Trisomy 12 in chronic lymphocytic leukemia detected by fluorescence in situ hybridization: analysis by stage, immunophenotype, and morphology

Fluorescence in situ hybridization (FISH) with a chromosome 12 specific alpha-centromeric probe was performed on interphase cells from 183 patients with B-cell chronic lymphocytic leukemia (CLL). Twenty one cases with trisomy 12 (11.5%) were detected. The number of trisomic cells ranged from 5.5% to 76% (mean 38.5%). No correlation was found between the presence of trisomy 12 and white blood cell count, hemoglobin level, platelet count, a specific immunophenotype, clinical stage, sex, splenomegaly, or lymphadenopathy. Morphologic review of all cases with trisomy 12 showed seven (33%) with more than 10% prolymphocytes and three (14%) with CLL of mixed cell type. While trisomy 12 is the most common chromosomal abnormality in CLL, it is more frequent in morphologically atypical cases, some of which may be undergoing transformation. There was a statistically significant difference in the incidence of atypical cases between those with (47%) and without (7.6%) trisomy 12 (P < .001). It remains to be determined whether this abnormality is associated with a worse prognosis; this is currently being investigated in the context of a national therapeutic trial. The technique used is more sensitive than conventional cytogenetic analysis, which in this series failed to detect trisomy 12 in six cases. FISH allows the systematic study on a large number of patients without the need of metaphase preparations.     

Impairments to the Establishment of the Various Hippocampal Fields in Rats as a Long-Term Consequence of Acute Perinatal Hypoxia

The aim of the present work was to study the long-term consequences of acute normobaric hypoxia during the perinatal period on the establishment of the hippocampal formation in rats. The experiments showed that hypoxia on day 2 of postnatal development led to significant damage to the structure of the hippocampal field, which showed different levels of sensitivity to the harmful factor. On day 20, all fields showed cell death and depletion of the pyramidal cell layers. The most marked neuron death occurred in fields CA4 and CA3. On day 30, a significant level of neuron death persisted in field CA4, though it decreased in field CA3 and was not seen in field CA1; neuron death in the granule layer of the dentate fascia increased. In addition, there were decreases in the sizes of pyramidal neuron bodies in all hippocampal fields. All hippocampal fields also showed activation of astrocyte reactions, which was more marked in field CA4, where gliosis persisted to prepubertal age (30 days).     

The Roles of Nitric Oxide and Carbon Dioxide Gas in the Neurotoxic Actions of Oxygen under Pressure

The hypothesis that in conditions of hyperbaric oxygenation, nitric oxide (NO) modulates the vasodilatory effect of CO₂ in the brain and thus accelerates the neurotoxic action of oxygen was verified experimentally. Conscious rats breathed atmospheric air or oxygen at 5 atm and blood flow in the striatum was measured before and after inhibition of carbonic anhydrase with acetazolamide, which causes retention of CO₂ in the brain. Acetazolamide (35 mg/kg) increased blood flow in the animals when breathing air by 38 ± 7.4% (p < 0.01), while preliminary inhibition of NO synthase with N^ω-nitro-L-arginine-methyl ester (L-NAME, 30 mg/kg) significantly weakened its vasodilatory action. Inhibition of carbonic anhydrase in animals breathing hyperbaric oxygen at 5 atm prevented cerebral vasoconstriction, increased brain blood flow, and accelerated the development of oxygen convulsions. The vasodilatory effect of acetazolamide in hyperbaric oxygenation was significantly reduced in animals pretreated with the NO synthase inhibitor, such that the latent period of convulsions increased. The results obtained here provide evidence that in conditions of extreme hyperoxia, NO modulates the cerebral hyperemia developing in conditions of CO₂ retention in the brain and accelerates the development of the neurotoxic actions of hyperbaric oxygen.__________Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 90, No. 4, pp. 428–436, April, 2004.     

Brain Blood Flow Modulates the Neurotoxic Action of Hyperbaric Oxygen via Neuronal and Endothelial Nitric Oxide

Studies on conscious rats with inhibition of NO synthase were used to assess the dynamics of brain blood flow and EEG traces during hyperbaric oxygenation at 4 or 5 atm. Oxygen at a pressure of 4 atm induced cerebral vasoconstriction in intact animals and decreased blood flow by 11–18% (p < 0.05) during 60-min exposure to hyperbaric oxygenation. Paroxysmal EEG activity and oxygen convulsions did not occur in rats at 4 atm of O₂. At 5 atm, convulsive activity appeared on the EEG at 41 ± 1.9 min, and blood flow decreased significantly during the first 20 min; blood flow increased by 23 ± 9%, as compared with controls, (p < 0.01) before the appearance of convulsions on the EEG. Prior inhibition of NO synthase I (NOS I) and NO synthase III (NOS III) with N-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg) or inhibition only of NOS I with 7-nitroindazole (7-NI, 50 mg/kg) prevented the development of hyperoxic hyperemia and paroxysmal spikes on the EEG during hyperbaric oxygenation at 5 atm. These results show that hyperbaric oxygen induces changes in cerebral blood flow which modulate its neurotoxic action via nitric oxide synthesized both in neurons and in cerebral vessels.