Showing papers by "Thomas Anderson published in 1974"
TL;DR: It is indicated that the glucose carrier of streptozotocin facilitates uptake of its cytotoxic group, 1-methyl-1-nitrosourea, into islets, and this mechanism of diabetogenicity differs from that of strePTozotOCin.
Abstract: The diabetogenic activity of streptozotocin has been correlated with a reduction in pyridine nucleotide synthesis in the mouse pancreatic islet. To determine the specificity of this reduction for diabetogenicity, a comparative study of streptozotocin, its cytotoxic moiety, 1-methyl-1-nitrosourea, and alloxan was performed. Streptozotocin administered intraperitoneally (i.p.) producd a dose-related reduction in islet NAD which was proportional to the degree of diabetogenicity. A diabetogenic dose, 200 mg/kg, attained a peak plasma N-nitroso intact streptozotocin concentration of 0.224 μmol/ml and reduced the mean islet NAD from a control of 0.78 to 0.15 pmol. At borderline, 150 mg/kg, and nondiabetogenic, 100 mg/kg, doses, plasma concentrations reached 0.161 and 0.136 μmol/ml, and NAD was 0.36 and 0.86 pmol/islet, respectively. 1-Methyl-1-nitrosourea, 100 mg/kg, attained a maximum N-nitroso intact 1-methyl-1-nitrosourea concentration of 0.162 μmol/ml and reduced the mean NAD to 0.58 pmol/islet, and was nondiabetogenic; 200 mg/kg attained a peak plasma concentration of 0.344 μmol/ml and depressed NAD to 0.38 pmol/islet, and was inconsistently diabetogenic. Islet NAD of 0.4 pmol/islet or greater is required for integrity of the beta cell. A diabetogenic dose of alloxan, 500 mg/kg, did not depress NAD, 0.85 pmol/islet, therefore confirming that its mechanism of diabetogenicity differs from that of streptozotocin.
In vivo uptake of [methyl-14C]streptozotocin by islets was 3.8 times that of [methyl-14C]-1-methyl-1-nitrosourea, whereas uptake by the exocrine pancreas favored 1-methyl-1-nitrosourea over streptozotocin 2.4:1. The decreased islet uptake of 1-methyl-1-nitrosourea correlates with the 3.5 times increased molar dosage required to produce islet NAD depression comparable to that of streptozotocin, 150 mg/kg. These studies indicate that the glucose carrier of streptozotocin facilitates uptake of its cytotoxic group, 1-methyl-1-nitrosourea, into islets.
94 citations
TL;DR: The NBT test proved to be a useful adjunct in distinguishing fever as a systemic manifestation of underlying lymphoma from that secondary to bacterial infection, and bacterially‐infected lymphoma patients had elevated resting NBT scores comparable to a control population with bacterial infections.
Abstract: A prospective evaluation of the nitroblue tetrazolium (NBT) dye reduction reaction revealed that the response of neutrophils from 76 lymphoma patients was comparable to a control population of 44 patients without underlying malignancy. The NBT test proved to be a useful adjunct in distinguishing fever as a systemic manifestation of underlying lymphoma from that secondary to bacterial infection. In contrast to lymphoma patients with „B”︁ fever, bacterially‐infected lymphoma patients had elevated resting NBT scores comparable to a control population with bacterial infections. Lymphoma chemotherapy, including prednisone, did not inhibit neutrophilic response to infection or latex particle phagocytosis, but Procarbazine may have produced a false positive response in some patients. It is essential to perform a simultaneous latex particle stimulation control to rule out an acquired intracellular defect that would otherwise be interpreted as a false negative response.
4 citations