Search PubMed⌕ Search

Biomedical subjects

J D Lane

Publications and source records attributed to J D Lane.

At least 91 records · Page 5Linked to original sources
PubMed1980

Characterization of experimental phenylketonuria. Augmentation of hyperphenylalaninemia with alpha-methylphenylalanine and p-chlorophenylalanine.

Phenylalanine in conjunction with p-chlorophenylalanine or alpha-methylphenylalanine was administered to suckling rats to induce hyperphenylalaninemia reminiscent of untreated phenylketonuria, and developmental parameters were monitored. The experimental model utilizing p-chlorophenylalanine was found to be unsatisfactory, in that the drug had general deleterious effects on growth, numerous side effects including increased mortality, and affected brain levels of biogenic monoamine neurotransmitters. The model utilizing alpha-methylphenylalanine was relatively free from nonspecific effects and thus, changes observed in the animals were attributable to experimental phenylketonuria. The latter animals had slightly decreased body and brain weights, and exhibited grossly elevated serum phenylalanine and urinary excretion of phenylketone metabolites. Hyperphenylalaninemia produced greatly disrupted brain amino acids at 10 days of age (prior to the formalization of the blood-brain barrier and specific transport systems) which was limited by 30 days of age to changes in glycine, gamma-aminobutyric acid and the aliphatic and aromatic amino acids which compete for uptake in the brain by a common carrier. These animals also exhibited a myelin deficit and changes in proteins from isolated nerve cell preparations. Mature animals which had daily treatment up to 60 days of age exhibited a long-term learning impairment. These observations are consistent with many aspects of the clinical picture of untreated phenylketonuric patients, and suggest that this animal model will be beneficial in studying the disease.

Age Factors↗
PubMed1980

Phenylketonuria: clinical and experimental considerations revealed by the use of animal models.

Phenylketonuria is a genetic defect that leads to imbecility, if the diagnosis is not made directly after birth. Since the development of imbecility can be almost totally halted by suitable dietary treatment, phenylketonuria is of more interest to neurochemists than to clinicians. This genetic defect is not known to occur in aminals. It is therefore necessary to develop suitable models for neurochemical analysis. Most successful is the simultaneous application to developing rats of alpha-methyl-phenylalanine (an inhibitor of phenylalanine hydroxylase), together with phenylalanine. With this treatment it is possible to induce changes in the central nervous system which are surprisingly similar to those found in patients with phenylketonuria. This model is therefore of great importance in the analyses of the disturbances of metabolism, which finally causes the severe defects in normal brain function.

Animals↗
PubMed1980

Dissociation of myelin from its 'enzyme markers' during ontogeny.

To avoid any loss of membranes, total particulate material prepared from the forebrain and spinal cord of rats of different ages was fractionated on linear sucrose gradients. Particle distribution, proteins and enzyme activities were measured. Beginning at early ages, optical density increases were observed around 0.60 M-sucrose, which corresponded to myelin deposition, and were expressed by the appearance of typical myelin proteins, which paralleled the peak activity of myelin-associated enzymes. During later development myelin proteins were found over a broad density range together with optical density shifts to higher (forebrain) and lower (spinal cord) values. In both regions myelin-associated enzymes shifted to heavier densities and were dissociated from the density region commonly considered to be compacted myelin.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1979

Carbonic anhydrase activity in myelin fractions from rat optic nerves.

The carbonic anhydrase activity of myelin fractions isolated from the optic nerves of adult and immature (20-day-old) rats was examined. The specific activity in both total homogenate and myelin fractions was about 2-fold higher in adult than in immature animals and at both ages, the activity in the homogenate was higher than in myelin. After subfractionation by zonal gradient centrifugation, it was shown that carbonic anhydrase activity was greatest in the heaviest myelin particles at both ages. These data are consistent with the hypothesis that a small proportion of the total enzyme activity is localised in myelin.

Aging↗
PubMed1979

The fluorescence scanning of microgels stained for glycoproteins with fluorescein isothiocyanate-labelled concanavalin A.

A technique is presented which allows one to label and quantitate glycoproteins. Small amounts of protein from biological samples (0.5-2.5 microgram for mixtures and less for individual proteins) are separated by sodium dodecyl sulfate gel electrophoresis on 1-30% polyacrylamide gradient microgels. The gels are stained with Co-omassie Brillant Blue R250 to evaluate relative migration or fixed in 2-propanol/acetic acid and stained with fluorescein isothiocyanate-labelled concanavalin A. The microgels are then scanned using a fluorescence microscope controlled by a computer, although simpler configurations are possible. Standards of known carbohydrate composition (e.g., glucose oxidase) are used for comparative purposes. Glycoproteins in the order of 5-30 ng protein (or 1-5 ng carbohydrate) can be detected without difficulty. This technique may prove valuable in evaluating glycoproteins when the available material is limited.

Animals↗