The binding and processing of monoclonal human IgG1 by cells of a human macrophage-like cell line (U937)

The goal of these experiments was to assess the relationship between the binding and processing of IgG by Fc-receptor-bearing cells. Cells of the U937 human macrophage-like cell line were incubated with 125I- labeled monomers, dimers, oligomers (composed of 2-4 IgG1 subunits), and HP (heavy polymers composed of 5 or more subunits per polymer) of monoclonal human IgG1 in vitro. Binding was assessed by spinning cells through a layer of phthalate oils. Internalization of IgG1 was assessed by quantitating residual binding to cells after surface-bound IgG was removed by a brief treatment with a solution containing 0.25 M acetic acid and 0.5 M sodium chloride. Catabolism was assessed by measuring the release of radioactive fragments of IgG1, which were not precipitated by 10% trichloroacetic acid. Unstimulated U937 bound about 10,000 molecules per cell of IgG1 monomer, with an equilibrium binding constant (Ka) of 5 X 10(8) M-1. After stimulation with a conditioned medium in vitro, binding per cell was increased 3-7--fold, and the Ka was decreased 2-4--fold. Both unstimulated and stimulated cells internalized and catabolized labeled IgG1 HP, but stimulated cells internalized and digested much more IgG1 HP per cell than unstimulated cells. Both monomers and dimers of IgG1 were internalized and degraded very slowly by stimulated cells, even though both preparations readily bound to cells. In contrast, oligomers and (to an even greater extent) IgG1 HP were internalized and degraded much more rapidly. Internalization of IgG1 HP was markedly inhibited by incubation at 4 degrees C, but not by incubation with a variety of metabolic inhibitors. Catabolism was inhibited by chloroquine and monensin (inhibitors of lysosomal acidification) and by cytochalasin (an inhibitor of microfilament polymerization). Binding to the surface of cells was not markedly inhibited by any agent tested. The capacity of cells to bind labeled IgG1 was markedly reduced by prior incubation in the presence of unlabeled IgG1. This reduction was in part due to the steric blockade of receptors caused by the avid, but reversible, binding of IgG1. In addition, IgG1 oligomers or HP (but not IgG1 monomers or dimers) also caused an irreversible reduction in the number of Fc receptors by a process analogous to receptor down-regulation, as observed in other receptor--ligand systems.     

Reasons for incomplete proctoscopy

Summary About one of four patients could not be proctoscoped 20 cm or more. Psychologic factors, normal anatomic variations, or pathologic lesions prevented complete proctoscopy in 277 of 1,113 cases. Incomplete proctoscopy for other than organic reasons may be reduced by letting the patient know what to expect and by advising him that the examination can be stopped at any time that he requests.     

Possibility of selection against mtDNA mutations in tumors

Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.     

Comparison of cryothermia and radiofrequency current in safety and efficacy of catheter ablation within the canine coronary sinus close to the left circumflex coronary artery

INTRODUCTION: A canine model was used to compare cryoablation and radiofrequency ablation (RFA) within the coronary sinus (CS) in the ability to create a transmural CS myocardial (Trans-CSM) lesion and risk of coronary artery stenosis. METHODS: After CS and left circumflex (LCx) coronary angiography, an intravascular ultrasound (IVUS) probe was placed in LCx in 29 dogs. An irrigated RFA catheter (8 dogs) or N(2)O cryoablation catheter (21 dogs) was inserted into the CS and positioned within 2 mm of LCx, confirmed by IVUS. RF (30-50W) was applied for 60 seconds at 10 CS sites. Cryoablation (-75 degrees C) was performed with one (n = 7) or two (n = 14) 4-minute applications. Dogs were sacrificed at 1 week (8 RFA and 13 cryoablation) or 3 months (8 cryoablation). RESULTS: During RFA, IVUS showed wall thickening and LCx narrowing in 9 of 10 sites. Angiography at 5-minute post-RFA identified LCx narrowing (25-90%) at 6 of 10 sites and 25-75% narrowing at 4 of 9 sites at 1-week post-RFA. During cryoablation, IVUS showed reversible ice ball compression of LCx, and no LCx narrowing by angiography at 5 minutes, 1 week, or 3 months. Histology showed Trans-CSM lesion at 10 of 10 RFA sites and 20 of 21 cryoablation sites. RFA produced LCx medial necrosis at 7 of 10 sites, involving 20-50%(median 32.5%) of LCx circumference with loss of intima at 5 of 7 sites. Single and twice 4-minute cryoablation produced LCx medial necrosis at 2 of 7 and 8 of 14 sites (5-40%, median 25% circumference). Intima was preserved at 1 week (13/13) with minor proliferation (without narrowing) at 2 of 8 sites at 3 months. CONCLUSIONS: Cryoablation in CS within 2 mm of LCx produces Trans-CSM lesions similar to RFA with lower risk of LCx stenosis than RFA.     

Bronchioloalveolar carcinoma: a review of the epidemiology, pathology, and treatment

Bronchioloalveolar carcinoma (BAC) is an important subtype of pulmonary adenocarcinoma. It has received increasing attention in recent years, due to its increasing incidence and its rate of sensitivity to epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs). This article reviews the epidemiology, risk factors, pathology, clinical presentation, and treatment of this disease. Special focus is paid to the emerging role of oral EGFR-TKIs in Bronchioloalveolar cell carcinoma.     

Stereotactic 11-gauge vacuum-assisted breast biopsy: influence of number of specimens on diagnostic accuracy

PURPOSE: To determine whether number of specimens obtained at stereotactic 11-gauge vacuum-assisted breast biopsy with the patient prone influences diagnostic accuracy and to determine whether this number varies depending on mammographic appearance of lesions as masses or microcalcifications. MATERIALS AND METHODS: Biopsy was prospectively performed in 100 patients (median age, 55 years; range, 31-81 years) with 100 lesions that were mammographically evident as masses (n = 50) and microcalcifications (n = 50) with standardized protocol to acquire 20 specimens per lesion in three 360 degrees probe rotations at one skin entry site. Specimens were histologically evaluated sequentially, and findings were compared with results of surgical excision or of mammographic follow-up for at least 24 months. Differences in diagnostic yield after each probe rotation and differences in diagnostic yield between masses and microcalcifications were determined with chi(2) test. RESULTS: Up to 12 specimens harvested within two 360 degrees probe rotations were necessary to yield correct diagnosis in 96% of patients with masses and 92% of patients with microcalcifications. Diagnostic yield was not improved with more than 12 specimens for masses or microcalcifications. In two (4%) of 47 patients with lesions that were eventually diagnosed as cancer, results at stereotactic biopsy indicated they were benign. Underestimation of diagnosis of lesions as atypical ductal hyperplasia and ductal carcinoma in situ occurred in two (50%) of four and two (17%) of 12 lesions, respectively. With 20 specimens harvested during three probe rotations, there was no statistically significant difference in diagnostic yield between patients with masses and those with microcalcifications (P =.68). CONCLUSION: At 11-gauge vacuum-assisted biopsy, highest diagnostic yield was achieved with 12 specimens per lesion, independent of mammographic appearance of the lesion. Even with standardized retrieval of 20 specimens per lesion, underestimation of disease still occurs.