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Biomedical subjects

A M Silverstein

Publications and source records attributed to A M Silverstein.

At least 55 records · Page 3Linked to original sources

MR imaging of the brain in five members of a family with Pelizaeus-Merzbacher disease.

MR imaging was performed in five members of a family afflicted with Pelizaeus-Merzbacher disease. The individuals imaged included a male proband, his mother, and three maternal uncles. Clinically affected members showed generalized white matter signal aberration consistent with dys- and demyelination, basal ganglia, and thalamic signal aberration suggestive of pathologic iron storage and diffuse brain atrophy. These findings are similar to those seen in other leukodystrophies. The proband's mother was normal by neurologic examination but showed a suspicious but not definitely abnormal similar pattern of basal ganglionic and white matter signal aberration. In our limited patient sample, MR appears to be able to: (1) demonstrate a pattern of imaging abnormalities characteristic of Pelizaeus-Merzbacher disease (we do not know if this pattern is specific); (2) potentially detect the obligate carrier state; and (3) detect the facultative carrier state.

Adult↗

Technetium-99m red blood cell venography in upper extremity deep venous thrombosis.

The efficacy of Tc-99m RBC venography has been demonstrated with respect to the study of lower extremity deep venous thrombosis. A case is presented where Tc-99m RBC venography was used to study the upper as well as lower extremities in a patient with upper extremity deep venous thrombosis (DVT) who was found to have pulmonary embolism.

Adult↗

Experimental autoimmune dacryoadenitis. I. Lacrimal gland disease in the rat.

Experimental autoimmune dacryoadenitis was produced in Lewis rats by immunization with a single intradermal administration of a 3M KCl extract of exorbital lacrimal gland in CFA, when enhanced by simultaneous i.v. injection of killed Bordetella pertussis. No significant lacrimal lesions were observed in control animals immunized with the extracts of Harderian or salivary glands. Gel filtration of the 3M KCl extract on Sephacryl S-300 column yielded three protein fractions. Only fraction III (MW = 10-55K) induced marked dacryoadenitis following a single injection of 2.0 mg protein in CFA plus pertussis. The infiltrates in the exorbital lacrimal lesions were first apparent around the ducts and associated vasculature. From this area, the infiltrates appeared to spread to the acini drained by these ducts, ultimately involving as much as 30-50% of the gland. The affected glands most commonly showed a diffuse nongranulomatous infiltrate of small lymphocytes, macrophages, and plasma cells; this was focal in nature, involving acinar atrophy and breakdown, and replaced the normal architecture in extreme cases. The Harderian and salivary glands were uninvolved in these animals, suggesting a restricted specificity of this response. Lewis rats immunized with exorbital lacrimal gland fractions I or II in CFA plus pertussis showed only minimal lesions, similar to controls receiving CFA and pertussis without antigen. These findings suggest that an autoantigen exists in the lacrimal gland of the rat that is capable of inducing a specific lymphoproliferative dacryoadenitis.

Animals↗

Experimental autoimmune dacryoadenitis. II. Harderian gland disease in the rat.

Experimental autoimmune dacryoadenitis was induced in 100% of Lewis rats by immunization with a KCl extract of Harderian gland in complete Freund's adjuvant (CFA), providing that the animals had received simultaneously i.v. injection of killed Bordetella pertussis. No significant pathological changes in the Harderian gland were observed in control animals immunized with KCl extracts of lacrimal or salivary glands. Gel filtration of the KCl extract on Sephacryl S-300 column yielded three protein fractions. Fraction II (MW = 50-100K) induced severe Harderian gland disease following a single injection of 2.0 mg protein in CFA plus pertussis. The initial lesions consisted of multiple focal infiltrates of mononuclear cells. Later, the inflammatory process assumed a more granulomatous form, with significant contribution by epithelioid and giant cells. In contrast, Lewis rats immunized with Harderian gland fractions I or III proteins, or with extracts of lacrimal or salivary gland, showed little or no inflammatory lesions. These data suggest that Harderian gland contains unique tissue-specific autoantigen(s) capable of inducing autoimmune granulomatous dacryoadenitis in the rat.

Animals↗

Experimental immunogenic granuloma of the orbit: transfer of granulomatous hypersensitivity with a subset of T lymphocytes.

An experimental model to investigate orbital granuloma formation in inbred rats was established. Animals sensitized to trinitrophenyl ovalbumin (TNP-OA) and challenged retro-orbitally with TNP-OA covalently linked o Sepharose 4B beads specifically developed a granulomatous response. This granulomatous reactivity was passively transferred into normal animals by lymph node cells, but not by serum antibody from sensitized donors. Lymphocytes which transfer granuloma formation in normal recipients were characterized by cell fractionation and membrane marker analysis. These experiments show that the effector cells capable of transferring granulomatous hypersensitivity are enriched in the lower density fractions on discontinuous Percoll gradients. These cells are lymphoblasts and express the W3/25 helper T lymphocyte marker. It was also demonstrated that lymphoid cells from sensitized donors in the higher density Percoll fraction appear to be incapable of adoptively transferring granulomatous responsiveness directly to normal recipients. However, incubation of these high density lymphocytes with specific antigen resulted in marked enhancement of their ability to transfer the disease. Antigen-induced activation also resulted in an increase in both lymphoblasts and the W3/25 marker. The authors conclude, therefore, that a subset of T cells which are lymphoblasts and express the helper-cell marker is responsible for granuloma formation in sensitized animals and is capable of transferring orbital granuloma formation to non-sensitized normal recipients.

Animals↗

In vitro enhancement of anterior chamber GVH reactions.

The injection of sensitized allogeneic lymphocytes into the anterior chamber of the rabbit eye results in a local graft-verus-host reaction, with focal destruction of the corneal endothelium. This experimental model permits in vitro manipulation of effector cells, and the study of the mechanisms involved in corneal graft rejection. The authors now show that the in vitro activation of sensitized lymphocytes is a one-way mixed lymphocyte reaction yields "supersensitized" effector cells which are quantitatively enriched and qualitatively altered to yield more severe and more rapid endothelial target cell destruction.

Animals↗

Complications of total knee replacement.

The records and radiographs of 162 patients with 224 total knee replacements were reviewed for evidence of complications. Early complications included cardiovascular abnormalities, in particular deep vein thrombosis (3%), and limitation of motion requiring manipulation under anesthesia (7%). Late problems included patellofemoral arthritis (11%), heterotopic bone formation (10%), loosening (7%), deformity (4%), fracture (3%), and infection (2%). Patellofemoral pain and arthritis is the most common and often the most disabling complication.

Adult↗

Development of the concept of immunologic specificity: IV.

We have attempted, in this series of essays on the development of the concept of immunologic specificity, to trace the history of one of the most central ideas in immunology (and indeed in biology in general). The result must be viewed as preliminary and incomplete and as an invitation to others to add, to amend, and even to disprove. Nevertheless, several interesting conclusions may be drawn, which reveal much about the workings of immunology in particular, and perhaps science in general. First, the roots of any important scientific concept (such as that of immunologic specificity) do not grow in isolation; they draw nourishment from many other disciplines. Similarly, the growth of an important concept within a given discipline will have far-reaching implications and fruits for other fields of science. Second, we may note a marked change in the manner in which immunology is currently practiced, compared with that of the end of the last century. The quantum leaps forward in funding, in numbers of scientists, and in masses of crucial data have not been without a certain cost--the substantial reduction in elegant personal style that characterized so many of our scientific forebears, and that makes so pleasant the reading of their reports. Finally, we see again and again how much his philosophical bases and disciplinary upbringing determine a scientist's approach, the questions that he asks, and the type of answers he will accept. Throughout much of immunology's history, as Jerne put it so well (44), cis- and trans-immunologists hardly spoke to one another. Or rather, a cis-immunologist sometimes spoke to a trans-immunologist, but the latter rarely answered! Fortunately, one of the attributes of scientific progress is a merging of these disparate languages, and eventual mutual comprehension.

Allergy and Immunology↗

The role of lymphokines in immunogenic uveitis.

Lymphokines were prepared from rabbit lymph node cells specifically activated in vitro with the insoluble antigen ovalbumin or nonspecifically activated with the insoluble mitogen concanavalin A. Intravitreal injection of either lymphokine caused uveitis in the normal rabbit eye, more severe and more prolonged with the concanavalin A-activated supernatants than with the ovalbumin-activated supernatants. The most striking difference between the two lymphokine preparations was in their ability to induce a secondary intraocular antibody response in the trinitrophenyl bovine gamma globulin-primed recipient. Concanavalin A supernatants stimulated polyclonal B cell activation with appreciable anti-TNP responses in animals primed either systemically or locally. In contrast, ovalbumin supernatants stimulated an intraocular anti-TNP response only in those animals that had been primed within the eye. We speculate that two or more different lymphokines are active, some of which attract lymphocytes nonspecifically to the local site and others of which excite polyclonal B cell activation and plasma cell formation.

Animals↗