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Biomedical subjects

T M Chang

Publications and source records attributed to T M Chang.

At least 271 records · Page 15Linked to original sources

Effect of rabbit antimotilin serum on myoelectric activity and plasma motilin concentration in fasting dog.

It is known that a cyclic increase in plasma motilin concentration occurs during the interdigestive state of dog and the increase coincides with migrating myoelectric complexes (MMCs) of the antrum as well as proximal duodenum. The purpose of the present study is to determine the role of endogenous motilin in the occurrence of MMCs in 10 dogs prepared with a gastric cannula and platinum monopolar electrodes in the gastric antrum, duodenum, jejunum, and ileum. After recording at least two consecutive cycles of MMCs from the proximal duodenum, each dog received an intravenous infusion of highly specific rabbit antimotilin sera in varying doses ranging from 3.5 to 15 ml for a period of 60 or 90 min. During the motility recording period ranging from 6 to 30 h following the administration of the antimotilin serum, several changes in the motility were observed. 1) The occurrence of MMCs in the antrum, duodenum, jejunum, and ileum was temporarily interrupted for varying periods depending on the individual dog studied and the amount of antiserum administered. When the higher dose of antimotilin was administered, a more profound and prolonged inhibition occurred. 2) Phase I activity rarely occurred. Instead, a phase II-like activity continued throughout the recording period. 3) MMCs in the jejunum or ileum occurred at irregular intervals without aboral propagation of MMCs from the duodenum or jejunum. 4) The plasma motilin concentration decreased to levels lower than that observed during phase I of the duodenum and exhibited no cyclic increase until the MMCs reappeared in the proximal duodenum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Secretin-like immunoreactivity and biological activity in the antral mucosa.

Using immunohistocytochemical techniques, secretin cells are again demonstrated in the antral mucosae of both dogs and rats. Secretin-like immunoreactivity was found in the crude extracts of antral mucosae in 15 dogs [1.18 +/- 0.48 (+/- SE) ng/g wet wt of mucosae], and a similar amount of SLI was also found in 82 rat antral mucosae. Upon ion exchange chromatography, the extracts of dog antral mucosae exhibited a predominant species eluted by the same salt concentration as porcine secretin. The rat antral mucosal extract also produced a chromatogram exhibiting the same predominant species on the ion exchanger. The main immunoreactive secretin peak, when gel filtrated on a Sephadex G-50 (superfine) column, produced an elution profile identical to that of standard natural porcine secretin. These results indicated that antral mucosae of both animal species contain an immunoreactive secretin-like material of the same charge and size as natural porcine secretin. Intravenous injection of a preparation of partially purified secretin from the extracts of canine antral mucosae resulted in a significant increase in the pancreatic flow in anesthetized rats. We conclude that a small number of secretin cells are, therefore, present in the antral mucosae of dog and rat, and this observation is supported by the presence of an immunologically and biologically active secretin-like molecule with charge and size similar to those of porcine secretin in the canine mucosal extracts.

Animals↗

In vitro adsorption spectrum of plasma amino acids by coated charcoal hemoperfusion.

In order to clarify whether coated charcoal hemoperfusion is capable of normalizing amino acid disturbances in hepatic coma, in vitro adsorption and in vitro hemoperfusion studies were carried out. We have found that collodion-coated activated charcoal beads preferentially removed much more aromatic acids (AAA) than branched chain amino acids (BCAA). In the in vitro adsorption experiment with 50 microM amino acid standards aqueous solution, 99% of AAAs were removed by charcoal while only 50 to 81% of BCAAs were removed. As the concentration of amino acids in solution was doubled from microM to 100 microM, BCAA removal was halved while about 90% of AAA was still being removed. In vitro hemoperfusion with heparinized blood from hepatic failure rats, the clearance and the removal of AAAs were significantly greater than those of BCAAs. Consequently, the molar ratio of BCAA over AAA was markedly improved from the initial 1.09 to 3.87 after 60 min of hemoperfusion. Thus, we have demonstrated the preferential adsorption of aromatic amino acids by collodion-coated charcoal beads. The correction of BCAA/AAA molar ratio is also demonstrated.

Adsorption↗

Middle molecules in the serum, brain, liver and urine of galactosamine-induced fulminant hepatic failure rats.

The middle-molecular weight compounds in the serum, liver, brain and urine were determined in normal and galactosamine-induced grade III coma fulminant hepatic failure (FHF) rats. Peak 7 and subpeak 7g middle molecules increased significantly in the serum of hepatic coma rats. In the brain of grade III coma FHF rats, subpeak 7g increased significantly but peak 7 and other subpeaks decreased significantly. In the liver and urine, both peak 7 and subpeak 7g decreased significantly in grade III coma FHF rats. This rather specific increase of subpeak 7g in the brain corresponding to the increase of subpeak 7g in the serum may contribute to further understanding of the role of middle molecules in hepatic coma.

Animals↗

Studies of the mechanism of cell intoxication by diphtheria toxin fragment A-asialoorosomucoid hybrid toxins. Evidence for utilization of an alternative receptor-mediated transport pathway.

In order to study the variables important for determining the cytotoxicity of protein-protein hybrid toxins, the disulfide and thioiether conjugates between diphtheria toxin fragment A (DTA) and asialoorosomucoid (ASOR) were synthesized, purified, and tested for cytotoxicity toward isolated rat hepatocytes as monitored by the inhibition of protein synthesis. After 4-h incubation at 37 degrees C, both DTA-ASOR conjugates were nontoxic, but were highly toxic in the presence of an inhibitor of 125I-ASOR degradation. At concentrations inhibiting 125I-ASOR degradation to the same extent, the efficiency of inhibitors to enhance the toxicity of both conjugates varied with the following rank order: colchicine greater than chloroquine greater than NH4Cl greater leupeptin greater than cytochalasin B. In the absence of an inhibitor, both conjugates, after 10-h incubation, also exhibited measurable toxicity at concentrations as low as 10(-9) M, and DTA-S-S-ASOR was 60 times more toxic than DTA-S-ASOR. In a physiological salt solution containing energy source and bovine serum albumin, both conjugates also exhibited partial inhibition of protein synthesis after 4-h incubation and were enhanced by 2 microM colchicine toward complete inhibition with similar C0.5 of 2 X 10(-10) M. The toxicity of the conjugates were prevented in the presence of excess ASOR. These results not only indicate that intracellular degradation is an important factor restricting the toxicity of the conjugates, but also indicate that the toxic entry of DTA activity from these hybrids is independent of lysosomal degradation. Consequently, it appears that conjugate toxicity is dependent on the release of DTA activity from an extralysosomal compartment whose pool size is increased by the inhibitors and the change of medium. The effects of the inhibitors to inhibit 125I-ASOR uptake and degradation were also studied to facilitate interpretation of their enhancement of conjugate toxicity. Specifically, colchicine inhibited both internalization and degradation of the ligand in a saturable fashion with a C0.5 of 0.5 microM and a maximum inhibition of 65%. The data of the present study are interpreted so as to support a hypothesis that two receptor-mediated pathways are involved in the internalization and transport to lysosomes of ASOR and DTA-ASOR conjugates, only one of which is colchicine-sensitive.

Animals↗

Intermittent vascular access for extracorporeal circulation in conscious rats: a new technique.

A new technique is described for repeated intermittent access to the systemic circulation in fully conscious rats for infusion or extracorporeal circulation. The femoral artery and vein of each rat were cannulated. The cannulas were then passed subcutaneously and exteriorized through the skin of the tail 2 cm from its base. The exposed cannulas were protected by a special plastic device. This new approach did not immobilize the rat except during access to the circulation; even then, only the distal portion of the tail was immobilized, thus allowing the animal to move freely. This way repeated access to the systemic circulation was easily achieved in the fully conscious rat.

Animals↗

Hemoperfusion in 1981.

The present status of hemoperfusion using the principle of artificial cells is described in detail using coated charcoal hemoperfusion as an example. The laboratory and clinical results show that in 1981 increasing numbers of new commercial models are approaching the efficiency and blood compatibility of the ACAC laboratory system. The results of hemoperfusion for uremia, acute intoxication and hepatic coma are analyzed. Other approaches are briefly discussed.

Albumins↗

Cross-linked stroma-free polyhemoglobin as a potential blood substitute.

Stroma-free hemoglobin is prepared from human blood and then cross-linked with glutaraldehyde to produce soluble polyhemoglobin. Results from animal studies show that in the case of polyhemoglobin, its level in the circulation remained unchanged at 77% of the injected amount when followed for 3 hours; whereas stroma-free hemoglobin was removed rapidly with a half-life of 87 minutes. Thus, cross-linking stroma-free hemoglobin into the polyhemoglobin form has solved the major problem of rapid removal of stroma-free hemoglobin from the circulation.

Animals↗