Biomedical subjects

R Crandall

Publications and source records attributed to R Crandall.

10 recordsLinked to original sources

PubMed1994

Resistance and disease in Brugia malayi infection of ferrets following prior infection, injection of attenuated infective larvae and injections of larval extracts.

A partial resistance expressed by a 53% to 78% reduction in lymphatic filariae from a challenge infection was induced in ferrets (Mustela putorius furo) by a prior infection and by injection of radiation attenuated infective larvae (L3) but not by injections of lyophilized microfilariae (mf) or L3. Equivalent acquired resistance was demonstrated with and without overt filarial disease. A prior infection resulted in peripheral lymphoedema in approximately one-third of the amicrofilaraemic resistant ferrets following challenge infection and injection of attenuated larvae resulted in inflammatory responses characteristic of a hyper-responsive syndrome in one-half of the amicrofilaraemic ferrets. Injections of lyophilized mf inhibited microfilaraemia and promoted development of lymphostatic disease. A limited examination of immune responses and histopathology suggested that disease in partially resistant ferrets was associated with high TH2 dependent responses directed, at least in part, to mature filariae and to mf. Mechanisms of resistance were not identified.

Animals↗

PubMed1992

Lymphatic imaging in experimental filariasis using magnetic resonance.

RATIONALE AND OBJECTIVES: To evaluate acquired lymphatic abnormalities caused by filariasis, the authors examined the peripheral lymphatic system in normal ferrets and those chronically infected with Brugia malayi using magnetic resonance imaging (MRI). The findings were compared with previously obtained lymphangioscintigraphic (LAS) images in ferrets both with and without experimental filariasis. METHODS: Fifteen ferrets (11 infected with B. malayi and four noninfected controls) underwent whole body coronal MRI using a quadrature transmission-receive head coil at 0.5 Tesla operating at a resonant frequency of 21.5 mHz for protons with a 25-cm field of view. RESULTS: In contrast to normal animals, infected ferrets showed dilated hindlimb dermal lymphatic collaterals, enlarged high-signal intensity groin lymph nodes with punctate low-signal intensity centers and separate low-signal intensity spots with irregular thin channels, suggestive of nests of viable adult nematodes within tortuous lymphatics and nodes. MRI correlated with the LAS findings, and the interpretations were supported by light, scanning electron, and video microscopy. CONCLUSIONS: T2-weighted MRI in conjunction with LAS accurately depicts the peripheral lymphatic system in filarial-infected ferrets. These two modalities are useful complementary techniques to examine disorders characterized by lymphatic insufficiency.

Animals↗

PubMed1991

Vascular abnormalities in experimental and human lymphatic filariasis.

Whereas clinical descriptions of grotesque lymphedema and standard light microscopy in human filariasis have elucidated the natural progression of this disease, the link between the nematode and vascular abnormalities including elephantiasis remains poorly understood. Accordingly, we examined the nature and distribution of lymphatic and blood vascular derangements in a variety of tissues and organs from 37 ferrets acutely and chronically infected with Brugia malayi and in 15 patients with Wuchereria bancrofti or Brugia malayi infestation (resected skin, subcutaneous tissue, and lymph nodes) using light and transmission electron microscopy, immunohistochemistry, and in vivo microscopy. In ferrets, eosinophilic abscesses and epithelioid and giant cell granulomas with fragmented worms in various stages of disintegration were found in multiple organs. Blood microvasculopathy consisted of endothelial hyperplasia, focal thickening and stenosis, vessel obliteration with marked perivascular infiltration of lymphocytes, plasma cells, eosinophils, and numerous large macrophages laden with a coarse golden-brown pigment. Endothelial ballooning and swelling, pavementing, denuding, scarring, and sludge formation were seen along with high endothelium in atypical locations. Dilated lymphatics were most prominent near adult worms and showed plump endothelium, thickened walls and valves, thrombus formation, and often perilymphangitis and adjacent tissue fibrosis. In vivo microscopy showed wriggling live adult worms in dilated incompetent sludge-filled groin lymphatics even when microfilaremia and peripheral edema were absent. In human tissues, in addition to "pachyderm" skin changes (keratosis, papillomatosis, acanthosis and collagen deposition), there was blood vessel and lymphatic vasculopathy similar to ferrets (angiocentric inflammation, congestion, vasculitis, thrombosis, thickened vessel walls, dilated lymphatics, lymphangitis, reactive lymph nodal hyperplasia and nodal fibrosis). These changes reflect generalized endothelial damage due to worm products, physical injury to valves and vessel walls from lymphatic-dwelling live worms, and host immune reactivity. Whereas adult worms target the lymphatic apparatus, their offspring and the host immune response primarily affects the blood microvasculature.

Animals↗

PubMed1988

Whole body lymphangioscintigraphy in ferrets chronically infected with Brugia malayi.

Whole body lymphangioscintigraphy was performed after intradermal injection of 99mtechnetium human serum albumin or antimony colloid in the distal hindlimbs and forelimbs of ferrets chronically infected with Brugia malayi. The findings were compared with control ferrets and those with surgical interruption of the iliac lymphatics. While only one infected ferret manifested chronic hindlimb lymphedema, all exhibited delayed transport of radioisotope from the hindpaw with obstruction in the groin, poor or absent visualization of central lymphatic channels and regional lymph nodes, a picture similar to that following surgically induced lymphatic obstruction. In control ferrets, there was prompt visualization of peripheral lymphatic channels and regional lymph nodes with sharper and more extensive channel visualization after radiolabeled albumin and more intense sustained nodal visualization after radiolabeled antimony colloid. This noninvasive technique provides a readily repeatable investigative tool adaptable to small animals to study the evolution of lymphatic filariasis and other conditions associated with lymphatic obstruction.

Animals↗

PubMed1987

Inverse diffusion methods for data peak separation.

Previous methods for separation of overlapping data peaks include geometrical assessment and Fourier deconvolution. On the basis of inverse diffusion theory, we present new separation methods suitable for convenient programming and rapid calculation of Gaussian area contributions. Both continuum and discrete inverse diffusion models are described. Example computations are given for biological data: density gradient centrifugation, isoelectric focusing electrophoresis, and high-pressure liquid chromatography.

Centrifugation, Density Gradient↗

PubMed1974