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Biomedical subjects

D F Wilson

Publications and source records attributed to D F Wilson.

At least 55 records · Page 3Linked to original sources

Molecular analysis of the POU3F4 gene in patients with clinical and radiographic evidence of X-linked mixed deafness with perilymphatic gusher.

The molecular defect in some patients with X-linked mixed deafness with perilymphatic gusher at stapes surgery (DFN3) was recently attributed to mutations in the POU3F4 gene. In this manuscript we describe the molecular analysis of the POU3F4 gene in 5 patients with clinical and radiographic evidence of DFN3. Novel mutations were found in 2 of the 5 patients analyzed, while 3 had an entirely normal protein coding sequence. The fact that 3 of the 5 patients with clinical histories and radiographic abnormalities characteristic of X-linked mixed deafness with perilymphatic gusher displayed normal POU3F4 gene sequences supports the possibility that not all patients with the characteristic phenotype have involvement of the POU3F4 gene.

Base Sequence↗

Endolymphatic sac obliteration for large vestibular aqueduct syndrome.

The objective of this study was to investigate the effects of endolymphatic sac obliteration for stabilization of progressive hearing loss in patients with the large vestibular aqueduct syndrome. This was a retrospective case review conducted at a private neurootologic office in a metropolitan area. Seven ears in six patients were subjected to surgery for obliteration of the endolymphatic sac in an effort to stabilize progressive hearing loss associated with the large vestibular aqueduct syndrome. The study population was composed of four boys and two girls 4-17 years of age. The large vestibular aqueduct was unilateral in two patients and bilateral in four patients. All seven ears demonstrated progressive sensorineural hearing loss preoperatively. Surgical tissue obliteration was performed via a transmastoid approach in seven ears. The main outcome measure was comparison of pre- and postoperative hearing levels and stability. Magnetic resonance imaging also was performed in all cases at least 6 months postoperatively to determine patency of the endolymphatic sac and vestibular aqueduct. Six of seven ears maintained stable hearing during the follow-up period, which ranged from 6 months to 6 years (mean 3.2 years). One patient showed continued progression of hearing loss postoperatively. All seven ears demonstrated continued obliteration on postoperative imaging studies. Surgical obliteration of the endolymphatic sac may stabilize hearing in patients with the large vestibular aqueduct syndrome and progressive hearing loss. These results support the theory of pressure or fluid reflux into the labyrinth as a cause of progressive hearing loss in these patients.

Adolescent↗

Extended porphyrins. New IR phosphors for oxygen measurements.

Tetrabenzoporphyrins (TBP) of Zn, Pd, Lu, Y, Sn and Pb show strong absorption bands in the near IR region of the spectrum. Phosphorescence in dimethylformamide (DMF) solutions at room temperature was measured for Pd and Lu complexes giving quantum yields of 7.9% and 3.5% and lifetimes of 250 microseconds and 870 microseconds, respectively. Pd meso-tetraphenyltetrabenzoporphyrin 1 (PdPh4TBP) shows a red shift of the absorption Q-band to 628 nm. 1 reacted with ClSO3H and obtained chlorosulfonato derivative 2 was converted to a set of water soluble chromophores: Pd meso-tetra(sulfophenyl)tetrabenzoporphyrin (Pd Ph4(SO3Na)4TBP) 3, corresponding sulfonamide (Pd Ph4(PEG)4TBP) 4 with aminopolyethyleneglycol (Av.M.W. 5,000) and sulfonamide derivatives of glucoseamine (Pd Ph4(glucoseamine)4TBP) 5 and aminophenylacetic acid (Pd Ph4(phenac)4TBP) 6. Electronic absorption and phosphorescence spectra of 1 and some of its derivatives were recorded and phosphorescence quantum yields and lifetimes were measured for deoxygenated solutions. The oxygen quenching constants were measured for the water soluble complexes 3 and 4 and found to be suitable for oxygen measurements in vivo. Tetranaphthaloporphyrin (TNP) complexes of Pd and Lu as well as Pd meso-tetraphenyltetranaphthaloporphyrin (PdPh4TNP) were synthesized and their absorption and emission properties were examined.

Animals↗

A critical appraisal of the role of auditory brain stem response and magnetic resonance imaging in acoustic neuroma diagnosis.

Auditory brain stem response (ABR) is the most sensitive and specific audiometric test for acoustic neuroma (AN) detection. The ABR sensitivity rate increases with tumor size; consequently, small tumors have notably low ABR sensitivity for detection. However, larger tumors also can fail recognition by ABR testing. The ABR must be viewed on its own merits compared to magnetic resonance imaging studies for the diagnosis of AN. Where does ABR fit into the screening process for detecting AN today?

Cochlea↗

The effects of induced apneic episodes on cerebral cortical oxygenation in newborn piglets.

The effect of different inspiratory oxygen levels (FiO2) on cortical oxygenation (pO2) during and after recovery from apnea, was investigated in 18 anesthetized, paralyzed, and mechanically ventilated newborn piglets. Heart rate (HR) and mean arterial blood pressure (MABP) were continuously monitored as the piglets were subjected to repeated episodes of apnea initiated by disconnecting the ventilator and terminated when HR decreased to less than 80 beats/min by reconnecting the ventilator. A closed cranial window was placed over the parietal cortex of the animals and cortical pO2 was measured optically by phosphorescence quenching. Apneic episodes induced in animals ventilated with 15%, 22% and 40% oxygen had mean duration's of apnea (time before HR decreased to less than 80 beats/min) of 80, 128 and 134 s, respectively. By the end of the apnea the MABP decreased to 82%, 64%, and 54% of control, respectively. The cortical pO2 decreased from control values of 24.1, 32.3 and 38.3 Torr at 15%, 22% and 40% oxygen, respectively, to 1.7 to 3.2 Torr at the end of the apneic episode. The duration of apnea necessary for the cortical pO2 to drop below 20.3 Torr was 18, 44 and 81 s at 15%, 22% and 40% oxygen, respectively. There was an inverse correlation between the rate of decline of cortical pO2 and baseline FiO2 levels. With reventilation, the cortical pO2 reached maximal values of 42.8, 51.9 and 57.2 Torr at 15%, 22%, and 40% oxygen, respectively, before returning to the pre-apnea values. The present results show that apnea of less than 30 s duration at an FiO2 of 22% do not result in significant cortical hypoxia in hemodynamically stable piglets. Increasing the FiO2 to above 22% may possibly increase the rate of recovery of tissue oxygenation but it also may facilitate post-hypoxic cortical hyperoxia, a factor that may predispose the immature brain to free radical injury.

Animals↗

The effect of hypoxia and catecholamines on regional expression of heat-shock protein-72 mRNA in neonatal piglet brain.

The present study has shown that hypoxia leads to expression of heat-shock protein in the brain of newborn piglets and this process is almost completely abolished by depletion of catecholamines prior to the hypoxic episode. The piglets were anesthetized and mechanically ventilated. One hour of hypoxia was generated by decreasing the oxygen fraction in the inspired gas (FiO2) from 22% to 6%-10%. FiO2 was then returned to the control value for a period of 2 h. Following the 2 h of reoxygenation, regional expression of the 72-kDa heat-shock protein (hsp72) mRNA was determined using in situ hybridization and autoradiography. The hypoxic insult (cortical pO2 = 3-10 mmHg) induced expression of hsp72 mRNA in regions of both white and gray matter, with strong expression occurring in the cerebral cortex of individual animals. Depleting the brain of catecholamines prior to hypoxia, by treating the animals with alpha-methyl-p-tyrosine (AMT), resulted in a major change in the hsp72 mRNA expression. In the catecholamine depleted group of animals, the intensity of hsp72 mRNA expression was greatly decreased or almost completely abolished relative to the nondepleted hypoxic group. These results suggest that the catecholamines play a significant role in the expression of the hsp72 gene in response to hypoxic insult in neonatal brain.

Animals↗

Calibration of oxygen-dependent quenching of the phosphorescence of Pd-meso-tetra (4-carboxyphenyl) porphine: a phosphor with general application for measuring oxygen concentration in biological systems.

Oxygen-dependent quenching of phosphorescence is a function of the frequency of collision between the phosphor and molecular oxygen and of the efficiency of energy transfer during these collisions. Thus, quenching is dependent on the rate of diffusion of the phosphor and its molecular environment. For measurements in biological samples, the Pd-porphyrin is bound to serum albumin, and this provides a uniform microenvironment for the phosphor which is relatively unaffected by changes in the pH and ionic composition of the medium. Calibration of the phosphor is of particular value because it is absolute, i.e., the calibration is valid independent of the laboratory and the time of measurement. This paper reports the calibration constants determined for Pd-meso-tetra (4-carboxyphenyl) porphine, as measured by two independent methods: by stoichiometric titration of the oxygen with ascorbate in the presence of ascorbate oxidase and by comparison with a high-accuracy oxygen electrode. The measurements were carried out in a specially designed thermostatted vessel in which the oxygen electrode and phosphorescence lifetime measurements of oxygen were made simultaneously. The calibration constants for the oxygen-dependent quenching of the phosphorescence of Pd-meso-tetra (4-carboxyphenyl) porphine were determined as a function of albumin concentration, ionic strength in medium, pH, and temperature.

Ascorbate Oxidase↗

Identification of basal lamina acidic glycoconjugates, particularly heparan sulphate proteoglycans, using a poly-L-lysine-gold probe in induced oral carcinomas.

Acidic glycoconjugates represent the major non-fibrous macromolecular components that form the extracellular and cell-associated matrices of all animal tissues. The constituent molecules are principally structural glycoproteins and proteoglycans. While their protein component is determined by gene pools, it is the polyanionic (acidic) nature of the polysaccharides, determined by their degrees of carboxylation and sulphation, which confers both functional and diagnostic status on these molecules. Sulphated glycoconjugates in the basal laminae have been reported to play a role in tumour invasion and metastasis. In this study, we used cationic colloidal gold together with transmission electron microscopic methods to compare the expression of acidic glyconconjugates in the basal lamina of both normal rat tongue mucosa and experimentally induced oral carcinomas. Results indicated that heparan sulphate rich glycoconjugates were predominant and were mostly confined to the lamina lucida of the basal lamina in normal oral mucosa. Conversely, observation of basal laminae associated with induced carcinomas showed less intense and more widely dispersed gold labelling for heparan sulphate. The observed differences in gold labelling may reflect modified metabolism of sulphated glycoconjugates or result from the action of degradative enzymes in the induced tumours.

4-Nitroquinoline-1-oxide↗

Noninvasive imaging of the distribution in oxygen in tissue in vivo using near-infrared phosphors.

A newly developed water-soluble phosphor suitable for measuring oxygen pressure in the blood (Green 2W) was used for noninvasive, in vivo imaging of oxygen distribution in the vascular systems of mice. Oxygen quenches the phosphorescence of Green 2W, measured in the presence of 2% albumin, according to the Stern-volmer relationship. This oxygen-dependent quenching of phosphorescence has been used to obtain digital maps of the oxygen distribution in the tissue vasculature. EMT-6 mammary carcinoma tumors were grown by injecting 1 x 10(6) cells in 0.1-ml carrier into the subcutaneous space over the muscle on the hindquarter. When the tumors were approximately 8 mm in diameter, 300 micrograms of phosphorescence probe (Green 2W; absorption maximum 636 nm) was injected into the tail vein. The mice were immobilized with intraperotoneal Ketamine (133 mg/kg) and Xylazine (10 mg/kg) and illuminated with flashes (< 4-microseconds t1/2) of light of 630 +/- 12 nm. The emitted phosphorescence (790-nm maximum) was imaged an intensified CCD camera. Images were collected beginning at 30, 50, 80, 120, 180, 240, 420, and 2500 microseconds after the flash and used to calculate digital maps of the phosphorescence lifetimes and oxygen pressure. Both the illumination light and the phosphorescence were in the near-infrared region of the spectrum, where tissue has greatly decreased absorbance. The light therefore readily passed through the skin and centimeter thicknesses of tissue. The oxygen maps could be obtained by illuminating from the side of the mouse opposite the camera (and tumor). The tumors were readily observed as regions with oxygen pressures substantially below those of the surrounding tissue. Thus, phosphorescence measurements can noninvasively detect volumes of tissue with below-normal oxygen pressure in the presence of much larger volumes of tissue with normal oxygen pressures. In addition, tissue oxygen pressures can be monitored in real time, even through centimeter thicknesses of tissue.

Animals↗

Regulation of oxidative metabolism and blood flow in skeletal muscle. Summary report of the first ACSM Basic Science Specialty Conference, Indianapolis, IN, September 28-30, 1995.

The first ACSM Basic Science Specialty Conference was held in Indianapolis, September 28-30, 1995. The topic was integration among cellular metabolism, blood flow regulation, and O2 supply during exercise, principally in skeletal muscle. The structure of the meeting was uniquely designed to emphasize free discussion among the 102 registrants; thus, this unique program design does not lend itself to a conventional collection of written symposium proceedings. On the other hand, the College, editor-in-chief Peter B. Raven, and the meeting organizers felt that a summary of the meeting's major points was important to compile and distribute to members via Medicine and Science in Sports and Exercise. Therefore, the organizing committee present a summary of the major issues discussed.

Endothelium, Vascular↗

Palatal changes associated with reverse smoking in Filipino women.

OBJECTIVE: To determine baseline data for the presence or absence of reverse-smoking and conventional smoking associated oral palatal mucosal changes in women. DESIGN: A cross-sectional evaluation of the clinical and cytological changes associated with the condition. SETTING: Nine rural barangays in Cabanatuan City, Philippines. SUBJECTS AND METHODS: Nine-one volunteer women smokers (61 reverse and 30 conventional) were examined clinically and photographically. Smears were also taken from three areas and the palate to investigate the cytology of palatal mucosal epithelium. MAIN OUTCOME MEASURES: Variations in colour, texture and topography of the palatal mucosa; determination of epithelial cell characteristics and inflammatory cell populations present in the lesions. RESULTS: Clinical findings showed that subjects could be grouped into three categories: Group A subjects showed pigmentation and some erythema only; Group B subjects included those with ulceration, marked erythema and non-descript mucosal roughening; Group C subjects (comprising the majority of reverse smokers) exhibited various combination of leukoplakia, fissuring, thickening and pigmentation of the palatal mucosa. Additional features, including nodularity, erythema, prominence and reddening of minor salivary gland duct openings were also occasionally observed in this group. Cytologic analysis revealed that, within each smoking group, there was a significant site-dependent difference in the predominant epithelial cell type present. CONCLUSIONS: This study reports the first systematic description of reverse smoking associated palatal mucosal changes in Filipino women. It also provides a basis for classification of the palatal mucosal changes among reverse smokers.

Adult↗

Impact of alpha-bungarotoxin on transmitter release at the neuromuscular junction of the rat.

The drug, alpha-bungarotoxin (BTX) is believed to be a 'pure' nicotinic antagonist. Hence, use of this drug should avoid the secondary actions associated with other nicotinic antagonists. The hypothesis that the motor nerve terminal responds to the presence of acetylcholine (ACh) by releasing less transmitter was tested by examining the effects of BTX on end-plate potentials (EPPs), miniature end-plate potentials (MEPPs), and quantal release at the rat diaphragm neuromuscular junction. Analysis of EPP and MEPP amplitudes and quantal release demonstrate that BTX significantly increases transmitter release at the onset of tetanic stimulation (50 Hz). Like other nicotinic antagonists, BTX was not able to sustain enhanced quantal release during a brief train of 40 stimuli and resulted in greater decline in EPP amplitude during tetanic stimulation. The data suggests that negative feedback regulation by presynaptic autoreceptors only serves a functional role at the onset of stimulation and that other factors such as transmitter supply or adenosine regulation may serve to dominate transmitter release during maintained tetanic stimulation.

Action Potentials↗