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Biomedical subjects

K Cho

Publications and source records attributed to K Cho.

At least 271 records · Page 15Linked to original sources
PubMed1986

Somatostatin analogue (SMS 201-995) in the management of gastroenteropancreatic tumors and diarrhea syndromes.

SMS 201-995 (Sandostatin) was studied using low doses (50 to 100 micrograms) administered subcutaneously every 12 hours. A single 50-micrograms dose of SMS 201-995 effectively controlled gastric acid and blood gastrin levels for 12 hours in three patients with benign gastrinomas and was useful in their perioperative management. Higher doses of the agent (500 to 800 micrograms per day) had no effect on metastases in one of two patients with metastatic gastrinoma. In the other patient, one tumor shrank but the other continued to grow after three months of treatment while serum gastrin levels did not change. Cultured metastatic tumor tissue from this patient released different forms of gastrin; growth rates varied, independent of uptake of SMS 201-995, and gastrin release increased. A neonate with nesidioblastosis maintained normal blood glucose levels while receiving SMS 201-995 therapy following a 95 percent pancreatic resection. In two elderly patients with organic hypoglycemia--one with a single benign adenoma and one with multiple adenomatosis--the somatostatin analogue did not prolong the hypoglycemia-free interval. In nine patients with carcinoid syndrome, flushing was uniformly controlled with 50 micrograms of SMS 201-995 administered every eight to 12 hours. One of the nine required exocrine pancreatic replacement. After six months of treatment, three of the nine had no change in tumor size and one had remission of symptoms and stopped treatment. In two patients with vipoma, SMS 201-995 controlled diarrhea and reduced levels of vasoactive intestinal peptide; tumor necrosis occurred in one patient. In a patient with diabetic diarrhea unresponsive to all treatments, SMS 201-995 therapy controlled the diarrhea but did not interfere with control of the diabetes.

Adenoma↗
PubMed1985

[Laboratory and clinical studies on BRL 25000 (clavulanic acid -amoxicillin) granules in the pediatric field].

Laboratory and clinical studies on BRL 25000 granules (containing clavulanic acid (CVA) 1 part plus amoxicillin (AMPC) 2 parts) were performed in infections in the pediatric field. Following oral administration of BRL 25000 granules at a dose of 15 mg/kg body weight, the maximum serum levels of AMPC and CVA achieved approximately 1 hour after dosing were 8.68 micrograms/ml and 4.09 micrograms/ml and declined thereafter with half-lives of 1.39 and 0.80 hours, respectively. The 6-hour urinary recovery rates for AMPC and CVA were 55.81% and 26.08%, respectively. Following oral administration of BRL 25000 granules at a dose of 22.5 and 24.3 mg/kg body weight, the serum levels of AMPC and CVA peaked at 7.37 micrograms/ml and 2.98 micrograms/ml after 1 hour and declined with half-lives of 2.52 and 0.99 hours, respectively. The 6-hour urinary recovery rates for AMPC and CVA were 40.02% and 13.95%, respectively. The clinical efficacy of BRL 25000 granules was evaluated in 23 patients with upper respiratory tract infections, skin infections, etc. Overall the clinical efficacy was good to excellent in 21/23 (91.3%). The bacteriological and clinical efficacy rates for beta-lactamase producing bacteria and non-producing bacteria were 50% (1/2) and 100% (12/12), respectively. Side effects were observed in 1 patient, who experienced mild diarrhea and abdominal pain but not of a severe nature.

Administration, Oral↗
PubMed1984

Peptide thioesters and 4-nitroanilides as substrates for porcine pancreatic kallikrein.

A series of 14 4-nitroanilide substrates and 17 thioester substrates have been used to measure kinetic constants with porcine pancreatic kallikrein. All of the substrates have a P1 arginine residue. The 4-nitroanilide substrates consist of seven P2-glycine and seven P2-phenylalanine tripeptides. As expected from previous results, the phenylalanine series substrates were generally 100-fold 'better' than those in the glycine series. The S3 subsite was found to 'prefer' lysine or phenylalanine, whereas glutamic acid in this position was distinctly unfavourable. The thioester substrates consisted of various thioester derivatives of arginine as well as 12 dipeptides. These substrates exhibited kcat./Km values generally 1000 times higher than the P2-phenylalanine 4-nitroanilides. With the thioesters, a P2 phenylalanine or tryptophan residue yielded the best substrates, but some of the simple derivatives of arginine were nearly as good. A comparison of the kinetic constants of the thioester substrates between the porcine enzyme and human plasma kallikrein provides further evidence that these enzymes have a similar preference for bulky P2 residues, but otherwise are quite different enzymes. The thioester substrates are nearly as reactive as oxygen ester substrates such as acetylphenylalanylarginine methyl ester for the porcine enzyme [Levison & Tomalin (1982) Biochem. J. 203, 299-302; Fiedler (1983) Adv. Exp. Med. Biol. 156A, 263-274], and owing to the greater ease in assaying with the thioesters, they should find use in routine assays for the glandular kallikreins.

Anilides↗
PubMed1984

Active-site mapping of bovine and human blood coagulation serine proteases using synthetic peptide 4-nitroanilide and thio ester substrates.

A series of 14 tripeptide 4-nitroanilide substrates of the type Z-AA-Gly-Arg-NA and Z-AA-Phe-Arg-NA where AA = Ala, Asn, Glu, Lys, Phe, Pro, or Ser were used to map the S3 subsite of several serine proteases involved in blood coagulation. The enzymes studied included bovine thrombin, factor IXa, factor Xa, factor XIa, human beta-factor XIIa (factor XIIa fragment), and activated bovine and human protein C. Kinetic constants (kcat, KM, and kcat/KM) for the enzymatic hydrolysis of the substrates by each enzyme were determined and used to compare the relative reactivities of the individual enzymes. Most of the enzymes reacted with all the substrates, although a few showed considerable specificity. Human beta-factor XIIa showed the highest reactivity of all the coagulation proteases studied and was also very substrate specific (kcat/KM ranged over 470-fold). The best substrate was Z-Lys-Phe-Arg-NA with kcat/KM = 140 000 M-1 s-1. Activated bovine protein C (best substrate = Z-Ser-Phe-Arg-NA), factor Xa (best substrate = Z-Glu-Gly-Arg-NA), and thrombin (best substrate = Z-Lys-Gly-Arg-NA) were the group of enzymes that showed next highest reactivity toward the substrates. Activated bovine protein C, thrombin, and factor Xa displayed relatively little substrate specificity. Activated human protein C (best substrate = Z-Ser-Phe-Arg-NA) and factor XIa (best substrate = Z-Glu-Gly-Arg-NA) are moderately reactive enzymes. Activated human protein C is an extremely specific enzyme since it has such a large range of kcat/KM values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Hydrostatic balloon dilatation for stomal stenosis after gastric partitioning.

Hydrostatic balloon dilatation has been used successfully to treat several patients with stomal stenosis occurring as a late complication of gastroplasty. The technique of hydrostatic balloon dilatation practiced in this institution is reviewed in detail. This technique appears to offer several advantages over previous techniques: 1) the procedure can be accomplished with intravenous sedation eliminating the need for general anesthesia; 2) trauma to the gastric channel is minimized because no attempt is made to manipulate the endoscope through the stoma into the distal stomach; 3) radiopaque markers on the polyethylene balloon catheter permit easy and accurate positioning of the balloon within the gastric channel; 4) the low compliance characteristics of the polyethylene balloon used permit inflation to a predetermined outer diameter with minimum risk of balloon deformity or overdistention and rupture; and 5) the procedure is easily standardized and can therefore be expected to yield reproducible results. Late stomal stenosis after gastric partitioning may respond to conservative therapy including nutritional support and dietary counselling. Hydrostatic balloon dilatation should be considered as the preferred method of stomal dilatation in patients refractory to alternative forms of management.

Adult↗
PubMed1983

Mammalian tissue trypsin-like enzymes. Comparative reactivities of human skin tryptase, human lung tryptase, and bovine trypsin with peptide 4-nitroanilide and thioester substrates.

The subsite specificity of human lung and skin tryptase (trypsin-like enzyme) has been studied at pH 7.5 using 17 amino acid and dipeptide thioester substrates and 14 tripeptide 4-nitroanilide substrates. The reactivity and specificity of the human tryptases were compared with bovine trypsin and other trypsin-like enzymes. Neither tryptase was similar to either kallikrein or factor XIIa (Hageman factor). The skin enzyme was the most reactive as measured by the specificity constant kcat/KM. The best substrate was benzyloxycarbonyl(Z)-Lys-Arg-S-CH2CH(CH3)2 which had a kcat/KM value of 59,000,000 M-1 S-1. Only a single substrate, Z-Glu-Phe-Arg-4-nitroanilide, was slightly more reactive with the lung tryptase. Both enzymes have extended substrate-binding sites and proline residues at P3 substantially decrease kcat/KM. Both enzymes preferred the tripeptide 4-nitroanilides with a P2 Gly residue over Phe, and both favored the substrate Z-Lys-Gly-Arg-4-nitroanilide over similar substrates containing six other representative amino acid residues at P3. The lung enzyme was inhibited over three times faster by p-amidinophenylmethanesulfonyl fluoride than the skin enzyme. The preference of the skin tryptase for substrates with two terminal basic residues indicates that this enzyme could process prohormones and proproteins which contain this structural feature at the cleavage site. The substrates reported in this paper should be useful for the further characterization of the physiologic function of tryptases.

Anilides↗
PubMed1982

Improved regional selectivity of hepatic arterial BCNU with degradable microspheres.

Starch microspheres 40 micrometers in diameter, which are rapidly degraded by serum amylase, have been administered through hepatic arterial catheters to five patients with primary and metastatic liver cancer to determine whether (1) arterial blood flow through the liver could be temporarily blocked, and (2) such occlusion at the level of the arteriolar capillary bed would enhance regional uptake and catabolism and decrease systemic exposure to simultaneously administered hepatic arterial bischlorethylnitrosourea (BCNU). It was possible with 10 ml of microspheres (9 X 10(6) microspheres/ml) injected into the hepatic artery to transiently (for 15-30 minutes) reduce hepatic flow by 80-100% in the five patients. When BCNU (50 mg/m2 in one minute) was given with microspheres there was a 30-90% reduction in systemic nitrosourea exposure and in peak levels. No myelosuppression was noted and hepatic toxicity consisted of acute pain due to BCNU and 1.5-2.0 fold transient enzyme elevations. One patient with cholangiocarcinoma showed a partial response lasting three months; three patients had stable disease and one patient with colon carcinoma had progressive disease. Thus, this pilot study suggests that concurrent intra-arterial microspheres and BCNU may have the potential to improve selective regional drug effect with marked diminution in systemic toxicity.

Carmustine↗
PubMed1982

Alpha-fetoprotein and carcinoembryonic antigen in pancreatobiliary disease with and without jaundice.

A comparative study of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) in serum was made by radioimmunoassay in 66 patients with pancreatobiliary disease with and without obstructive jaundice. biliary concentrations of these proteins were assayed in 12 patients with benign and 7 patients with malignant disease. There was no statistical difference in serum AFP between these two groups but there was a difference in serum CEA. Although CEA and AFP in bile in both groups were higher than in serum there was no statistical difference in serum CEA and AFP in patients with and without obstructive jaundice in either benign or malignant disease. In benign disease, patients with inflammation had higher serum CEA than normal. Although there was no statistical difference in serum CEA in patients with a without liver metastases, the serum CEA in liver metastases was significantly higher than in benign disease. We concluded that AFP is unlikely to be important in the assessment or management of patients with cancers other than those derived from the liver or yolk sac, and that the elevation of serum CEA in patients with malignant pancreatobiliary disease either with or without obstructive jaundice occurs mainly in the presence of widespread malignancy, especially in liver metastases.

Adult↗