Biomedical subjects
Publications and source records attributed to M Christ.
Paraplegia developed in a 70-year-old man with a 15-year history of polycythemia rubra vera and a two-year history of myelofibrosis, due to extensive epidural involvement by extramedullary hematopoiesis. Early diagnosis and aggressive therapy is essential if permanent paralysis is to be avoided.
Aneurysmal bone cysts occurring within the calvarium are uncommon. The following case report describes the radiological and pathological findings of a temporal bone aneurysmal bone cyst with intra- and extracranial manifestations. The pertinent literature is reviewed.
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Autoimmune hemolytic anaemia (AIHA) in childhood is associated with antibodies produced by the patient himself, which coat his red cells causing their hemolysis. Although in some cases no underlying disease could be found, in the majority of children a virus etiology is apparent. There are very few reports regarding the use of treatment with immunsuppressive agents and the possible benefit. The article reports one case of AIHA. The patient developed at age 6 months a prolonged chronic form of AIHA complicated by thrombopenic purpura. The recent knowledge about pathogenesis, clinical phenomena, serology and prognosis is discussed. Treatment with corticosteroids, azathioprine or cyclophosphamide failed to benefit. Splenectomy and 6-mercaptopurin therapy (3 months) resulted in a complete remission.
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The genomic theory of steroid action has been the unquestioned dogma for the explanation of steroid effects over the past four decades. Despite early observations on rapid steroid effects being clearly incompatible with this theory, only recently has nongenomic steroid action been recognized more widely and led to a critical reappraisal of unsolved questions about this dogma. Evidence for nongenomic steroid effects come from all fields of steroid research now, and mechanisms of agonist action are studied with regard to membrane receptors and second messengers involved. A prominent example of a receptor/effector-cascade for nongenomic steroid effects has been described for rapid aldosterone effects in various cell types, including lymphocytes, cultured vascular smooth muscle, and endothelial cells involving nonclassical membrane receptors with a high affinity for aldosterone, but not for cortisol, and phosphoinositide turnover. As another important second messenger, [Ca2+]i is consistently increased by aldosterone within 1-2 min. In vascular smooth muscle cells, calcium is released from perinuclear stores, while in endothelial cells a predominant increase of subplasmalemmal calcium is seen. Effects are half maximal at physiological concentrations of free aldosterone (0.1 nmol/L), while cortisol is inactive up to 0.1 micromol/L; the classical mineralocorticoid antagonist canrenone is ineffective in blocking the action of aldosterone. The data show that intracellular signaling for nongenomic aldosterone effects also involves calcium, but pathways of cell activation may vary between different cell types. Future research will have to target the cloning of the first membrane receptor for steroids, and the evaluation of the clinical relevance of these rapid steroid effects.
A case of surgically proven left atrial myxoma presented with multiple episodes of cerebral infarctions, both ischemic and hemorrhagic, documented on serial CT and magnetic resonance (MR). Magnetic resonance studies showed, as well, dilated blood vessels in the hemorrhagic areas, proven by angiography to represent mycotic aneurysms. One of these lesions was surgically removed and confirmed to represent a combination of hematoma, infarction, myxomatous nodules, and underlying mycotic aneurysms, as shown on MR scans. This case demonstrates a known delayed neurologic complication of cardiac myxoma that can occur long after resection of the tumor.
In the classical concept of steroid action, steroids bind to cytoplasmic receptors and modulate nuclear transcription after translocation of steroid-receptor complexes into the nucleus. Due to similarities of molecular structure, receptors for steroids, retinoids, vitamin D3 and thyroid hormone are considered to represent a superfamily of receptors. While genomic steroid effects been evident for several decades, rapid effects of steroids have been characterized only recently. These rapid actions are likely to be transmitted by specific membrane receptors. Binding sites in membranes have been characterized which display binding features compatible with an involvement in rapid steroid signaling. Characteristics of putative membrane receptors are completely distinct from those of intracellular steroid receptors, a fact which is further supported by the inability of classic steroid receptor antagonists to suppress nongenomic steroid actions. The cloning and functional expression of a putative progesterone membrane receptor has been achieved. Drugs that specifically modulate nongenomic action alone or even both genomic and nongenomic actions may be applied in various areas such as the cardiovascular and central nervous systems, and treatment of infertility and electrolyte homeostasis.
The geographic distribution and host range of Borna disease (BD), a fatal neurologic disease of horses and sheep, are larger than previously thought. The etiologic agent, Borna disease virus (BDV), has been identified as an enveloped nonsegmented negative-strand RNA virus with unique properties of replication. Data indicate a high degree of genetic stability of BDV in its natural host, the horse. Studies in the Lewis rat have shown that BDV replication does not directly influence vital functions; rather, the disease is caused by a virus-induced T-cell mediated immune reaction. Because antibodies reactive with BDV have been found in the sera of patients with neuropsychiatric disorders, this review examines the possible link between BDV and such disorders. Seroepidemiologic and cerebrospinal fluid investigations of psychiatric patients suggest a causal role of BDV infection in human psychiatric disorders. In diagnostically unselected psychiatric patients, the distribution of psychiatric disorders was found to be similar in BDV seropositive and seronegative patients. In addition, BDV-seropositive neurologic patients became ill with lymphocytic meningoencephalitis. In contrast to others, we found no evidence is reported for BDV RNA, BDV antigens, or infectious B DV in peripheral blood cells of psychiatric patients.
Oxysterols, a family of naturally occurring products, have been shown to possess several biological activities. In particular, they are more toxic towards tumor cells than towards normal cells. In addition, they markedly modify immune cell responses. To carry out in vivo studies, we have synthesized phosphodiesters of 7 beta-hydroxycholesterol (JB69 and XA29). These water-soluble prodrugs have a similar toxicity to their parent compound under in vitro conditions. When administered intraperitoneally to mice bearing the P815 mastocytoma, they induced significant increases in life span. The results depend on the administration protocol. Under appropriate conditions, 20 to 40% of treated mice recover completely. This, together with their immunological effect, suggests that these oxysterols should be considered to be agents for immunochemotherapeutic investigations. By their ability to inhibit HMG CoA reductase, they may prevent the biosynthesis of prenyl groups whose coupling to oncogenes is responsible for the biological activity expression of the latter. Several indications are compatible with an effect on the cell membrane. Our recent studies have shown Protein Kinase C to be a target of oxysterols. On the basis of results obtained by our group and by others, we believe that oxysterols may form a new class of antitumor agents.
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Among their biological properties, several oxysterols display a stronger toxicity towards tumor cells than towards normal cells. Water-soluble phosphodiesters of 7 beta-hydroxycholesterol (JB69 and XA29), that were proved to retain a specific antitumoral activity in vitro, have been recently developed, allowing in vivo studies. They have been assayed on transgenic mice expressing the Large T antigen of SV40 in their liver and developing systematically hepatocarcinoma within 8 months. We show that JB69 and XA29 administered intraperitoneally into transgenic mice, before the onset of adenoma, may prevent or delay the tumor development. Consequently, oxysterol derivatives might constitute new efficient prodrugs against naturally occurring tumors.