P-glycoprotein (P-gp) is an energy-dependent drug extrusion pump with broad specificity for diverse hydrophobic anticancer agents and compounds known to reverse multidrug resistance (MDR). Among MDR reversing agents, phenothiazines (PTZs) and related compounds may sensitize MDR by interacting with a specific binding site(s) on P-gp and by other mechanisms. In order (1) to identify a binding site for PTZs and related compounds on P-gp, (2) to examine whether these compounds and other MDR modulators bind to the same domains of P-gp, and (3) to identify proteins with high specificity for these neuroleptic agents and other MDR modulators, we used a butyrophenone D2-dopamine receptor photoaffinity probe, N-(p-azido-3-[125I]iodophenethyl)spiperone ([125I]NAPS). [125I]NAPS was actively effluxed from vincristine (VCR)-resistant SH-SY5Y/VCR human neuroblastoma cells, and nonradioactive I-NAPS was a potent chemosensitizing agent. After photolabeling, the probe bound specifically and with high efficiency to P-gp and to another multidrug binding 17-kDa membrane-bound protein, spiperophilin, in these cells. The efficiency of [125I]NAPS binding to P-gp was 5-6-fold more than [3H]azidopine and [125I]arylazidoprazosin ([125I]AAP), known photoaffinity analogs for P-gp. [125I]NAPS photolabeling of P-gp was preferentially competed by MDR-related drugs, with vinblastine > VCR > colchicine > doxorubicin > actinomycin D. Many drugs that are known to reverse MDR were potent inhibitors of [125I]NAPS binding to P-gp. While PTZs and related compounds were potent inhibitors of [125I]NAPS binding to P-gp, most of them enhanced the binding of [125I]AAP significantly. cis-Flupentixol increased the binding of [125I]AAP to P-gp 9-fold more than did trans-flupentixol, but both were potent inhibitors of [125I]NAPS binding, suggesting their stereoselective effect on the [125I]AAP binding site. Proteolysis of [125I]NAPS-bound P-gp with Staphylococcus aureus V8 protease revealed that this probe binds to two major peptides, 6 and 8 kDa, and a number of minor ones, while [125I]AAP binds to only an 8-kDa peptide. These results suggest that modulators of MDR may interact with separate or overlapping domains. Furthermore, most MDR modulators, dopaminergic drugs, and beta-adrenergic antagonists used also inhibited binding of [125I]-NAPS to spiperophilin, suggesting that this protein may be a target for these drugs.
Xanthogranulomatous pyelonephritis (XGP), an uncommon chronic inflammatory renal disorder of middle-aged women, is rarely seen in childhood. We report the sonographic findings in a 2-year-old girl with the diffuse form of XGP and discuss the role of newer imaging modalities in the diagnosis and management of this disorder.
Elongation of the anterior tubercle of a transverse process of a cervical vertebra is a congenital anomaly that should be considered in a patient demonstrating a bony mass projecting anterior to the vertebral body on a lateral radiograph of the cervical spine. Reported is a case of elongation of the tubercles of the transverse processes of both C5 and C6 with the formation of an articulation. Computed tomography was used to definitively differentiate this variant from a fracture fragment, bone tumor, or osteophyte. This anomaly is probably a form of supernumerary cervical rib developing at a level above the lowest cervical vertebra.
Six cases of abdominal wall hernias involving the stomach are reported. Three of the hernias were incisional, 2 were epigastric, and 1 was umbilical. All the patients were middle-aged or elderly women. In 2 cases, the gastric herniation produced gastric outlet obstruction with resulting severe dehydration and electrolyte disturbances. Radiographically, the abnormality involved deformity of the stomach with shortening in the frontal views. Lateral profile views were essential in demonstrating the cause of this deformity. In 5 cases, there was mesenteroaxial torsion of the herniated stomach so that the efferent limb of the hernia was superior to the afferent limb. Two of these were associated with obstruction which developed at the neck of the efferent limb.
Enterolithiasis is a rarely encountered clinical and radiologic entity. Stasis of intestinal contents is the underlying cause of the stone formation. Four cases are presented, 3 in the colon and 1 in the small bowel. The chemical composition of these stones varies according to their site of origin. The clinical setting varies widely as does the radiologic differential diagnosis.
Serial erect roentgenograms of the gallbladder during oral cholecystography were taken in 50 patients before and after a fatty meal. In the presence of good opacification, layering of opaque and nonopaque bile was noted in most cases 2 hours after the fatty meal. The degree of layering was related to the extent of gallbladder contraction produced by the fatty meal and the degree to which the gallbladder refilled by the inflow of nonopaque liver bile. The layering phenomenon thus appears to be a manifestation of a normally functioning gallbladder and occurs when the gallbladder refills with fresh nonopaque bile.
Postmortem examination of a child with osteodysplastia (Melnick-Needles syndrome) showed peculiar fibro-osseous tissue in the marrow cavity, with areas of bone constriction but no abnormality of endochondral ossification. Pectus excavatum and scalloping of the vertebral bodies were also present.
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