ABSTRACT
The transannular Diels-Alder reaction of trans-trans-trans macrocyclic triene A, bearing two cis substiuents in C(12) and C(13) as well as a gem-dimethyl in C(4), was studied. Under thermal conditions, only the desired trans-anti-cis tricycle B was obtained. This tricycle represents an advanced intermediate toward the total synthesis of cassaine C.
ABSTRACT
The expression of Mac-1 antigen (macrophage surface antigen) was studied by the immunoperoxidase method in the nervous system of the twitcher mouse (an authentic murine model of globoid cell leukodystrophy) from day 10 to day 39, to elucidate the origin of the globoid cells. Mac-1 positive cells were seen in peripheral nervous system (PNS) at all ages examined. The positive cells in central nervous system (CNS) showed staining characteristics similar to those in PNS, but in the CNS positive cells they appeared first at day 15 and increased significantly in older mice. These cells were always predominant in the white matter. There were few positive cells in the neural parenchyma of control mice before day 10 but none thereafter. The occurrence and the preferential distribution indicate that it is quite likely that Mac-1 positive cells in the twitcher mouse represent globoid cells. Twitcher mice which were previously given colloidal carbon intravenously, had some Mac-1 positive cells which contained carbon particles both in the CNS and PNS. These facts indicate that globoid cells are the cells of monocytic lineage and at least some of them are derived from blood monocytes.
Subject(s)
Antigens, Surface , Leukodystrophy, Globoid Cell/immunology , Monocytes/immunology , Phagocytes/immunology , Animals , Disease Models, Animal , Humans , Immunoenzyme Techniques , Leukodystrophy, Globoid Cell/pathology , Macrophage-1 Antigen , Mice , Mice, Inbred C57BL , Mice, Neurologic Mutants , Nervous System/pathologyABSTRACT
Myelinogenesis was followed in organotypic cultures of the spinal cord of the neurological mutant mouse, the Twitcher. As a clinically, pathologically and biochemically equivalent model of Krabbe disease this mutant is an important tool for investigating the nervous system. Normal initiation and development of myelination was observed. At 35 days in vitro (DIV) the Twitcher cultures exhibited blisters attached to the intact myelin sheath and bubbling of myelin suggestive of myelin breakdown. Myelin degeneration progressed thereafter. The Twitcher spinal cord survived in culture for more than two months, a period much longer than the life span of affected mice. In order to correlate pathological and biochemical changes, the activity of UDP-galactose:ceramide galactosyltransferase was quantitated in normal and Twitcher cultures. In both the Twitcher and the control groups the galactosyltransferase activity rapidly increased up to 20-25 DIV and then declined. The galactosyltransferase activity of the Twitcher tended to be lower than the controls even during the early myelination period. At 35 DIV the activity in the Twitcher was definitely lower than the controls, and at 52 DIV it was nearly negligible. The galactosyltransferase activity therefore correlated well with the morphologically observed early normal myelination and subsequent myelin degeneration.