Response of patients with IgM and IgA-associated peripheral polyneuropathies to "off-line" immunoadsorption treatment using the Prosorba protein A column.

Sensory or sensorimotor demyelinating polyneuropathies may be associated with monoclonal immunoglobulins (paraproteins). Our prior experience suggests that "off-line" Prosorba(R) column treatments may be effective therapy for patients with polyneuropathies associated with paraproteins of the IgG class. We report herein the treatment, using Prosorba(R), of 2 patients with peripheral neuropathies and paraproteins of the IgM class and 1 patient with peripheral neuropathy whose paraprotein was of the IgA class. All three patients were treated "off-line" with Prosorba(R) six times in a 2-week period. Each time they were phlebotomized 1 U of whole blood. The plasma and red cells were separated in the blood bank. The plasma was passed over the column while the red blood cells were returned to the patient through a heparin lock. Then the treated plasma was returned separately. There were no adverse effects of treatment, and, in one patient with an IgM paraprotein and one with an IgA paraprotein, neurological symptoms and signs improved over the subsequent 2 weeks. Prosorba(R) appears effective for predominantly sensory demyelinating polyneuropathies associated with M-components of all major immunoglobulin classes. Our current experience further suggests that the mechanism of action of Prosorba(R) may not depend on removal of small amounts of IgG-containing immune complexes from patients' plasma. A proper large-scale clinical trial is warranted.

Conditional expression of wild-type topoisomerase II complements a mutant enzyme in mammalian cells.

Alterations in the amino acid composition, phosphorylation pattern, or intracellular levels of topoisomerase II have been associated with resistance to antineoplastic agents whose effects are mediated through interactions with this enzyme. To develop a model system with which to investigate the determinants of topoisomerase II sensitivity or resistance to antineoplastic agents that target this enzyme, a cDNA encoding the wild-type Drosophila melanogaster topoisomerase II was ligated into a mammalian expression vector containing a glucocorticoid-inducible mouse mammary tumor virus promoter and transfected into an epipodophyllotoxin-resistant Chinese hamster ovary cell line (VPM(r)-5). In two transfectants carrying an intact, full-length Drosophila topoisomerase II cDNA, exposure to the inducing agent, dexamethasone (10 microM), resulted in complementation of the endogenous mutant topoisomerase II and phenotypic reversion to etoposide sensitivity. In the presence of glucocorticoid, etoposide-induced cytotoxicity increased 20-fold, despite the fact that Drosophila topoisomerase II mRNA expression was only 0.1% of that of the endogenous mammalian topoisomerase II. Induced cells demonstrated a marked increase in DNA single strand breaks compared with uninduced resistant cells, thereby providing biochemical evidence supporting increased DNA strand cleavage due to activation of the Drosophila enzyme. These observations demonstrate the ability of a wild-type Drosophila topoisomerase II to complement a mutant mammalian enzyme and suggest that transfectants capable of conditional topoisomerase II expression represent a useful model for studies of the biochemical pharmacology and structure-function relationships of normal and mutant enzymes.

[Clinical and hematological analysis of acute granulocytopenia]. / Analiza kliniczna i hematologiczna ostrych granulocytopenii.

Retrospective analysis of 13 patients treated for the acute granulocytopenia at the Institute of Haematology for the last 10 years was carried out. Drugs were the most common causative factor. Comparing the results of the similar analysis several years ago in which the significant role was played by chloramphenicol, non-steroidal anti-inflammatory agents were the main cause. Infective complications were seen in all analysed patients. Broad spectrum antibiotics were used in all patients. Glycocorticosteroids were given to 9 patients while leucocytic concentrates to 7 patients. Remission was achieved in 12 patients, one female patient with the history of exposition to plant protection agents and increased levels of chlorinated aromatic hydrocarbons--died. Intensive antibacterial therapy significantly lowered mortality of the analysed patients in comparison with the similar group analysed earlier. Recurrence of granulocytopenia was seen in 5 patients following the contact with causative agent. Recurrencies were finished with remission.