Dose-volume histogram analysis of techniques for irradiating pituitary adenomas.

PURPOSE: Three-dimensional treatment planning was performed to evaluate three standard coplanar irradiation techniques (two-field parallel-opposed, three-field, and 110 degrees bilateral arcs), the 330 degrees single rotational arc, and a four noncoplanar arc technique for the treatment of pituitary adenomas. We sought to identify the optimal technique for minimizing the dose delivered to the normal tissues around the pituitary gland. METHODS AND MATERIALS: Contours of the pituitary tumor and normal tissues were traced onto computed axial tomography (CT) scans and reconstructed in three dimensions using a three-dimensional planning system. A total dose of 45 Gy was delivered to the pituitary lesion with the five techniques using 6 MV and 18 MV photons, and dose-volume histograms were generated. RESULTS: The 18 MV photons delivered a lower dose to the temporal lobe than did the 6 MV photons in the two-field technique, but this advantage was not evident for the other techniques. The three-field technique improved dose distribution throughout the temporal lobes with low doses being delivered to the frontal lobe. The bilateral arc and the 330 degrees arc techniques were superior to stationary two- and three-fields techniques for sparing the temporal lobes. The four noncoplanar arc technique delivered less doses to the temporal and frontal lobes than did the other techniques. However, the lens dose (3.6 Gy/25 fractions) was higher compared to the other techniques. CONCLUSION: Analysis of the dose-volume histograms shows the various dosimetric advantages and disadvantages of the five techniques. Based upon individual considerations, including the patient's age and medical history, one can decide the optimal technique for treatment.

Macrophage cytoskeleton association with CR3 and CR4 regulates receptor mobility and phagocytosis of iC3b-opsonized erythrocytes.

Alveolar macrophages (AM phi) were examined for CR1 (C3b receptor, CD35), CR3 (iC3b receptor; CD11b/CD18), and CR4 (iC3b receptor; CD11c/CD18) by assays for binding of C3-opsonized sheep erythrocytes (EC3b or EC3bi) and uptake of specific monoclonal antibodies (mAbs). In AM phi isolates from nine normal volunteers, 49% of cells bound EC3b and 71% bound EC3bi. Quantitation of receptors per cell with [125I]mAbs showed 8.5 x 10(4) CR4, 5.1 x 10(4) CR3, and 2.6 x 10(4) CR1. With most AM phi preparations, CR3 was the major receptor mediating attachment of EC3bi, despite the predominance of CR4 antigens. Anti-CR3 inhibited EC3bi rosettes by > or = 50%, whereas anti-CR4 blocked rosettes by < or = 18%. U937 cells differentiated with phorbol myristate acetate resembled AM phi in receptor expression but exhibited almost no CR4-dependent rosetting. Despite the relative inability of CR4 to mediate EC3bi attachment, AM phi ingestion of [51Cr]EC3bi was blocked by either anti-CR3 or anti-CR4. Two lines of evidence indicated that CR3 were more mobile within the membrane than were CR4. Immunofluorescence staining demonstrated patching and occasional capping of CR3, whereas CR4 remained uniformly distributed. This patching and capping of CR3 required the actin cytoskeleton, as it was inhibited by cytochalasin D. Modulation experiments using surfaces coated with anti-CR3 or anti-CR4 also showed that CR3 was more mobile than was CR4. However, there was some variation among AM phi isolates from different donors. In seven isolates, no CR4 modulation was produced with anti-CR4, whereas in six other isolates, CR4 was modulated by 66%. Incubation of cells in cytochalasin D increased modulation of both CR3 and CR4 on mAb-coated surfaces. Cells exhibiting increased mobility of CR4 showed an increased ability to form CR4-dependent EC3bi rosettes. The data are consistent with the hypothesis that CR3 and CR4 exhibit a variable association with the cytoskeleton that regulates their mobility and function. A relatively mobile subset of CR3 and/or CR4 mediates EC3bi attachment, whereas a relatively immobile subset of CR3 and/or CR4 fails to mediate EC3bi attachment but functions to promote ingestion of EC3bi.

Synthesis of complement component C5 by human B and T lymphoblastoid cell lines.

Human B and T lymphoblastoid cell lines were shown to synthesize C5. C5 synthesis was quantitated with an enzyme-linked immunosorbent assay (ELISA) that utilized a pool of C5-specific monoclonal antibodies (mAbs). Some level of C5 synthesis was detected in all eight of the B and T cell lines examined. In three of the cell lines, C5 was detected in both culture supernatants and whole cell detergent lysates, whereas in the other five cell lines, C5 was detected only in the cell lysates. Lymphoblastoid cells with both distributions of C5 were shown to synthesize a messenger RNA that was similar in size to the C5 mRNA expressed by the HepG2 hepatoma cell line. Estimates of the concentration of the C5 transcript in poly(A)+ RNA from lymphoblastoid and HepG2 cells suggested that C5 mRNA levels in the lymphoblastoid cell lines were comparable and about one-tenth of the levels in HepG2 cells. Lymphoblastoid C5, isolated by immunoaffinity chromatography from the supernatants of 35S-labeled cultures, had the same subunit composition as plasma-derived C5, but had an alpha subunit of slightly smaller relative mass.

Neutrophil and monocyte cell surface p150,95 has iC3b-receptor (CR4) activity resembling CR3.

Previous investigations of p150,95 (CD11c), the third member of the CD18 membrane glycoprotein family that includes CR3 (Mac-1 or CD11b) and LFA-1 (CD11a), had demonstrated that solubilized p150,95 bound to iC3b-agarose in a manner similar to isolated CR3. The current study showed that membrane surface p150,95 also expressed iC3b-receptor activity and was probably the same as the neutrophil receptor for iC3b- or C3dg-coated erythrocytes (EC3bi or EC3dg) that had been previously designated CR4. Normal neutrophil and macrophage CR4-dependent EC3bi rosettes were inhibited by monoclonal anti-p150,95, and cells from a patient with CD18 deficiency did not form CR4-dependent EC3bi rosettes. With neutrophils that bore large amounts of CR1 and CR3 and little p150,95, EC3bi were found primarily via CR1 and CR3, and demonstration of p150,95-dependent rosettes required large amounts of fixed iC3b, low-ionic strength buffer, and antibody blockade of CR1 and CR3. By contrast, culture-derived macrophages expressed eight times more p150,95 than did monocytes and EC3bi were bound to both p150,95 and CR3 when EC3bi bore small amounts of fixed iC3b and assays were carried out in isotonic buffer. Comparison of the amounts of CR1, CR3, and CR4 in various tissues by immunoperoxidase staining revealed that CR4 was the most abundant C3 receptor molecule on tissue macrophages, and suggested that CR4 might be involved in clearance of C3-opsonized particles or immune complexes.

Treatment of autochthonous rat brain tumors with fractionated radiotherapy. The effects of graded radiation doses and of combined therapy with BCNU or steroids.

The avian sarcoma virus-induced glioma model in rats was used to evaluate radiation dose response (survival curves), giving fractionated treatments to the whole head. Groups of 14 to 20 rats received total doses of 2300, 4600, or 5750 rads over 2, 4, or 5 weeks, respectively. Median group survival times were compared to controls and to each other. All doses of radiation significantly prolonged survival with reference to control. The 4600- and 5750-rad doses were significantly more effective than the 2300-rad dose. In another series of experiments, BCNU chemotherapy (10 mg/kg) was combined with 2300 and 4600 rads radiation therapy. Synergism of therapies was demonstrated. Methylprednisolone acetate (2 mg/kg twice weekly over 4 weeks) alone did not affect survival curves, and its combination with 4600 rads radiation therapy negated the prolongation of survival achieved with 4600 rads alone.