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D F Wilson

Publications and source records attributed to D F Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1994

Relationship of extracellular dopamine in striatum of newborn piglets to cortical oxygen pressure.

The present studies describes the relationship between extracellular dopamine in striatum of newborn piglets and cortical oxygen pressure. The extracellular level of dopamine was measured by in vivo microdialysis and the oxygen pressure in the cortex was measured by phosphorescence lifetime of oxygen probe in the blood. Controlled, graded levels of hypoxic insult to the brain of animals were generated by decreasing of the oxygen fraction in the inspired gas (FiO2) from 21% to 14%, 11%, and 9%. This resulted in decrease in the cortical oxygen pressure from 31-35 Torr to about 24 Torr, 15 Torr and 4 Torr, respectively. The changes in extracellular level of dopamine, DOPAC and HVA were dependent on changes in cortical oxygen pressure. Stepwise decrease in the cortical oxygen pressure (see above) caused increases in extracellular dopamine of about 80%, 200% and 550%, respectively. The levels of DOPAC and HVA progressively decreased and when cortical oxygen decreased to 4-6 Torr were about 50% and 70% of control, respectively. After return of FiO2 to control (21%), the cortical oxygen pressure rapidly increased to above normal, then returned to control values. The extracellular levels of dopamine, DOPAC, and HVA recovered more slowly, attaining control values in about 30 minutes. The data show that extracellular levels of dopamine increase with even very small decreases in oxygen pressure. Thus, there is no "oxygen reserve" which protects dopamine release and metabolism from decrease in oxygen pressure.

Analysis of Variance↗
PubMed1994

3,4-dihydroxyphenylalanine (dopa) metabolism and retinoic acid induced differentiation in human neuroblastoma.

In mature cells of the sympathetic nervous system and the adrenal gland, the activity of dihydroxyphenylalanine decarboxylase (DDC) is higher than that of tyrosine hydroxylase and 3,4-dihydroxyphenylalanine (dopa) does not accumulate in the cells. On the other hand, it is known that in some neuroblastoma cells there is a relative deficiency of DDC, resulting in accumulation and secretion of dopa. Such a relative deficiency of DDC is a characteristic of neural cells at an early stage of neural crest development, suggesting the neuroblastoma are cells arrested in early neural crest development. If this were the case, it is possible that agents such as retinoic acid (RA) could induce neuroblastoma to differentiate into mature cells with respect to their metabolism of catecholamines. We have measured the effect of RA on the metabolism of dopa and expression of tyrosine hydroxylase and DDC in human neuroblastoma cell lines, CHP-126, CHP-134, IMR-32, NB-69, and LA-N-5. When the cell cultures were treated with RA, they showed wide variations in response as measured by morphological change, growth inhibition, enzyme activities and enzyme expressions. The RA treatment modulated the activities of tyrosine hydroxylase and DDC, but does not increase DDC relative to tyrosine hydroxylase. It is concluded that RA does not induce biochemical differentiation of the neuroblastoma into mature cells even when there are extensive morphological changes and suppression of growth rate.

Cell Differentiation↗
PubMed1994

Distribution of basal lamina type IV collagen and laminin in normal rat tongue mucosa and experimental oral carcinoma: ultrastructural immunolocalization and immunogold quantitation.

The relationship of basal lamina, a form of specialised extracellular matrix which separates epithelial cells and other cell types from adjacent stroma, to the behaviour of malignant neoplasms of epithelial origin is not well understood. However, it is widely acknowledged that the properties of local invasion and metastasis of carcinomas are linked to extracellular matrix (including basal lamina) changes. In the present study, the distribution of the major basal lamina components, type IV collagen and laminin, in normal rat tongue mucosa and experimentally induced oral carcinomas was investigated using post-embedding immunogold techniques and electron microscopy. The expression of these components was also quantitatively analysed using morphometry and immunocytochemistry. Results indicated that type IV collagen and laminin were confined to the lamina densa of normal oral epithelial basal lamina, and that both components were also detected in the lamina densa of basal lamina associated with carcinomas, and in the extracellular matrix of tumours. Furthermore, laminin was detected within stromal fibroblasts in normal tissues and experimental carcinomas. Quantitative analysis indicated that expression of laminin was significantly increased in carcinomas. In contrast, type IV collagen expression was significantly decreased. The quantitative changes observed in the two basal lamina constituents may be related to the process of tumour invasion, reflecting altered metabolic activities of tumour and stromal cells. These observations may be of use in understanding the architectural characteristics of oral mucosa basal lamina and in assessing the malignant potential of epithelial dysplasias or "premalignant" lesions.

4-Nitroquinoline-1-oxide↗
PubMed1994

Phosphorescence lifetime analysis with a quadratic programming algorithm for determining quencher distributions in heterogeneous systems.

A new method for analysis of phosphorescence lifetime distributions in heterogeneous systems has been developed. This method is based on decomposition of the data vector to a linearly independent set of exponentials and uses quadratic programming principles for x2 minimization. Solution of the resulting algorithm requires a finite number of calculations (it is not iterative) and is computationally fast and robust. The algorithm has been tested on various simulated decays and for analysis of phosphorescence measurements of experimental systems with descrete distributions of lifetimes. Critical analysis of the effect of signal-to-noise on the resolving capability of the algorithm is presented. This technique is recommended for resolution of the distributions of quencher concentration in heterogeneous samples, of which oxygen distributions in tissue is an important example. Phosphors of practical importance for biological oxygen measurements: Pd-meso-tetra (4-carboxyphenyl) porphyrin (PdTCPP) and Pd-meso-porphyrin (PdMP) have been used to provide experimental test of the algorithm.

Algorithms↗
PubMed1994

Oxygen pressure distribution in the heart in vivo and evaluation of the ischemic "border zone".

Quantitation of the oxygen pressure distribution in the heart provides an accurate definition of metabolically viable cells adjacent to ischemic injury. By injection of a phosphorescent oxygen probe into the blood of newborn piglets and illumination of the heart with monochromatic light, a series of images of the heart were collected with use of a gated intensified CCD camera. These sets of images were used to calculate two-dimensional maps of the oxygen pressure in the epicardial microvasculature. Occlusion of a distal arterial vessel resulted in a hypoxic area containing a central focus of near-zero oxygen pressure bordered by tissue with diminished but nonzero oxygen pressures. These border zones extended for several millimeters from the hypoxic core, with the oxygen pressures progressively increasing from the focus to the normoxic region. The maps of oxygen distribution obtained by phosphorescence imaging provide rapid and quantitative measure of the oxygen pressures in the beating heart in vivo. They accurately show the degree of oxygen deprivation and the extent of an ischemic border zone that may respond to treatment.

Animals↗
PubMed1994

Factors affecting the rate and energetics of mitochondrial oxidative phosphorylation.

Mitochondrial oxidative phosphorylation in vivo is dependent on the degree of reduction of the intramitochondrial reducing power ([NADH]/[NAD+], cytoplasmic energy state ([ATP]/[ADP][Pi]) and intracellular oxygen pressure. Each parameter is independently regulated, and increased reducing power by activating the mitochondrial dehydrogenases allows higher energy state at a given rate of ATP synthesis or a higher rate of ATP synthesis at a given energy state. The mitochondrial respiratory rate is determined by demand, i.e., the rate of ATP utilization by the cell, while the cellular energy state at that demand level is determined by supply, i.e., activity of the dehydrogenases expressed as [NADH]/[NAD+] and of cytoplasmic oxygen pressure.

Adenosine Diphosphate↗
PubMed1994

Computed tomographic diagnosis of X-linked congenital mixed deafness, fixation of the stapedial footplate, and perilymphatic gusher.

Stapes surgery for fixed footplate associated with X-linked congenital mixed hearing loss usually results in a "gusher" and severe worsening of hearing. Four patients with X-linked deafness were diagnosed by the characteristic temporal bone computed tomography (CT) findings of enlarged internal auditory canal, hypoplasia of the cochlear base, absent bony modiolus, abnormal vestibular aqueduct, and enlarged labyrinthine facial nerve canal. Three patients were scanned after stapes surgery resulted in a gusher and, in two patients, severe worsening of their hearing loss. Stapes fenestration in the other patient was avoided by CT recognition of the dysplasia. The authors believe that young males presenting with congenital mixed hearing loss should be studied with temporal bone CT prior to middle ear exploration.

Adolescent↗
PubMed1993

Laminin and type IV collagen in experimental rat oral carcinomas.

The pattern of staining and the distribution of laminin and type IV collagen in normal rat tongue mucosa and induced tongue carcinomas were investigated by immunohistochemical techniques. Both normal and neoplastic epithelial basement membrane revealed positive staining for laminin and type IV collagen. However, compared with normal tissue, carcinomas exhibited areas of increased density and thickness for laminin. Focal tumour basement membrane discontinuities were observed in some specimens stained for type IV collagen.

4-Nitroquinoline-1-oxide↗
PubMed1993

Ultrastructural features of normal epithelium and 4-nitroquinoline 1-oxide-induced carcinomas of the rat tongue.

An electron microscopical examination of normal rat lingual mucosa and 4-nitroquinoline 1-oxide (4NQO)-induced tongue carcinomas was undertaken. In normal rat tongue, the epithelium of papillae and interpapillary regions exhibited two distinct keratohyalin granule types and essentially similar ultrastructural cellular features in the different epithelial compartments. The interface between epithelium and connective tissue showed a continuous basal lamina. Compared with normal rat tongue epithelium, 4NQO-induced oral carcinomas revealed cellular and nuclear pleomorphism, atypical tonofilament aggregates, increased and swollen mitochondria, dilated intercellular spaces, local discontinuities and thickening of the basal lamina.

4-Nitroquinoline-1-oxide↗
PubMed1993

The effect of neurocatin on protein phosphorylation in striatal synaptosomes from rat brain.

Neurocatin, a neuroregulatory factor isolated from mammalian brain, is a powerful affector of protein phosphorylation in rat striatal synaptosomes. Two major synaptosomal phosphoproteins of approximately 80 and approximately 60 kDa, possibly synapsin I and tyrosine hydroxylase, were especially sensitive to neurocatin. Immunoprecipitation experiments confirmed that the 60-kDa protein is the enzyme tyrosine hydroxylase. At low concentrations of neurocatin (to approximately 7.5 ng/100 microliters of suspension), incorporation of 32P orthophosphate into these proteins increased with increasing neurocatin concentration. At 7.5 ng of neurocatin, incorporation of the label into the two proteins increased by 22 and 26%, respectively. Concentrations of neurocatin > 7.5 ng/100 microliters caused progressive decrease in incorporation of 32P into many synaptosomal proteins; by a concentration of neurocatin of approximately 45 ng/100 microliters, the level of 32P incorporation into many proteins was < or = 70% of control. The effects of neurocatin on synaptosomal protein phosphorylation were also dependent on the time of incubation. At a constant concentration of approximately 7.5 ng/100 microliters of neurocatin, increased incorporation of 32P into many proteins was measurable within 0.5 min and was maximal by 1 min. Incubation times > 2.0 min, showed progressive decrease in 32P incorporation. Removing extrasynaptosomal Ca2+ with EGTA attenuated the increased 32P incorporation induced by low neurocatin concentrations, suggesting that calcium plays a role in neurocatin-induced phosphorylation of rat striatal synaptosomal proteins. The reduced incorporation of label induced by high neurocatin concentrations, however, was not calcium dependent. The effects of neurocatin on the level of 32P incorporation into proteins were observed only in intact synaptosomes, consistent with this compound acting through receptors on the plasma membrane.

Animals↗
PubMed1993

Activity of tyrosine hydroxylase in the striatum of newborn piglets in response to hypocapnic hypoxia.

The effect of graded hypoxia induced by hyperventilation on the activity of tyrosine hydroxylase was measured in vivo by microdialysis. Microdialysis probes were inserted into the striatum of newborn piglets and perfused with medium containing 3-hydroxybenzylhydrazine, an inhibitor of L-aromatic amino acid decarboxylase. The level of 3,4-dihydroxyphenylalanine (DOPA) measured in the effluent dialysate was then an index of tyrosine hydroxylase activity. The oxygen pressure in the veins and capillaries of the cortex was measured, through a cranial window placed over the parietal cortex, by the phosphorescence lifetime of palladium-meso-tetra(4-carboxyphenyl)porphine added to the blood. After baseline measurements, PaCO2 was decreased from 38 torr (control value) to 19, 13, and 11 torr resulting in decreases in the cortical oxygen pressure from 40 +/- 6 torr to 26 +/- 3, 23 +/- 4, and 20 +/- 4 torr, respectively. Decrease in the oxygen pressure to 26 +/- 3 torr caused a statistically significant increase of 25-30% in the level of DOPA in the effluent perfusate. During the next step of increase in ventilator rate, when oxygen decreased only slightly, the level of DOPA remained at the higher level. Ventilation rates that lowered the oxygen pressure to below 20 torr, however, caused a progressive decrease in the level of DOPA. During recovery, the level of DOPA steadily increased, attaining 160% of control value after 1.5 h. When the oxygen pressure was decreased to 16 +/- 2 torr by a single increase in ventilator rate, the DOPA level decreased in the effluent to 15-20% below control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of graded levels of tissue oxygen pressure on dopamine metabolism in the striatum of newborn piglets.

The effect of graded levels of tissue hypoxia on the extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid has been monitored in vivo by microdialysis. Reproducible levels of decreased oxygen in the brain were obtained by increasing the rate of ventilation from the control value of 25/min to as high as 95/min. With increasing ventilatory rate, the oxygen pressure in the cortex decreased from approximately 40 torr to 16 torr. As the oxygen pressure decreased stepwise from 40 to 27, 22, and 16 torr, the dopamine levels in the extracellular medium rose by 70, 90, and 150%, respectively, returning to baseline within a few minutes of return to control ventilation rates. Levels of the catabolic products 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid decreased with decreasing tissue oxygen. Unlike the dopamine levels, these catabolite levels continued to decrease through 30 min of recovery (to 50% of control), returning to baseline only after recovery periods of 1-2 h. These data suggest that hypoxia induces long-term alterations in the neurotransmitter turnover. The marked effects of mild tissue hypoxia (decrease of oxygen from 40 torr to 26 torr) on both the extracellular dopamine concentration and dopamine metabolism indicate that the metabolic consequences of decreased tissue oxygen pressure extend to higher values than generally appreciated.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Microvascular damage in the cortex of cat brain from middle cerebral artery occlusion and reperfusion.

Oxygen-dependent quenching of phosphorescence provides an extraordinarily powerful method for examining the effects of ischemia/hypoxia on the cortex of the brain. Video camera technology has permitted imaging, through a window in the skull, of the phosphorescence of an oxygen probe, Pd meso-tetra-(4-carboxyphenyl)-porphine, bound to albumin in the blood of anesthetized animals. Images of the phosphorescence taken at different times after the flash of excitation light were used to generate high-resolution two-dimensional maps of the oxygen pressure. These maps show that cortical oxygenation is spatially heterogeneous and that there is dynamic time-dependent modulation of regional oxygen pressures. When the middle cerebral artery was occluded, the region for which it supplied blood became hypoxic, the severity of the hypoxia varying among animals. Release after 60 min of occlusion resulted in a rapid rise of the oxygen pressure to above-normal levels followed by onset of a delayed period of hypoxia. This period is characterized by generally low tissue oxygen pressures with local regions of more severe hypoxia. The delayed period of hypoxia appears to result from damage to the microvasculature, and this microvascular damage is proposed to be an important determinant of the extent of irreversible brain damage.

Animals↗
PubMed1993

Contribution of in vivo microvascular PO2 in the cat carotid body chemotransduction.

To understand the interplay between microcirculatory control and carotid body (CB) function, we simultaneously measured carotid body microvascular PO2 (CBM PO2) and chemosensory activity in the cat in vivo under several experimental conditions. Cats were anesthetized with pentobarbital sodium, paralyzed, and artificially ventilated. CBs were exposed, and steady-state CBM PO2 was measured by the O2-dependent quenching of the phosphorescence of Pd-meso-tetra-(4-carboxyphenyl)porphine, which was administered intravenously. A few fibers of the carotid sinus nerve were used to record chemosensory discharges. At arterial PO2 (PaO2) of 103.4 +/- 4.1 Torr, CBM PO2 was 52.5 +/- 3.6 Torr (n = 9). Graded lowering of PaO2 from 160 to 50 Torr resulted in nearly proportional decreases in CBM PO2, but at lower PaO2 the decrease in CBM PO2 became more substantial. As PaO2 decreased, chemosensory discharge increased in parallel with CBM PO2. Hypercapnia and hypocapnia did not significantly change the relationship between PaO2 and CBM PO2, although the chemosensory discharge responded significantly. CBM PO2 and chemosensory discharge were not affected by hemorrhagic hypotension until arterial blood pressure fell below approximately 50 Torr and then CBM PO2 decreased and chemosensory discharge increased. The lack of a significant effect of hemorrhagic hypotension indicated that O2 delivery to CB was almost independent of the systemic blood pressure. Taken together, the observations suggest that CB microcirculation and PO2 are subject to control by intrinsic mechanisms and that CBM PO2 is compatible with oxidative metabolism playing a role in O2 chemoreception during hypoxia.

Animals↗