Anemia of the Belgrade rat: evidence for defective membrane transport of iron

The mechanisms underlying the impaired utilization of transferrin-bound iron by erythroid cells in the anemia of the Belgrade laboratory rat were investigated using reticulocytes from homozygous anemic animals and transferrin labeled with 59Fe and 125I. The results were compared with those obtained using reticulocytes from phenylhydrazine-treated rats and iron-deficient rats. Each step in the iron uptake mechanism was investigated, ie, transferrin-receptor interaction, transferrin endocytosis, iron release from transferrin, and transferrin exocytosis. Although there were quantitative differences, no fundamental difference was found in any of the abovementioned aspects of cellular function when the reticulocytes from Belgrade rats were compared with those from iron-deficient animals. The basic defect in the Belgrade reticulocytes must therefore reside in subsequent steps in iron uptake, after it is released from transferrin within endocytotic vesicles, ie, in the mechanism by which it is transferred across the lining membrane of the vesicles into the cell cytosol. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reticulocyte ghosts extracts demonstrated a prominent protein band of mol wt 69,000 that was absent or present only in low concentration extracts from the other two types of reticulocytes. This may be a result of the genetic defect.     

Effectiveness of methyl-GAG (methylglyoxal-bis[guanylhydrazone]) in patients with advanced malignant lymphoma

We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl- GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma.     

Effects of a novel antiplatelet agent in mural thrombogenesis on collagen-coated glass

A parallel plate flow chamber and an epifluorescence video microscopy system were used to investigate the inhibitory effect of a novel antiplatelet agent (GT-12), a carbamoylpiperidine congener, on surface platelet aggregation and on the kinetics of thrombus growth induced by collagen-coated glass under controlled flow. Both macroscopic and microscopic measurements revealed that increasing concentrations of the drug correspondingly decreased the reaction rate between platelets at the surface, thereby reducing thrombus rate of growth at the surface. Because of decreased platelet/platelet adhesion, there was some embolization of the larger thrombi near the inlet of the reactive surface. In the presence of GT-12, average thrombus size and number of platelets per thrombus were both strikingly lowered. In addition, the net rate of growth of individual thrombi decreased to zero after short exposure times (about 60 seconds), in sharp contrast to controls. In contrast to chlorpromazine, GT-12 was effective in inhibiting platelet aggregation and thrombus rate of growth at relatively low concentrations (less than 100 mumol/L) in whole blood. The drug's effectiveness relative to controls in impeding platelet/platelet interactions was found to increase with decreasing incubation time and increasing perfusion time.     

Evaluation of atypical human immunodeficiency virus immunoblot reactivity in blood donors

Blood donors reactive by enzyme-linked immunosorbent assay for antibody to the human immunodeficiency virus (HIV) who showed atypical patterns of viral core protein reactivity on Western blot were monitored for several months. Characterization of their antibodies was performed by 1) use of recombinant HIV proteins; 2) determination of cross-reactivity to HTLV-I, HTLV-II, and HTLV-IV: 3) assessment of immune status; and 4) identification of potentially interfering autoantibodies. Nineteen of 20 donors maintained the same HIV antibody reactivity throughout the follow-up period; the other donor became fully antibody-positive. Eighteen of 20 donors' sera showed clear reactivity with HIV recombinant core proteins. Ten of 19 donor samples demonstrated cross-reactivity to HTLV-IV; 3 of these 10 also cross-reacted with HTLV-I. The immune status of all donors was normal, although the medical histories and HLA antibody screens suggested possible autoimmune reactivity in 9 of 18 donors. During follow-up interviews, three donors reported possible risk factors for HIV infection that had not been acknowledged at the time of blood donation. We conclude that exclusion of donors with these atypical serologic test results is warranted while further studies to determine significance are being conducted.     

Neurofibromatosis type 1: a diagnostic mimicker at CT.

Neurofibromatosis type 1 (NF1) is the most common of the phakomatoses and has a variety of localized or, more frequently, systemic manifestations throughout the thorax, abdomen, pelvis, and extremities. Classic computed tomographic (CT) findings in NF1 with thoracic involvement include small, well-defined subcutaneous neurofibromas, focal thoracic scoliosis, posterior vertebral scalloping, enlarged neural foramina, and characteristic rib abnormalities due to bone dysplasia or erosion from adjacent neurofibromas. However, more atypical manifestations are occasionally seen, and magnetic resonance (MR) imaging can be useful in equivocal cases. NF1 with abdominopelvic involvement tends to arise in the retroperitoneal, mesenteric, and paraspinal regions; it may be quite extensive and therefore difficult to distinguish from adenopathy at CT. The multiplanar capabilities of MR imaging, particularly with T2 weighting, make this modality helpful in evaluating affected patients and making the diagnosis. The classic peripheral manifestations of NF1 include limb hemihypertrophy, pseudarthrosis, peripheral nerve neurofibromas, and subcutaneous common and plexiform neurofibromas. In some cases of NF1, imaging findings are inconclusive, and biopsy and subsequent pathologic analysis are required. Familiarity with the various manifestations of NF1 in different anatomic locations is important in making the diagnosis and optimizing postdiagnostic treatment.