Pathobiology annual最新文献

Virus-type interferon is capable of suppressing the antibody response both in vivo and in vitro. Interferon induced by antigen or mitogen (immune interferon), primarily in T-lymphocytes, also appears capable of suppressing the antibody response. Cyclic AMP has a regulatory effect on the induction of both virus-type and immune interferon. The immunosuppressive effects of virus-type and immune interferon may differ at the cellular or subcellular level.

If the full potential for the use of radionuclides in the treatment of cancer is to be realized, the problem of locating internal emitters with a short range of action in the sensitive targets of the cell must be solved. It is already clear that only two types of radioactivity will satisfy these requirements: alpha decay and, as this review has attempted to demonstrate, electron capture with subsequent Auger cascade. Although mechanisms have yet to be clarified, it is clear that an Auger emitter located within the genetic apparatus is extremely radiotoxic with as little as a single disintegration being lethal in some organisms. Moreover, the available experimental evidence suggests that the extreme lethality is confined to a very small volume, probably that of molecular dimensions. These facts highlight the advantages as well as the limitations of using the Auger effect for cancer therapy. A favorable feature is that extreme damage is confined only to the cell in which radioactive decay takes place; a disadvantage is that the biochemical specificities are very great. Not only must the radioactivity be directed specifically to malignant calls, but it must also be very closely approximated to their genetic structures as well. This circumstance has its counterpart in considering the use of electron capture emitters for diagnostic purposes since their potential hazard depends in large measure on their cellular localization. These microscopic considerations have largely been neglected in traditional radionuclide dosimetry but, considering the magnitude of the effect and the widespread use of such radionuclides as chromium-51, gallium-67, selenium-75, iodine-123, and thallium-201, they should be reexamined. In some cases, such as with 67Ga, we may find that standard dosimetric calculations have overestimated the hazard. In others, the opposite may be true. Whichever the result, it should serve as an impetus to obtain data on the cellular localization of commonly employed radionuclides and on the microscopic distribution of dose. Lastly, it is clear that Auger emitters can be used as ultramicroscopic probes to define the radiosensitive targets of the cell and to destroy regions of subcellular dimensions. This potential use in radiation and cellular biology has only now begun to be exploited.

Multiple endocrine neoplasia, type 2b, is a disorder of unknown etiology with major involvement of the thyroid and adrenal glands, the autonomic nervous system, and connective tissue. It is transmissible with an autosomal dominant pattern of inheritance, but since most cases are not familial, they presumably represent mutations. The thyroid gland exhibits bilateral medullary carcinoma, which is a metastasizing lethal neoplasm in the syndrome requiring total thyroidectomy once abnormal basal or stimulated concentrations of plasma immunoreactive calcitonin have been demonstrated. The adrenal medullary tumors--pheochromocytomas--although rarely malignant, are potentially lethal because of their cardiovascular effects. Since the adrenal involvement is usually bilateral, total bilateral adrenalectomy with excision of any extraadrenal paraganglioma is the surgical treatment. Parathyroid hyperplasia occurs rarely in the syndrome. Treatment of it should be conservative, that is, limited to excision of enlarged parathyroid glands. Major portions of the autonomic nervous system, both sympathetic and parasympathetic, nerves and ganglia, exhibit hypertrophy, hyperplasia, and disorder of structure--a group of changes designated ganglioneuromatosis. This may be largely responsible for the striking eye and oral findings--the hallmarks of the syndrome--and also for some of the serious symptoms and complications of the syndrome, particularly those referable to the alimentary tract. Ganglioneuromatosis is also found in the salivary glands, pancreas, gallbladder, upper respiratory tract, and urinary bladder. The connective tissue abnormality is manifested by increased growth of long bones, ribs, and skull, resulting in a marfanoid habitus, and also by skeletal and joint abnormalities together with increased laxity of ligaments. Ninety cases of MEN 2b have been reported, and although follow-up information is incomplete, 27 patients (30 percent) are known to be dead because of the syndrome. The causes of death have been medullary thyroid carcinoma (15 deaths), pheochromocytoma (10 deaths), and alimentary tract complications (2 deaths). An additional 21 patients (22 percent) are known to have metastatic MTC. We are aware of only 2 patients who, 5 years after thyroidectomy, have apparently been cured of MTC, but both are still at risk for adrenal medullary disease. MEN 2b is, therefore, a very serious disorder that requires urgent treatment of the endocrine tumors. Fortunately, the majority of patients with the syndrome are easily recognized because of an abnormal phenotype typified by thick, bumpy lips and a marfanoid habitus. Since these findings signal high risk for the potentially lethal endocrine neoplasms, patients having the characteristic appearance need evaluation of thyroidal C-cell and adrenal medullary function.