Alvin F. Wells

Increased hyaluronan in acutely rejecting human kidney grafts

The glycosaminoglycan hyaluronan is not only involved in cellular differentiation and migration but may also play a role in several inflammatory diseases. We have previously demonstrated an increased local production of hyaluronan in chronically rejected kidneys and the correspondingly affected renal vessels. In this report, we demonstrate the presence of hyaluronan in acutely rejecting kidneys. A total of 77 biopsies classified as either acute rejection or nonrejecting were analyzed using a biotin-labeled hyaluronan-binding protein in conjunction with an avidin-biotin peroxidase detection system and graded using an arbitrary scale from 0 to 3. Those biopsies classified as nonrejecting did not contain any peritubular hyaluronan in the cortex, with hyaluronan being localized only in the medulla. In contrast, those biopsies exhibiting acute rejection had an increase of hyaluronan both in the cortex and in the medulla. This increase was significantly different (P=0.0001) and correlated with edema and interstitial inflammation. The detection of the local hyaluronan production may be a useful marker to measure acute rejection episodes.

The localization of hyaluronan in normal and rejected human kidneys.

Hyaluronan (HYA) is a large glycosaminoglycan with a high capacity to immobilize water. Increased levels of HYA have previously been observed in plasma as well as in affected tissues in various inflammatory conditions. The morphological localization of HYA has, however, not been described in normal or rejected human kidneys. Using a recently developed method for localization of HYA in tissue sections by means of a biotin-labeled hyaluronan binding protein used as a probe, we have now investigated the distribution of HYA in normal and irreversibly rejected human kidneys. In the normal kidney HYA was essentially confined to the medulla. In the rejected kidneys increased amounts of HYA were observed primarily in the cortex and in sclerotic vessels. Incubating tissue sections with hyaluronidase abolished the staining for HYA, showing the specificity of the staining procedure. The increased amounts of HYA of the rejected kidney may play a role in local edema formation, and thereby alter graft function.

Localization of hyaluronan in normal breast tissue, radial scar, and tubular breast carcinoma☆

Hyaluronan (hyaluronic acid [HYA]) is one of the extracellular matrix components involved in normal cell physiology and is localized mainly in bodily fluids and connective tissues. Increased amounts of HYA in serum have been demonstrated in a number of neoplastic and inflammatory conditions, among them breast cancer. Tubular breast carcinoma (TC) and radial scar (RS) are two breast lesions that microscopically display characteristic stromal alterations and possess gross and microscopic similarities. Due to the importance of HYA as a component of the extracellular matrix, we investigated its presence in these lesions and in normal breast tissue. Using a biotinylated HYA-binding region for the in situ detection of HYA, we noted an increased amount of HYA in both TC and RS as compared with that in normal breast tissue specimens. A strong reactivity was observed predominantly around glandular structures and in the interlobular stroma of both TC and RS. Perivascular HYA staining also was distinctly observed in these lesions (TC and RS). Some HYA was observed in the connective tissue of the intralobular regions, around small blood vessels, and in the perivascular connective tissue of the normal breast. The distribution of HYA adjacent to the epithelium in the normal breast suggests a role for HYA in the interaction between epithelium and stroma of the normal breast. Its increase in the connective tissue of both TC and RS reflects the derangement of the stroma commonly observed in these conditions and supports the notion that these lesions may be associated.

Localization of hyaluronan in regions of the human female reproductive tract

Accumulation of hyaluronan has previously been observed in various organs as an inflammatory response. To study the presumed connection between infertility due to a tubal factor and inflammation, we performed an analysis of the hyaluronan distribution in biopsy specimens from the female reproductive tract, using a biotinylated hyaluronan binding protein (HABP) as a histochemical probe. In normal specimens hyaluronan was localized in the dense, irregular connective tissue surrounding blood vessels of various sizes. Smooth muscle and columnar epithelium were devoid of hyaluronan. The isthmic part of the normal Fallopian tube showed moderately intense staining of the entire lamina propria, whereas normal fimbriae stained weakly. No cyclic changes in hyaluronan content were observed. In biopsy specimens from women with infertility due to a tubal factor, intense staining, stronger than in normal tubes, was detected in the adhesions and in the lamina propria of sactosalpinx. This may indicate that infertility due to a tubal factor is associated with an ongoing inflammatory and/or proliferative process.

Changes in Ultrasonographic Vascularity Upon Initiation of Adalimumab Combination Therapy in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate.

To assess joint disease activity by ultrasound (US) in patients with rheumatoid arthritis (RA) initiating treatment with adalimumab (ADA) plus methotrexate (MTX).