Biomedical subjects

Richard J Young

Publications and source records attributed to Richard J Young.

3 recordsLinked to original sources

PubMed2006

Imaging the embryonic kidney.

The structural and functional development of the permanent mammalian kidney or metanephros is a complex process involving the actions of thousands of gene products, complex cell movements and tissue patterning in three dimensions (3D). This review focuses on the recent advances made in imaging technology, processing and analysis combined with mouse genetics and the generation of protein-reporter mice which has enabled us to monitor the development and movement of defined cell populations within the developing kidney in 3D and over time (4D).

Animals↗

PubMed2002

Glomerular size and glomerulosclerosis: relationships to disease categories, glomerular solidification, and ischemic obsolescence.

In focal segmental glomerulosclerosis (FSGS), a biphasic change in glomerular size is described in which glomeruli are enlarged with early glomerulosclerosis. Hyperperfusion of larger glomeruli is believed to contribute to progressive glomerular injury. This study was undertaken to investigate whether similar alterations in glomerular size can be found in other renal diseases. Volumes of sclerotic and nonsclerotic glomeruli were estimated in renal biopsy specimens using the Weibel and Gomez method (1962). Glomerulosclerosis was graded on individual glomeruli from 0 to 4, with 0 as no sclerosis and 4 as 76% to 100% sclerosis. Primary and secondary FSGS showed a biphasic change in which grade 2 glomeruli were 50% larger than grade 0 glomeruli and grades 3 and 4 glomeruli were solidified and smaller than grade 0 glomeruli. In essential hypertension, no increase in glomerular size was seen with early glomerulosclerosis, and the latter stages consisted of ischemic obsolescence in which collapsed tufts were 50% smaller than solidified glomeruli of FSGS. Grade 0 glomeruli of membranous glomerulonephritis (MGN) were significantly larger than grade 0 glomeruli of FSGS, and no significant difference in size was seen between grades 0 and 2 glomerulosclerosis. Solidified diabetic glomeruli maintained a large size with grades 3 and 4 sclerosis. Glomeruloscleroses of FSGS, hypertension, MGN, and diabetes have stereologically distinct features. A biphasic change in glomerular size is characteristic of primary and secondary FSGS, but not hypertension, in which tuft collapse supports reduced rather than increased perfusion in the pathogenesis of its glomerular obsolescence.

Adult↗

PubMed2002

Correlation of histopathological features and renal impairment in autosomal dominant Alport syndrome in Bull terriers.

BACKGROUND: Bull terrier hereditary nephritis represents a model for autosomal dominant Alport syndrome, as affected dogs have the characteristically lamellated glomerular basement membrane and demonstrate vertical male-to-male disease transmission. METHODS: This study compared the histopathological features in kidneys from affected Bull terrier neonates, puppies, and adult dogs with normal or impaired renal function, with the histopathological appearance of kidneys from age- and size-matched normal dogs. RESULTS: There were fewer glomeruli per unit area of cortex in kidneys from affected neonatal kidneys (P<0.05), increased numbers of fetal glomeruli in affected puppy kidneys (P<0.05), and a separate population of glomeruli with larger renal corpuscles and glomerular tufts in kidneys from affected adult dogs with normal renal function (both P<0.0001) compared with normal dogs. Other histological features that are characteristic of human X-linked and autosomal recessive Alport syndrome and that were present included hypercellular glomeruli, occasional crescents, segmental and global glomerular sclerosis, periglomerular fibrosis, interstitial fibrosis without significant cellular infiltrates and cystic dilatation of Bowman's capsular space and tubules. In dogs with renal impairment, the tubular index was the best predictor of increased urinary protein:creatinine (r=0.92) compared with glomerular, interstitial and vascular indices (r=0.77, 0.88 and 0.81), and medullary fibrosis correlated best with serum creatinine (r=0.72, P=0.0002). CONCLUSIONS: The demonstration in Bull terrier kidneys of fewer nephrons in neonates increased fetal glomeruli, and a separate population of glomeruli with larger corpuscles and tufts reflects the effects of the underlying genetic mutation that are first manifest antenatally. The major determinant of renal impairment in adult affected Bull terriers is, however, progressive tubulointerstitial damage after birth.

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