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Biomedical subjects

A B Morrison

Publications and source records attributed to A B Morrison.

17 recordsLinked to original sources

Humoral inhibitors of the immune response in uremia. II. Further characterization of an immunosuppressive factor in uremic serum.

The serum of Lewis rats with chronic renal insufficiency (induced by subtotal nephrectomy) contains a nondialyzable inhibitor of the mixed lymphocyte reaction. Fractionation of uremic serum by gel filtration on Sephadex G-200 shows that the inhibitory activity elutes with an apparent molecular weight of greater than 200,000 daltons. To establish the possible relationship of the uremic inhibitor to known immunosuppressive components of normal serum, uremic serum was further fractionated on a DEAE cellulose column. The inhibitory activity elutes in 10 mM sodium phosphate at pH 8.0. This fraction contains both alpha-macroglobulin and IgG. The inhibitory activity of this fraction is completely inactivated by treatment with 2-mercaptoethanol, indicating that the inhibitor is a protein. The inhibitory activity is partially inactivated by periodate treatment, suggesting that it may be a glycoprotein. To determine whether or not the inhibitory factor is an immunoregulatory alpha-macroglobulin, or an immune complex, the uremic serum was fractionated by affinity chromatography procedures, which do not induce artifactual inhibitory properties in control serum. The alpha-macroglobulin was removed by affinity chromatography on a column of Con A-Sepharose; its removal had no effect on the inhibitory activity of serum in the mixed lymphocyte reaction. To examine the possibility that immune complexes may be the uremic inhibitor, the serum was fractionated by affinity chromatography on Protein A-Sepharose or by adsorption to a suspension of Staphylococcus aureus, cowan I. Neither of the two latter procedures had any effect on the inhibitory activity of uremic serum. So far all of our findings indicate that the immunosuppressive factor of uremic serum is distinct from two major immunoregulatory factors, alpha-macroglobulin and immune complexes.

Animals

Embedding in large plastic blocks. Diagnostic light and potential electron microscopy on the same block.

Specimens destined for light and electron microscopy were fixed in a modified buffered formalin, postosmicated, dehydrated, and embedded in a mixture of epoxy resins (Epon-araldite) in large plastic molds. These blocks were sectioned at 0.5 to 1 micron on a JB-4 microtome and stained with a combined nuclear and cytoplasmic stain (Paragon). The sections were examined by light microscopy for diagnostic evaluation. If ultrastructural examination was also desired, the selected area was isolated using the "mesa" technique. The trimmed block was then sectioned on an ultramicrotome, picked up on grids, stained, and examined in the electron microscope. We think these techniques offer the diagnostic pathologist the potential of viewing 1-micron sections at a light microscopy level with the option of subsequent electron microscopy of the same area of the same block.

Histological Techniques

Humoral inhibitors of the immune response in uremia. I. Effect of serum and of the supernatant of spleen cultures from uremic rats on the mixed lymphocyte reaction.

The effects of the serum of rats with experimentally induced chronic renal failure and of the supernatant of cultured spleen cells obtained from these animals were tested in the mixed lymphocyte reaction (MLR). Serum of uremic rats with blood urea nitrogen levels greater than 35 mg. per 100 ml. and supernatant of spleen cultures from animals with blood urea nitrogen levels greater than 60 mg. per 100 ml. were found to be inhibitory to the MLR. The inhibitory activity of uremic serum was directly correlated with blood urea nitrogen levels. The inhibitory activities both of uremic serum and of the supernatant of cultured uremic spleen cells were further studied and compared. Dialysis in vitro does not remove the suppressing effect of serum or of supernatant on the MLR. Irreversible inhibition of the MLR is observed after 48 hours' exposure to the serum or to the supernatant; this inhibition occurs whether the MLR culture is exposed during the first 48 hours or last 48 hours of incubation. In some uremic rats the inhibitory activity of the serum disappears or is weakened after splenectomy, despite a continued rise in blood urea nitrogen levels.

Animals

A stereologic study of glomerular hypertrophy in the subtotally nephrectomized rat.

Subtotal nephrectomy in the rat is followed by glomerular hypertrophy, glomerulosclerosis, and, ultimately, renal failure. To gain more insight into this sequence, we have made a morphometric study of the glomerular changes following subtotal nephrectomy in the rat during the period of functional compensation before glomerulosclerosis appears. We found a twofold increase in glomerular volume as compared with controls 2 weeks after operation (to approximately 2 X 10(6) cu mu) followed by a linear increase to approximately 5 X 10(6) cu mu at 21 weeks. The rate of increase in glomerular volume in controls did not significantly exceed that of body weight. The volume increase after subtotal nephrectomy is a true hypertrophy, since other morphometric parameters expressed per unit glomerular volume (surface and length densities) were approximately 80% of control values at 2 weeks and constant thereafter. Glomerular hypertrophy up to 21 weeks is accompanied by a stable BUN and a gradually increasing proteinuria. We conclude that glomerular hypertrophy in this system is a pathologic rather than a compensatory process and suggest that it may represent a counter-productive response to hemodynamic changes serving to increase the glomerular filtration rate.

Animals

The Canadian influenza decision, 1976.

This paper explains the Canadian decision process following the isolation and identification of A/New Jersey/8/76 at Fort Dix, New Jersey in February 1976. The cause for concern was the emergence of a swine-like strain related to that which caused the 1918-19 pandemic, together with proved man-to-man transmission. This concern was reinforced since all new influenza A strains known to have infected the number of persons involved at Fort Dix have become strains of epidemic importance. The Fort Dix outbreak gave sufficient warning to allow implementation of a national vaccination program, to prevent and protect against influenza. In the past such an opportunity had not occurred, and vaccine use had, at best, constituted an intervention in the course of an outbreak. The National Advisory Committee on Immunizing Agents had all available information when it reached its decision to recommend vaccination with bivalent (A/Victoria and A/New Jersey) or with monovalent (A/New Jersey) vaccine for selective, high-risk groups. This was an independent, scientifically based decision.

Adolescent

A decrease in cell-mediated immunity in uremia associated with an increase in activity of suppressor cells.

The graft-versus-host (GVH) reactivity of uremic and control spleen cells was studied by popliteal lymph node assay in the rat. The reaction evoked by cells from animals with severe uremia was conspicuously weaker than that evoked by control cells. The magnitude of the GVH reaction induced by control cells was directly proportional to dose, while with the uremic cells the same increases in dose led only to insignificant increases in the strength of the GVH reaction. When mixtures of syngeneic control and uremic cells were used, the GVH reactivity of the control cells was suppressed. The activity of uremic spleen cells can be enhanced (restored) by removal of the sub-population of cells adherent to glass wool. The GVH reaction induced by uremic cells so treated became directly proportional to dose. The removal of the adherent cell population from the uremic spleen cell suspension also led to the disappearance of the suppressor effect in mixtures of control and uremic cells. These results indicate that a decrease in GVH activity of rat uremic spleen cells is due to an increase in suppressor cell activity in the uremic spleen cell population.

Animals

A progressive glomerulosclerosis occurring in partial five-sixths nephrectomized rats.

A chronic renal disease was induced by 5/6 nephrectomy in young adult Wistar albino male rats. Groups of 3 rats were killed at varying time intervals from 10 to 50 weeks after nephrectomy, and the glomerular structure was studied by light and electron microscopy. By light microscopy, increase in glomerular size and hypertrophy of the visceral glomerular epithelial cells were evident as early as the tenth week. Significant degree of glomerular hyalinization started on the 25th week and gradually became more extensive in involvement towards the 50th week. By electron miscroscopy, the hypertrophied glomerular epithelia showed many osmiophilic bodies and vacuoles in their cytoplasm and fusion of foot processes. Beginning on the 30th week, increase of the mesangial matrix was quite evident, and endothelial and epithelial cells disappeared from the areas where the increase was prominent. The increased matrix gradually encroached and occluded capillary lumina and Bowman's space, leading to a formation of obsolescent glomeruli. Whether or not these glomerular changes are due to the glomerular hyperfiltration which has been known to occur after 5/6 nephrectomy remains to be elucidated.

Animals