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Biomedical subjects

R Christie

Publications and source records attributed to R Christie.

18 recordsLinked to original sources

Structural and functional disruption of vascular smooth muscle cells in a transgenic mouse model of amyloid angiopathy.

The deposition of amyloid Abeta peptide in the wall of cerebral vessels (cerebral amyloid angiopathy), can lead to weakness and rupture of the vessel wall, resulting in hemorrhagic stroke. The Tg2576 transgenic mouse line, overexpressing mutant amyloid precursor protein in an age-dependent manner, forms amyloid angiopathy morphologically similar to that seen in the human. We report here the structural and functional disruption of smooth muscle cells (SMCs) in the walls of pial vessels affected by amyloid deposition in the Tg2576 mouse. We demonstrate, using multiphoton imaging, that the arrangement of SMCs becomes disorganized before the onset of cell death, and that these disorganized SMCs are unable to respond appropriately to application of endothelial-dependent and endothelial-independent vasodilators in a closed-cranial window preparation.

Acetylcholine↗

Multiphoton microscopy and amyloid angiopathy.

The underlying pathophysiological processes of amyloid angiopathy have been difficult to study because the vessel size affected is too smallfor imaging in the human condition, and animal models have not yet been adequately developed or characterized. Herein we present characterization of animal models of overexpression of the human AbetaPP gene, initially developed as models of Alzheimer's disease, but which fortuitously also develop marked cerebral amyloid angiopathy. We also present a novelform of microscopy that allows in vivo imaging of vessels affected by amyloid in the anesthetized, but intact, animal.

Alzheimer Disease↗

Recurrent varicose veins: patterns of reflux and clinical severity.

Duplex scanning was used to determine patterns of recurrent varicose veins in 264 limbs and to relate these to clinical factors. All limbs had previously undergone sapheno-femoral ligation in the groin. A recurrent sapheno-femoral junction was present in 172 (65.2%). Incompetence was found in long or short saphenous veins in 232 limbs (87.9%), perforators in 176 (66.7%), and deep veins in 156 (59.1%). Residual long saphenous veins were present in 43.4% and 73.6% of limbs that were with and without stripped long saphenous veins, respectively. An incompetent thigh perforator was present in 14.0% and 15.3% of these two groups, respectively. Multiple sites of incompetence were observed in the majority (75.4%). In general, no particular reflux pattern in the groin was related to an increased incidence of ulceration. However, ulceration was more frequent in limbs with deep reflux to knee or below-knee levels. None of those with isolated reflux in the groin that was unrelated to the common femoral vein had ulceration. The pattern of reflux was unrelated to striping or non-striping of the long saphenous veins and the time since initial surgery. A history of deep vein thrombosis was invariably associated with some degree of deep reflux. A system of recurrent patterns in the groin is described for the purpose of surgical audit. In 15.1%, recurrence was attributed with some confidence to inadequate surgery. These results indicate that the pattern of recurrence is highly variable and often with multiple sites of incompetence. In a few instances, the pattern of recurrence was associated with specific clinical factors. A full work-up including duplex scanning is recommended.

Aged↗

Aggregation and disaggregation of senile plaques in Alzheimer disease.

We quantitatively analyzed, using laser scanning confocal microscopy, the three-dimensional structure of individual senile plaques in Alzheimer disease. We carried out the quantitative analysis using statistical methods to gain insights about the processes that govern Abeta peptide deposition. Our results show that plaques are complex porous structures with characteristic pore sizes. We interpret plaque morphology in the context of a new dynamical model based on competing aggregation and disaggregation processes in kinetic steady-state equilibrium with an additional diffusion process allowing Abeta deposits to diffuse over the surface of plaques.

Alzheimer Disease↗

Lack of association of trinucleotide repeat polymorphisms in very-low-density lipoprotein receptor gene with Alzheimer's disease.

Inheritance of the apolipoprotein E epsilon 4 allele is a risk factor for Alzheimer's disease (AD). A recent report studying Japanese patients suggested that a polymorphism of a trinucleotide repeat in the 5' untranslated region of an apolipoprotein E receptor, the very-low-density lipoprotein receptor, is genetically associated with AD, with overrepresentation of the allele containing five copies of the repeat. We determined the allele frequencies of the very-low-density lipoprotein receptor in 3 white populations totaling 469 individuals. In contrast to the previous report, we found no differences in allele frequencies between case patients and control subjects. The discrepancy could be due to differences in Japanese and white populations. Nonetheless, these data weaken the likelihood that this polymorphism in the very-low-density lipoprotein receptor gene is strongly associated with AD.

Alleles↗

Laparoscopic excision of distal pancreas including insulinoma.

A case of sporadic occult insulinoma treated by laparoscopic distal pancreatectomy using a laparoscopic ultrasound probe to facilitate localization of the insulinoma and a laparoscopic surgical stapler to transect the pancreas is presented. This is believed to be the first case description of a laparoscopic pancreatic resection.

Aged↗

The use of video image analysis for the measurement of venous ulcers.

The accurate measurement of the size of skin wounds and ulceration is important for comparing the efficiency of treatment modalities and for monitoring progress in the individual patient. Although various methods of differing sophistication are in use, many of the common simpler techniques lack accuracy and reliability. We describe a new technique of ulcer measurement which uses video image recording, capture and computer analysis. A method of correcting for limb convexity in a two-dimensional image is presented. The method has an overall accuracy of 1.82% and a clinical precision of 3.41%, both of which are significantly better than acetate tracings or photographic methods. The technique is simple and rapid, and once established it incurs minimal ongoing costs.

Humans↗

Anatomic and physiologic characteristics of venous ulceration.

PURPOSE: The purpose of this study was to describe the combination of physiologic and anatomic changes present in limbs with venous ulceration. METHODS: Limbs with venous ulceration (chronic venous insufficiency [CVI] class 3) were assessed prospectively by air plethysmography and color-flow duplex scanning. Findings were compared with clinically normal contralateral limbs and normal control limbs (CVI class 0), as well as with limbs without skin changes (CVI class 1). RESULTS: Of the 120 ulcerated limbs studied, only 28% had deep system incompetence. Reflux at the saphenofemoral or saphenopopliteal junctions without perforator incompetence was present in 40%. Raised venous filling indexes (> 2 ml/s) and high residual volume fractions (> 20%) were present in 90% and 95%, respectively. Although levels of these parameters were significantly different from the other groups (p < 0.05), absolute ejection volumes and outflow parameters were the same (p > 0.05). One third of contralateral "normal" limbs (class 0) had abnormal duplex scanning findings. The ratio of venous filling time to residual volume fraction produced a useful discriminating index for the ulcerated limb. CONCLUSION: The ulcerated limb was characterized by high rates of reflux and high residual volumes that were independent of the site of reflux. This study highlights the important association of venous ulceration and isolated superficial venous system incompetence.

Adult↗

Evidence that pepper mottle virus and potato virus Y are distinct viruses: analyses of the coat protein and 3' untranslated sequence of a California isolate of pepper mottle virus.

Pepper mottle virus (PepMoV) is a member of the large and complex genus Potyvirus, and is classically distinguished from other members of the genus by differential host range and cytopathology as well as serology of the coat protein and cytoplasmic inclusion body proteins. Here we report the deduced amino acid sequence of the coat protein of a California potyvirus identified by a variety of classical methods as PepMoV (PepMoV C). Comparison of the 3' untranslated nucleic acid sequence and the deduced coat-protein amino acid sequence of the PepMoV C isolate with those of PVY and other potyviruses indicates that PepMoV C is sufficiently diverged to be considered a distinct virus species. Thus, comparative sequence analyses of the PepMoV C isolate support earlier serological and biological evidence that PepMoV and PVY are distinct viruses.

Amino Acid Sequence↗

Prenatal ethanol exposure alters immune capacity and noradrenergic synaptic transmission in lymphoid organs of the adult mouse.

Clinical and experimental evidence indicates that exposure to alcohol in utero is associated with altered immune capacity. The mechanisms underlying such abnormalities are not clear. However, the suggestion that reciprocal interactions between the immune and the nervous systems are necessary for a competent immune response may be relevant. This work examined the consequences of prenatal ethanol exposure on cellular immune responses and noradrenergic synaptic transmission in lymphoid organs of the adult C57B1/6 mouse. Pregnant mice were fed a liquid diet containing 25% of the calories as ethanol (4.8% w/v) or pair-fed an isocaloric equivalent of this diet throughout gestation, followed by foster-nursing the neonates on normal dams. As young adults, mice exposed to ethanol prenatally displayed immunologic and selective neurochemical changes: (1) depressed ability to produce cellular immune responses, including contact hypersensitivity and a local graft-vs-host response, and (2) altered noradrenergic synaptic transmission, including enhanced norepinephrine turnover, and a reduction in norepinephrine levels and beta-adrenoceptor density in the thymus and spleen, but not the heart. However, both the integrity and compartmentation of noradrenergic nerve fibres in the spleen were intact. It is suggested that altered noradrenergic synaptic transmission selectively in lymphoid organs may contribute to the impaired immune capacity associated with fetal alcohol exposure.

Adrenergic Fibers↗

Carotid artery exteriorisation in the red deer.

A technique for the surgical relocation of the carotid artery, to permit repeated percutaneous puncture, in red deer, is described. An incision was made through the skin distal to the ramus of the jaw parallel to and dorsal to the superficial jugular vein. The brachiocephalicus muscle was divided by blunt dissection to reveal the carotid artery. The carotid artery was dissected free of connective tissue and the vagus nerve and enclosed in a polythene prosthesis. The brachiocephalicus muscle was sutured dorsal to the now enclosed artery. The wound was closed taking care that the line of sutures did not overlie the prosthesis. Repeated percutaneous puncture of the artery was possible for periods of up to 18 months.

Journal Article↗

Lesch-Nyhan disease: clinical experience with nineteen patients.

The clinical phenotype in Lesch-Nyhan disease has been analyzed in 19 patients studied in hospital. In each case the diagnosis was made on the basis of inactivity of the enzyme hypoxanthine guanine phosphoribosyltransferase in erythrocyte lysates. All had hyperuricemia, and the presence of 'orange sand' in the diaper was a prominent early complaint. All had self-mutilative behavior, of which the most characteristic form was biting the fingers or lips. All had the neurological syndrome of spasticity and choreoathetoid involuntary movements. All but one had less-than-normal intelligence.

Adolescent↗

Analytical study of a Rift Valley fever epidemic.

Three epidemiological investigations were carried out during and after the 1987 Rift Valley fever (RVF) epidemic in South Mauritania: a case control study, a cross-sectional study in the town of Rosso and a cross-sectional study of villages and encampments around Rosso. The case control study showed an association between epizootic and epidemic outbreaks. The study in Rosso town showed housing and district effects. Also, a medical survey of hospital staff showed the absence of interhuman contamination. The cross-sectional study of villages and encampments around Rosso showed heterogeneity corresponding to a village and ethnic effect. The human epidemic was linked to epizootic disease, but the "vectors" of the disease are not as yet known.

Animals↗