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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Examination of 30 patients with immunodeficient diseases showed that the system of natural antibodies was considerably changed depending on the form and the extent of deficiency of the immune system: in agammaglobuinemia the antibodies under study were almost completely absent, and in immunological insufficiency with ataxia-teleangiectasis the production of antibacterial antibodies proved to be sharply decreased. The data obtained can be used both for the diagnosis of immunodeficiencies and for control of the restoration of the immunological competence after a number of therapeutic measures, particularly after the transplantation of the thymus-sternum complex.
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PMID:[Natural antibodies (isohemagglutinins, heterophilic, antierythrocytic and antibacterial) in children with congenital immunologic deficiency syndromes]. 35 90

The toxicity of maytansine given by sc administration was studied in 5-week-old mald F344 rats. The LD50 (14-day) was 0.48 mg/kg. A dose response to drug administration was indicated by body weight changes and diarrhea. A single, acutely toxic dose of maytansine was shown to possess marked activity against dividing cells which was regarded as an important factor in the pathogenesis of acute lesions in tissues with a normal high rate of cell division. Histologically, mitotic figues were observed in many tissues from 6 to 24 hours after drug administration. Subsequently, necrotizing lesions led to atrophic changes in gastrointestinal tract mucosa, thymus, spleen, bone marrow, and testis. Maytansine also induced hemorrhagic lesions in parenchymatous organs and brain and perivascular monomuclear infiltration in the meninges, and chromatolysis and vacuolation of dorsal root ganglion cells, accompanied by clinical signs of ataxia. Ulcerative skin lesions were observed at the sc site of drug administration.
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PMID:Acute toxicity of maytansine in F344 rats. 56 88

A clinico-morphological study of ataxia-teleangiectasia permits to establish the depth and distribution of lesions. Morphological findings indicate to lesions mainly in the extrapyramidal system, cerebellum, subcortical structures and in the stem structures and spinal cord. Besides, there were changes in the hemispheres in the form of cell atrophy, demyelinization, degeneration and gliosis. Demyelinization was found in the posterior and lateral columns of the spinal cord; in the extrapyramidal conductive paths. A study of lipid metabolism in 14 patients with ataxia-teleangiectasia also demonstrated an increase of lipid content in myelin, free cholesterol, etherconnected cholesterol, triglycerides and diglycerides in the plasma. There was a correlation between the degree of the nervous system demyelinization and an increased level of the main fractions in the lipid spectrum. In some patients following a transplantation of a neonatal thymus-sternum complex there was a drop in the previously increased content of the lipid fractions. The authors discuss some problems of the pathogenesis of ataxiateleangiectasia.
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PMID:[Lipid metabolism disorder in ataxia-telangiectasia]. 93 65

A second family is described with a combination of defective thymus-dependent immunity and cerebral palsy. The cerebral palsy comprised nonprogressive dysequilibrium and mild spastic diplegia without limb ataxia. This genetic entity of presumed autosomal recessive inheritance is clearly distinguished from ataxia-telangiectasia. Immunological abnormalities should be sought in other familial or unexplained cerebral palsy syndromes.
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PMID:Familial dysequilibrium-diplegia with T-lymphocyte deficiency. 108 13

Although an isolated clinical case report was published in 1926 and another in 1941, ataxia-telangiectasia (A-T) was not established as a distinct entity until 1957, when it was first delineated clinicopathologically. Susceptibility to sinopulmonary infection was identified as the main cause of death and as the third major component of the syndrome; its heredofamilial nature was documented, and it was designated "ataxia-telangiectasia." In a later review of 101 published cases, lymphoreticular malignancy emerged as the second most frequent cause of death. Although the thymus was found to be absent in the first reported autopsy in 1957 and the serum IgA deficiency was first recorded in 1961, A-T was not established as an immunodeficiency disease until 1963. Thymic abnormality and dysgammaglobulinemia explain the 2 main causes of death, sinopulmonary and neoplastic, but the immunodeficiency is probably not the central defect. It does not appear to explain either of the 2 main clinical diagnostic keys, the ataxia and the telangiectasia, or any of the other seemingly unrealted multisystemic facets of this complex disorder. Some of our most provocative long-term clinical observations and recent pathologic findings in our series of 9 autopsies are discussed.
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PMID:Ataxia-telangiectasia: some historic, clinical and pathologic observations. 109 82

The acute toxicity of ammonium metavanadate (15.5 mg/kg) in mice was investigated to examine the induction of lymphoid necrosis to (1) verify the reproducibility of the lesions in the thymus, lymph nodes, and spleen; (2) determine whether the necrosis of lymphoid tissue previously observed during the first 3 days post-treatment but absent at 14 days was the result of differences in sensitivity of the mice or the result of recovery from the effects of vanadium; and (3) determine whether differences in the presence and the degree of necrosis between thymus and spleen were correlated with differences in the uptake of vanadium in these tissues. A timed sacrificed study was conducted in conjunction with a 48V tracer. In this study, BALB/C mice were injected subcutaneously (s.c.) with ammonium metavanadate solution (15.5 mg/kg). Groups of mice were sacrificed at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 21, and 28 days postexposure. Lymphoid necrosis was found in the thymus, spleen, lymph nodes, and bone marrow, with the necrosis being most severe in the thymus. The necrosis was moderate at 0.5 days, most severe at 2 to 3 days, with recovery beginning at 4 days, and proceeding to full recovery at 14 to 28 days. At 0.5 days post-treatment, the concentration of vanadium in thymus and spleen was 4.4 and 8.3 micrograms/g, respectively. At all post-treatment periods, with the exception of the 1- and the 4-day periods, the concentration of vanadium in spleen was significantly higher than in the thymus, p less than 0.05. The treated animals showed neurological signs (ataxia, convulsion, dyspnea, and paralysis of hind legs) between 5 min and 54 hr post-treatment, but the concentration of vanadium in the brain was very low during this period (less than 5.2% of blood concentration).
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PMID:The lymphotoxic action of vanadate. 157 59

The results of a broad pharmacological screening on 1-[(2,4-dichlorophenyl)-methyl] -1H-indazole-3-carboxylic acid ( lonidamine ) a new antitumour agent which also possesses antispermatogenic and embryotoxic effects, are reported. Lonidamine does not affect general behaviour and autonomic functions and is devoid of anticonvulsant, anti-reserpine, anti-apomorphine, anti-amphetamine, antitremor , antipyretic, antiinflammatory and analgesic effects. It also lacks those side effects which are considered characteristic of different antitumour agents, such as thymus and spleen atrophy, delay in skin wound healing and damage to the gastrointestinal mucosa. At doses 40 times higher than that of hydrochlorothiazide, lonidamine produces diuretic effects. The practical importance of these findings in the current therapeutic use of lonidamine appears to be limited. The most typical signs of acute intoxication produced by high doses of lonidamine are salivation, lacrimation, diarrhea, ataxia, muscle rigidity and prostration with superimposed convulsions.
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PMID:Pharmacological investigations on lonidamine. 654 Jan 4

Morphological changes of the thymus, tonsils, lymph nodes, spleen, and other organs in two observations of severe combined insufficiency (SCIN) in infants of the first year of life are described. In both cases there was hypoplasia of the thymus with the lack or occasional thymic bodies and poor content of thymocytes in the lobules. In one infant, hypoplasia of the thymus was combined with intestinal angiomatosis which suggested the syndrome of ataxia-teleangiectasia. In the other infant, SCIN was associated with severe granulocytopenia of the Kostman type. In this case epithelial cells of the lobules formed adenomatous structures. Both infants died with sepsis developing against the background of SCIN.
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PMID:[Hypoplasia of the thymus gland in children]. 686 Jan 70

Mice that are heterozygous for the ragged (Ra) mutation, which is semidominant, have ragged coats caused by an absence of certain hair types. Ra/Ra homozygous mice usually die soon after birth, are naked, and have edema. Mice that are homozygous for the recessive mutation wasted (wst) appear normal until soon after weaning, but then develop tremors and ataxia, undergo atrophy of the thymus and spleen, and die by around 28 days of age. The Ra and wst loci map to distal mouse chromosome 2, but have never been positioned with respect to molecular markers. We have now mapped each of these genes in interspecific backcrosses that were also typed for available molecular markers. The results show that Ra maps very close to D2Mit74 and Acra-4, with no recombinants in 165 mice, whereas wst maps 3 cM distal to the most telomeric molecular marker on mouse chromosome 2, Acra-4.
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PMID:Linkage mapping around the ragged (Ra) and wasted (wst) loci on distal mouse chromosome 2. 802 Sep 60

Consumption of large amounts of ethanol (EtOH) in a single drinking episode is common, but very little is known about the immunological effects of such occurrences. Exposure to EtOH for several days is immunosuppressive in rodent models, and a single dose of EtOH causes substantial increases in endogenous glucocorticoid levels which might have immunosuppressive effects. In the present study, the effects of a single dose of EtOH on the thymus and the role of endogenous glucocorticoids in these effects were examined in B6C3F1 female mice. A single dose of EtOH decreased thymus weight and cellularity, predominantly by elimination of CD4+CD8+ (immature) thymocytes. This occurred over a broad range of EtOH doses and was associated with behavioral effects (ranging from mild ataxia to unresponsiveness) similar to those noted in human binge drinkers. Several lines of evidence indicate that the effects of EtOH on the thymus are mediated by endogenous glucocorticoids: (1) corticosterone levels in EtOH-treated mice increased more than 10-fold and remained significantly elevated for up to 12 hr; (2) the most glucocorticoid-sensitive thymocytes (CD4+CD8+ cells) were preferentially depleted by EtOH; (3) before thymocyte depletion was evident, substantial DNA fragmentation occurred in the thymus as would be expected in the case of glucocorticoid-induced apoptosis; (4) the glucocorticoid antagonist, RU 486, blocked thymic atrophy and DNA fragmentation in EtOH-treated mice; (5) EtOH and its major metabolites at concentrations comparable to or greater than expected in vivo did not decrease thymocyte viability in 20-hr cultures, indicating that direct action of EtOH or its metabolites on thymocytes does not play an important role in EtOH-induced thymic atrophy. These results suggest that a single dose of EtOH induces thymic atrophy which is predominantly mediated by increased levels of endogenous glucocorticoids. The mouse model described here should be useful in evaluating other effects of binge drinking on the immune system, and the experimental strategy described should be applicable in investigating the role of endogenous glucocorticoids in thymic atrophy induced by other chemicals and drugs.
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PMID:Thymic atrophy caused by ethanol in a mouse model for binge drinking: involvement of endogenous glucocorticoids. 823 55


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