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Biomedical subjects

J Cheng

Publications and source records attributed to J Cheng.

At least 55 records · Page 3Linked to original sources

Study of renal function matching between Banna Minipig Inbred line and human.

Pigs have been thought to be ideal candidates for xenotransplant donors. However besides the immunological barrier, physiological and pharmacokinetic comparabilities of kidney function between donor animals and humans are important factors for successful xenotransplantation. As a unique large inbred animal, Banna Minipig Inbred (BMI) has been reported to be a potential large animal suitable for xenotransplantation. However, its physical and pharmacokinetic compatibilities with humans have not been documented. The purpose of this investigation was to measure renal routine function, glomerular filtration rate (GFR), renal blood flow (ERPF), and drug metabolism to evaluate comparability to humans. The results suggested that the renal function of BMI was similar to that of humans to eliminate nonprotein nitrogenous end products of metabolism. Pharmacokinetics of p-aminohippurate (PAH) and inulin--the most widely used methods to assess ERPF and GFR--showed that BMI showed lower values than humans for GFR, but similar function to humans in ERPF. The pharmacokinetics of cefazolin; a widely used model drug to study kidney drug metabolizing capacity, showed greater overall renal drug elimination of BMI than of humans. These results suggested that BMI did show comparable data to human renal function.

Adult↗

Activation of human coagulation system by liver-derived clotting factors of Banna minipig inbred line.

The liver synthesizes most of the coagulation factors that play a major role in arresting hemorrhage. Matching hepatic coagulation factors is an important premise in successful xenotransplantation. As a unique inbred pig, the Banna minipig inbred (BMI) animals have a huge potential value for pig-to-human xenotransplantation, due to its clear genetic background and tiny interindividual differences. Whether the coagulation factors synthesized by porcine liver can trigger human clotting pathways has not been reported. This study focused on the activities of BMI coagulant factors synthesized exclusively by the liver to activate human clotting pathways. In these experiments we prepared coagulant factors II, V, VII, X, and XII synthesized exclusively by liver from BMI and humans. The factors were used in common correction tests, added to the corresponding factor-deficient human plasma to determine prothrombin times or activated partial thromboplastin time, thereby calculating BMI and human coagulant factor activities. BMI clotting factors XII, VII, and X triggered human intrinsic, extrinsic, and common pathways, respectively. BMI clotting factors II, V, VII, X, and XII activities were 3.2-, 3.7-, 4.7-, 2.9-, and 4.5-fold as potent as those from humans.

Adult↗

Study of hepatic function matching between Banna minipig inbred and humans.

As a unique inbred pig Banna minipig inbred (BMI) is potentially suitable for pig-to-human xenotransplantation due to its clear genetic background and minor interindividual differences. Previous studies of BMI have focused on immunological barriers between BMI and humans. However, a comparison of liver function between donor animals and humans is an essential premise for successful xenotransplantation. In this study, we investigated routine hepatic functions, protein electrophoresis, and drug metabolism to compare capacity of liver synthesis, metabolism, and drainage between BMI and humans. The results showed no significant differences in the concentrations of albumin and globulin synthesized in the liver (alpha1, alpha2, and beta-globulin). Serum enzyme activities in BMI were higher than those in humans, and levels of total bilirubin and direct-reacting bilirubin of BMI were lower than those of humans. In BMI, the clearance of antipyrine, a widely used model drug to study hepatic drug metabolism, was 16 times greater than that by humans, with a mean residual time of antipyrine in BMI, one-tenth of that in human. These findings suggested that BMI livers are similar to humans in albumin and alpha, beta-globulin synthesis, but stronger in bilirubin elimination, enzyme activity, and drug metabolism. BMI livers may have stronger functions compared with those of humans. No incompatibility was identified in hepatic function between BMI and humans.

Adult↗

Gal alpha 1,3Gal expression on porcine pancreatic islets, testis, spleen, and thymus.

Gal alpha 1,3Gal (Gal) is the first target in antibody-mediated rejection of pig-to-non-human primate xenograft. Its expression may vary between organs and constituents of organs. Gal expression was studied in pancreas, testis, spleen and thymus of 22 pigs, with ages ranging from 1 to 22 months. The immunoperoxidase technique using the biotinylated lectin, Griffonia simplicifolia (IB4), was used. In the pancreas, neither endocrine (islet cells) nor exocrine cells expressed Gal. The Sertoli cells in the testis were negative. The spleen capsule and trabeculae did not stain for Gal, although both splenic T and B lymphocytes expressed Gal (B > T). Thymocytes were weakly positive, whereas thymic epithelial cells were negative for Gal. No age-related differences were seen in any tissues. Porcine islets of Langerhans, Sertoli cells, and the splenic and thymic structural frameworks did not express Gal, and therefore, should be relatively resistant to anti-Gal antibody-mediated rejection. The availability of pigs deficient in Gal as a source of islets may therefore not be beneficial in extending islet graft survival in non-human primate models.

Animals↗

In vitro and in vivo investigation of a novel monoclonal antibody to plasma cells (W5 mAb).

Natural antibodies (Abs), predominantly anti-Gal alpha 1-3Gal (Gal) Abs, in non-human primates and human beings present a major hurdle to successful pig-to-primate xenotransplantation. Attempts to inhibit anti-Gal Ab production in naïve baboons using non-specific immunosuppressive or B cell-specific reagents have failed. A new rat monoclonal antibody (W5 mAb) has been generated, which binds to all B cells, including memory cells, and to the majority of plasma cells, but not to T cells. It has been tested in vitro and in vivo. By immunoprecipitation, W5 mAb bound a human leukocyte antigen class II (HLA-DR) determinant. Sorting splenic or bone marrow W5+ cells resulted in a highly enriched anti-Gal Ab and total immunoglobulin (Ig)-secretory population. In vivo studies in baboons demonstrated that W5 mAb was safe but, despite the concomitant administration of an anti-CD154 mAb to inhibit sensitization, anti-rat Abs were detected within 10 days and inhibited the effect of the W5 mAb. High levels of W5 mAb were able to completely deplete B cells in the blood, but not in lymphoid tissues. Enzyme-linked spot-forming assay (ELISPOT) demonstrated that only 50 to 60% of secreting cells (SC) were depleted in the bone marrow. No reduction in the serum levels of anti-Gal Ab was observed. W5 mAb did not cause complete inhibition of anti-Gal Ab production, probably as a result of its inability to completely deplete B and plasma cells from all lymphoid compartments.

Animals↗

Utilization of treated swine wastewater for greenhouse tomato production.

An integrated system has been developed to recycle waste organics and treated wastewater from a swine farm to make value-added products and to protect the environment from potential contamination. The farm is a farrow-to-wean swine operation with approximately 4,000 sows. A high-strength wastewater (chemical oxygen demand, 18,000 mg/l; total Khejdal nitrogen, 1,600 mg/l; total phosphorus, 360 mg/l) is produced from the swine operation. An ambient-temperature anaerobic digester has been used to treat the swine wastewater and to produce biogas (from an average 475 m3/day in winter to 950 m3/day in summer). The biogas is combusted in an engine to produce electricity (around 900 kW-hr/day). The digester effluent that is rich in nutrients (N, P, and minerals) is then utilized for fertigation for greenhouse tomato production. A trickling nitrification biofilter has been developed to convert ammonium in the effluent into nitrate. The nitrified anaerobic effluent is used as both fertilizer and irrigation water for approximately 14,400 tomato plants in greenhouses. Experimental data indicate that the tomato greenhouses have used approximately 12 m3 of the effluent and 3.84 kg nitrogen per day. At the same time, the greenhouses have a daily yield of 520 kg (37 g/plant) of marketable fruit.

Agriculture↗

Prediction of response to incision using the mutual information of electroencephalograms during anaesthesia.

This paper presents a new approach to predict response during isoflurane anaesthesia by using mutual information (MI) time series of electroencephalograms (EEGs) and their complexity analysis. The MI between four lead electrodes was first computed using the EEG time series. The Lempel-Ziv complexity measures, C(n)s, were extracted from the MI time series. Prediction was made by means of artificial neural network (ANN). From 98 consenting patient experiments, 98 distinct EEG recordings were collected prior to incision during isoflurane anaesthesia of different levels. During and after skin incision, each patient was observed carefully for 2 min to detect subsequent responses (purposeful movement, changes in hemodynamic parameters and respiratory pattern) and then the EEG was labelled as 0.0 for responder or as 1.0 for non-responder. Training and testing the ANN used the 'drop-one-patient' method. The prediction was tested by monitoring the response to incision and the result given by the ANN. The system was able to correctly classify purposeful response in average accuracy of 91.84% of the cases. The results showed that the method has a better performance than other methods, such as spectral edge frequency, median frequency, and bispectral analysis. This method is computationally fast and acceptable real-time clinical performance was obtained.

Adult↗

Hepatocyte growth factor and c-Met (HGF/c-Met) in adenoid cystic carcinoma of the human salivary gland.

BACKGROUND: Hepatocyte growth factor (HGF) enhances cell growth, morphogenesis, and scattering of various epithelial cells. The aim of this study was to evaluate the hypothesis that HGF/c-Met plays a biological role in the invasive growth of adenoid cystic carcinoma (ACC). METHODS: Immunohistochemically, expression of HGF and its receptor c-Met was examined in 15 cases of ACC. To examine the direct effects of HGF on ACC, cell line derived from of ACC (ACC3) was used. The expression of HGF and c-met in ACC3 was investigated by RT-PCR. Analysis of mechanisms of invasion was done by performing scattering assay and matrigel invasion chamber assay. RESULTS: Positive staining of HGF was found in all cases, and that of c-Met was 67%. In ACC3, c-met was expressed, but not HGF. Stimulation of ACC3 by rhHGF induced scattering and promoted invasion. CONCLUSION: The present results suggest that HGF/c-Met increases tumor cell scattering and may play a part in invasiveness of ACC.

Carcinoma, Adenoid Cystic↗

Is neck ultrasound necessary for early stage oral tongue carcinoma with clinically N0 neck?

OBJECTIVES: To define the necessity of neck ultrasound for investigation of T1 and T2 oral tongue carcinoma with N0 neck. METHODS: The medical records of all patients with early stage (T1-2 N0) oral tongue cancer treated surgically between January 1985 and December 2000 were reviewed. Patients with 30 neck dissections were identified for analysis. The result of neck ultrasound examination was correlated with the histological examination. RESULTS: The sensitivity, specificity and overall accuracy of ultrasound examination were found to be 47%, 93% and 70%, respectively. The implication of ultrasound examination with respect to elective neck treatment was discussed in the management of the N0 neck. CONCLUSIONS: It is concluded that ultrasound alone is inadequate for making decisions regarding neck management of patients with T1 and T2 N0 carcinoma of the tongue and cannot replace a policy of elective neck dissection.

Carcinoma↗

Single nucleotide polymorphism discrimination assisted by improved base stacking hybridization using oligonucleotide microarrays.

Efficiencies of mismatch discrimination using size-varied capture probes were examined at various hybridization temperatures. The probes were 17, 15, 13, 11, 9, and 7 nucleotides long and contained single-base mismatches at their 3' ends. The optimal signal intensity and efficiency of base stacking hybridization on mismatch discrimination were observed for capture probes with a melting temperature (Tm) value of 36 degrees C, in the detection of DNA sequence variations at 40 degrees C. We employed asymmetric PCR to prepare single-stranded target DNA labeled with a fluorescent dye, and the PCR product was hybridized on the DNA microarray with no further purification. Our efforts have enhanced the sensitivity and simplified the procedures of base stacking hybridization on mismatch discrimination. As a model experiment, this improved technology was used to identify plasmid templates of human leukocyte antigen (HLA)-A alleles 2601, 2902, and 0206 on oligonucleotide microarrays. It is now possible to apply this simple, rapid, sensitive, and reliable base stacking hybridization technology to detect DNA sequence variations on microarrays in clinical diagnosis and other applications.

Alleles↗

Restricted neuronal expression of ubiquitous mitochondrial creatine kinase: changing patterns in development and with increased activity.

Whereas ATP consumption increases with neural activity and is buffered by phosphocreatine (PCr), it is not known whether PCr synthesis by ubiquitous mitochondrial creatine kinase (uMtCK) supports energy metabolism in all neurons. To explore the possibility that uMtCK expression in neurons is modulated by activity and during development, we used immunocytochemistry to detect uMtCK-containing mitochondria. In the adult brain, subsets of neurons including layer Va pyramidal cells, most thalamic nuclei, cerebellar Purkinje cells, olfactory mitral cells and hippocampal interneurons strongly express uMtCK. uMtCK is transiently expressed by a larger group of neurons at birth. Neurons in all cortical layers express uMtCK at birth (P0), but uMtCK is restricted to layer Va by P12. uMtCK is detected in cerebellar Purkinje cells at birth, but localization to dendrites is only observed after P5 and is maximal on P14. Hippocampal CA1 and CA3 pyramidal neurons contain uMtCK-positive mitochondria at birth, but this pattern becomes progressively restricted to interneurons. Seizures induced uMtCK expression in cortical layers II-III and CA1 pyramidal neurons. In the cortex, but not in CA1, blockade of seizures prevented the induction of uMtCK. These findings support the concept that uMtCK expression in neurons is (1) developmentally regulated in post-natal life, (2) constitutively restricted in the adult brain, and (3) regulated by activity in the cortex and hippocampus. This implies that mitochondrial synthesis of PCr is restricted to those neurons that express uMtCK and may contribute to protect these cells during periods of increased energy demands.

Adenosine Triphosphate↗

Laparoscopic radiofrequency ablation and hepatic artery infusion pump placement in the evolving treatment of colorectal hepatic metastases.

BACKGROUND: Laparoscopic radiofrequency ablation (LRFA) and laparoscopic hepatic artery infusion pump (LHAIP) placement are new treatment options for patients with colorectal liver metastases. This study investigates the selection criteria, safety, efficacy, and preliminary outcomes of patients treated with LRFA and LHAIP placement. METHODS: Fourty five patients with colorectal metastases confined to the liver, 37 of whom had failed systemic chemotherapy, were treated with LRFA and/or LHAIP between September 1996 and December 2001. Treatment selection was individualized, based on each patient's general health, liver function, and tumor size, number, location, and distribution. RESULTS: Twenty patients (44%) had LRFA alone, 10 (22%) had LHAIP placement alone, and 15 (33%) patients had combined LRFA and LHAIP therapy. The LRFA group had a significantly shorter mean operative time and blood loss (p <0.05), but hospital stays were similar when compared to patients receiving LRFA + LHAIP or LHAIP alone. Tumor characteristics were worse in both LHAIP groups, with a higher incidence of tumors >or=4 cm, major vascular involvement, diffuse tumor pattern, bilobar distribution, and involvement of more than three segments. During a mean follow-up period of 11.5 +/- 7.8 months (range, 1-38), the actuarial survival was 70%, 67%, and 50% for LRFA, LRFA + LHAIP, and LHAIP, respectively. LHAIP only patients had the shortest estimated mean survival time of the three groups by Kaplan-Meier survival curves (p = 0.001). CONCLUSION: LRFA and/or LHAIP placement are safe and feasible treatment options for the treatment of colorectal hepatic metastases. The choice of treatment for patients should be based primarily on tumor characteristics. Long-term studies, which will elucidate the role of these evolving treatments, are now under way.

Adult↗

Differential distribution of interneurons in the neural networks that control walking in the mudpuppy (Necturus maculatus) spinal cord.

Locomotor behavior is believed to be produced by interneuronal networks that are intrinsically organized to generate the underlying complex spatiotemporal patterns. In order to study the temporal correlation between the firing of individual interneurons and the pattern of locomotion, we utilized the spinal cord-forelimb preparation from the mudpuppy, in which electrophysiological recordings of neuronal activity were achieved during walking-like movement of the forelimb induced by bath application of N-methyl- D-aspartate (NMDA). Intra- and extracellular recordings were made in the C2 and C3 segments of the spinal cord. These segments contain independent flexor and extensor centers for the forelimb movement about the elbow joint during walking. Among the 289 cells recorded in the intermediate gray matter (an area between the ventral and dorsal horns) of the C2 and C3 segments, approximately 40% of the cells fired rhythmically during "walking." The firing rates were 6.4+/-0.4 impulses/s (mean +/- SE). These rhythmically active cells were classified into four types based on their phase of activity during a normalized step cycle. About half the rhythmic cells fired in phase with either the flexor (F) or extensor (E) motoneurons. The rest fired in the transitions between the two phases (F-->E and E-->F). Longitudinal distributions of the four types of interneurons along the spinal cord were in agreement with observations that revealed distinct but overlapping flexor and extensor centers for walking. Some cells triggered short-latency responses in the elbow flexor or extensor muscles and may be last-order interneurons. These observations suggest that there is a differential distribution of phase-specific interneurons in the central pattern generator of the mudpuppy spinal cord for walking.

Action Potentials↗

Initial study of using a laminar fluid diffusion interface for sample preparation in high-performance liquid chromatography.

This report describes a new microfluidic device called the H Filter for sample preparation prior to HPLC. The H Filters make possible a diffusional transfer of an analyte from a sample stream into a stream of a "receiver" fluid. Existing mathematical models can be used for optimizing experimental conditions. The authors have selected the extraction of the antibiotic cephradine from blood to demonstrate the utility of the new device. The extracts of blood samples spiked with cephradine levels between 0.2 and 100 microg/ml were analyzed using a C8 reversed-phase column and UV detection at 260 nm. The HPLC results were in good agreement with theory. The recovery of 32.2+/-2.8% was uniform over the entire range of cephradine concentrations. The new method completely avoids the use of centrifuges, that is otherwise typical for most current methodologies for the preparation of blood samples prior to HPLC analysis.

Cephradine↗