Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rabbits immunized with particulate and soluble preparations of rat lymphoid tissue of the HO strain produced antisera which reacted without strain specificity on rat lymphocytes. Absorption of the sera with tissue from the AS strain of rat removed the antibodies reacting with AS tissue leaving activity against HO cells only. Studies with backcross rats showed that the antigens detected by these sera were products of the AgB genes or genes segragating with them. The immunosuppressive activity of rabbit antisera specific for Ag-B5 rat transplantation antigens was tested in a rat renal allograft assay. Some of the antisera markedly prolonged the survival of (AS X HO)F1 kidneys transplanted to AS rats. The prolongation of graft survival was not due to ALS activity since the sera were active in the absence of antibody directed against recipient antigens. There was no correlation between in vivo enhancement and anti-donor lymphocytotoxic titres of the xenoantisera.
 ...
PMID:Immunological enhancement of rat renal allografts using rabbit antisera with specificity for rat transplantation antigens. 6 35

Lymphoid cells were isolated from mouse mammary tumors by isokinetic gradient centrifugation. theta-bearing and ALS-sensitive cells were always the largest subpopulations found in these tumors. In fractions 4 to 6 from the isokinetic gradient, theta-positive cells ranged from 8 to 46% in autochthonous tumors and 14 to 47% in passaged tumors, and ALS-positive cells ranged from 34 to 46% in autochthonous tumors and 14 to 100% in passaged tumors. SIg-positive cells were only found in occasional tumors and, where present, averaged 2% of the separated population. Fc receptor-bearing cells averaged 15% and phagocytic cells averaged 8% of the cells found in fractions 4 to 6 of the gradient. Occasional ALS-positive and one-third of the Fc receptor-bearing and phagocytic cells also separated in fractions 7 to 10 of the isokinetic gradient. Although the individual tumors were very variable in the proportions of the various lymphoid subpopulations that they contained, this variability was a stable characteristic for at least one passage generation.
 ...
PMID:In situ lymphoid cells of mouse mammary tumors. II. The characterization of lymphoid cells separated from mouse mammary tumors. 65 82

Some aspects of the mechanisms by which antilymphocyte serum, its globulin fraction, or phytohaemagglutinin act to reduce the stem cell content of murine haemopoietic tissues were studied, using the method of clonal proliferation of stem cells in the spleens of lethally irradiated (830R) mice. The transplants were treated in vitro with ALS, ALG or PHA for 30 min. at 37 degrees C. Direct treatment of spleen or bone marrow cells with ALS or PHA resulted in pronounced inhibition of the colony-forming capacity of haemopoietic tissues in syngeneic irradiated recipients. The degree of inhibition was dependent on the concentration of ALS or PHA. It was found that the inhibition of CFC with ALS was mediated by lymphoid cells: bone marrow CFC were reduced after 30-min incubation at 37 degrees C with syngeneic lymph node or thymus cell pretreated with ALG and washed free of its excess. It was further demonstrated that ALG-treated thymocytes released, upon 30-min. incubation at 37 degrees C, some material capable of inhibiting bone marrow CFC. No release was observed with PHA-treated thymocytes. Some properties of the active supernatants are described and it is suggested to designate the observed inhibitory activity as Stem-cell Inhibitory Factor.
 ...
PMID:Inhibition of haemopoietic stem cells by syngeneic lymphocytes treated with antilymphocyte serum. 110 Apr 42

The survival of C3H/He skin grafts can be prolonged on B6AF1 mice immunosuppressed with ALS by the injection of C3H/He marrow 1 week postgrafting. The precursor frequencies of donor-reactive CTL in the spleen and lymph nodes of ALS-treated, grafted mice given donor marrow were compared with CTL frequencies observed in ALS-treated, grafted controls. Spleens and nodes were removed from experimental and control mice on days +8, +14, +21, +58, and 1 year postgrafting, and used as effectors in the LDA. Donor-reactive CTL in the marrow-injected group remained suppressed as long as the recipients maintained their grafts. The frequency of CTL to third-party antigens was normal in mice bearing long-term C3H/He grafts. When marrow-injected mice rejected their grafts, the total donor-reactive CTL frequency returned to normal. In contrast, in ALS-treated controls that did not receive marrow, the total number of donor-reactive CTL returned to normal levels with recovery from the immunosuppressive effects of ALS. These results suggest that donor marrow suppresses the regeneration of donor-reactive CTL in the lymphoid tissues of ALS-treated mice, possibly by veto cell activity.
 ...
PMID:The effect of injection of donor bone marrow on the frequency of donor-reactive CTL in antilymphocyte serum-treated, grafted mice. 141 58

Although chronic immunosuppression has been extremely successful in clinical organ transplantation, it is associated with severe complications such as opportunistic infections, spontaneous neoplasms, drug toxicities, metabolic complications, and the inability to control rejection. We therefore have investigated the ability of allogeneic donor lymphoid cells to produce specific tolerance following intrathymic (IT) injection into allograft recipients. Groups of B6AF1 mice received ALS on days -1 and +2 relative to C3H/He skin grafts on day 0; experimental groups received 1, 5, or 10 x 10(7) syngeneic (B6AF1) or allogeneic (C3H) spleen cells (SPCs) by IT injection on day +7. IT injection of C3H splenocytes significantly prolonged allograft survival at all cell doses tested when compared with ALS controls. The best survival was obtained following IT injection of 5 x 10(7) C3H cells (median survival time [MST] = 132 days; ALS controls = 21.5 days), with 8 of 13 skin grafts surviving longer than 100 days. IT injection of syngeneic splenocytes or third-party DBA/2 splenocytes did not prolong allograft survival beyond that observed in ALS controls. C3H spleen cells injected IT into ALS treated mice on day 0 relative to grafting of C3H skin also produced significant allograft survival (1, 5, or 10 x 10(7) SPCs = MSTs of 75, 47, and 35, respectively) but the results were inferior to those obtained by 5 x 10(7) SPCs IT on day +7. Spleen cells (1 or 5 x 10(7)) injected intraperitoneally or intravenously prolonged allograft survival beyond that seen in ALS controls but were inferior to IT injection at all doses and times studied. Bone marrow, thymocytes, or lymph node cells (5 x 10(7) cells) were substituted for SPCs for IT injection. IT injection of BM, LN or thymocytes all significantly prolonged graft survival over ALS controls. However none of these cell types was as effective as IT splenocytes. Eight B6Af1 recipients of IT splenocytes bearing C3H skin grafts for > 100 days received a second C3H skin graft as well as a simultaneous third-party B10.AKM skin graft. All rejected third-party grafts in normal first-set fashion. Three tolerated both 1st and 2nd C3H grafts without any sign of rejection; 1 rejected the 2nd C3H graft while tolerating the 1st graft; and 4 rejected the 2nd C3H graft in an attenuated fashion but also rejected the 1st graft at the same pace.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Induction of specific unresponsiveness (tolerance) to skin allografts by intrathymic donor-specific splenocyte injection in antilymphocyte serum-treated mice. 146 74

Skin grafts can be significantly prolonged in ALS-treated mice by the injection of 25 x 10(6) donor bone marrow cells or 50 x 10(6) spleen cells. Lymph node cells and thymocytes are only minimally effective in prolonging grafts. The effect of a hematopoietic growth factor, granulocyte-macrophage colony stimulating factor (GM-CSF) was studied in this model of unresponsiveness. C3H/He lymphoid cell donors were treated with GM-CSF. Either normal or GM-CSF-treated cells were injected into ALS-treated B6AF1 mice grafted with C3H/He skin. GM-CSF treatment significantly augmented the effect of marrow in prolonging graft survival at doses of 1 to 25 x 10(6) cells. In contrast, GM-CSF had no effect on the graft-prolonging effect of spleen cells when 50 x 10(6) cells were given. When the dose of cells was reduced to 25 x 10(6), graft survival in the group given GM-CSF-treated cells was prolonged compared with survival in the group given normal cells. Grafts in the group given GM-CSF-treated lymph node cells were rejected in sensitized fashion. When marrow and spleen are separated on a Percoll gradient, the cell active in promoting graft survival is recovered primarily in the 52.5% fraction. The graft-prolonging effect of the 52.5% marrow fraction was not affected by GM-CSF treatment. In contrast, GM-CSF-treated marrow cells in the 60% fraction significantly prolonged graft survival, while normal marrow cells in this fraction had no effect on graft survival. GM-CSF-treated spleen cells in the 52.5% and 60% fractions significantly decreased graft survival compared with normal cells when given at a dose equal to the number of cells recovered from 50 x 10(6) cells. When the dose of fractionated spleen cells was reduced, GM-CSF-treated spleen cells were more effective than normal cells in prolonging graft survival. These results indicate that GM-CSF activates a cell in marrow that promotes graft survival. This cell is recovered in the 60% Percoll fraction. In contrast, GM-CSF appears to affect two cell populations in spleen, one beneficial and one detrimental to graft survival. The predominant effect depends on the dose of spleen cells that is given.
 ...
PMID:Effect of granulocyte-macrophage colony-stimulating factor on the induction of unresponsiveness by lymphoid cells. 167 Sep 70

Monoclonal antibody immunocytochemistry was used to examine spinal cord and muscle in amyotrophic lateral sclerosis for changes that would indicate ongoing or potential immune activity. Increased expression of class I and II major histocompatibility complex (MHC) antigens was seen in the affected areas of spinal cord. New MHC expression was concentrated in phagocytes, particularly in degenerating white matter in which they were dispersed in the tissue and also packed around blood vessels. MHC antigen was not revealed in motor neurons or skeletal muscle fibers. An anti-pan-T-cell monoclonal revealed small numbers of T cells in degenerating white matter. Similar changes have been seen in other neurodegenerative disorders. They suggest a potential for (secondary) cell-mediated activity in the affected areas rather than an ongoing MHC-restricted T-cell response. Vessel-associated phagocytes may be a source of antigen to peripheral lymphoid tissue, stimulating production of the autoantibodies that have been described.
 ...
PMID:Major histocompatibility complex antigen expression in the affected tissues in amyotrophic lateral sclerosis. 224 Nov 18

To study the mechanism of induction of specific unresponsiveness to allografts in animals treated with antilymphocyte serum and donor bone marrow cells, we examined the effect of donor BMC on second-set graft rejection responses caused by antidonor-sensitized spleen cells (SSC) in mice bearing donor ear skin grafts. Anti-C3H SSC were obtained from skin-grafted, ALS-treated B6AF1 mice after rejection of their grafts. The second-set rejections of C3H skin grafts were assessed in B6AF1 mice following adoptive i.v. transfer of 30 x 10(6) SSC one day after grafting. Median survival time (MST) of C3H skin grafts in the group injected with SSC was 7 days, which is significantly lower than an MST of 11 days observed in the control group, which exhibited a first-set graft rejection response. Addition of 50 x 10(6) C3H BMC to 30 x 10(6) SSC abrogated the second-set rejection of C3H skin grafts (MST = 11 days). This abrogation effect of BMC is strain-specific, since BMC of a third-party strain (DBA/2) failed to abrogate the second-set rejection responses caused by anti-C3H SSC. Of the different C3H lymphoid cells tested for abrogation of the second-set graft rejection, BMC were the most effective. Splenocytes were more effective than thymocytes, which showed a partial effect. Lymph node cells had no effect. Our data suggest that unresponsiveness to allografts in animals treated with the ALS/bone marrow protocol may result from the inactivation of graft-reactive cells by donor BMC.
 ...
PMID:Abrogation of alloreactive spleen cell-induced second-set skin graft rejection in mice with donor-specific bone marrow cells. 265 23

Small bowel and its mesentery contain considerable amounts of lymphoid tissue that can mediate graft-versus-host disease in small bowel transplant (SBT) recipients. Present studies determined the existence of GVHD in a fully allogeneic SBT model and examined the effect of donor pretreatment with ALS in eliminating GVHD. Adult male Lewis (Lew) rats received orthotopic small bowel transplants from untreated (LewxBN)F1 (LBNF1) donors (group 1) or Brown Norway (BN) donors that were untreated (group 2) or pretreated with ALS (days -2 and -1) (group 3). All recipients were treated with cyclosporine 15 mg/kg/day i.m. on days 0-6 postoperatively. Animals were weighed and examined daily for signs of rejection and GVHD. No animals in groups 1 or 3 showed any physical signs of GVHD, but all of those in group 2 had characteristic weight loss, diarrhea, and dermatitis between 4 and 6 weeks postoperatively, from which they all recovered. Histologic examination of skin and spleen at this time confirmed the presence of GVHD. The relative spleen weight [( spleen weight/body weight] x 100) of group 2 animals was also significantly greater than that of unoperated control Lew animals. Spleen cells obtained from group 2 animals at the time of subclinical GVHD, but not cells from group 1 or 3 animals, caused enlargement of popliteal lymph nodes when they were injected into the footpads of Lew rats. This study shows that GVHD can manifest itself in recipients of a fully allogeneic small bowel transplant even when rejection is prevented by effective immunosuppression with CsA. However, combined use of recipient treatment with CsA and pretreatment of donor animals with ALS eliminates all manifestations of GVHD.
 ...
PMID:Graft-versus-host disease in fully allogeneic small bowel transplantation in the rat. 291 75

Adult CBA mice may be made tolerant of August rat tail skin grafts by short intensive treatments with antilymphocyte serum followed by massive ( approximately 100 x 10(6) cells) injections of August rat lymphoid cells. Prolonged tolerance can be achieved only in thymectomized mice, and is accompanied by lymphoid cell chimerism and the manufacture of rat protein. The rat lymphoid cell donors must be treated beforehand with antirat ALS to avoid complications associated with graft versus host reactions. Rejection of rat skin grafts is accompanied by the formation of high titres of antirat hemolysins and lymphocytotoxins, but in "tolerant" mice the rat skin survives in the continual presence of antirat antibodies. Under certain circumstances, however, passive transfusion of high titre mouse antirat serum can precipitate the breakdown of rat skin grafts. It is doubtful if this represents the primary mechanism of rejection. The reaction of normal mice against rat skin is essentially an intensified allograft reaction; it is at all events wholly immunological in character.
 ...
PMID:Tolerance of rat skin grafts in adult mice. 439 16


1 2 3 Next >>