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Biomedical subjects

S C Chu

Publications and source records attributed to S C Chu.

35 records · Page 2Linked to original sources

Functional status of pancreatic islet in acute leukemia.

Using enzymatic assay and radioimmunoassay, we studied the functional status of pancreatic islet in 50 patients with acute leukemia. Oral glucose tolerance test and insulin and C peptide release were made in 40 patients before and after treatment. 14 patients who revealed diabetic curve and delayed insulin and C peptide release before treatment showed normal values in 6 after therapy. Five patients with impaired glucose tolerance and decreased insulin and C peptide release before treatment showed normalization of these parameters following therapy. Five patients with normal pretreatment values disclosed abnormal post-treatment results. The remaining 16 patients displayed normal results both before and after therapy. Anti-insulin antibodies were negative, and glucagon level was normal in all the 50 patients. The red cell insulin receptor binding rate analysed in 47 patients was significantly higher than in controls (P < 0.001). We considered that the disturbed glucose metabolism in acute leukemia was not uncommon mainly due to the dysfunction of pancreatic islet beta cells as a result of islet damage by leukemic cells, the effect of corticosteroid and chemotherapy and the preexisting diabetes. Impaired glucose metabolism had no influence on therapeutic effect.

Adolescent↗

Use of 1H/23Na and 1H/31P double frequency tuned birdcage coils to study in vivo carbon tetrachloride-induced hepatotoxicity in rats.

In vivo 1H and 23Na magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) techniques were used to study CCl4-induced acute hepatotoxicity in rats in situ. One or two hours following exposure to CCl4, a localized edematous region was detected in the liver by 1H MRI. The CCl4-induced edema was localized in a region surrounding the hepatic portal vein. With the use of a 23Na/1H double frequency tuned bird-cage imaging coil an increase in Na+ ion flux was also observed in the same region as the edematous region detected by 1H-MRI. Pretreatment with alpha-phenyl-tert-butyl nitrone (PBN), a free radical spin trap, 30 min prior to CCl4 exposure, was found to reduce the CCl4-induced edematous response in the liver observed in either 1H or 23Na-NMR images. Inhibition of the CCl4-induced edematous response in rat liver by PBN demonstrates that free radical intermediates, arising from the metabolism of CCl4, are possibly the key causal agents in the initiation of the edematous response. In addition, with the use of a 31P/1H double frequency tuned bird-cage imaging/spectroscopy coil, localized 31P spectra (ISIS) were obtained from the regions of CCl4-induced "tissue damage" observed in the 1H-MRI images. The most notable changes observed from the 31P spectra were an increase in inorganic phosphate (Pi) and a decrease in hepatocytosolic pH in the CCl4-treated rat livers in comparison to saline-treated control livers.

Animals↗

Inhibitory effects of flavonoids on Moloney murine leukemia virus reverse transcriptase activity.

Several flavonoids were tested for their effects on Moloney murine leukemia virus reverse transcriptase activity. Four groups of flavonoids, namely flavones, flavanones, flavonols, and flavanonols, were studied, and it was found that flavonols and flavanonols were very active in this regard while flavones and flavanones displayed very low activity. Among the flavonoids tested, fisetin, quercetin, myricetin, kaempferol, morin, (+/-)-taxifolin, (+)-catechin, and (-)-epicatechin were shown to be highly effective in inhibiting the reverse transcriptase activity. Structure-activity relationship analysis of these flavonoids revealed that the simultaneous presence of free hydroxyl groups at positions 3 and 4' enhanced the reverse transcriptase inhibitory activity. Replacement of the 3-hydroxyl group with a monosaccharide or of the 4'-hydroxyl group with a methyl group reduced inhibitory activity. The double bond at position 2 and 3 of the flavonoid's pyrone ring is not essential for inhibiting reverse transcriptase activity. The flavonoids studied demonstrated ability to inhibit the reverse transcriptase activity using either (rA)n(dT)12-18 or (rC)n(dG)12-18 as template-primers.

DNA Polymerase I↗

Trypsin inhibitor from the seeds of Acacia confusa.

A trypsin inhibitor (ACTI) was isolated and purified from the seeds of Acacia confusa by gel filtration, and trypsin-Sepharose 4B column affinity chromatography. The molecular weight of ACTI was found to be 21,000 +/- 1,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and amino acid composition analysis. ACTI contained four half-cystine and no methionine residues, and was rich in aspartic acid, glutamic acid, glycine, leucine, and lysine residues. The native trypsin inhibitor was composed of two polypeptide chains, and it inhibited trypsin and alpha-chymotrypsin stoichiometrically at the molar ratio of 1:1 and 2:1, respectively. The amino-terminal sequence analysis of the A. confusa trypsin inhibitor A and B chains revealed a more extensive homology with Acacia elata and silk tree trypsin inhibitors, and a less extensive homology with Kunitz soybean trypsin inhibitor.

Acacia↗

Bulk magnetic susceptibility shifts in NMR studies of compartmentalized samples: use of paramagnetic reagents.

The bulk magnetic susceptibility (BMS) shift of a nuclear resonance frequency caused by a paramagnetic compound is of importance in vivo NMR, both magnetic resonance spectroscopy and magnetic resonance imaging. However, since it is a rather complicated phenomenon, it has been the source of many misinterpretations in the literature. We have reworked and organized the theory of the BMS shift. This includes accounting for the important effects of local susceptibility. We have conducted experiments on phantom samples in order to illustrate the principles involved. Our phantoms consist of capillaries and coaxial cylinders. They simulate the situations of blood vessels oriented parallel and perpendicular to the magnetic field and the interstitial spaces surrounding them. In most of our experiments, the paramagnetic compound was one of several different hyperfine shift reagents for cation resonances. These were chosen to cover a range of potencies, in both magnitude and sign, of the shifts they produce. However, we also used a reagent which was incapable of inducing a hyperfine shift and thus could cause only a BMS shift. Although we report only 23Na spectra in this paper, the latter samples simulate the cases where one observes the water 1H resonance in experiments employing hyperfine shift reagents for cations. There have been a number of such investigations recently reported in the literature. The principles considered in this paper allow us to offer new interpretations for the results of several experiments published in the last few years.

Electron Spin Resonance Spectroscopy↗

Chimeric protein: abrin B chain-trypsin inhibitor conjugate as a new antitumor agent.

Abrin B chain and trypsin inhibitor isolated from Acacia confusa (ACTI) were covalently linked to form a chimeric protein (ANB-ACTI) with N-succinimidyl-3-(-2-pyridyldithio)propionate. The chimeric protein had 31% of trypsin inhibitory activity of ACTI and 7% of hemagglutinating activity of abrin B chain, but no inhibition on protein biosynthesis. ANB-ACTI had strong inhibitory effects on the growth of sarcoma 180 cells and Hela cell culture while the mixture of an equivalent amount of free abrin B chain and ACTI did not. The results suggests that abrin B chain of chimeric protein may act as a vector to carry ACTI into the tumor cells. ACTI into the tumor cells. ACTI in the chimeric protein potentiates its antitumor activity as well as its resistance to tryptic digestion.

Abrin↗

Dependence of the solvent proton 1/T1 on the iron content in normal human serum.

The iron content dependence of the spin-lattice relaxation rates (1/T1) of solvent protons in healthy human serum has been studied by FT NMR at 60 MHz. A linear relationship has been established between 1/T1 and the iron content (with a correlation of 0.89). Our data suggest that Fe(III)-transferrin can contribute to the relaxation rate in healthy human serum.

Humans↗

Successful replantation in ten-digit complete amputations.

The authors report a case of successful replantation of all fingers in a ten-finger complete amputation. Among the factors responsible for the successful outcome were an adequate number of microsurgically-trained resident surgeons and staff, good organization and supervision by senior staff, emphasis on precision and perseverance in the operative procedures, and postoperative management. Follow-up is 15 months, and the patient now has a pair of functionally and cosmetically good hands.

Adult↗

Adipose tissue abnormalities in cystic fibrosis: noninvasive determination of mono- and polyunsaturated fatty acids by carbon-13 topical magnetic resonance spectroscopy.

Natural abundance in vivo carbon-13 topical magnetic resonance (TMR) spectroscopy was used to assess human adipose tissue stores of essential (polyunsaturated) fatty acids. TMR spectra were obtained from 17 normal volunteers and nine cystic fibrosis patients using an Oxford TMR-32 with a surface coil that sampled tissue less than 1 cm below the surface of an extremity. Spectra were taken of lower leg adipose tissue. Polyunsaturated fatty acid content was determined by comparing peak heights of the polyunsaturated peak (internal unsaturated carbons, 128 ppm) to C-1 carboxyl groups (173 ppm). Monounsaturated fatty acid content was determined by subtracting the polyunsaturated peak from the peak observed for all unsaturated carbons (external unsaturated carbon, 130 ppm) and dividing this ratio by the carboxyl peak. In vivo TMR of normal volunteers resulted in observed polyunsaturated fatty acid content of 17.8 +/- 2.1% and a monounsaturated content of 44.8 +/- 3.8%. The polyunsaturated and monounsaturated fatty acid content of adipose tissue from the cystic fibrosis patients was 15.0 +/- 2.0% (p less than 0.005 versus normal volunteers) and 47.8 +/- 6.5% (NS), respectively. One cystic fibrosis patient without fat malabsorption had decreased adipose polyunsaturates, whereas another patient on high calorie gastrostomy feeds had normal levels. Carbon-13 TMR spectroscopy is a sensitive, noninvasive technique for determining essential fatty acid status in subcutaneous adipose tissue of patients with cystic fibrosis.

Adipose Tissue↗

The isolation and purification of pre-S2 containing hepatitis B virus surface antigen by chemical affinity chromatography.

A simple, rapid, and efficient method was developed to isolate and purify pre-S2 containing HBsAgs from the plasma of a single chronic carrier of HBsAg (adw) by ammonium sulfate fractionation, hydroxyapatite column chromatography, and polymerized human serum albumin-affinity column chromatography. About 500 micrograms of pre-S2 containing HBsAg was obtained from 140 mL of plasma containing 4,200 micrograms of HBsAg. Two purified pre-S2 containing HBsAgs were analyzed by SDS-polyacrylamide gel electrophoresis and their molecular weights were determined to be 31,000 and 68,000 respectively. No significant amount of HBsAg or its derivative was detected in the final product.

Chromatography↗

Biochemical and morphological studies on the percutaneous uptake of [14C] ethylenediamine in the rat.

Male Wistar rats were exposed to aqueous [14C]ethylenediamine (EDA) solutions (10, 25, or 50%) percutaneously over a 7 x 7 cm area on the back with occlusion for 24 h. For each rat dosed, three types of studies were conducted: (1) plasma kinetics, (2) material balance, and (3) histological evaluation, including autoradiography of the skin sample from the dosing area. Adequate kinetic measurements were obtained only from animals treated with 25 and 50% EDA, but not from the 10% treatment group, due to analytical limitations. The uptake of [14C]EDA percutaneously by the rat was relatively slow in comparison with uptake following peroral or endotracheal administration. The absorption of EDA by the animals was estimated to be greater than 61, 55, and 12%, respectively, for the 50, 25, and 10% treatment groups. A large portion (11-32%) of the dose was left on/in the dosing area. Urinary excretion was the predominant route for the disposition of EDA. The recovery of the administered dose was low (70-83%), possibly due to volatilization of EDA from the skin during dosing and holding. Histologic examination of skin sections (dosing areas) revealed a normal, intact epidermis in rats dosed with 10% EDA, but full-thickness epidermal necrosis in rats dosed with 25% or 50% EDA solutions. The damage of the epidermis apparently enhanced the penetration of EDA. Autoradiographic preparations revealed a concentration of the [14C]EDA radiolabel over the keratin layer and hair shafts.

Administration, Topical↗

The resistance of crosslinked insulin derivatives to pepsin and trypsin.

The introduction of a crosslink between the amino groups of A1-glycine and B29-lysine of the insulin molecule leads to a marked decrease in sensitivity towards pepsin. Under conditions where insulin is completely degraded over 70% of N alpha A1, N epsilon B29-(carbonyl-bis-methionyl) insulin [OC(Met)2] remain intact. The resistance increases with the length of the crosslink, i.e. oxalyl less than OC(Met)2 less than dodecanedioyl insulin. The carbonyl-bis-methionyl derivative is also stabilized against tryptic attack, but to a smaller degree.

Animals↗

Intramolecular enzymatic peptide synthesis: trypsin-mediated coupling of the peptide bond between B22-arginine and B23-glycine in a split crosslinked insulin.

The resealing of a split peptide bond (B22/23) in a crosslinked insulin derivative by a trypsin-mediated coupling reaction in Tris buffer/glycerol/dimethylsulphoxide 1 : 1 : 1 at pH 6.5 is described. The coupling yield obtained with N alpha A1, N epsilon B29-(carbonyl-bis-methionyl) insulin [OC(Met)2] was 55-60%, and reproducible yields of OC(Met)2-insulin were 40%. After removing the crosslink and purification, crystalline resynthesized insulin of high biological activity was obtained in a yield of 43% and an overall yield, based on split OC(Met)2-insulin, of 18%.

Animals↗