Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to develop the usefulness of Fanconi's anemia (FA) lymphoblast lines for biochemical and genetic studies, we have determined their sensitivity to a variety of DNA-damaging chemicals. We have adapted a growth inhibiton protocol in which the sensitivity of a cell line is characterized by the drug concentration yielding a 50% inhibiton of growth (EC50). The DNA-cross-linking agents, mitomycin C, nitrogen mustard, melphalan, 1,3-butadiene diepoxide, cis-diaminedichloroplatinum(II), and cyclophosphamide, were all more toxic to four FA cell lines than to five normal lines. Three lines, HSC 72 (FA), 99 (FA) and 230 (FA), had EC50s that were 10 to 20 times lower than that of controls while the fourth line, HSC 62 (FA), had an intermediate EC50. Three nitrosourea compounds were also more toxic to FA cells than to controls. However, 2 normal cell lines (HSC 92 and 93) had nitrosourea EC50s 4 to 7 times lower than the other nine controls and overlapped the sensitivity of the intermediate [HSC 62 (FA)] cell line. The same 2 normal cell lines were also more sensitive than 12 other controls, including FA heterozygotes, xeroderma pigmentosum, and ataxia telangiectasis, to the monofunctional alkylating agents, ethyl methane sulfonate, methyl methane sulfonate, and N-methyl-N'-nitro-N-nitrosoguanidine. Heterogeneity was also found with FA lines. Two FA cell lines (HSC 72 and 230) had EC50s lower than all control lines while one FA line (HSC 99) had an EC50 similar to that of the resistant normal lines. FA and normal cells had nearly the same sensitivity to 4-nitroquinoline-1-oxide and bleomycin. These results demonstrate that FA lymphoblast lines are more sensitive than normal cell lines to all DNA-cross-linking agents examined. These cell lines should therefore be useful for the analysis of DNA cross-link repair and the biochemical defect in FA. We have also found an unexpected sensitivity of some FA and normal lines to monofunctional alkylating agents.
Cancer Res 1982 Oct
PMID:Susceptibility of Fanconi's anemia lymphoblasts to DNA-cross-linking and alkylating agents. 680 8

FD-1, 1,3-bis(tetrahydro-2-furanyl)-5-fluorouracil, is an anticancer agent newly developed in Japan and is a kind of marked compound of 5-fluorouracil. FD-1 changes to 3-FT and tegafur and is then converted to 5-fluorouracil. From our clinical observations, FD-1 showed excellent clinical effects in a daily dose of 600 mg. However, in some instances toxicities of central nervous system were developed. On the other hand, there is evidence that uracil enhances antitumor activity of FD-1 in the treatment of sarcoma 180 bearing mice and AH130 bearing rats. On oral administration of FD-1 plus uracil in various combination ratios, the high T/B value (ratio of the concentration of 5-fluorouracil in the tumor and blood) is obtained at a ratio of uracil to tegafur of 20 to 50. Fifteen cases with advanced cancer were treated with UFD-1 (mixture of FD-1 and uracil under molar ratio of 1: 20) in a daily dose of 300 mg of FD-1. However, no tumor regression was observed in any of our cases. On the contrary, toxic manifestations were experienced in five of fifteen cases. They mainly consisted of mild G.I. toxicities. Furthermore, in one case, ataxia developed. Our clinical studies revealed no usefulness of UFD-1 in the treatment of advanced adenocarcinoma cases.
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PMID:[Clinical experiences with UFD-1]. 682 Sep 5

From 1976 to 1981 Listeria monocytogenes was second only to Neisseria meningitidis as the cause of bacterial infections of the central nervous system in adults at our hospital. None of the patients with Listeria infection was immunosuppressed or had an underlying malignancy. Ataxia was an initial feature in five of the eight patients, and in three of them it persisted beyond their discharge from the hospital. Ataxia was not a feature of the clinical picture of 14 other adult patients with meningococcal and pneumococcal meningitis. Our data indicate that L monocytogenes should be suspected as the etiologic agent in an adult with ataxia and infection of the central nervous system.
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PMID:Ataxia in Listeria monocytogenes infections of the central nervous system. 684 62

Acivicin, an L-glutamine antagonist, was administered to 37 evaluable patients with refractory advanced solid tumors in a phase I trial. A total of 67 evaluable 72-hr iv infusions were given at 3- to 4-week intervals. Doses ranged from 3.0 to 90 mg/m2/course. Reversible CNS toxicity was dose-limiting and included lethargy, somnolence, anxiety, hallucinations, and paranoid psychoses. Four of five patients experienced unacceptable CNS toxicity at 90 mg/m2. Three of eight patients experienced reversible diaphoresis and chills without fever at 75 mg/m2, and two had dizziness and ataxia. Hematopoietic toxicity, nausea, emesis, and diarrhea were mild and dose-related. One patient developed a blue-green discoloration of the infusion arm. Serial plasma and urine specimens from 13 patients were assayed for acivicin using a microbiologic method. Peak plasma levels at the end of the 72-hr infusions correlated with dose and ranged from 0.09 to 1.10 microgram/ml. When data from six patients were fitted to a two-compartment open model, alpha-half-life ranged from 1.1 to 63 mins, while beta-half-life ranged fro 338 to 629 mins. Renal clearance ranged from 6 to 24 mL/min, and nonrenal clearance accounted for 58%-83% of the total drug clearance. CNS toxicity correlated with plasma acivicin levels which exceeded 0.9 microgram/ml for greater than 16 hrs, but not with peak plasma levels or with the integrals of the concentration x time curves. Minor responses were seen in one patient with melanoma, in one with epidermoid pulmonary carcinoma, and in two with colon carcinoma. A starting dose of 60 mg/m2/course was recommended for phase II trials, with possible escalation to 75 mg/m2 in the second course if the drug was well-tolerated.
Cancer Treat Rep
PMID:Phase I trial and pharmacokinetics of acivicin administered by 72-hour infusion. 687 83

In a family with ataxia and pancytopenia, the proband had cerebellar ataxia, developed hypoplastic anemia at age 3 years, and died of acute myelomonocytic leukemia at age 7. Serial cytogenetic studies of the proband's hypoplastic bone marrow over a 25-month period revealed progressive expansion of a clone of cells with C(6 - 12 + X) monosomy from 33% to 94% of metaphases. The missing chromosome by banding was deduced to be No.7. No increased sensitivity of the patient's cells was found in response to ultraviolet or ionizing radiation or to mitomycin C. Cerebellar atrophy was confirmed at autopsy. Family studies revealed cerebellar ataxia in the proband's father and all four siblings. Two brothers, including one with C-monosomy, died with hypoplastic anemia and another brother died with acute myelocytic leukemia. The only surviving sibling is a 19-year-old sister who has unexplained anemia, decreased mitotic activity in bone marrow, and slow progressive cerebellar ataxia. The name ataxia-pancytopenia syndrome is proposed to encourage study of additional patients with this disorder, which predisposes to pancytopenia and acute leukemia.
Cancer Genet Cytogenet 1981 Nov
PMID:Ataxia-pancytopenia: syndrome of cerebellar ataxia, hypoplastic anemia, monosomy 7, and acute myelogenous leukemia. 694 57

A subacute progressive cerebellar brainstem syndrome developed in a patient with systemic lupus erythematosus in remission. Cerebellar biopsy documented the diagnosis of progressive multifocal leukoencephalopathy (PML). Data from this patient and 10 others in the literature emphasize the need to consider this diagnosis when ataxia develops in any patient with underlying malignancy, chronic infection, or other disease that involves immunological incompetence. Although the ataxic form of PML is not of nosological relevance, early diagnosis may eventually have therapeutic importance.
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PMID:Primary cerebellopontine progressive multifocal leukoencephalopathy diagnosed premortem by cerebellar biopsy. 707 54

A Phase I trial of acivicin [L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid] has been performed on an escalating-dosage 24-hr continuous i.v. infusion schedule. Thirty-one patients received 77 courses of treatment, and all but one were evaluable for toxicity. Pharmacological monitoring in selected patients demonstrated that peak plasma levels correlated with dose. Postinfusion t1/2 beta was 6 to 9 hr, and urinary recovery of the administered dose was 14 to 19% as unchanged drug during the 24-hr infusion. Hematological and gastrointestinal toxicities were variable and not dose related. In contrast, neurotoxicity characterized by lethargy, fatigue, confusion, disorientation, hallucinations, nightmares, and truncal ataxia was dose limiting and related to plasma drug levels. A minimal antitumor response was observed in a patient with colorectal carcinoma, and a partial response occurred in a patient with liver metastases from gastric carcinoma. The recommended dose for Phase II trial by 24-hr infusion is 160 mg/sq m.
Cancer Res 1982 Sep
PMID:Phase I and pharmacological study of acivicin by 24-hour continuous infusion. 710 49

A phase I study of 13-cis-retinoic acid was done in 16 patients with head and neck malignancies using a modified Fibonacci search scheme, with individual doses ranging from 20 to 120 mg/m2. Drug doses greater than 60 mg/m2 induced intense headaches, urethritis, desquamative dermatitis, vertigo, and ataxia. The severity of these side effects precludes the use of 13-cis-retinoic acid as a potential chemopreventive agent at doses greater than 60 mg/m2.
Cancer Treat Rep 1982 Sep
PMID:Phase I study of 13-cis-retinoic acid toxicity. 711 51

Lead, cadmium, mercury and arsenic are widely dispersed in the environment. Adults are primarily exposed to these contaminants in the workplace. Children may be exposed to toxic metals from numerous sources, including contaminated air, water, soil and food. The chronic toxic effects of lead include anemia, neuropathy, chronic renal disease and reproductive impairment. Lead is a carcinogen in three animal species. Cadmium causes emphysema, chronic renal disease, cancer of the prostate and possibly of the lung. Inorganic mercury causes gingivitis, stomatitis, neurologic impairment and nephrosis, while organic mercurials cause sensory neuropathy, ataxia, dysarthria and blindness. Arsenic causes dermatitis, skin cancer, sensory neuropathy, cirrhosis, angiosarcoma of the liver, lung cancer and possibly lymphatic cancer.
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PMID:Occupational and community exposures to toxic metals: lead, cadmium, mercury and arsenic. 716 33

Spirogermanium is a new azaspirane antitumor agent, with the metal germanium substituted for a one-carbon moiety in the ring structure. This drug inhibits DNA and RNA synthesis in HeLa cells, is cytotoxic in vitro, and has curative in vivo antitumor activity against the ascitic Walker 256 carcinosarcoma in rats. No hematologic toxicity was recorded during the preclinical toxicologic evaluation. The principal clinical toxic effects observed in this phase I trial were neurologic, manifested as lethargy, dizziness, and ataxia, while a grand mal seizure was produced after an accidental overdose. There was no evidence of hematologic, renal, or hepatic toxicity. A partial response was achieved in a patient with a well-differentiated lymphocytic lymphoma. We recommend that phase II trials be conducted with a twice or thrice weekly dose of 50-80 mg/m2, administered in a 30-minute iv infusion.
Cancer Treat Rep
PMID:Phase I clinical trial of spirogermanium. 745 90


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