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T T Casey

Publications and source records attributed to T T Casey.

23 records · Page 2Linked to original sources

Polymerization of intact beta 2-microglobulin in tissue causes amyloidosis in patients on chronic hemodialysis.

Systemic amyloidosis with a predilection for bone and synovium may complicate the course of patients on long-term hemodialysis. This form of amyloidosis can be typed as distinct from other amyloid diseases by using small tissue samples obtained by bone biopsy and at postmortem. Immunoblot analysis of two-dimensional gels of partially solubilized amyloid fibrils established that tissue deposits are composed of monomers, dimers, and higher polymers of beta 2-microglobulin (beta 2m) and that amyloid P component was also present. Anti-beta 2m antiserum recognized fibrils, as shown by immunoelectron microscopy. Purified monomer isolated from dissociated fibrils yielded peptides corresponding to the entire known sequence of beta 2m. Virtually all serum beta 2m, as well as that present in tissue fluid bathing amyloid fibrils, was monomeric. Hemodialysis-related amyloidosis is an example of a deposition disease occurring in hemodialysis patients. We have shown conclusively that, in this amyloid disease, polymerization of an intact normal serum protein to a fibrillar configuration may occur without proteolysis. We propose the designation A beta 2m for this form of amyloid fibril subunit protein.

Amino Acid Sequence↗

Pathologic fractures associated with idiopathic amyloidosis of bone in chronic hemodialysis patients.

Amyloid bone lesions were found in 2 chronic hemodialysis patients presenting with pathologic hip fractures. These amyloid deposits were noted as lytic defects on plain skeletal radiographs. No evidence for disseminated amyloidosis was discovered on physical examination, skin biopsy, or bone marrow biopsy. Myeloma, other plasma cell dyscrasia, and preceding chronic inflammatory states were not found in either patient. The amyloid deposits had staining characteristics suggestive of secondary amyloid based on the potassium permanganate reaction. Isolated amyloid bone deposits should be included in the differential diagnosis of lytic bone lesions or pathologic fractures in chronic dialysis patients.

Aged↗

OKT4 epitope deficiency in significant proportions of the black population. A cause for underestimation of helper/suppressor lymphocyte ratios.

Monoclonal antibodies such as OKT4, OKT4A, Coulter T4, and Leu 3a are commonly used to define subsets of human peripheral blood lymphocytes having helper activity in vitro. Analysis of peripheral blood lymphocyte populations is a useful aid in the diagnosis of immunodeficiency syndromes. Peripheral blood lymphocytes of certain black and oriental patients do not mark with the conventional OKT4 antibody but do mark with OKT4A and Leu 3a antibodies. We determined helper subset populations of peripheral blood lymphocytes as delineated by OKT4, OKT4A, and Coulter T4 antibodies in 103 unselected patients from two tertiary care hospitals. Twenty percent of black patients without clinical immunodeficiency demonstrated marked reduced numbers of cells marking with OKT4 antibody, but normal numbers of cells marking with OKT4A and Coulter T4 antibodies. No white patients demonstrated this trait to the degree seen in black patients. Use of OKT4 antibody to define helper cell percentages in black patients may lead to underestimation of these percentages in certain hospital populations.

Adult↗

Beta-2 microglobulin is an amyloidogenic protein in man.

Curvilinear fibrils with the tinctorial properties of amyloid were isolated from a patient with bone and joint involvement complicating chronic dialysis for renal disease. Subunit fractions of 24,000 and 12,000 mol wt were identified after gel filtration under dissociating conditions, the latter containing a significant amount of a dimer of the former. This was confirmed by Edman degradation of each fraction, which yielded the amino terminal sequence of normal human beta-2 microglobulin (B2M) to residues 20 and 30, respectively. The size of the subunit protein (12,000 mol wt) and the amino acid composition make it likely that intact B2M is a major constituent of the fibrils. B2M is thus another example of a low molecular weight serum protein, with a prominent beta-pleated sheet structure, that may adopt the fibrillar configuration of amyloid in certain pathologic states.

Aged↗