when high dialysate fill volume was used. RESULTS: Addition of 0.01% hyaluronan significantly decreased peritoneal fluid absorption rate (K(E)) (by 22%, p < 0.01). The decrease was more marked with hyaluronan at high MW or high concentration, or with high dialysate fill volume. The net ultrafiltration tended to be higher in all hyaluronan groups compared to their control groups except in the 4 MD group; this difference was mainly due to a lower K(E) in all the hyaluronan groups. The direct lymphatic flow was significantly decreased in the 0.5% HA group. The transcapillary ultrafiltration rate (Qu) was significantly lower in the 4 MD group as compared to the control group. No difference in Qu was found between the other groups as compared to their control groups. CONCLUSIONS: (1) Intraperitoneal addition of hyaluronan may increase net peritoneal fluid removal, mainly because hyaluronan decreases peritoneal fluid absorption rate. The decrease was more marked when high dialysate fill volume was used, indicating that intraperitoneal addition of hyaluronan can prevent the decreased net ultrafiltration caused by an increase in dialysate fill volume. (2) The decrease in peritoneal fluid absorption rate may be both MW-dependent and concentration-dependent: that is, a higher MW as well as a higher concentration of hyaluronan result in a more marked decrease in peritoneal fluid absorption rate. (3) Low concentrations of high MW hyaluronan may also decrease Qu. However, Qu did not decrease when high concentrations of hyaluronan were used despite a significant decrease in peritoneal fluid absorption rate.

Absorption↗
PubMed1999

Peritoneal fluid kinetics: comparison between polyglucose solution and albumin solution.

Polyglucose (PG) solution has been shown to be capable of inducing peritoneal ultrafiltration despite its hypo-osmolality. However, the mechanism of osmosis by PG is not clear. In this study, we compared the fluid kinetics of albumin (ALB) solution (thought to be an ideal solution that should induce ultrafiltration through colloid osmosis) and PG solution. A 4-hour dwell study with frequent sampling was conducted in Sprague-Dawley rats (six rats in each group). The study used 25 mL of dialysate buffer, 10% ALB dialysis solution, 15% ALB dialysis solution, 20% ALB dialysis solution, or 7.5% PG solution, with 131I albumin as an intraperitoneal volume marker. All solutions were prepared by adding ALB or PG to a base dialysis solution (without osmotic agent). The initial osmolality values of the five solutions were 250 mOsm/kg, 284 mOsm/kg, 300 mOsm/kg, 320 mOsm/kg, and 280 mOsm/kg, and the dialysate drainage volumes at 4 hours were 17.0 +/- 0.8 mL, 22.4 +/- 0.8 mL, 25.4 +/- 0.6 mL, 27.3 +/- 0.9 mL, and 26.3 +/- 0.6 mL (buffer, 10% ALB, 15% ALB, 20% ALB, and 7.5% PG groups, respectively). The higher initial osmolality in the ALB groups was partially due to the sodium content in the ALB powder. The intraperitoneal volume was decreasing in the 10% ALB group, rather stable in the 15% ALB group, but slowly increasing in the 20% ALB group. In the PG group, intraperitoneal volume decreased initially and then started to increase after 2 hours. This pattern was closely related to the increase in the dialysate osmolality (to higher than plasma level). At 4 hours, the dialysate osmolality was significantly higher (and higher than plasma level) in the PG group as compared to all the ALB groups. No differences in peritoneal fluid absorption rate were observed among the four treatment groups. In the 15% ALB and 20% ALB groups, the transcapillary ultrafiltration rate (Qu) was lower in the later part of the dwell than in the initial part of the dwell; in the PG group, the opposite pattern was observed. Our results suggest that the osmosis of albumin dialysis solution is different from the osmosis of polyglucose solution. Polyglucose solution induces net ultrafiltration only when the dialysate osmolality increase to higher than plasma level, suggesting that degradation of polyglucose may be important for effective ultrafiltration.

Albumins↗
PubMed1999

Vasodilatation by intraperitoneal addition of nitroprusside is not a model for high peritoneal transport.

It has been suggested that the peritoneal capillary is the major determinant for peritoneal fluid transport and that an increase in the number of peritoneal capillaries may be the reason for an increased peritoneal transport rate. In this study, we investigated the impact on peritoneal fluid and solute transport of vasodilatation (which may increase the number of perfused capillaries) by intraperitoneal addition of nitroprusside. A 4-hour dwell was performed in four groups of Sprague-Dawley rats (4-8 rats in each group) with 131I albumin as an intraperitoneal volume marker. Nitroprusside at concentrations of 0% (control), 0.0005%, 0.001%, and 0.002% was added to the 3.86% glucose solution before intraperitoneal infusion. Net ultrafiltration (NUF) was 13.2 +/- 0.6 mL, 14.5 +/- 0.7 mL, 13.4 +/- 0.9 mL, and 6.3 +/- 2.0 mL for the control group and the 0.0005%, 0.001%, and 0.002% nitroprusside groups, respectively. No significant differences in peritoneal fluid absorption rate (KE) were observed among the four groups. The intraperitoneal volume, transcapillary ultrafiltration rate (Qu), and peritoneal small-solute transport rate (glucose and urea) as assessed by diffusive mass transfer coefficient were significantly higher or tended to be higher in the 0.0005% nitroprusside group as compared to control. However, with further increase in the dose of nitroprusside, these parameters started to decrease as compared to the 0.0005% nitroprusside group, and NUF was significantly lower in the 0.002% nitroprusside group, conceivably suggesting a reduction in blood flow owing to the systemic effects of nitroprusside. Our study showed that: (1) a low dose of nitroprusside increased the peritoneal small-solute transport rate, but did not decrease peritoneal transcapillary ultrafiltration rate; (2) although a high dose of nitroprusside decreased peritoneal fluid removal, the decrease was not due to an increased small-solute transport rate, but more likely to a significant drop in peritoneal blood flow; (3) vasodilatation by nitroprusside did not change peritoneal fluid absorption rate. Overall, vasodilatation does not seem to produce a pattern of peritoneal fluid kinetics similar to that seen in high transporters, who have a higher peritoneal transport rate, lower transcapillary ultrafiltration rate, and higher peritoneal fluid absorption rate.

Animals↗
PubMed1999

Pharmacodynamic and pharmacokinetic studies of anthraquinone 2-carboxylic acid on passive cutaneous anaphylaxis in rats.

The objectives of this study are to describe the inhibitory effect of 9,10-anthraquinone 2-carboxylic acid (AQCA) on IgE-mediated passive cutaneous anaphylaxis (PCA) reaction, and the pharmacokinetics of AQCA. Pharmacodynamic assessments were performed at 0.5, 1 and 2 mg/kg (i.v.) and 5, 10 and 20 mg/kg (p.o) dose levels. In separate groups, pharmacokinetics were assessed at 5 mg/kg (i.v.) and 5, 10, and 20 mg/kg (p.o.) dose levels. Intravenous and oral administration of AQCA inhibited the PCA reaction in rats in a dose-dependent manner. The PCA-inhibitory activity of AQCA (20 mg/kg) lasted more than 12 hrs after oral administration. The oral bio-availability decreased with increasing dosage, from 96% (5 mg/kg) to 81% (10 and 20 mg/kg). The absorption after oral administration was prolonged with Tmax values ranging from 1 to 6 h; while t(1/2) (4.8-16 h) values appeared to be comparable. These results suggest that AQCA has a potent and long acting anti-PCA activity. It is likely to be therapeutically useful in the treatment of asthma.

Administration, Oral↗
PubMed1998

Synthesis and cytotoxicity of acetyl-4H,9H-naphtho[2,3-b]thiophene-4,9-diones.

Several new acetyl-4H,9H-naphtho[2,3-b]thiophene-4,9-diones were synthesized and evaluated for in vitro cytotoxicity by NCI against seven cancer cell types. 2,7-Diacetyl naphtho[2,3-b]thiophene-4,9-dione (9) showed significant cytotoxicity against leukemia cells with log GI50 values of -7.61 against SR cells and -7.18 against MOLT-4 cells. 3-Acetyl-naphtho[2,3-b]thiophene-4,9-dione (6) also demonstrated potent cytotoxicity in the latter cell line with log GI50 < -8.

Antineoplastic Agents↗
PubMed1998

A comprehensive microsatellite linkage map of the chicken genome.

A comprehensive linkage map of the chicken genome has been developed by segregation analysis of 430 microsatellite markers within a cross between two extreme broiler lines. The population used to construct the linkage map consists of 10 families with a total of 458 F2 individuals. The number of informative meioses per marker varied from 100 to 900 with an average of 400. The markers were placed into 27 autosomal linkage groups and a Z-chromosome-specific linkage group. In addition, 6 markers were unlinked, 1 of which was Z chromosome specific. The coverage within linkage groups is 3062 cM. Although, as in other species, the genetic map of the heterogametic sex (female) is shorter than the genetic map of the homogametic sex (male), the overall difference in length is small (1.15%). Forty-five of the markers represent identified genes or ESTs. Database homology searches with the anonymous markers resulted in the identification of a further 9 genes, bringing the total number of genes/ESTs on the current map to 54. The mapping of these genes led to the identification of two new regions of conserved synteny between human and chicken and confirmed other previously identified regions of conserved synteny between human and chicken. The linkage map has 210 markers in common with the linkage maps based on the East Lansing and Compton reference populations, and most of the corresponding linkage groups in the different maps can be readily aligned.

Animals↗
PubMed1998

Mapping quantitative trait loci for binary traits using a heterogeneous residual variance model: an application to Marek's disease susceptibility in chickens.

A typical problem in mapping quantitative trait loci (QTLs) comes from missing QTL genotype. A routine method for parameter estimation involving missing data is the mixture model maximum likelihood method. We developed an alternative QTL mapping method that describes a mixture of several distributions by a single model with a heterogeneous residual variance. The two methods produce similar results, but the heterogeneous residual variance method is computationally much faster than the mixture model approach. In addition, the new method can automatically generate sampling variances of the estimated parameters. We derive the new method in the context of QTL mapping for binary traits in a F2 population. Using the heterogeneous residual variance model, we identified a QTL on chromosome IV that controls Marek's disease susceptibility in chickens. The QTL alone explains 7.2% of the total disease variation.

Algorithms↗
PubMed1998

Hyaluronan prevents the decreased net ultrafiltration caused by increased peritoneal dialysate fill volume.

In the present study, we investigated (1) the effect of an increase in dialysate fill volume on peritoneal fluid and solute transport using a 1.36% glucose solution, and (2) the effect of intraperitoneal administration of hyaluronan on peritoneal transport characteristics when different fill volumes were used. A four-hour dwell study with frequent dialysate and blood sampling was performed in 26 male Sprague-Dawley rats with 131I albumin as the intraperitoneal volume marker. Each rat was injected intraperitoneally with 25 ml (group Con25, N = 6) or 40 ml (group Con40, N = 7) of 1.36% glucose dialysis solution alone or 25 ml (group HA25, N = 6) or 40 ml (Group HA40, N = 7) of 1.36% glucose dialysis solution with 0.01% hyaluronan. The peritoneal transport of fluid, glucose, urea, and total protein as well as the intraperitoneal hydrostatic pressure (IPP) with different fill volumes were evaluated. We found that IPP and peritoneal fluid absorption rate significantly increased with the increase in fill volume (P < 0.01), and therefore the net ultrafiltration volume was significantly lower in the Con40 group compared to the Con25 group despite a higher transcapillary ultrafiltration rate in the Con40 group. The addition of hyaluronan to dialysate significantly (P < 0.01) decreased the peritoneal fluid absorption rate (by 22% in HA25 vs. Con25 and by 29% in HA40 vs. Con40) and thus significantly increased the net peritoneal fluid removal. The diffusive mass transport coefficients for glucose, urea and total protein did not differ between the Con25 and Con40 groups or between the two hyaluronan groups as compared to their respective control groups. The peritoneal clearance of urea increased significantly in the high fill volume group (by 58% in Con40 vs. Con25) and in the two hyaluronan groups (by 21% in HA25 vs. Con25 and by 16% in HA40 vs. Con40). We conclude that: (1) An increase in dialysate fill volume using 1.36% glucose dialysis solution results in higher intraperitoneal hydrostatic pressure and higher peritoneal fluid absorption rate, and therefore lower net ultrafiltration. (2) Intraperitoneal addition of hyaluronan significantly decreases the peritoneal fluid absorption rate, and the decreasing effect is even more marked when a high fill volume is used. (3) Small solute clearances increase markedly with increases in fill volume, and then further increase by adding hyaluronan to the dialysate due to the increase in drainage volume. Thus, intraperitoneal administration of hyaluronan during a single peritoneal dialysis exchange may significantly increase the peritoneal fluid and solute removal by decreasing peritoneal fluid absorption, and may thereby prevent the decreased net ultrafiltration caused by an increase in dialysate fill volume.

Animals↗
PubMed1998

Mapping chicken genes using preferential amplification of specific alleles.

To map the chicken genome, an international reference population was developed at our laboratory (East Lansing, MI) using an F2 backcross between inbred jungle fowl (JF) and inbred white leghorns (WL). To augment the number of type I genes on the East Lansing (E) map, segregation of the JF-specific allele was followed using preferential amplification of specific alleles (PASA) in polymerase chain reactions (PCR). Among 15 functional genes that were added to the E map, agrin and mannose-6-phosphate receptor genes were found to occur in conserved syntenic groups. Using this PCR-based approach, six conserved groups spanning more than 243 centimorgans (cM) in the chicken were syntenic with human and mouse.

Alleles↗
PubMed1998

Genetic mapping of quantitative trait loci affecting susceptibility to Marek's disease virus induced tumors in F2 intercross chickens.

Marek's disease (MD) is a lymphoproliferative disease caused by the MD virus (MDV), which costs the poultry industry nearly $1 billion annually. To identify quantitative trait loci (QTL) affecting MD susceptibility, the inbred lines 6(3) (MD resistant) and 7(2) (MD susceptible) were mated to create more than 300 F2 chickens. The F2 chickens were challenged with MDV JM strain, moderately virulent) at 1 wk of age and assessed for MD susceptibility. The QTL analysis was divided into three stages. In stage 1, 65 DNA markers selected from the chicken genetic maps were typed on the 40 most MD-susceptible and the 40 most MD-resistant F2 chickens, and 21 markers residing near suggestive QTL were revealed by analysis of variance (ANOVA). In stage 2, the suggestive markers plus available flanking markers were typed on 272 F2 chickens, and three suggestive QTL were identified by ANOVA. In stage 3, using the interval mapping program Map Manager and permutation tests, two significant and two suggestive MD QTL were identified on four chromosomal subregions. Three to five loci collected explained between 11 and 23% of the phenotypic MD variation, or 32-68% of the genetic variance. This study constitutes the first report in the domestic chicken on the mapping of non-major histocompatibility complex QTL affecting MD susceptibility.

Analysis of Variance↗