In vitro strain distribution in the proximal tibia. Effect of varus-valgus loading in the normal and osteoarthritic knee

Six human cadaver legs were tested with strain-gauge rosettes to determine the effects of varus/valgus loading on the distribution of strain on the cortical bone of the proximal tibia at loads of up to 250 kg. Changes in the femorotibial angle of 1.5 degrees and 3.1 degrees, to create varus/valgus deformities, produced significant unloading of the opposite aspect of the normal leg. A varus deformity of 3.1 degrees in the medial compartment osteoarthritic model virtually unloaded the lateral compartment and, because of the bending effect, placed the whole of the lateral aspect of the leg into axial tension. Under these conditions, the axial strains in almost the whole of the medial aspect of the tibia were doubled, from an initial value of 250 microstrain (compressive) to a value of approximately 500 microstrain (compressive). While a change in load-action, to simulate a 3.1 degrees valgus deformity in the medial compartment osteoarthritic model, did not completely unload the medial plateau of the tibia, it was suggested that such unloading could be achieved with slightly greater valgus loading. Successful clinical results, employing valgus osteotomies in patients with medial compartment osteoarthritis, are obtained by unloading the medial compartment while markedly increasing compressive loads on the whole of the lateral aspect of the leg.     

Father to son transmission of decreased Ns activity in pseudohypoparathyroidism type Ia

We found both renal resistance to endogenous and exogenous PTH and reduced activity of the stimulatory guanine nucleotide-binding regulatory protein (Ns) of adenylate cyclase in a man with clinical signs of pseudohypoparathyroidism type Ia (PHP-Ia). Both of his children also had reduced Ns levels and short stature. The girl, 11 yr old, had evidence of partial resistance to PTH, while the son, age 7 yr, had no apparent abnormalities in calcium metabolism or response to administered PTH. Variable expression of the metabolic abnormalities of PHP during childhood has been previously described. The occurrence of reduced Ns activity in father and son is consistent with autosomal dominant inheritance for the primary biochemical defect of PHP-Ia in this family.     

Cell culture block array for immunocytochemical study of protein expression in cultured cells.

Immunocytochemical staining of cultured cells using specific antibodies is a powerful technique to study the expression and subcellular localization of proteins. However, this technique is associated with sample-to-sample variations because samples are handled individually and manually. Cell permeation is needed when intracytoplasmic or nuclear proteins are studied. Storage of cultured cells is difficult, and experiments must be repeated if additional studies are desired later, which introduces more variations. We developed a cell culture block array technique that converts cultured cells into a permanently fixed form identical to tissue sections prepared for pathologic examination. Cells from different cultures can be embedded in a single block. Many identical sections, each containing cells from multiple cultures, may be stained with different antibodies using an automated stainer. As a result, sample-to-sample variation is eliminated. Because cells in these blocks are sectioned by knives, all cellular proteins come into direct contact with antibodies, and cell permeation is not needed. Such blocks can be conveniently stored for years without loss of antigens, providing a constant source for future studies. We demonstrated the utility of this technique by studying the proliferation and neuroendocrine differentiation of prostate cancer-derived LNCaP cells cultured in vitro.