Number of nexin links detectable at standard electron microscopy of normal human nasal cilia and at nexin link deficiency.

BACKGROUND: Eleven years ago we had described three patients with missing nexin links as a possible cause of primary ciliary dyskinesia (PCD). The assumption was substantiated last year by finding a mutation in these patients. MATERIALS AND METHODS: We counted the nexin links, inner (IDA) and outer (ODA) dynein arms and microtubuli in each of, if possible, 50 cilia in 41 patients with normal cilia, 4 patients with deficiency of nexin links only and 4 with deficiency of nexin links and IDA. RESULTS: In the control group the median number of nexin links was 4.5 per cilium, range 3.4-5.3. In the second group the mean numbers of nexin links per cilium were 1.1-1.4, in the third group 0.8-1.2, per patient. The median number of IDA was in the control group 4.2, range 3.3-5.2. In groups 2 and 3 the numbers were 3.0-3.5 and 0.2-1.0, respectively. Numbers of ODA were normal in all groups. CONCLUSIONS: It is possible to reliable count the number of nexin links in nasal human cilia and to distinguish cases with missing nexin links from normal controls.

Evidence for a morphologically distinct and functionally robust cell type in the proximal tubules of human kidney.

Acute tubular necrosis (ATN), elicited by ischemia and/or toxicity, is a potentially life-threatening condition. Histologically, ATN corresponds to necrosis and detachment of renal tubular epithelial cells. However, the tubules possess a considerable regenerative capacity and may be restored. We have previously identified a scattered population of progenitor-like cells within the proximal tubules, sharing marker expression with the parietal epithelial cells of Bowman's capsule as well as with renal tubules regenerating after ATN. In the present analysis, we use transmission electron microscopy, immunoelectron microscopy and immunofluorescence of human kidney cortex to further explore these cells. We demonstrate that the cells are smaller and have drastically fewer mitochondria than the surrounding proximal tubule cells. They also display strong expression of several structural proteins such as vimentin, collagen-7A1 and the tight junction protein claudin-1. To functionally assess these cells, we also developed a novel human kidney explant model of ATN demonstrating that the cells are more resilient to injury than the surrounding proximal tubular cells. Taken together the results suggest a novel robust cell type with a contrasting biological role to that of the bulk of proximal tubular epithelium.