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M Luo

Publications and source records attributed to M Luo.

At least 181 records · Page 10Linked to original sources
PubMed1988

Crystallization and preliminary X-ray analysis of type B influenza virus neuraminidase complexed with antibody Fab fragments.

Fab fragments from four different monoclonal antibodies have been complexed with influenza B virus neuraminidase (B/Lee/40) and the complexes have been crystallized. Three of the complex crystals are, so far, not suitable for X-ray diffraction studies, but the fourth (B/Lee/40 NA-B1Fab) forms large crystals which diffract X-rays to 3.0 A resolution. The crystals have a space group of F432, a = 441.21 A. Vm calculations show that the asymmetric unit contains two monomeric complexes.

Antibodies, Monoclonal↗
PubMed1987

The atomic structure of Mengo virus at 3.0 A resolution.

The structure of Mengo virus, a representative member of the cardio picornaviruses, is substantially different from the structures of rhino- and polioviruses. The structure of Mengo virus was solved with the use of human rhinovirus 14 as an 8 A resolution structural approximation. Phase information was then extended to 3 A resolution by use of the icosahedral symmetry. This procedure gives promise that many other virus structures also can be determined without the use of the isomorphous replacement technique. Although the organization of the major capsid proteins VP1, VP2, and VP3 of Mengo virus is essentially the same as in rhino- and polioviruses, large insertions and deletions, mostly in VP1, radically alter the surface features. In particular, the putative receptor binding "canyon" of human rhinovirus 14 becomes a deep "pit" in Mengo virus because of polypeptide insertions in VP1 that fill part of the canyon. The minor capsid peptide, VP4, is completely internal in Mengo virus, but its association with the other capsid proteins is substantially different from that in rhino- or poliovirus. However, its carboxyl terminus is located at a position similar to that in human rhinovirus 14 and poliovirus, suggesting the same autocatalytic cleavage of VP0 to VP4 and VP2 takes place during assembly in all these picornaviruses.

Antigens, Viral↗
PubMed1987

Comparison of the three-dimensional structure of two human rhinoviruses (HRV2 and HRV14).

An attempt has been made to build a model of human rhinovirus 2 (HRV2) based on the known human rhinovirus 14 (HRV14) structure. HRV2 was selected because its amino acid sequence is known and because it belongs to the minor rhinovirus receptor class as compared to HRV14, which belongs to the major class. Initial alignment of HRV2 with HRV14 based on the primary sequence and the knowledge of the three-dimensional structure of HRV14 showed that the most probable position of the majority of insertions and deletions occurred in the vicinity of the neutralizing immunogenic sites (NIm). Out of a total of 855 amino acids present in one copy of each of the capsid proteins VP1 through VP4 of HRV14, 411 are different between the two viruses. There are also 6 amino acid residues inserted and 14 residues deleted in HRV2 relative to HRV14. Examination of amino acid interactions showed several cases of conservation of function, e.g., salt bridges or the filling of restricted space. The largest variation amongst the residues lining the canyon, the putative receptor binding site, was in the carboxy-terminal residues of VP1.

Amino Acid Sequence↗
PubMed1987

Implications of the picornavirus capsid structure for polyprotein processing.

Mature picornaviral proteins are derived by progressive, posttranslational cleavage of a precursor polyprotein. These cleavages play a role in the control of virus functions. Although the processed termini are separated by as much as 75 A in the native virus capsid, the fold and arrangement of polypeptide chains in a protomer before proteolysis are likely to be similar to that found in the mature virus. The three-dimensional structures of rhinovirus and Mengo virus suggest that the cleavage sites within the protomeric precursor are in structurally flexible regions. The final proteolytic processing event, maturation of the virion peptide VP0 (also called peptide 1AB) appears to occur by an unusual autocatalytic serine protease-type mechanism possibly involving viral RNA basic groups that would serve as proton-abstractors during the cleavage reaction.

Capsid↗
PubMed1986

The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating.

WIN 51711 and WIN 52084 are structurally related, antiviral compounds that inhibit the replication of rhino (common cold) viruses and related picornaviruses. They prevent the pH-mediated uncoating of the viral RNA. The compounds consist of a 3-methylisoxazole group that inserts itself into the hydrophobic interior of the VP1 beta-barrel, a connecting seven-membered aliphatic chain, and a 4-oxazolinylphenoxy group (OP) that covers the entrance to an ion channel in the floor of the "canyon." Viral disassembly may be inhibited by preventing the collapse of the VP1 hydrophobic pocket or by blocking the flow of ions into the virus interior.

Antiviral Agents↗
PubMed1986

Ontogenesis of nuclear T3 receptors in primary cultured astrocytes and neurons.

Nuclear T3 receptor (NTR) have been characterized in separated cultures of neurons and astrocytes. Scatchard analysis indicated the presence of a single class of high-affinity sites in both cell lines. The apparent equilibrium association constant ranged from 1.80 +/- 0.41 X 10(10) M-1 to 3.27 +/- 0.74 +/- 10(10) M-1 in neurons and from 1.01 +/- 0.09 to 1.80 +/- 0.73 X 10(10) M-1 in astrocytes depending on the time in culture. In neurons, the maximal binding capacity (MBC) increased from 0.049 +/- 0.008 ng T3/mg DNA to 0.328 +/- 0.052 ng T3/mg DNA between 3 and 12 days of culture. In astrocytes, the changes in MBC were less pronounced ranging from a minimum of 0.095 +/- 0.024 ng T3/mg DNA at the 7th day of culture to a maximum of 0.198 +/- 0.048 ng T3/mg DNA at the 21st day. The relative binding affinity of the receptor for thyroid hormone analogs was in the order TRIAC greater than L-T3 greater than D-T3 greater than L-T4 in both cell lines. These results show that nuclear T3 receptors similar to those found in vivo are present in primary cultures of both astrocytes and neurons.

Animals↗
PubMed1986

Regulation of protein phosphorylation by triiodothyronine (T3) in neural cell cultures. Part I: Astrocytes.

Dissociated cells from 2-day-old rat cerebral hemispheres were cultured for 17 days in absence of thyroid hormones using conditions yielding mainly glial cells. Triiodothyronine (10(-8) M) was added for 0-72 h before the end of the incubation and [32P]phosphate was added for the last 4 h. Soluble (105,000 X g supernatant), particulate (105,000 X g pellet) and HMG (high mobility group; 0.75 M perchloric acid-soluble proteins) fractions were prepared and phosphorylated proteins in each fraction were analyzed by polyacrylamide gel electrophoresis. In the soluble fraction a protein (Mr = 19,000) incorporates less [32P]phosphate after only 4 h of T3 treatment. The maximal effect is attained after 7 h (-42%) and remains unchanged up until 72 h. In this fraction, the phosphorylation of some other proteins is increased but the maximal effect is observed 48 and 72 h after T3 administration. In the particulate fraction, exposure to T3 rapidly (4 h) increases the amount of a protein (Mr = 45,000) identified as beta-actin. Protein phosphorylation in this fraction is slightly, or not at all, affected by T3. In contrast, a rapid (between 4 and 7 h) increased phosphorylation of a 17 kDa protein in the HMG fraction is observed following T3 stimulation. This nuclear protein was further characterized as HMG 14. These results show that thyroid hormones can produce direct effects (not mediated by neurons) on the phosphorylation of specific proteins in cultured glial cells. Possible functional implications of the observed protein changes are discussed in this paper.

Actins↗
PubMed1986

Regulation of protein phosphorylation by triiodothyronine (T3) in neural cell cultures. Part II: Neurons.

Cerebral hemisphere from 16- to 18-day-old rat fetuses were dissociated and cells were cultured in absence of thyroid hormones. Neuron-enriched cultures were obtained either by using cells after 6 days of culture (before extensive glial cell proliferation) or by adding cytosine arabinoside for 48 h after 4 days of culture and using cells on day 9. Cells were incubated with T3 (10(-8) M) for 0-72 h and [32P]phosphate was added for the last 4 h of incubation. HMG (high mobility group; 0.75 M perchloric acid-soluble proteins) were prepared and phosphorylated proteins were analyzed by polyacrylamide gel electrophoresis. T3 rapidly (4-7 h) increased the phosphorylation of histone H1 and of a protein with apparent molecular mass of 17000 Da identified as HMG 14. In addition, in cells not treated with cytosine arabinoside, histone H1 was resolved into 3 subfractions and each of these responded to the hormone with a different time course. These results indicate that thyroid hormones act on the phosphorylation of specific nuclear proteins and therefore may influence chromatin structure and gene expression in primary neuronal cell cultures.

Animals↗
PubMed1984

Picornaviruses of two different genera have similar structures.

Crystals of Mengo virus were used to collect three-dimensional X-ray diffraction data to 7 A resolution. A self-rotation function showed the precise orientation of the Mengo particles in the crystal unit cell. A cross-rotation function against similar data of cubic rhinovirus crystals showed a peak when the orientations of these two icosahedral viruses were superimposed. This demonstrates similarity of capsid construction between two picornaviruses of different taxonomic genera.

Crystallization↗
PubMed1984

Virion orientation in cubic crystals of the human common cold virus HRV14.

A new cubic crystal form (a = 445.1 A) of space group P23 is reported for human rhinovirus R14. There are four particles per unit cell, each situated on a crystallographic 3-fold axis. The orientation of these particles has been determined with a rotation function and their approximate positions have been derived from a Patterson map. The crystals diffract to at least 2.8 A resolution. Limitations to the possible surface features of the virus are set by a comparison of the cubic and orthorhombic crystal forms.

Animals↗
PubMedDate not supplied

Phenacetin O-deethylation in extrahepatic tissues of rats.

Phenacetin O-deethylation is a marker reaction of CYP450 1A2 activity. The drug-metabolizing enzyme is constitutively expressed in liver. In this study, an in vivo rat model for assessment of extrahepatic metabolism was used to investigate phenacetin O-deethylation and the alterations in the disposition of phenacetin due to the loss of liver function. Rats were divided into the model and normal control groups. The model was established according to our previously described method. The concentrations of phenacetin and its major metabolites acetaminophen, glucuronate-acetaminophen and sulfate-acetaminophen in plasma and urine were determined by HPLC. 30 min after intravenous administration of 0.16% phenacetin 10 mg x kg(-1), plasma acetaminophen in the model group was only 3.6% of that in the control group (0.09+/-0.04 microg x mL(-1) vs 2.49+/-0.85 microg x mL(-1), n = 8). 30 min after intragastric injection of 0.4% phenacetin 30 mg x kg(-1), plasma acetaminophen formation was very slight, about 8.6% of plasma phenacetin in the model group (0.74+/-0.43 microg x mL(-1) acetaminophen vs 8.57+/-8.42 microg x mL(-1) phenacetin) and 6.8% in the control group (1.06+/-0.59 microg x mL(-1) acetaminophen vs 15.47+/-7.21 microg x mL(-1) phenacetin, n = 8); no significant differences were observed in plasma phenacetin, total acetaminophen and the ratio of acetaminophen to phenacetin between control and model groups. In the urine collected for 3 h after intravenous administration of 0.16% phenacetin 10 mg x kg(-1), the total recovery of acetaminophen (as free, glucuronate- and sulfate-acetaminophen ) in the model group was 4.6% of that in the control group (4.47+/-4.27 microg vs 96.63+/-8.50 microg, n = 6), but phenacetin recovery in the model group was 9 times higher than that in the control group (15.03+/-17.72 microg vs 1.66+/-0.50 microg). The results indicate that phenacetin O-deethylation in the extrahepatic tissues and the first-pass metabolism of the probe compound seem to be negligible in rats, but the renal excretion of phenacetin, as a compensation, dramatically increases in model rats.

Acetaminophen↗
PubMedDate not supplied

In vitro and in vivo antioxidant properties of gliclazide.

Diabetes is a state of increased oxidant stress and there is evidence that oxidation may play a role in the genesis of complications. Gliclazide, a sulfonylurea hypoglycemic drug, has been shown to possess free radical scavenging properties. This study examined the effects of in vitro supplementation with gliclazide and other sulfonylureas as on low-density lipoprotein (LDL) oxidation and the total plasma antioxidant capacity (TPAC). In a separate study, the effects of 10 months of oral gliclazide therapy on oxidative parameters were assessed in 44 type 2 diabetic patients. Gliclazide, but not glibenclamide, glimepiride, glipizide or tolbutamide, inhibited LDL oxidation and enhanced TPAC. With the addition of 1 microM gliclazide, oxidation lag time increased from 53.6+/-2.6 to 113.6+/-5.1 min (p<0.001), and TPAC increased from 1. 09+/-0.11 to 1.23+/-0.11 mM (p<0.01). Administration of either modified release or standard gliclazide to type 2 diabetic patients resulted in a fall in 8-isoprostanes, a marker of lipid oxidation, and an increase in the antioxidant parameters TPAC, SOD and thiols. These studies show that gliclazide possesses antioxidant properties that produce measurable clinical effects at therapeutic doses.

Antioxidants↗