Laparoscopic surgery. A difference.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
T M Chang
Publications and source records attributed to T M Chang.
Dedication to Dr. Willem Johan Kolff.
Explore the source record for details and available documents.
Artificial Organs↗
Artificial cells: 35 years.
The first artificial cells were prepared 35 years ago. They contain biologically active materials. They are now being used in medicine and biotechnology. Artificial cells containing adsorbents are already a routine form of treatment in hemoperfusion. This includes treatment for acute poisoning, high blood aluminum and iron, kidney failure, some types of acute liver failure, and other conditions. Artificial cells are being tested for use as red blood cell substitutes. Artificial cells containing cell culture are being tested in animals for the treatment of diabetes, liver failure, and others. Artificial cells containing enzymes are being tested for treatment in hereditary enzyme deficiency diseases and other diseases. Artificial cells containing complex enzyme system can convert wastes like urea and ammonia into useful amino acids. In biotechnology, artificial cells are being used for the production of monoclonal antibodies, interferons, and other biotechnological products. They are also being investigated for use in other applications in biotechnology, chemical engineering, and medicine.
Animals↗
Artificial liver support based on artificial cells with emphasis on encapsulated hepatocytes.
Artificial liver support requires more than a detoxification system. We have investigated additional approaches. Microencapsulated hepatocytes increased the survival time of fulminant hepatic failure (FHF) rats. They also lowered the bilirubin in Gunn rats. Xenograft of microencapsulated rat hepatocytes into mice are immunoisolated. The viability of hepatocyte increased from 62 to 100% after 29 days. This is because of accumulation of a hepatic stimulatory factor (> 100,000 D) secreted by the hepatocytes in the artificial cells. A novel two-step method of cell encapsulation greatly improved immunoisolation and biocompatibility. Other metabolic approaches included a multienzyme system for conversion of ammonia to essential amino acid, and removal of bilirubin.
Animals↗
Identification of a transcriptional enhancer important for enteroendocrine and pancreatic islet cell-specific expression of the secretin gene.
It is well established that the gene encoding the hormone secretin is expressed in a specific enteroendocrine cell, the S cell. We now show that the secretin gene is transiently expressed in insulin-producing B cells of the developing pancreatic islets in addition to the intestine. Furthermore, secretin is produced by most established islet cell lines. In order to identify and characterize the regulatory elements within the secretin gene that control tissue-specific expression, we have introduced secretin reporter gene constructions into the secretin-producing HIT and STC-1 cell lines as well as the nonexpressing INR1-G9 glucagonoma line. Analysis of deletion mutants revealed that sequences between 174 and 53 bp upstream from the transcriptional start site are required for maximal expression in secretin-producing cells. This positive element functioned independently of position and orientation. Further deletions into the enhancer resulted in a stepwise loss of transcriptional activity, suggesting the presence of several discrete control elements. The sequence CAGCTG within the secretin enhancer closely resembles that of the core of the B-cell-specific enhancer in the insulin gene. Point mutations introduced into this putative element led to greater than 85% reduction in transcriptional activity. Gel mobility shift assays suggested that a factor in B cells closely related or identical to proteins that bind to the insulin enhancer interacts with the CAGCTG motif in the secretin gene.
Animals↗
Artificial cells in immobilization biotechnology.
Artificial cells contain biologically active materials. Artificial cells containing adsorbents have been a routine form of treatment in hemoperfusion for patients. This includes acute poisoning, high blood aluminum and iron, and supplement to dialysis in kidney failure. Artificial cells are being tested for use as red blood cell substitutes. Artificial cells encapsulated cell culture are being tested in animals for the treatment of diabetes and liver failure. A novel 2 step method has prevented xenograft rejection. Artificial cells containing enzymes are being studied for treatment in hereditary enzyme deficiency diseases and other diseases. Recent demonstration of extensive enterorecirculation of amino acids in the intestine has allowed its oral administration to deplete specific amino acids. Artificial cells containing complex enzyme system convert wastes like urea and ammonia into essential amino acids. Artificial cell is being used for the production of monoclonal antibodies, interferons and other biotechnological products. It is also being investigated for drug delivery, and for use in other applications in biotechnology, chemical engineering and medicine.
Biocompatible Materials↗
Blood substitutes based on modified hemoglobin prepared by encapsulation or crosslinking: an overview.
Modified hemoglobin consists of (1) encapsulated hemoglobin and (2) crosslinked hemoglobin (polyhemoglobin, intramolecularly cross-linked hemoglobin and conjugated hemoglobin). There have been new advances in all types of modified hemoglobins. Modified hemoglobins are effective in hemorrhagic shock. However, it is important to define hemorrhagic shock models and experimental designs. Important progress has been made in research on vasoactivities, organ perfusion, organ preservation, biodistribution, hematology, complement activation immunology and other areas. A preclinical screening test may bridge the gap between animal safety studies and injection into human. Potential new sources of hemoglobin included bovine hemoglobin, recombinant human hemoglobin and synthetic heme.
Animals↗
Bovine hemoglobin anaerobically reacted with divinyl sulfone: a potential source for hypothermic oxygen carriers.
The bifunctional reagent divinyl sulfone was anaerobically reacted with bovine hemoglobin to give a noncrosslinked intramolecularly-modified new derivative (HbBv-DVS). By employing a high molar ratio of divinyl sulfone to HbBv-DVS, it was possible to effect anaerobic intermolecular crosslinkage. The polymerized material (Poly HbBv-DVS) was shown to consist of a mixture of modified intermolecularly-crosslinked hemoglobins characterized by molecular masses ranging from 130 to -500 kDa. Some functional properties of HbBv-DVS and Poly HbBv-DVS have been evaluated in vitro and in vivo. Viscosities of HbBv-DVS solutions at temperatures as low as 15 degrees C and concentrations up to 14.0 g/dl were proved to be much lower than that of normal human blood at 37 degrees C (-4 cp). Poly HbBv-DVS (14.0 g/dl) was iso-oncotic (COP = 23 mm Hg) with plasma, and had viscosities of 3.37 and 4.57 cp at 37 and 15 degrees C, respectively. The clearance of Poly HbBv-DVS from the circulation was significantly delayed (T1/2 = 270 min), compared with those of HbBv and HbBv-DVS (T1/2 = 80 and 100 min, respectively. The P50 values were substantially increased (P50 = 52 and 61 mm Hg at 37 degrees C, 0.15 M Cl- and pH 7.4 for HbBv-DVS and Poly HbBv-DVS, respectively). Due to their right-shifted oxygen equilibrium curves, these derivatives still yielded P50 values of about 20 mm Hg at the low temperature of 15 degrees C, as compared with only 7 mm Hg for native bovine hemoglobin. These properties make HbBv-DVS and Poly HbBv-DVS potential new candidates for low-temperature organ perfusion.
Animals↗
Preparation of carboxymethylchitin-incorporated submicron bilayer-lipid membrane artificial cells (liposomes) encapsulating hemoglobin.
Explore the source record for details and available documents.
Animals↗
Purification and quantitative determination of carboxymethylchitin incorporation into submicron bilayer-lipid membrane artificial cells (liposomes) encapsulating hemoglobin.
The separation of carboxymethylchitin-coated hemoglobin-loaded liposomes (CMC-LEHb)s from the non-adsorbed CMC has been achieved by gel chromatography. This purification takes place at the physiological pH of 7.4 favoring HbO2 preservation. A comparative study between experimental techniques for the quantitative determination of the absorption of carboxymethylchitin (CMC) onto liposomes encapsulating hemoglobin (LEHb)s has been conducted. Results suggest that FT-IR spectroscopy gives a more accurate quantitative absorption index while the chitinase-based enzymatic assay should be used as a qualitative detection tool. Quantitative bilayer and surface characterization show that the RBC membrane composition has been closely simulated by that of CMC-LEHbs in terms of total lipids and carbohydrates at 87.8% (phospholipids and cholesterol) and 12.2% CMC respectively.
Animals↗
Endotoxin removed from hemoglobin solution using polymyxin-B immobilized fibre (PMX-F) followed by a new turbidometric endotoxin assay.
Endotoxin contamination in modified hemoglobin can result in side effects. Accurate measurement and effective elimination of endotoxin are important in producing safe hemoglobin preparation. A new turbidometric endotoxin assay (Toxinometer) was studied, in which absorbance of wavelength was applied at 660 nm. This method is not affected by the presence of hemoglobin in solution. This way, toxinometer can accurately measure endotoxin concentration in hemoglobin solution. For the elimination of endotoxin, polymyxin-B immobilized fiber (PMX-F) was studied in-vitro and compared with commercial materials. The PMX-F was found to be a convenient and less expensive approach.
Animals↗
Effect of a single replacement of one of Ringer lactate, hypertonic saline/dextran, 7g% albumin, stroma-free hemoglobin, o-raffinose polyhemoglobin or whole blood on the long term survival of unanesthetized rats with lethal hemorrhagic shock after 67% acute blood loss.
This study is based on an unanesthetized lethal hemorrhagic shock rat model (67% blood volume bled in 2 stages). The 8 groups studied were as follows. 1. Control--no resuscitation fluid. 2. Reinfusion of rat's own shed whole blood. 3. Ringer lactate solution--3 times shed blood volume. The following 4 fluids were each given as equal to the shed blood volume. 4. 7.5g% NaCl hypertonic saline/6% Dextran 70, followed by 3 volumes Ringer lactate dextran. 5. Ringer lactate solution. 6. Human albumin 7g% in Ringer lactate. 7. Stroma-free hemoglobin in Ringer lactate 8. o-raffinose polyhemoglobin in Ringer Lactate. Blood pressure and other vital signs were recorded continuously during the control period, bleeding periods, infusion period and 60 minutes after infusion. After this all surviving animals were followed for 14 days with no other special treatments. Group 4 had transient (10 minutes) returned of blood pressure to control levels. The 3 groups with sustained blood pressure at control level when followed for 1 hour were groups 2, 6 and 7. The 2 groups with 100% survival on days 14 were group 2 and group 7.
Animals↗
A preclinical screening test for modified hemoglobin to bridge the gap between animal safety studies and use in human.
The infusion of large amount of modified hemoglobin as blood substitute can potentially result in hypersensitivity and anaphylactic reactions, antibody-antigen reactions and others. Animal safety studies are important. However, response in animals may not be the same as in human. Before injecting into human, we may need to use an in-vitro screening procedure. One approach is based on testing the effects of modified Hb on complement activation (C3a) of human plasma. This paper describes this screening test. It also discusses how this may potentially be used. For instance using this to test for contamination from trace membrane fragments with blood group antigen or lipids, antibody-antigen complexes, endotoxin, trace fragments of microorganisms, residual amounts of some polymers, emulsifying agents, and organic solvents. There is also the possibility of obtaining plasma from a very large human population and analyse each of these to study the epidemiology of adverse reactions in different groups and types of patients.
Anaphylaxis↗
Immunological effects of hemoglobin, encapsulated hemoglobin, polyhemoglobin and conjugated hemoglobin using different immunization schedules.
Repeated subcutaneous immunizing injections into rats of Freund's adjuvant containing rat hemoglobin or o-raffinose rat polyhemoglobin did not result in increase in IgG antibody titers. However, heterologous hemoglobin injected as above is antigenic (49.50 + 6.70 % CPM). Crosslinking heterologous hemoglobin into o-raffinose polyhemoglobin further increased its antigenicity (75.60 + 4.08). Thus, unlike homologous hemoglobin, cross-linking of heterologous hemoglobin increased its antigenicity. Liposome encapsulated homologous hemoglobin injected subcutaneously with or without Freund's adjuvant did not show antigenicity. Encapsulated heterologous hemoglobin resulted in a minimal increase in antibody titers (10.73 + 4.64) only with Freund's adjuvant, but no increase when injected without Freund's adjuvant. Conjugated heterologous hemoglobin (PEG-Hb) injected intravenously by itself at weekly intervals did not result in significant increase in antibody titers on the 5th week.
Animals↗
Therapeutic applications of immobilized proteins and cells.
Explore the source record for details and available documents.
Animals↗
Radioimmunoassay of vasoactive intestinal polypeptide.
Explore the source record for details and available documents.
Animals↗
Long-term clinical assessment of combined ACAC hemoperfusion-ultrafiltration in uremia.
ACAC hemoperfusion was used in series with a small fluid removal system for a clinical trial in the treatment of uremia. A 22-month trial included a pretest control period, test period and a post-test control period. The most significant observations from this trial are: 1) the predialysis body weight of the patient could be maintained closer to the patient's dry weight; 2) there was a significant increase in hematocrit; and 3) there was insufficient removal of urea. With the development of an effective urea removal system, a more compact artificial kidney than any presently available will become feasible.
Blood Chemical Analysis↗
Effects of glucose dehydrogenase in converting urea and ammonia into amino acid using artificial cells.
A microencapsulated multienzyme system containing urease, glutamate dehydrogenase and glucose dehydrogenase has been used to convert urea and ammonia into an amino acid. The effect of two different glucose dehydrogenases was studied in detail. High-specific-activity glucose dehydrogenase requires minimal cofactor and glucose and can greatly facilitate the further development of this approach for possible clinical applications.
Ammonia↗