Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.     

Specific MR imaging of human lymphocytes by monoclonal antibody-guided dextran-magnetite particles.

Human lymphocytes were labeled with biotinylated anti-lymphocyte-directed monoclonal antibodies, to which streptavidin and subsequently biotinylated dextran-magnetite particles were coupled. This labeling resulted in a strong and selective negative contrast enhancement of lymphocyte suspensions at 2.0 T, caused predominantly by the specific increase of R2 with a small but significant specific increase of R1. The R1 was found to decrease with increasing field strength. The immunolabeling procedure described here may be used for the selective signal depletion of target cells in MR imaging.     

Rate and classification of interval cancers in the breast screening programme.

There has been concern about the number of interval cancers which have been detected within the National Breast Screening Programme. A series of 134 women presenting with interval cancers was studied by prospective audit and the rate and radiological classification of the tumours determined. The cancers were classified as true (67), false-negative (22), unclassifiable (28), occult (12), and minimal sign (5). The interval cancer rate did not achieve the new National Guidelines in either the first 2 years or the 3rd interval year. The false-negative cancers presented mainly in the 1st interval year, whereas the true cancers were predominantly confined to the 2nd and 3rd years. These data suggest that alterations to the screening programme may be beneficial. It may be, however, that the programme is still on the learning curve and this should be taken into account when interpreting these data.     

The desipramine-induced growth hormone response and the dexamethasone suppression test in obsessive-compulsive disorder.

Ten patients with DSM-III-R obsessive-compulsive disorder (OCD) underwent the desipramine (DMI) growth hormone (GH) stimulation test as well as the dexamethasone suppression test (DST). The results were compared with the responses in a group of matched healthy controls. The GH response to DMI did not differ between patients and controls and 9 of 10 patients showed cortisol suppression in response to dexamethasone. The data suggest that neither alpha 2 adrenergic dysfunction nor DST non-suppression are features of primary OCD.     

Accidental bronchial intubation An analysis of AIMS incident reports from 1988 to 1994 inclusive

Accidental bronchial intubation was examined in the first 3947 cases reported to the Australian Incident Monitoring Study and was found to have accounted for 154 (3.7%) of the total incidents reported. Most incidents were detected in the operating theatre (93.5%) and during maintenance of anaesthesia (77.9%), by unexplained oxygen desaturation alone (63.6%). Capnography remained normal or unremarkable during 88.5% of the episodes. One-third of cases were associated with head or neck surgery and possible flexion of the patient's head. A RAE tube was used in 20% of incidents, a greater frequency than occurred in the study overall. A third party was implicated in 36 (23.4%) of cases. Ninety per cent of cases were considered preventable. Major morbidity occurred in three cases and unplanned intensive care admission was required in a further five. Almost two-thirds (61.1%) of the incidents might have been avoided by the proposed markings on the tracheal tube. We conclude that when arterial desaturation occurs at any stage during anaesthesia the possibility of bronchial intubation must be considered. Asymmetrical ventilation may be difficult to detect clinically and in most cases there is no change in capnography.     

Expression of an oncofetal protein (OFP) in rat and human leukemia cells.

A unique oncofetal protein (OFP) previously identified in rat fetal tissue and rat and human solid tumors, is now shown to be present in rat and human leukemia cells by use of a monoclonal antibody-based assay. Using a highly specific anti-rat OFP monoclonal antibody OFP has been unquivocally immunolocalized to the cytoplasm of the rat leukemia cells. The factor is rapidly released to the circulation as 50 and 55 kD species which share the immunological determinants. When leukemia cells are transplanted to normal rats, OFP increases in the circulation in a biphasic manner which may be due to immune clearance since circulating anti-OFP antibodies have been demonstrated. Induction of differentiation in the human HL-60 leukemia cell line by 13-cis-retinoic acid caused a down regulation of OFP synthesis, both intra- and extra-cellular levels dropping to essentially zero. Induction of differentiation with dibutyryl cyclic AMP caused a cessation of secretion of OFP, with a marked increase in its intracellular concentration, a condition resembling the retention in fetal cells. Leukemia cells add to a growing list of tumors previously shown to produce OFP, suggesting that OFP is intimately involved in some facet of tumorigenesis.