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Biomedical subjects

T M Chang

Publications and source records attributed to T M Chang.

At least 253 records · Page 14Linked to original sources
PubMed1985

Pyridoxylated polyhemoglobin as a red cell substitute for resuscitation of lethal hemorrhagic shock in conscious rats.

In our previous work, pyridoxylated polyhemoglobin (PP-PolyHB) was shown to have a P50 = 16-18 torr, and a half-life (T 1/2) of 20 hrs in the circulation of rats given a 75% isovolemic exchange transfusion. For the present study, a rapid and lethal hemorrhagic shock model has been specifically designed to assess the ability of PP-PolyHB to function as an emergency resuscitation fluid. Using 48 fully conscious rats with special chronic arterial and venous cannulations, shock was induced by bleeding 67% of total blood volume in less than 40 min; producing 100% mortality in nonresuscitated controls. Resuscitation was carried out using one of the following infusion fluids equivalent in volume to the bled volume: Ringer's solution, albumin solution, stroma-free Hb (SFHb), pyridoxylated SFHb (PP-SFHb), PP-PolyHb, and whole blood. Long-term (greater than 8 day) survival rate of rats (n = 12) resuscitated with PP-PolyHb was 75% compared to 83% for autologous whole blood. Survival following resuscitation with the other fluids was substantially lower. These results indicate that PP-PolyHb could effectively resuscitate lethal hemorrhagic shock in conscious rats, and provide long-term survival afterwards, even in the absence of any additional fluid maintenance.

Animals↗
PubMed1984

Diacytosis of 125I-asialoorosomucoid by rat hepatocytes. A non-lysosomal pathway insensitive to inhibition by inhibitors of ligand degradation.

Diacytosis of 125I-asialoorosomucoid by rat hepatocytes was studied by preincubating the cells with the labelled ligand at 37 degrees C for 30 min or 18 degrees C for 2 h, washing free of cell surface receptor-bound tracer at 4 degrees C and then reincubating at 37 degrees C. The cells preloaded at 37 degrees C released a maximum of 18% of the total intracellular ligand as undegraded molecules after 1 h of incubation with an apparent first-order rate constant of 0.018 min-1 (t1/2 = 39 min). When the preloaded cells were incubated in the presence of 100 micrograms/ml unlabelled asialoorosomucoid or 5 mM ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, the amount of the released ligand increased to 32 and 37%, respectively, without apparent change in kinetics, indicating that these agents prevented rebinding of the released ligand. In the presence of 5 microM colchicine, 20 microM cytochalasin B, 20 microM chloroquine, 10 mM NH4Cl, 10 microM monensin or 20 microM leupeptin, degradation of the preloaded ligand was inhibited, whereas the release of the ligand was either slightly increased or unchanged. Similar effects of leupeptin, colchicine and asialoorosomucoid were observed with cells preloaded at 18 degrees C. These results indicate that diacytosis of 125I-asialoorosomucoid occurs from a prelysosomal compartment via a route insensitive to inhibition by the inhibitors of ligand degradation.

Animals↗
PubMed1984

Influence of cisternal pressure on passage of neuropeptides from the cerebrospinal fluid into the peripheral circulation.

Passage of neuropeptides from the cerebrospinal fluid to circulation depends upon cisternal pressure. When cisternal collecting pressure was kept at -20 cm, plasma levels of gastrin-17 and somatostatin-14 remained at basal values despite perfusion of high doses of the peptides into the cerebro-ventricular system. Progressive reduction of this pressure above -15 cm results in a progressive rise of the peripheral concentration of the peptides. Discrimination between central and peripheral action of centrally administered neuropeptides is, therefore, possible.

Animals↗
PubMed1984

Artificial cells in medicine and biotechnology.

Since the feasibility of artificial cells was first demonstrated in 1957 [Chang (1, 2)], an increasing number of approaches to their preparation and use have become available. Thus artificial cell membranes can now be formed using a variety of synthetic or biological materials to produce desired variations in their permeability, surface properties, and blood compatibility. Almost any material can be included within artificial cells. These include enzyme systems, cell extracts, biological cells, magnetic materials, isotopes, antigens, antibodies, vaccines, hormones, adsorbents, and others. Since cells are the fundamental units of living organisms, it is not surprising that artificial cells can have a number of possible applications. This is especially so since artificial cells can be "tailor-made" to have very specialized functions. A number of potential applications suggested earlier have now reached a developmental stage appropriate for clinical trial or application. These clinical applications include the use of such cells as a red blood cell substitute, in hemoperfusion, in an artificial kidney or artificial liver, as detoxifiers, in an artificial pancreas, and so on. Artificial red blood cells based on lipid-coated fluorocarbon or crosslinked hemoglobin are being investigated in a number of centers. The principle of the artificial cells is also being used in biotechnology to immobilize enzymes and cells. Developments in biotechnology have also resulted in the use of the principle underlying the artificial cell to help produce interferons and monoclonal antibodies; to create immunosorbents; to develop an artificial pancreas; and to bring enzyme technology usefully into biotechnology and biomedical applications. Artificial cells are also being used as drug delivery systems based on slow release, on magnetic target delivery, on biodegradability, on liposomes, or other approaches. The present status and recent advances will be emphasized in this paper.

Animals↗
PubMed1984

Artificial cell-microencapsulated phenylalanine ammonia-lyase.

Phenylalanine ammonia-lyase (PAL) is immobilized in collodion artificial cells. Once technical problems associated with the encapsulation of this enzyme were solved, the enzyme kinetics were compared to PAL in free solution. Microencapsulated PAL has an apparent enzyme activity that is 20% of the activity of enzyme in free solution. The Km for both free and immobilized PAL is 475 microM. The Vm for the microencapsulated PAL is 9 microM/min, whereas that of PAL in free solution is 55 microM/min.

Ammonia-Lyases↗
PubMed1984

Selection and microencapsulation of an "NADH-oxidizing" bacterium and its use for NAD regeneration.

An alternative approach to the regeneration of coenzymes is described here using immobilized microorganisms possessing "NADH-oxidase" function. Bacteria containing NADH-oxidase activity are immobilized by microencapsulation within artificial cells. In this form, the microencapsulated bacteria can recycle NADH back to NAD in the presence of molecular oxygen as an electron acceptor. The only byproduct of the recycling reaction is water. In order to perform the biological regeneration of NAD, the activity of NADH-oxidase was investigated in 13 strains of aerobic bacteria and yeast. The NADH-oxidizing bacteria Leuconostoc mesenteroides exhibited the highest activity among the microorganisms tested. The permeabilized bacteria showed 10% of their initial activity after microencapsulation. Light and electron microscopy studies of bacteria loaded microcapsules have been done. Enzymatic properties of microcapsule-immobilized bacteria were investigated in comparison with those of the free enzyme complex. Leuconostoc mesenteroides, containing NADH-oxidase, has been microencapsulated together with 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSDH) for stereospecific steroid oxidation. In a batch reactor, 2 mg of NAD, with recycling, allowed the same substrate consumption as 4.4 mg of NAD without recycling. The microencapsulated system can be used repeatedly. The system is functional for 10 h, during which time each molecule of NAD has been used 7.6 times.

3-Hydroxysteroid Dehydrogenases↗
PubMed1984

Preparation and in vitro characteristics of a blood substitute based on pyridoxylated polyhemoglobin.

Stroma-free hemoglobin (SFHb) is prepared from outdated blood. Red cells are washed, lysed in hypotonic phosphate buffer, and stromal lipid is then removed by toluene extraction and high-speed centrifugation. Pyridoxal-phosphate (PP) added in a 4:1 molar ratio to deoxygenated SFHb, is covalently linked across the polyphosphate binding site of the Hb tetramer by reduction with NaBH4 under N2 for 18 h. Excess reagents are removed by dialysis. Subsequent crosslinking using 5.0% glutaraldehyde in the presence of lysine for 12-36 h yields soluble, macromolecular polyhemoglobin (PolyHb). Progress of the reaction is monitored by gel chromatography. In vitro work shows that different molecular weight (MW) PolyHb can be produced, ranging in weight from 130,000 to over 1,000,000. Intermediate MW PolyHb (less than 600,000) remains stable for months at 4 degrees C, withstands prolonged incubation at 37 degrees C, and has a viscosity similar to blood. SFHb has a low P50 = 15 torr, which has been raised to 26 torr by pyridoxylation. When PP-SFHb is crosslinked into PP-PolyHb, it can reversibly carry oxygen with a lower affinity (P50 = 16 torr) than nonpyridoxylated PolyHb (P50 = 11 torr). These favorable physicochemical properties of PP-PolyHb suggest that further progress toward a potential artificial blood substitute has been made.

Blood Substitutes↗
PubMed1984

Potentiating effect of secretin on cholecystokinin-stimulated pancreatic secretion in dogs.

A possible potentiating effect of cholecystokinin octapeptide (CCK-OP) on the action of secretin on exocrine pancreatic secretion was studied in five dogs with gastric fistulas and modified Herrera pancreatic fistulas. Secretin in a dose, 2.45 pmol (0.03 clinical units) X kg-1 X h-1, that mimics the plasma secretin level in the postprandial state increased pancreatic bicarbonate secretion, but the increase was not statistically significant. CCK-OP in graded doses, 26.2, 52.5, 109, and 219 pmol (0.03, 0.06, 0.125, and 0.25 microgram) X kg-1 X h-1, given intravenously produced a significant increase in both bicarbonate and protein secretion, and the increase was dose related. The plasma concentrations of immunoreactive CCK during intravenous infusion of CCK-OP in doses of 26.2 and 52.5 pmol X kg-1 X h-1 were found to mimic the postprandial plasma concentrations of immunoreactive CCK in eight dogs. When CCK-OP in four graded doses was added to intravenous infusion of secretin, 2.45 pmol X kg-1 X h-1, the actual bicarbonate output at each dose level of CCK-OP was greater than the sum of the bicarbonate outputs produced by secretin alone and CCK-OP alone in a corresponding dose. Thus, we conclude that the action of secretin in a physiological dose that mimics the plasma level of secretin after a meal is potentiated by CCK-OP in a dose range that produces a plasma CCK-OP level comparable with that in the postprandial state and vice versa. The study indicates that, like secretin, CCK-OP is another necessary agent for pancreatic secretion of bicarbonate during digestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Artificial cells in hemoperfusion and other applications.

The present status of artificial cells is discussed. Discussions include the applications of artificial cells for acute intoxication, artificial kidney, artificial liver, immunosorbents, red blood cell substitutes, enzyme replacements and other areas.

Albumins↗
PubMed1984

Non-gastrin secretogogue in ulcerogenic tumors of the pancreas.

In 18 patients with hypersecretion of acid, severe ulcer diathesis, and pancreatic islet cell tumor or hyperplasia, 14 had hypergastrinemia and 4 had normal plasma gastrin concentration. The neoplasms contained several gut peptides beside gastrin. The immunoreactive gastrin in the tumor extracts measured less than 7 ng/g, less than the amount previously reported. The extracts of each patient's tumor also contained a secretogogue other than gastrin that stimulated gastric acid secretion in rats. In addition, the plasma extracts of 2 patients also contained a secretogogue that stimulated acid secretion. After surgical resection of a recurrent metastatic tumor in 1 patient, basal acid secretion decreased from 13.9 to less than 1 meq/h, and the bioactivity of the plasma disappeared. These observations suggest the existence of a secretogogue that appears to be a protein in the pancreatic tumors of some patients with severe ulcer diathesis and hypersecretion.

Adenoma↗
PubMed1984

Amino acid disturbances in experimental hepatic coma rats.

In our previous paper (1), we discussed the in-vitro adsorption spectrum of plasma amino acids by coated charcoal hemoperfusion. We now describe the general amino acid disturbances in plasma, CSF and cerebrum in the galactosamine induced hepatic coma model in rats. All aromatic amino acids (AAA) increased significantly in the three compartments studied. Branched chain amino acids (BCAA) were either elevated to a much lesser extent or remained unchanged. The molar ratio of BCAA:AAA was consequently reduced. This is similar to findings in fulminant hepatic failure in human and other animal models. Most of the 20 amino acids analyzed were increased significantly in the plasma. Increases of amino acids were minimal in the brain tissue studied, i.e. the cerebrum.

Amino Acids↗
PubMed1984

Effect of charcoal hemoperfusion on amino acid disturbance in experimental hepatic coma.

Using the galactosamine induced hepatic coma rat model, we studied the effects of coated charcoal hemoperfusion on amino acids in plasma and CSF in grade III hepatic coma. We found that 1 hour of hemoperfusion significantly reduced AAAs and BCAAs in plasma and increased the molar ratio of BCAA:AAA. When rats in grade III coma were treated with 2 consecutive 1-hour hemoperfusions, the substantial reduction of plasma AAAs resulted in a significant decrease of AAA levels in CSF.

Adsorption↗
PubMed1983

Effect of desferrioxamine on removal of aluminum and iron by coated charcoal haemoperfusion and haemodialysis.

An intravenous infusion of desferrioxamine (3 g) was given to 17 chronic renal failure patients stabilised on standard haemodialysis. Aluminium clearance 48 h after desferrioxamine was 65.3 +/- 11.0 ml/min for 'Dialaid 4000' with 70 g coated charcoal haemoperfusion system; 44.6 +/- 13.7 ml/min for 'Rhondial 75' with polyacrylonitrate membrane; 35.8 +/- 11.0 ml/min for 'Monitral' with polyacrylonitrate membrane; and 4.0 +/- 17.8 ml/min for haemodialysers with a 'Cupraphane' membrane. None of these 4 systems removed any aluminium in the absence of desferrioxamine in the same patients. Even at a desferrioxamine concentration of 40 mg/dl, coated activated charcoal (CAC) was not saturated. CAC did not absorb ferric ions in vitro. But when 40 mg/dl of desferrioxamine was present CAC absorbed increasing concentrations of ferric ions in a linear fashion.

Adsorption↗
PubMed1983

Radioimmunoassay of cholecystokinin.

A highly sensitive and specific radioimmunoassay for cholecystokinin (CCK) has been developed. Fully immunoreactive [125I]CCK33 was prepared by chloramine T-catalyzed iodination followed by purification by gel filtration and ion exchange chromatography. A high titer of antiserum was obtained by multiple immunizations of rabbits with 15% pure porcine CCK without conjugation. The antiserum was highly specific for CCK33 and CCK39, with 40% of the binding sites recognizing CCK8 at high affinity, but reacted weakly with gastrin. Plasma interference was eliminated by an XAD-2 resin column extraction technique with high recovery of CCK. The overall assay sensitivity was 3.3 pM with intra- and interassay coefficients of variation determined with a plasma of 11.2 pM at 9.6 and 20.8%, respectively. The assay was capable of detecting linear increments of both CCK33 and CCK8 added into plasma and intravenous infusion of CCK8 as low as 0.03 micrograms/kg/hr in dogs. The assay was validated by its ability to monitor increase of plasma CCK immunoreactivity after ingestion of a meat meal in both humans and dogs, as well as following intragastric infusion of liver extract meal and intraduodenal infusion of phenylalanine in dogs. When the CCK8 and gastrin binding sites of the antiserum were removed by immunoadsorption, the treated antiserum remained capable of measuring a postprandial change in plasma CCK concentration, indicating that CCK33-like immunoreactivity was present in the plasma.

Adsorption↗
PubMed1983

Intrahepatic stones: the Taiwan experience.

From 1970 to 1979, 95 patients with intrahepatic stones were seen. Since 1974, however, the annual rate of cases has been only half that of the previous decades. Patients with this disease are young; onset of symptoms in over a third of the patients occurred before 20 years of age and in 14 patients before 15 years. Average length of time between onset of symptoms and definitive diagnosis was 8.3 years. Southeast Asian stones are multiple, soft, muddy, pigmented, and located in the primary and secondary biliary radicles (particularly in the left hepatic lobe). Transhepatic cholangiography is the best diagnostic maneuver. Many procedures have been tried but no one procedure is entirely satisfactory. Previously unoperated patients (44) had cholecystectomy and exploration of the common bile duct. Patients whose stones recurred after exploration needed reoperation after an average of 2.5 years; patients whose stones recurred after cholecystectomy were seen an average of 5.7 years later, and 11 of 18 were treated medically. The mortality rate was surprisingly low.

Adolescent↗
PubMed1983

Cause-and-effect relationship between motilin and migrating myoelectric complexes.

We investigated the cause-and-effect relationship between plasma motilin levels and migrating myoelectric complexes (MMCs). Each dog was implanted with a set of eight bipolar electrodes on the small intestine. Premature phase IIIs were initiated by morphine bolus injections. Plasma samples were assayed for motilin and gastrin. All spontaneous and morphine-initiated phase IIIs were associated with peaks of plasma motilin, which always occurred after phase IIIs had started in the proximal duodenum. The plasma motilin level decreased consistently during phase I and started to increase again only after phase II had started in the duodenum. Either a meal or somatostatin infusion disrupted MMC cycling, but morphine boluses overcame this disruption and initiated phase IIIs that propagated distally. The phase IIIs thus initiated were associated with peaks in plasma motilin levels. In contrast, bolus injections of motilin did not initiate phase IIIs during the fed state or during somatostatin infusion. Our findings suggest that endogenous motilin does not initiate spontaneous MMCs. Instead, MMC contractions release motilin. The physiological role of motilin, thus released, may be to act as an endocrine agent to coordinate secretory and motor events with the start of phase III activity in the upper small intestine.

Animals↗