Search PubMed⌕ Search

Biomedical subjects

M C Kuo

Publications and source records attributed to M C Kuo.

62 records · Page 4Linked to original sources

Determination of individual side-chain conformations, tertiary conformations, and molecular topography of tyrocidine A from scalar coupling constants and chemical shifts.

We report for the decapeptide tyrocidine A: (a) H alpha and H beta chemical shifts and scalar coupling constants for most residues of tyrocidine A in methanol-d4 and dimethyl-d6 sulfoxide (Me2so-d6) and the H alpha and H beta chemical shifts for other residues; (b) scalar coupling constants 3J alpha beta for nine side chains in methanol-d4 but only seven side chains in Me2SO-d6, due to chemical shift degeneracy; the Gln9 and Tyr10 side chains in methanol-d4 were only approximately analyzed; (c) a total spin-spin analysis of Pro5 in Me2SO-d6 and, partly by comparison, also in methanol-d4; (d) conversion of 3J alpha beta values to side-chain conformations for all residues in methanol-d4; comparisons, where possible, led to the conclusion that side-chain conformations are similar in methanol-d4 and Me2SO-d6; (e) an absolute conformational analysis of Pro5 from 3J values and a method of assigning all pro-R,S protons; Pro5 has a Ramachandran B, C2-Cexo-Cendo conformation; (f) chi 1, chi 2 conformations of several aromatic residues based upon proton-chromophore distance measurement from anomalous chemical shifts and Johnson-Bovey diagrams; (g) pro-R and pro-S assignments of H beta's from anomalous chemical shifts, high-temperature dependence of anomalous chemical shifts, and backbone side-chain nuclear Overhauser effects; (h) most tertiary conformations of the whole tyrocidine A molecule possessing residues 4--8 and 10 in highly preferred (ca. 90%) chi 1 conformations, but residues 1--3 and 9 having at least two chi 1 rotamers; (2) description of three topographical regions of the molecule--a hydrophobic region, a flat hydrophilic surface on the other side of the molecule, and a hydrophilic region consisting of two peptide backbone units and the side chains of Asn8, Gln9, and Tyr10; (j) proposed side chain, beta-turn, and beta-pleated sheet conformations that readily account for all "normal" and anomalous chemical shifts.

Amino Acids↗

The quantitation of nuclear Overhauser effect methods for total conformational analysis of peptides in solution. Application to gramicidin S.

The [1H:1H] nuclear Overhauser effects (NOE's) and spin-lattice relaxation times (T1's) are reported for the backbone protons of the decapeptide gramicidin S. Several methods for calculating interproton distances from these measurements are presented. Ratios of interproton distances were obtained from [1H:1H] NOE's and from the combination of [1H:1H]NOE'S and T1 values. Actual proton-proton distances were calculated from these ratios either by using the known distance between two geminal protons or distances derived from scalar coupling constants. The interproton distances calculated for gramicidin S are consistent with a II' beta-turn/antiparallel beta-sheet conformation.

Gramicidin↗

Effects of thrombopoietin on megakaryocyte colony formation from leukemic cells at diagnosis and from marrow cells after induction chemotherapy for acute leukemias.

We have studied the effects of recombinant human thrombopoietin (TPO, mpl ligand) on the megakaryocyte colony formation from control human bone marrow cells, human leukemia cells at diagnosis, and human bone marrow cells after induction chemotherapy for acute leukemias. In the control human bone marrow cells from four adults and nine children who had localized malignancy and histologically normal-looking marrow. TPO alone effectively stimulated megakaryocyte colony formation, and interleukin-3 (IL-3) synergized this. In 17 patients (13 adults and four children) with acute myeloid leukemia (AML) at diagnosis, TPO stimulated leukemic colony formation in only one patient with FAB M7 subtype. In 11 children with acute lymphoblastic leukemia (ALL) at diagnosis, TPO did not enhance leukemic colony formation. After 17 courses of induction chemotherapy, nine for AML and eight for ALL, TPO stimulated megakaryocyte colony formation to a level of 51%, of that in the control human bone marrow cells. This may suggest that the administration of TPO to patients with M7 subtype warrants caution, whereas it is probably safe to give TPO at any time to patients with ALL. The administration of TPO to patients with acute leukemias after induction chemotherapy could stimulate megakaryocytopoiesis.

Acute Disease↗

Granulopoiesis in newly diagnosed childhood solid tumors.

Granulopoiesis at the diagnosis of solid tumors has not been previously reported. The purpose of this study is to detect the changes of granulopoiesis of patients with solid tumors in different clinical stages. Granulocyte-macrophage colony-forming unit (CFU-GM) assays and liquid suspension cultures of bone marrow and peripheral blood were studied in 90 children with newly diagnosed solid tumors, including 5 benign tumors and 85 malignant tumors. The malignant tumors were categorized into nonadvanced, advanced, or marrow-invaded ones. Bone marrow from children with immune thrombocytopenic purpura and peripheral blood from adult volunteers were used as controls. Granulocyte-macrophage colony formation from bone marrow in benign or nonadvanced malignant tumor was not significantly different from that of controls. However, granulocyte macrophage colony formation from bone marrow in advanced or marrow-invaded malignant tumor was significantly less than that of controls or nonadvanced malignant tumor. Furthermore, the bone marrow of patients with advanced malignant tumor occasionally had a defective proliferation pattern and the bone marrow of those with marrow-invaded malignant tumor often had a defective proliferation pattern. Peripheral blood in marrow-invaded malignant tumor had colony and cluster formations in very wide ranges. As a malignant tumor progresses into advanced stages, irrespective of marrow infiltration, bone marrow CFU-GM levels may decline and defective granulopoiesis may occur.

Adolescent↗

Clinical use of single-dose surfactant TA therapy for premature infants with severe respiratory distress syndrome.

A single dose of surfactant TA was given as rescue therapy to four small premature infants with severe respiratory distress syndrome requiring mechanical ventilation. Birth weights ranged from 810 to 1200 gm. The dose of 100-120 mg/kg was given at the mean age of 5 hours, with range of 3 to 7 hours. Following surfactant therapy, there was a significant improvement (p < 0.05) in a/APO2 (raising from 0.11 +/- 0.05 before treatment to 0.34 +/- 0.19 at 6 hours after treatment). There was also a significant reduction in the severity of respiratory distress syndrome at 24 hours post-therapy. One baby died of sepsis at 40 hours of life; one survived without complications. The other two cases developed severe bronchopulmonary dysplasia later. We concluded that early use of exogenous surfactant is beneficial in small premature infants with severe respiratory distress syndrome.

Female↗