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Biomedical subjects

N Miller

Publications and source records attributed to N Miller.

At least 199 records · Page 11Linked to original sources

Elemental analysis in murine central nervous system: elevation of rubidium subsequent to Newcastle disease virus encephalopathy.

The Cg strain of Newcastle disease virus (NDV) produces neurologic signs and death in mice. This illness is unusual because of the lack of typical features of a viral encephalitis. Specifically, there is a paucity of infectious virus, detectable cellular inflammatory reaction, cytopathic effect, and viral antigen by immunofluorescence. We previously showed an elevation of alpha-aminoisobutyric acid in the CNS of moribund NDV-infected mice, indicating cellular membrane dysfunction. In an attempt to further our understanding of the pathogenesis of the illness, we evaluated CNS concentrations of sodium, potassium, iron, copper, zinc, magnesium, selenium, and rubidium. Elemental analysis revealed no difference between infected and control mice for all elements except for rubidium, which was significantly elevated in infected mice. Elevation in rubidium was detected in infected mice by X-ray fluorescence and atomic absorption spectrophotometry, whereas rubidium concentrations for control mice were similar by both methods. Neurologic symptoms correlated directly with rising rubidium concentrations. Our data suggest that abnormal trace element levels during viral infection may be one mechanism responsible for the clinical symptoms.

Animals↗

An aggressive, nonshunting approach for control of bleeding esophageal varices.

Morbidity and mortality from variceal hemorrhage can be significantly reduced. A well-defined treatment protocol which obviates delay, procrastination and excessive blood loss is essential. Early aggressive endoscopic sclerotherapy is extremely safe and effective in controlling the acute hemorrhagic event. However, technical details remain to be standardized; rebleeding can be significant and sclerosing until roentgenologic obliteration is essential. Stapled esophageal transection and coronary vein ligation are a reasonable and effective surgical approach when necessary; however, the exact timing and place of this procedure in the therapeutic schema are not yet defined. It requires further phase one studies and not more randomized control trials! It can be difficult after recent sclerotherapy and would appear to require upper gastric devascularization or perhaps percutaneous embolization if gastric varices are venographically prominent. We have recently attempted to modify the procedure in such patients by stapling across the anterior and posterior gastric walls as an alternative or addition to complete esophageal transection. This is accomplished through a small gastrotomy adjacent to the gastroesophageal junction. Shunting procedures or more extensive surgical intervention does not appear necessary, desirable or warranted at this time; however, longer follow-up study is essential.

Aged↗

Association of isoapolipoprotein-E3 deficiency with heterozygous familial hypercholesterolaemia: implications for lipoprotein physiology.

A prepubertal girl with both homozygous isoapolipoprotein-E3 deficiency (the genetic defect underlying type-III hyperlipoproteinaemia) and heterozygous familial hypercholesterolaemia (familial type-IIa hyperlipoproteinaemia) presented with severe hypercholesterolaemia and antecubital and popliteal planar xanthomas. She responded dramatically to clofibrate. Her mother was normolipidaemic and heterozygous for apo-E3-deficiency. Her father, an obligate apo-E3-deficient heterozygote, and his similarly affected brother died prematurely with severe hypercholesterolaemia which had been refractory to clofibrate. Her paternal grandfather, who had the same combination of disorders as the proband, also responded to clofibrate, whereas her grandmother was normolipidaemic. Hence homozygous apo-E3 deficiency may present during childhood as severe hypercholesterolaemia when combined with familial hypercholesterolaemia, suggesting that the low-density-lipoprotein receptor may represent one mechanism whereby apo-E3-deficient remnants of very-low-density lipoproteins and chylomicrons are cleared from the plasma compartment. The removal of such apo-E3-deficient remnants is especially facilitated by clofibrate.

Apolipoprotein E3↗

Dry artificial lung surfactant and its effect on very premature babies.

Artificial lung surfactant prepared with pure dipalmitoylphosphatidylcholine and phosphatidylglycerol in a ratio of 7:3 was made as a dry powder and then blown down an endotracheal tube into the lungs of 22 very premature babies at birth. Only one dose was given. The treated babies did better than their 33 controls. Fewer needed ventilation, and those who did required lower pressures in the first six hours of life. None of the treated babies died, compared with 8 of the controls.

Clinical Trials as Topic↗

Central ocular motor abnormalities in Duane's retraction syndrome.

Duane's retraction syndrome (DRS) is a congenital eye movement disorder characterized by marked limitation or absence of abduction, variable limitation of adduction, and narrowing of the palpebral fissure with retraction of the globe on attempted adduction. We have recently recorded and quantitated ocular motility in five patients with unilateral DRS. In all patients, abduction of the affected eye was greatly limited, whereas adduction was limited, whereas adduction was limited to a lesser degree. Abnormalities in saccadic velocities were found in both the affected eye and the sound eye. Results of testing of the vestibulo-ocular reflex, optokinetic nystagmus, and optokinetic afternystagmus showed notable asymmetry. Our results suggest that DRS is produced by a primary brainstem abnormality involving premotor structures.

Adolescent↗

Artificial surfactant and natural surfactant. Comparative study of the effects on premature rabbit lungs.

Premature newborn rabbits, delivered on day 27 of gestation, were treated with tracheal deposition of dry artificial surfactant containing dipalmitoyl phosphatidylcholine and unsaturated phosphatidylglycerol (7:3), or crude natural surfactant prepared by centrifugation of lung wash from adult rabbits. Before receiving surfactant, the animals were allowed to breathe for 7--27 min; they were then subjected to artificial ventilation under standardised conditions. In comparison with littermate controls, both groups of surfactant-treated animals showed statistically significant improvement in lung-compliance 30 and 60 min after onset of ventilation. However, necrosis of bronchiolar epithelium and hyaline membranes was present in nearly all animals, even in those treated with natural surfactant; this suggests that in order to prevent epithelial lesions, surfactant should be given as soon as possible and preferably at birth. Our findings confirm earlier observations that treatment with supplementary surfactant has a beneficial effect on lung mechanics in the premature neonate. The fact that this effect can be obtained not only with natural surfactant but also with dry artificial surfactant should increase the possibility of clinical application.

Animals↗

Splanchnic production of discoidal plasma high-density lipoprotein in man.

The morphology of human plasma high-density lipoprotein (H.D.L.) subfractions in arterial and hepatic venous blood from seven human subjects was investigated by electron microscopy. The H.D.L.3 subclass from both sources and the H.D.L.2 subclass from arterial blood were composed of spherical particles, identical with normal human peripheral venous H.D.L. In contrast, H.D.L.2 isolated from hepatic venous blood was composed of a mixture of spherical and discoidal particles. The latter tended to form rouleaux, and had a diameter similar to that of nascent H.D.L. particles obtained from the peripheral venous blood of a patient with lecithin: cholesterol acyltransferase deficiency. This supports the view that nascent H.D.L. is secreted into the splanchnic bed in man.

Adult↗

Effect of load, speed, and activity history on the EMG signals from the intact human muscle.

A specially instrumented bicycle ergometer is utilized in this investigation to induce reproducable loading conditions on the muscles of the lower extremity at different speeds. Various tehcniques for evaluating the electromyographic signals from the vastas medialis muscle are investigated for different load and speed conditions and shown to be essentially equivalent. The RMS signal power computed by means of a real time spectral analyzer is shown to be a convenient means of quantification of the dynamic EMG signals. The electromyographic signals are shown to be stable under repeated static or dynamic conditions but not under sustained isometric static loading.

Action Potentials↗

Alteration of mitochondrial function and lipid composition in Morris 7777 hepatoma.

Mitonchondria isolated from the Morris hepatoma 7777 demonstrated a markedly different phospholipid composition from those of control mitochondria, both with respect to the amounts of the various types present and the fatty acid composition. The level of polyunsaturated fatty acids in the mitochondrial phospholipids was lowered, wheras there was an increase in the level of monounsaturated fatty acids. Moreover, the usual distribution of saturated fatty acids at position 1 and polyunsaturated fatty acids at position 2 does not exist in hepatoma phospholipids; a high percentage of monounsaturated fatty acids was found at both positions. The cardiolipin content was lower in hepatoma mitochondria (3.7%) than in livers of animals with hepatomas (5.2%). There was, however, some compensation in the amount of acidic phospholipids in these mitochondria due to an increase in phosphatidylserine (4.9% versus 1.3%). The force-area curves of the hepatoma phospholipids spread on a monomolecular film demonstrated a smaller area per molecule than those from liver mitochondria. The zeta potential of liposomes of the hepatoma phospholipids (-45) was less than those of control mitochondria (-81), as determined by microelectrophoresis. The calcium-stimulated phospholipase A activity of the hepatoma mitochondria appeared to be more readily expressed than the same activity in liver organelles. The maximal activity was lower, however, than that noted in liver mitochondria. Furthermore, by following the incorporation of [3H]ethanolamine into mitochondria phospholipids, it was established that the conversion of glycerophosphorylethanolamine to glycerophosphorylcholine was increased in the hepatoma. These observations suggest dramatic changes in phospholipid metabolism in the hepatoma, at the level of both the endoplasmic reticulum and the mitochondrion. Accompanying the changes in phospholipid compositon and metabolism were alterations in mitochondrial energy-linked processes. The hepatoma mitochondria demonstrated lower respiratory control ratios even when isolated in an isotonic solution containing 1mM ethylenediaminetetraacetate and bovine serum albumin (0.5 mg/ml). This was due to increased state 4 respiration.

Animals↗