Diffuse malignant leptomeningeal gliomatosis in a child: a case report and review of the literature.

Diffuse leptomeningeal gliomatosis is a rare condition characterized by glioma in the leptomeninges without a dominant mass lesion. The difficulty in diagnosis of this condition, its rarity. and its extensive nature have hampered its successful treatment. Most cases of primary diffuse leptomeningeal gliomatosis have occurred in adults. Reported here is a case of this condition in a 9-year-old girl; to the authors' knowledge, she is the youngest patient with diffuse leptomeningeal gliomatosis and the longest survivor of the malignant variety.

Chemotherapeutic purine analogs alter the level of interferon-beta mRNA induced by poly I-poly C in cultured osteosarcoma cells.

The purine nucleoside analogs fludarabine, 2-chlorodeoxyadenosine, and 2'-deoxycoformycin exhibit impressive activity in lymphoproliferative malignancies of adults and children. Their mechanism of action is not clear. Studies have suggested that their use is associated with significant myelosuppression, immunosuppression, and in some circumstances, increased infection with viral and opportunistic pathogens. Because interferons (IFNs) are known to have immunomodulatory activity as well as potent antiproliferative and antiviral activity, we examined whether the chemotherapeutic purine nucleoside analogs alter interferon-beta (IFN-B) gene expression in MG63 in human osteosarcoma cells. Northern blot analysis showed a dose-dependent inhibition of IFN-B mRNA accumulation in response to a known inducer (Poly I-Poly C) all three purine analogs. Hybridization analysis also revealed that inhibition of IFN-beta mRNA accumulation by the purine analogs is not a result of decreased mRNA stability. Further analysis of gene expression by PCR differential display indicated that the effect of the purine analogs was restricted to only a limited number of inducible genes. The data suggest that these molecules alter the signaling process involved in regulating the expression of specific genes, including IFN-beta. These findings predict that the use of purine nucleoside analogs may reduce IFN production in vivo and thereby abrogate host defenses against infectious pathogens.

Positive correlation between high aryl hydrocarbon hydroxylase activity and primary lung cancer as analyzed in cryopreserved lymphocytes.

Blood samples from closely monitored patients at the Veterans Administration Hospital in Houston, Texas, were collected, coded, and sent to Microbiological Associates over an 8-month period. Lymphocytes were isolated and cryopreserved at -190 degrees. Lymphocyte samples were simultaneously thawed, phytohemagglutinin activated, and analyzed for benz(a)anthracene-induced aryl hydrocarbon hydroxylase (AHH) levels, [3H]thymidine incorporation, and reduced nicotinamide adenine dinucleotide-dependent cytochrome b5 (cytochrome c) reductase activity. Determinations were made at both 96 and 120 hr in culture, and peak activities were compared among a total of 51 individuals who expressed such lesions as squamous cell carcinomas (22%), adenocarcinomas (14%), oat cell carcinomas (6%), chronic obstructive pulmonary disease (22%), and other nonmalignant diseases. Of the 14 highest AHH/cytochrome c activities observed, all were found in patients with primary lung cancer. Mean AHH/cytochrome c activities were 0.89 for lung cancer patients (a total of 21) and 0.47 for noncancer patients (a total of 30) (p less than 0.001). No relationship was observed between AHH/cytochrome c activity and age of patient, numbers of cigarettes smoked, family history of cancer, location or histological type of tumor, or level of phytohemagglutinin blastogenesis ([3H]thymidine cpm/cytochrome c). Whether the higher AHH levels are the cause or the result of the primary lung cancer remains to be determined.

A method for detecting aryl hydrocarbon hydroxylase activities in cryopreserved human lymphocytes.

Aryl hydrocarbon hydroxylase (AHH) activity, NADH-dependent cytochrome c reductase (cyt c) activity, and [3H]thymidine (3H-TdR) incorporation were monitored in human lymphocytes cryopreserved for periods up to 1 year. A standard procedure for freezing, thawing and culturing of these lymphocytes was developed. Kinetics for expression of benz[a]anthracene-(BA)-induced AHH activity, cyt c activity, and 3H-TdR incorporation were similar in both freshly cultured and cryopreserved cells. Lymphocyte samples from 10 individuals were collected once per month over a 3-month period and cells were either cultured at the time of donation or cryopreserved for later assay. Results indicated that the cryopreserved lymphocytes efficiently responded to mitogen activation. The intra-individual variation in AHH activities was reduced in the cryopreserved lymphocytes compared to the freshly cultured cells, and the relative ranking of these individuals in terms of their AHH activities remained constant for both fresh and cryopreserved samples. Cryopreservation seems to offer significant advantages over the freshly cultured lymphocytes because it allows for lymphocyte samples to be collected in diverse geological locations and over extended periods of time and yet permits for the culture and assay of all the cell samples at exactly the same time.