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This 32-hour required curriculum in palliative medicine for third-year medical students improved knowledge. They came to the course with appropriate attitudes that did not change.

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T cells of patients with rheumatoid arthritis (RA) do not control the rate of B lymphoblast transformation induced by Epstein-Barr virus (EBV) as efficiently as T cells from healthy individuals; thus, lymphoblast cell lines are established more readily in RA lymphocytes in vitro after EBV infection. In the present experiments, we have asked whether this T cell regulation can be reproduced by lymphocytes. We found that normal T cells, activated in allogeneic or autologous mixed leukocyte reactions (MLR), produce lymphokines that inhibit in vitro EBV-induced B cell proliferation. Allogeneic MLR supernatants inhibited EBV-induced DNA synthesis 62 +/- 4% (mean +/- SE) at 10 d post-infection, whereas autologous MLR supernatants suppressed it 50 +/- 3%. RA T cell supernatants produced in an allogeneic MLR suppressed as well as normal T cell supernatants (64 +/- 5% inhibition). In contrast, supernatants from RA autologous MLR had little inhibitory activity. EBV-induced DNA synthesis at 10 d was reduced only 8 +/- 3%, compared with the 50 +/- 3% suppressive activity of normal autologous MLR supernatants. The magnitude of the proliferative responses in the autologous MLR regenerating the lymphokines was similar in the normal and RA populations. After depletion of adherent cells from the RA auto-MLR stimulators, supernatant inhibitory activities increased to normal levels (from 11 +/- 6 [SE] to 52 +/- 6% [SE]). The inhibitory factor involved in the regulation of in vitro EBV infection is a protein with a molecular weight of approximately 50,000. Its activity is eliminated by hearing at 56 degrees C and by exposure to acid at pH 2. The inhibitory activity is blocked by mixing the MLR supernatants with a polyvalent antisera or monoclonal antibodies specific for human gamma interferon. Gamma interferon produced by activating T cells in allo- or auto-MLR can reproduce T cell-mediated regulation of EBV-induced B cell proliferation, and the failure of RA auto-MLR to generate that lymphokine parallels the defective T cell regulation of EBV-induced B cell proliferation characteristic of RA lymphoid cells.

e f o r s t r o k e s , c r a n i a l n e u r o p a t h i e s , o r t r a n s v e r s e m y e l i t i s , b u t t h e y a r e l e s s l i k e l y t o be t h e cause o f o r g a n i c mental syndromes, encephalopathic p i c t u r e s , psychoses, o r chorea.Also, i n r e c o g n i t i o n o f t h e f a c t t h a t these more d i f f u s e c e r e b r a l syndromes a r e o f t e n t r a n s i e n t o r r e v e r s i b l e , i t seems u n l i k e l y t h a t b r a i n c e l l d e a t h i s r e s p o n s i b l e . R a t h e r we would a n t i c i p a t e t h a t these m a n i f e s t a t i o n s w i l l r e s u l t from processes t h a t i n t e r f e r e w i t h e l e c t r i c a l impulses o r n e u r o t r a n s m i t t e r s .Postmortem examination o f t h e b r a i n s o f p a t i e n t s d y i n g w i t h SLE have, i n general, been l i m i t e d t o l i g h t microscopy. The two l a r g e s t s t u d i e s , a l t h o u g h separated by more t h a n t e n years, a r e remarkably s i m i l a r ( 1 , Z ) .They found t h a t i n f l a m m a t o r y c e l l i n f i l t r a t e s and f i b r i n o i d n e c r o s i s o f t h e w a l l s o f small and medium s i z e d a r t e r i e s , so t y p i c a l i n t h e k i d n e y and o t h e r systemic l e s i o n s o f SLE, a r e o n l y o c c a s i o n a l l y seen i n t h e b r a i n .More o f t e n , t h e r e were d e g e n e r a t i v e and p r o l i f e r a t i v e changes i n small vessels, s i m i l a r t o those of h y p e r t e n s i v e encephal opathy and t h r a n b o t i c thrombocytopenic purpura. S c a t t e r e d about t h e c e r e b r a l c o r t e x were m i c r o i n f a r c t s and g l i o s i s around s m a l l b l o o d vessels.A f f e c t e d a r t e r i o l e s showed t h i c k e n i n g a n d v a s c u l o p a t h y i s r e m i n i s c e n t o f t h e a b n o r m a l i t i e s seen i n t h e c o r o n a r y a r t e r i e s o f v a r i o u s s t r a i n s o f autoimmune mice, many o f whom develop thrombosis and myoc a r d i a l i n f a r c t i o n ( 3 , 4 ) . Immunofluorescence and e l e c t r o n m i c r o s c o p i c e x a m i n a t i o n o f those l e s i o n s show immune complexes d e p o s i t e d i n t h e vessel w a l l s , y e t t h e r e i s a conspicuous absence o f an inflammatory component. I t i s i m p o r t a n t t o p o i n t o u t , however, t h a t w h i l e m i c r o v a s c u l a r l e s i o n s can account f o r t h e c l i n ic a l f i n d i n g s i n some SLE p a t i e n t s , t h e r e i s o f t e n a remarkable l a c k o f c l i n i c a l -p a t h o l o g i c c o r r e l a t i o n s . P a t i e n t s w i t h obvious l u p u s encephalopathy may show o n l y m i n i m a l f i n d i n g s a t postmortem examination, w h i l e o t h e r s w i t h no h i s t o r y o f c e r e b r a l m a n i f e s t a t i o n s d u r i n g l i f e have c h a r a c t e r i s t i c changes. Any t h e o r y o f pathogenesis must d e a l w i t h t h i s discrepancy.A p p r o x i m a t e l y t e n y e a r s ago, A t k i n s e t a1 (5) observed...

The very late activation antigens (VLA) are a subset of the superfamily of cell surface glycoproteins that serve as receptors from extracellular matrix proteins. One or more of the VLA heterodimers are present on T lymphocytes and most other cell types, including platelets. We have used VLA-specific monoclonal antibodies to isolate the reactive platelet membrane molecules. We have identified them as previously characterized platelet surface glycoproteins and have compared them with VLA molecules isolated from lymphocytes and other cells. Utilizing one-dimensional SDS-PAGE, twodimensional O'Farrell gel electrophoresis, and nonreduced-reduced two-dimensional gel electrophoresis, we show that re-

An empiric observation of the rapid development of B lymphoblast cell lines after in vitro infection with Epstein‐Barr virus (EBV) in peripheral blood mononuclear cells (PBM) from patients with rheumatoid arthritis (RA) led us to compare cellular regulation of EBV‐induced lymphoblast outgrowth in RA and normal lymphoid cell populations. We found that RA PBM developed proliferating B lymphoblast colonies in a median time of 10 days after exposure to an EBV containing culture supernatant, while normal PBM took 18 days to grow out under the same conditions. The more rapid outgrowth of RA cells was not due to therapy with antiinflammatory or antirheumatic drugs. The time to outgrowth of the normal cells decreased to 11 days after T cell depletion. T cell depletion of the RA cells had less effect on the time to outgrowth but it was shortened to 8 days. B lymphoblast cell lines were established from “purified” T cell populations from 18 of 20 RA patients, while populations of T cells from normal donors with the same percentage of T and B cells did not produce lymphoblast cell lines when infected with EBV. In addition, we found that the non‐ T lymphoid cells from 7 of 20 RA patients established permanent B lymphoblast cell lines spontaneously without EBV infection. Spontaneous outgrowth of lymphoid cells from normal donors occurred only once in 48 experiments. These results indicate abnormalities in cell‐mediated regulation of EBV‐induced cell proliferation in lymphoid cells from patients with RA.