The biological effectiveness of antiproton irradiation.

BACKGROUND AND PURPOSE: Antiprotons travel through tissue in a manner similar to that for protons until they reach the end of their range where they annihilate and deposit additional energy. This makes them potentially interesting for radiotherapy. The aim of this study was to conduct the first ever measurements of the biological effectiveness of antiprotons. MATERIALS AND METHODS: V79 cells were suspended in a semi-solid matrix and irradiated with 46.7MeV antiprotons, 48MeV protons, or (60)Co gamma-rays. Clonogenic survival was determined as a function of depth along the particle beams. Dose and particle fluence response relationships were constructed from data in the plateau and Bragg peak regions of the beams and used to assess the biological effectiveness. RESULTS: Due to uncertainties in antiproton dosimetry we defined a new term, called the biologically effective dose ratio (BEDR), which compares the response in a minimally spread out Bragg peak (SOBP) to that in the plateau as a function of particle fluence. This value was approximately 3.75 times larger for antiprotons than for protons. This increase arises due to the increased dose deposited in the Bragg peak by annihilation and because this dose has a higher relative biological effectiveness (RBE). CONCLUSION: We have produced the first measurements of the biological consequences of antiproton irradiation. These data substantiate theoretical predictions of the biological effects of antiproton annihilation within the Bragg peak, and suggest antiprotons warrant further investigation.     

Digital radiology. Clinical experience

The authors report the experience achieved at the Stanford University (USA) with a digital radiography system which allows the digitization of the film and of the images collected with photostimulable phosphors. The phosphor is essentially an intensifying screen where a latent image is stored after exposure to X-rays and is extracted by a laser scanning. The images collected with the digitized film and with the phosphor (chest, breast, bone) have been analyzed. The digitized film offers potential diagnostic advantages over the conventional film, because of the contrast manipulation and many other processing options. The possibility to recover the information of overexposed films appears very attractive. The photostimulable phosphors allow to get good quality images, with a consistent reduction of dose and costs. These plates offer the possibility, in the next future, to replace the conventional screen-film systems.     

An integrated anatomic,physiologic and cineradiologic study of the canine gastroesophageal sphincter

Cineradiographs were taken before and after implantation of four strain transducers on the muscle of the distal esophagus of each of 10 healthy female beagles. After appropriate physiologic studies, the dogs were sacrificed and necropsied.A transition zone of mucosa, 1.4±0.6 mm wide, was found caudad to the squamocolumnar junction. Thickening of the circular muscle started 1.4±0.3 mm distal to the squamocolumnar junction and was 10.7±0.4 mm wide. The circular striated muscle of the esophagus terminated abruptly at the proximal edge of the muscle thickening. The striated longitudinal muscle continued its progress to the distal end of this muscle thickening, covering it like a mantle. The phrenoesophageal membrane was inserted 6.3±0.9 mm distal to the squamocolumnar junction. Transducers implanted over the muscle thickening showed relaxation with a swallow; those placed 1 cm proximal to the insertion of the phrenoesophageal membrane showed only contractions. Cineradiographic studies revealed a biconcave area in the portion of the esophagus that showed relaxation on physiologic study.The area of muscle thickening represented the inferior esophageal sphincter which, in the dog, is composed of smooth rather than striated muscle. Relating the findings to those in man, it was noted that the squamocolumnar junction of man is more caudad. Man does not have a well defined smooth muscle band as a sphincter, although opinions vary concerning the presence of muscle thickening in the distal esophagus. He does have a biconcave area but this is 2–3 cm orad to the position in the dog. Man has a vestibule distal to the biconcave area, but the dog does not. The peristaltic wave in the dog stops at the biconcave area and, in this respect, it is similar to that in man. In the preparation studied, the sphincter did not move proximally with a swallow as some believe it does in man.Supported by Mount Carmel Research and Education Corporation.     

CT of benign soft-tissue masses of the extremities

The computed tomographic (CT) scans and medical records of 35 patients with proven benign soft-tissue masses of the extremities were reviewed to assess the contribution of CT in the evaluation of such masses. CT demonstrated the mass in all 35 cases and was able to provide a specific diagnosis in 28 (80%); 25 prospectively, three retrospectively. Correct diagnoses made using CT included hematomas (five), synovial cysts (seven), myositis ossificans (six), fatty tumors (four), aneurysms (three), pseudoaneurysms (two), schwannoma (one), and abscess (one). The CT appearance of a hematoma depends on its age. Synovial cysts are near-water-density masses, often associated with a small joint effusion. Myositis ossificans can be differentiated from parosteal osteosarcoma by virtue of its characteristic zonal ossification. Lipomas are recognized on noncontrast scans by the characteristic low attenuation of fat, while aneurysms and pseudoaneurysms are best diagnosed on postcontrast scans. In seven cases (20%) a specific diagnosis could not be made on the basis of the CT scan. However, in these cases CT delineated the extent of the mass and demonstrated its relation to surrounding structures; this anatomic information was helpful in planning surgical excision or percutaneous biopsy. The authors conclude that CT is a valuable noninvasive imaging method for the evaluation of soft-tissue masses of the extremities.     

Ability of the xid gene to prevent autoimmunity in (NZB X NZW)F1 mice during the course of their natural history, after polyclonal stimulation, or following immunization with DNA.

F1 hybrid offspring of New Zealand Black mothers and New Zealand White fathers [(NZB X NZW)F1] female mice develop antibodies to single-stranded (ss) and native DNA, immune complex glomerulonephritis, massive proteinuria, and premature death with renal failure. By a series of matings, congenic (NZB X NZW)F1 . xid/xid mice were prepared. These mice were different from (NZB X NZW)F1 mice in having the X chromosome-linked immune deficiency gene, xid, in homozygous form. Such congenic (NZB X NZW)F1 . xid/xid females failed to develop antibodies to single-stranded or native DNA. They also failed to develop fatal renal disease as measured by proteinuria, glomerular histology, glomerular immunofluorescence, and survival. To control for unknown genetic factors, studies were performed with littermates that were derived by mating NZB . xid/+ females with NZW . xid/Y males such that the resulting offspring were either (NZB X NZW)F1 . xid/xid (and therefore "defective") or (NZB X NZW)F1 . xid/+ [phenotypically like (NZB X NZW)F1]. In these and in additional studies, mice were housed in the same cages and identified by ear tagging so as to avoid possible environmental variations from cage to cage. In these studies, xid/xid mice failed to develop the characteristic signs of autoimmunity, whereas the controls did. Similar results were also obtained with (NZW X NZB)F1 xid/xid mice compared with (NZW X NZB)F1 xid/+ mice. The effect of xid/xid upon (NZB X NZW)F1 mice was further investigated by assessing responses to immunization and polyclonal B cell activation in vivo. The xid/xid mice failed to produce anti-ssDNA following immunization with ssDNA complexed to a protein carrier in fluid form or even emulsified in adjuvant. Finally, the xid/xid mice failed to produce antiDNA in response to multiple injections of the polyclonal activator, bacterial lipopolysaccharide (LPS), or the polyclonal activator, polyribose inosinic acid . polyribose cytidylic acid. However, the xid/xid mice were neither generally hyporesponsive nor unable to recognize LPS because they made normal antibody responses following immunization with LPS to which multiple trinitrophenyl groups were chemically attached. We conclude from these studies that xid/xid, which is known to cause the deletion of a B cell subset, has a profound affect upon (NZB X NZW)F1 mice, rendering them insusceptible to the naturally occurring autoimmune disease characteristic of (NZB X NZW)F1 mice, and preventing them from producing antibodies to DNA despite purposeful immunization and polyclonal B cell activation. These results force a reevaluation of previous concepts regarding the mechanisms by which xid/xid might interfere with the development of autoimmunity, and a consideration of therapeutic implications.     

Interaction of Nocardia asteroides with cultured rabbit alveolar macrophages.

The interaction between virulent and less virulent strains of Nocardia asteroides and cultured rabbit alveolar macrophages was studied. It was shown that cells of the less virulent strain (N. asteroides 10905) were rapidly phagocytized and destroyed. However, some cells were able to avoid being killed, and they persisted within the macrophage in an altered, gram-negative form. These variants apparently increased in numbers after several days within the macrophage population, so that at 9 days postinfection more colony-forming units per macrophage were recovered than at 3 h. Little or no extracellular growth was observed in the tissue culture medium. During the increase at 9 days, both transitional-phase variants and L-forms of N. asteroides were isolated from the macrophages but not from the medium. Gram-positive bacterial cells were never observed in 9-day infected macrophages. In contrast, cells of the more virulent strain (N. asteroides 14759) were not destroyed after being ingested. After 6 h postinfection, it was observed that the number of colony-forming units per macrophage had increased significantly. There was no corresponding increase in extracellular organisms observed in the culture medium. Therefore, cells of N. asteroides 14759 were able to grow rapidly within cultured rabbit alveolar macrophages. Upon continued incubation of the infected cells (24 h postinfection), it was shown that this strain of Nocardia grew out of the macrophages as acid-fast branching filaments. From these data, it is clear that the initial interaction between N. asteroides and unstimulated, nonimmune alveolar macrophages depends upon the relative virulence of the nocardial strain.     

Approach to the study of the role of sex hormones in autoimmunity

Investigators from this laboratory have been studying sex hormones in normal and autoimmune mice for the past 10 years. We have found that immune responses to DNa are influenced by sex hormones. Androgens reduce and estrogens increase both spontaneous and immunization-induced antibodies to single-stranded DNA in NZB X NZW, NZB X C3H, NZB X CBA, NZB X DBA mice. Treatment of female NZB/W mice with testosterone or 5 alpha dihydrotestosterone retards the progress of autoimmunity. Castration is not necessary for this effect. In contrast, danazol has no favorable effect on the disease process. Estrogens cause a marked acceleration of autoimmunity and a reduction in thymus weight. During the course of these studies, we found that a number of problems or variables arise in studying sex hormone effects, including: 1) X-linked genes, 2) metabolism of testosterone to estrogens, 3) dose of hormone, 4) age at which administration is initiated, 5) differential effects of sex hormones on different autoantibodies and various immune responses.