Effect of chronic administration of different Bence Jones proteins on rat kidney

The role of Bence Jones proteins (BJPs) in the genesis of the renal dysfunction that develops in patients with multiple myeloma is not clearly defined. We previously evaluated renal function and morphology in a unique strain of rats (LOU/m) bearing tumors which synthesized BJPs with isoelectric points of 5.2, 4.3 and 6.7. Myeloma cast nephropathy developed in one tumor bearing group (pI 5.2), tubular necrosis was observed in another (pI 4.3), and renal function and histology remained normal in a third group (pI 6.7). To see if these renal outcomes were a function of the BJP being excreted or other factors which could be present in the tumor bearing animals, we have examined the effect of chronic intravenous administration of these three BJPs on renal function and histology in non-tumor-bearing LOU/m rats. Urine containing the BJP was collected from tumor bearing rats, sterilized by passage through a 0.2 mu millipore filter, concentrated to 50 mg/ml, and dialyzed extensively so as to remove material with a molecular weight less than 3500. Chronic indwelling-venous catheters were placed in non-tumor-bearing LOU/m rats and these rats were given 100 mg/day for five days of one of the three BJPs. Polyfructosan clearance (Cin) was measured prior to and following the five days of BJP administration. Renal histology was examined at the completion of the second Cin. In the pI 5.2 group (N = 6), a severe distal nephron cast nephropathy occurred and Cin fell from 2.88 +/- 0.24 to 0.90 +/- 0.17 ml/min (P less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)     

Peri-ventricular grey stimulation versus motor cortex stimulation for post stroke neuropathic pain.

Central post stroke pain is often difficult to manage satisfactorily with conventional treatment modalities for pain. In the last decade functional neurosurgery has offered hope with motor cortex stimulation achieving significant alleviation of pain in some patients. Unfortunately this has led to the neglect of chronic stimulation of deep grey matter as another modality of treating this condition. In this article we present our experience with motor cortex stimulation and that with deep grey matter stimulation in patients with post stroke pain. We argue that both modalities have a significant role and that what is required are better methods of identifying particular patients who are more likely to respond to one or the other.     

Human immunodeficiency virus-related connective tissue diseases: a Zimbabwean perspective

Our clinical experience with patients in Zimbabwe suggests that an arthropathy may be a feature of HIV disease. This takes two forms: the first is a reactive arthropathy usually affecting the large, lower limb joints with no other clinical features of a connective tissue disease. The second form is seen in association with features of complete or incomplete Reiter's syndrome with involvement of large and small peripheral joints (having an asymmetric distribution). Although this arthropathy may been seen in association with HIV positive asymptomatic disease and often is the reason for first presentation at hospital, the majority of our patients have clinical features of persistent generalized lymphadenopathy, plus or minus features of constitutional illness (such as fever, weight loss, and diarrhea). A small percentage of our patients have arthropathy in association with secondary systemic infection. Other locomotor conditions have been observed, although their numbers are too small to determine whether or not they truly are related to HIV disease. In Zimbabwe there is no association between the development of HIV-associated arthropathy and the presence of HLA-B27.     

Comparison of antigen expression on normal urothelial cells in tissue section and tissue culture

Antigenic characterization of urothelial cells cultured from normal adult ureter was performed. These cells were cultured using a simplified isolation and culture technique and a commercially available serum-free medium. The cells growing in these cultures had epithelioid morphology and normal quantities of DNA. The antigen expression on these cultured normal urothelial cells was evaluated using a panel of monoclonal antibodies: 5G6.4, AN43, URO-5, anti-keratin and anti-blood group antibodies, and 425 (anti-epidermal growth factor receptor). Lower levels of anti-A and AN43 binding on cultured cells were observed than are seen on urothelial cells in sections of normal ureter, while the binding of anti-blood group H, 5G6.4, and URO-5 was unchanged. Binding of anti-epidermal growth factor receptor antibody 425 was improved if the cells were grown in medium lacking epidermal growth factor. These results confirm the urothelial origin of these cultured urothelial cells but indicate that some antigenic differences between cultured normal urothelial cells and urothelial cells in situ in the normal ureter exist.     

Structural Characterization of Variant Forms of Arylsulfatase A that Associate with Alcoholism

Several electrophoretic forms of human platelet arylsulfatase A (ASA), including variant type III_a and normal type IV_a, have been identified by nondenaturing polyacrylamide gel electrophoresis. An alcoholic population that we have analyzed is enriched in variant type III_a compared with nonalcoholic psychiatric and normal controls. Individuals with the III_a enzyme possess greatly reduced levels of ASA activity. To understand further the structural basis for the differences and their potential biological consequences, the nature of the ASA variant expressed by fibroblasts from different individuals was explored. The electrophoretic patterns of fibroblast ASA from the III_a and IV_a individuals differ in degree of phosphorylation. Furthermore, fibroblast ASA from III_a individuals lacks an N -linked glycan found in ASA from IV_a individuals. In addition, differences in peptide and/or posttranslational modification unrelated to the N -linked carbohydrate or phosphorylation exist between the fibroblast ASA from III_a and IV_a individuals. The finding that both fibroblasts and platelets exhibit related electrophoretic isoform patterns characteristic of the donor's ASA type allows for the use of fibroblasts to study the impact of ethanol on the metabolism of cells possessing different ASA types.