Cladribine treatment of multiple sclerosis.
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Cladribine↗
Biomedical subjects
M Ryba
Publications and source records attributed to M Ryba.
Depressed immune surveillance against cancer: role of deficient T cell: extracellular matrix interactions.
Although T cells infiltrate malignant tumors, the local immune response is usually inefficient and tumors escape destruction. While extracellular matrix proteins strongly costimulate T cell responses in normal individuals, our studies indicate that peripheral blood T cells from cancer patients and tumor infiltrating cells respond poorly or are resistant to stimulative signals mediated by collagen I and IV and fibronectin. Moreover, the adhesive properties of cancer T cells are markedly depressed. Those functional deficiencies are paralleled by variable deficits in integrin and non-integrin T cell receptors for extracellular matrix. Immunotherapy with BCG causes a dramatic but transient increase in T cell: ECM interactions.
BCG Vaccine↗
Systemic administration of 2-chloro-2'-deoxyadenosine (2-CdA) in patients with systemic scleroderma.
Three patients with diffuse variety of systemic scleroderma were treated with 2-chloro-2'-deoxyadenosine. In two of them a moderate improvement of skin involvement was observed. No significant effects of the drug on the immunological parameters have been found.
CD4-Positive T-Lymphocytes↗
2-Chloro-2'-deoxyadenosine (2-CdA) combined with cyclosporine A successfully prevents rejection of fetal brain stem allograft in rabbits.
Allografts of brain stem from 20-day-old fetuses to nucleus caudatus of adult rabbits were performed. To prevent graft rejection immunosuppression with 2-CdA and cyclosporine A was transiently induced. Graft survival were assessed by histological and electrophysiological techniques. Both morphological (synaptogenesis, myelinization) and functional (generation of rhythmic neuronal activity) signs of graft maturation were found after nine weeks. The data suggest that transient immunosuppression used is sufficient to induce tolerance to neural graft, and no interference with maturation of implanted fetal tissue occurs.
Animals↗
Modulation of lymphocyte-fibroblast interactions by 2-chloro-2'-deoxyadenosine (2-CdA) in subarachnoid hemorrhage.
The adherence to monolayers of human fibroblasts of chromium-51 labelled peripheral blood mononuclear cells (PBMC) from normal subjects, and from patients after single or multiple subarachnoid hemorrhage (SAH), and the effect of 2-CdA on cell adhesion have been quantified. The fraction of cells adhering to fibroblasts were the lowest for multiple SAH patients and the highest for normal subjects, which can be explained by depletion of activated lymphocytes from peripheral blood of SAH patients. 2-CdA decreased the fraction of adhering cells isolated from normal subjects, did not change the adherence of cells from single SAH patients and increased the fraction of adhering cells isolated from multiple SAH patients. We conclude that the influence of 2-CdA on the adherence of PBMC to fibroblasts is inversely related to the degree of immune system activation.
Autoimmunity↗
Determination of 2-bromo and 2-chloro derivatives of 2'-deoxyadenosine in human blood serum by high performance liquid chromatography.
The aim of this study was to determine 2-chloro, and 2-bromo derivatives of 2'-deoxyadenosine (2-CdA and 2-BdA respectively) in the serum of human blood by high performance liquid chromatography (HPLC). 2-CdA is a substance with anticancer and immunosuppressive activity. Caffeine or 5,6-dimethylbenzo-1,2,4-triazole-1-beta-D-ribofuranoside was added to 1 cm3 of serum as internal standard. 2-CdA and 2-BdA were isolated from serum using acetone as deproteinizing reagent. LiChrosorb Si 60 column was used for the separation of drugs and the internal standard from endogenous compounds in the sample. A mixture of potassium dihydrophosphate-methanol was used as a mobile phase.
Chromatography, High Pressure Liquid↗
Successful prevention of neurological deficit in SAH patients with 2-chlorodeoxyadenosine.
Twenty patients suffering from subarachnoid haemorrhage due to ruptured intracranial aneurysm and operated on within 72 h after SAH were treated with an experimental immunosuppressive drug 2-chlorodeoxyadenosine (2-CDA), dose 0.05 mg/kg/day i.v. for 7 days. The 2-CDA treatment was started immediately after angiographic confirmation of ruptured aneurysm, and the standard pharmacological treatment (nimodipine and steroids) was also given. 50% of patients were severely threatened by "delayed vasospasm" or late neurological deficit (Fisher's score 3 or 4). The neurological outcome (assessed 8-12 weeks after SAH) was good (GOS = 1) in 70%, and fair (moderate disability, GOS = 2) in 25%. A single case of severe disability (GOS = 3), as well as two cases of less than perfect outcome (GOS = 2), were related to unusual pre- or intraoperative complications. We conclude that the low doses of 2-CDA can be considered as a valuable adjunct to the standard pharmacotherapy of SAH patients operated on early.
Adult↗
2-Chloro-2' deoxyadenosine prevents angiopathic changes in cerebral arteries in experimental SAH in rabbits.
We compared the morphology of the basilar artery walls in rabbits with experimental subarachnoid haemorrhage (SAH) without and with concomitant treatment with a novel immunosuppressive drug, 2-chloro-2'-deoxyadenosine (2 CdA). The treatment was successful in the prevention of the angiopathic changes, most likely due to its ability to inhibit lymphocyte activation in response to mitogenic signals. Since lymphocyte (and monocyte?) activation may play an important role in the development of the delayed neurological deficits in patients following SAH, the use of 2 CdA to prevent these deficits shall be considered.
Animals↗
Is vascular angiopathy following intracranial aneurysm rupture immunologically mediated?
Immunofluorescence studies showed the presence of IgM and/or C3 in the endothelium of intracranial aneurysms in 5 out of 6 patients with subarachnoid haemorrhage (SAH). In none of them were the immune deposits found in the gyrus rectus. Cortical tissue of 4 epileptic patients which served as a control give negative results. Serum studies on femoral artery wall used as an antigenic substrate did not reveal circulating antibodies of the IgM or IgG class. Our studies strongly suggest that the IgM and/or C3 immune deposits located in the endothelium of intracranial arteries may play a role in post SAH neurological complications.
Adult↗
HLA antigens and intracranial aneurysms.
The frequencies of the HLA-A, -B and -DR were determined in a group of 59 transplant donors who died from subarachnoid haemorrhage within three days following the rupture of intracranial aneurysm (the SAH group) and compared with those of a control group consisting of 389 donors who died from other causes. The only significant difference was in the increased frequency in the SAH group of non-typed ("empty")-DR loci in association with the DR7 phenotype. The most probable explanation of this finding is that in the SAH group the frequency of DR7 homozygotes is several times higher than in the general population, and that bearing the DR7 allele in homozygotic form is associated with a very high risk of developing potentially fatal intracranial aneurysmal haemorrhage.
Autoimmune Diseases↗
The possible role of endothelium in prevention of rebleeding in experimental subarachnoid hemorrhage (SAH).
Experiments were performed on six male cats under nitrous oxide in oxygen anesthesia. Animals were paralysed and artificially ventilated. Subarachnoid hemorrhage (SAH) was produced by basilar artery puncture following clivectomy. After 10 minutes (3 cats) and 60 minutes (3 cats) the basilar artery was dissected and fixed for electronmicroscopic examination. Ultrastructural examinations revealed in the cytoplasm of the endothelial cells on the side of the vessel lumen, the presence of spherical or flattened cylindrical structures identified as Weibel-Palade bodies. In the endothelium of the proximal segment, 10 and 60 minutes after puncture, the number of these electron-dense bodies increased, and was higher than in the corresponding distal segment. The possible role of the Weibel-Palade bodies in SAH after-effects is discussed.
Animals↗
Cyclosporine A prevents neurological deterioration of patients with SAH--a preliminary report.
In the present study we found that the neurological outcome in patients anaesthetized for early clipping (up to 72 h after SAH) of a ruptured aneurysm and treated with cyclosporine A was significantly better than the neurological state of control patients without immuno-suppressive treatment. The results justify the presumption that auto-immune reactions are involved in the deterioration of the postoperative neurological state of patients with SAH after rupture of an intracranial aneurysm. Supplementing a standard surgical and pharmacological treatment with cyclosporine A seems to reduce the undesirable neurological consequences of the immunologically, induced vascular disturbance after SAH.
Adult↗
Immunomodulators interfere with angiopathy but not vasospasm after subarachnoid haemorrhage in rabbits.
The present study deals with the effects of immunomodulators on the morphology of intracerebral arterial walls in rabbits with experimental subarachnoid haemorrhage (SAH). Immunostimulators:thymostimuline and inosine dimethylamino-isopropanol-p-acetamido-benzoate were found to aggravate the angiopathic changes, whereas immunosuppressive drugs-cyclosporine A and azathioprine appeared to prevent the damage. The authors consider the possibility of using immunosuppressive drugs in patients with ruptured intracranial aneurysms.
Animals↗
The respiratory response to magnetic stimulation of the cortex in the unanaesthetized baboon.
Transcranial magnetic stimulation has been used to study cortical input to the respiratory system in unanaesthetized baboons. Single magnetic pulse caused usually a short-latency excitation with subsequent inhibition in stimulated inspiratory phase and change in the amplitude and timing of the respiratory cycle. The results suggest that cortical information is processed by the medullary pattern generator.
Animals↗
Cyclosporine A for the prevention of neurological deficit following subarachnoid hemorrhage.
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Animals↗
[Active immunization against varicella-zoster virus].
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Chickenpox↗
An electron immunocytochemical study of the basilar artery in rabbits after subarachnoid haemorrhage (SAH): a preliminary report.
Vascular endothelial cells of the basilar artery and secretory axons of the neurohypophysis from rabbits after experimental subarachnoid haemorrhage were investigated by postembedding peroxidase--anti-peroxidase technique for electron microscopy to detection of vasopressin (VP). The results indicate an lack of VP-positive endothelial cells in basilar artery, while VP-positive secretory granules were commonly present in the neurohypophysis. The results are discussed in terms of pathophysiological aspect of subarachnoid haemorrhage.
Animals↗
Immunological method for prediction of progress in neurological deficit in patients with intracranial aneurysm rupture.
Skin tests of nonspecific antigens (immunoskin test Sevac) were performed on patients suffering from intracranial aneurysms, scheduled for surgical clipping. It was found that high antibody titre correlated well with the severity and progress of neurological deficit developing after surgery. This deficit was absent in patients who exhibited low antibody titre in response to the skin test before surgery. These results indicate that the immunological processes may play a role in the development of neurological deficit after neurosurgical procedures. Thus the skin test employed may have prognostic value in predicting neurological deficit following intracranial aneurysm surgery.
Adult↗