PubMed Health⌕ Search

Biomedical subjects

G Neal

Publications and source records attributed to G Neal.

9 recordsLinked to original sources
PubMed2003

Ultra scale-down approach for the prediction of full-scale recovery of ovine polycolonal immunoglobulins used in the manufacture of snake venom-specific Fab fragment.

In this article, we describe a new approach that allows the prediction of the performance of a large-scale integrated process for the primary recovery of a therapeutic antibody from an analysis of the individual unit operations and their interactions in an ultra scale-down mimic of the process. The recovery process consisted of four distinct unit operations. Using the new approach we defined the important engineering parameters in each operation that impacted the overall recovery process and in each case verified its effect by a combination of modelling and experimentation. Immunoglobulins were precipitated from large volumes of dilute blood plasma and the precipitated flocs were recovered by centrifugal separation from the liquor containing contaminating proteins, including albumin. The fluid mechanical forces acting on the precipitate and the time of exposure to these forces were used to define a time-integrated fluid stress. This was used as a scaling factor to predict the properties of the precipitated flocs at large scale. In the case of centrifugation, the performance of a full-scale disc stack centrifuge was predicted. This was achieved from a computational fluid dynamics (CFD) analysis of the flow field in the centrifuge coupled with experimental data obtained from the precipitated immunoglobulin flocs using the scale-down precipitation tank, a rotating shear device, and a standard swing-out rotor centrifuge operating under defined conditions. In this way, the performance of the individual unit operations, and their linkage, was successfully analysed from a combination of modelling and experiments. These experiments required only millilitre quantities of the process material. The overall performance of the large-scale process was predicted by tracking the changes in physical and biological properties of the key components in the system, including the size distribution of the antibody precipitates and antibody activity through the individual unit operations in the ultra scale-down process flowsheet.

Animals↗
PubMed1996

Clostridial meningitis as a result of craniocerebral arrow injury.

We report a case of a 6-year-old girl who presented with an arrow lodged in the temporal lobe and carotid sinus. Her postoperative recovery was complicated by a rare penicillin-resistant clostridial meningitis. A review of the literature reveals no other cases of this nature in the pediatric population.

Anti-Bacterial Agents↗
PubMed1988

Dominance in lambda S mutations and evidence for translational control.

Phenotypic analysis of a collection of point mutations in the lysis gene S of bacteriophage lambda indicates that many of the S alleles exhibit at least partially dominant character, suggesting that the S gene product (gpS) must oligomerize to achieve its lethal membrane effect. Moreover, mutations found 5' to the coding sequence also show a dominant character and appear to define a site, designated sdi (structure directed initiation) where mRNA secondary structure controls the choice of initiation codons. We propose that formation of the sdi structure occludes the consensus Shine-Dalgarno sequence and results in initiation at the Met3 codon, generating a lethal 105 residue polypeptide. The model predicts that, in the absence of the sdi stem-and-loop, initiation occurs at the Met1 codon, generating a 107 residue polypeptide, which is a non-lethal inhibitor of lysis. In support of the model, alteration of the first codon was achieved using site-directed mutagenesis, resulting in an S allele that is more lethal and induces lysis significantly sooner than the wild-type.

Amino Acid Sequence↗
PubMed1986

Mutational analysis of bacteriophage lambda lysis gene S.

A plasmid carrying the bacteriophage lambda lysis genes under lac control was subjected to hydroxylamine mutagenesis, and mutations eliminating the host lethality of the S gene were selected. DNA sequence analysis revealed 48 single-base mutations which resulted in alterations within the coding sequence of the S gene. Thirty-three different missense alleles were generated. Most of the missense changes clustered in the first two-thirds of the molecule from the N terminus. A simple model for the disposition of the S protein within the inner membrane can be derived from inspection of the primary sequence. In the first 60 residues, there are two distinct stretches of predominantly hydrophobic amino acids, each region having a net neutral charge and extending for at least 20 residues. These regions resemble canonical membrane-spanning domains. In the model, the two domains span the bilayer as a pair of net neutral charge helices, and the N-terminal 10 to 12 residues extend into the periplasm. The mutational pattern is largely consistent with the model. Charge changes within the putative imbedded regions render the protein nonfunctional. Loss of glycine residues at crucial reverse-turn domains which would be required to reorient the molecule to reenter the membrane also inactivate the molecule. Finally, a number of neutral and rather subtle mutations such as Ala to Val and Met to Ile are found, mostly within the putative spanning regions. Although no obvious explanation exists for this subtle and heterogeneous class of mutations, it is noted that all of the changes result in a loss of alpha-helical character as predicted by Chou-Fasman theoretical analysis. Alternative explanations for some of these changes are also possible, including a reduction in net translation rate due to substitution of a rare codon for a common one. The model and the pattern of mutations have implications for the probable oligomerization of the S protein at the time of endolysin release at the end of the vegetative growth period.

Alleles↗
PubMed1983

Metabolic basis of the species difference to aflatoxin B1 induced hepatotoxicity.

Primary metabolism of aflatoxin B1 by the liver microsomal enzymes from a range of animal species showed both quantitative and qualitative differences. Quail was shown to have the most rapid metabolism of aflatoxin B1. The major product of metabolism in this case was found to be aflatoxin B1-8,9-dihydrodiol suggesting that the quail microsomes produced high levels of the proposed reactive intermediate aflatoxin B1-8,9-epoxide. Using this system to generate the epoxide, the ability of the cytosol prepared from each species to conjugate epoxide with reduced glutathione was investigated. Large differences in ability to conjugate were observed ranging from 0 to 72% for quail and mouse respectively. Differences in both primary and secondary metabolism of AFB1 were noted between male and female Fischer 344 rats.

Aflatoxin B1↗
PubMed1980

The early changes in retinol-binding protein and prealbumin concentrations in plasma of protein-energy malnourished children after treatment with retinol and an improved diet.

1. Changes in total retinol-binding protein (RBP), the holoprotein (holoRBP) and prealbumin (PA) concentrations have been monitored in plasma of thirty protein- and vitamin A-deficient preschool children from within a few hours up to 7 weeks after treatment with retinol and a good-quality protein diet. 2. The children were classified into groups according to nutritional status as having either kwashiorkor, marasmus-kwashiorkor or marasmus, and given formula diets whose protein and energy contents increased stepwise from 1 g and 105 kJ/kg body-weight respectively up to 4 g and 733 kJ/kg body-weight after 4 weeks. Retinol was administered in the forms of retinyl palmitate either orally or intramuscularly. 3. PA and total RBP were determined by electroimmunoassay procedures and the holoRBP by its fluorescence after separation from other plasma proteins. 4. RBP in plasma of the vitamin A-deficient child is largely denatured and incapable of binding administered retinol, which must first be taken up by the liver before native holoRBP is released. An increased pool of native apoprotein accumulates in the liver during vitamin A deficiency which is released into plasma quickly after retinol uptake to form peak concentrations of total and holoRBP approximately 3 h after dosing intramuscularly and 6 h orally. 5. The accumulated pool of RBP was highest in livers from the marasmus group and lowest in those from the kwashiorkor group, reflecting their relative capacities to synthesize plasma proteins. 6. The mean plasma concentrations of total and holoRBP for the various groups were minimal 24-48 h after dosing with retinol and then improved almost linearly over the following week. 7. Mean plasma PA concentrations of the various groups on admission were also in order of the severity of their malnutrition. There was little or no change in this protein concentration over the first 24 h after dosing with retinol, but thereafter the mean values rose almost linearly over 2 weeks. Albumin on the other hand changed little during the first week. The results show that PA is the more sensitive measurement of protein nutritional status.

Child, Preschool↗
PubMed1980

Acute nickel intoxication by dialysis.

Nickel intoxication was observed in a group of 23 dialyzed patients when leaching of nickel-plated stainless steel water heater tank contaminated the dialysate. Symptoms occurred during and after dialysis at plasma nickel concentrations of approximately 3 mg/L. Symptoms included nausea (37 of 37), vomiting (31 of 37), weakness (29 of 37), headache (22 of 37), and palpitation (two of 37). Remission of symptoms occurred spontaneously, generally 3 to 13 hours after cessation of dialysis. The evidence indicated that the nickel became bound in the plasma after crossing the membrane, resulting in a higher concentration in the plasma than in the dialysate and preventing its removal by dialysis.

Heating↗