Urban energy mining from sewage sludge.

This work showed that sewage sludge could be a strong candidate for biodiesel production. High lipid content (18-20%) with C(16-18)-carbon range was experimentally identified and measured. These lipids from sewage sludge were converted into biodiesel via the transesterification reaction with MgO-CaO/Al(2)O(3) derived from magnesium slag, and biodiesel conversion was ~98%. The experimental work enabled explaining that temperature is the main driving force for the transesterification reaction, which can be enhanced in the presence of CO(2). This also enables combination of esterification of free fatty acids and transesterification of triglycerides into a single process within 1 min in the temperature range of 350-500°C. Sewage sludge residue after extracting lipids was also a good feedstock for recovering energy via thermo-chemical processes. The impact of CO(2) co-feed on the pyrolysis/gasification process of SS residue was also investigated in this work. The CO(2) injected into the thermo-chemical process remarkably increased the generation of CO by a factor of 2. Moreover, the introduction of CO(2) into the pyrolysis/gasification process enabled reducing condensable hydrocarbons (tar) by expediting cracking; thus, utilizing CO(2) as chemical feedstock for the gasification process not only leads to higher thermal efficiency but also has environmental benefits.

Immunopathology of secondary-progressive multiple sclerosis.

Twenty-three plaques obtained at early autopsy from 2 patients with secondary-progressive multiple sclerosis were examined immunohistochemically for microglia/macrophages, and for immunoglobulins and components of activated complement. Most of the lesions examined in both cases exhibited evidence of low-grade active demyelination of an unusual type (frustrated phagocytosis) in periplaque white matter. This included linear groups of microglia engaging short segments of disrupted myelin that were associated with deposits of C3d, an opsonin formed during complement activation. Similar microglia/C3d/myelin profiles were not observed in newly forming lesions in cases of acute multiple sclerosis or other central white matter diseases. As C3d coupling is known to increase the immunogenicity of potential antigens enormously, present findings point to disrupted myelin close to plaques as a possible source of the putative multiple sclerosis antigen. Ongoing myelin destruction found in a high proportion of old, established plaques was surprising. It suggests that slowly expanding lesions (progressive plaques), in which ongoing myelin breakdown occurs in the absence of florid perivascular cell cuffing or other histological signs of acute inflammation, contribute to disease progression in cases of secondary-progressive multiple sclerosis.

Blood-brain barrier abnormalities in longstanding multiple sclerosis lesions. An immunohistochemical study.

Thirty-five randomly selected plaques from five patients with longstanding multiple sclerosis were examined immunohistochemically for evidence of extravascular serum proteins. One lesion showed histological evidence of active demyelination and 34 were inactive. In the one active lesion and in 26 of the 34 inactive lesions, serum proteins were detected outside blood vessels in a distribution consistent with leakage during life. The findings suggest that the blood-brain barrier (BBB) is permanently damaged in many old plaques, although to a degree not often detectable by current gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI). The findings also suggest that in patients with multiple sclerosis, a breached BBB is not by itself sufficient to induce active demyelination. Continuous exposure of demyelinated axons and glia to cytokines, antibody or other factors present in the circulation might be important, however, in preventing oligodendrocyte regeneration and new myelin formation in longstanding lesions.

Multiple sclerosis. Pathology of recurrent lesions.

Recent autopsy studies suggest that remyelinated shadow plaques located in otherwise intact white matter are the outcome of a previous single episode of acute demyelination. In the present study, of 98 remyelinated plaques examined in 15 patients with multiple sclerosis who died between 27 days and 5 years after clinical onset, 15 showed evidence of a superimposed new demyelinating lesion. Inspection of old shadow plaques in a separate series of patients with subacute and long-standing multiple sclerosis revealed that such lesions sometimes exhibit punched-out areas of demyelination and gliosis similar in size and shape to fresh lesions located within or overlapping remyelinated shadow plaques. The findings support magnetic resonance imaging evidence that local recurrence may be as important or more important than progressive edge activity in determining plaque growth and the conversion of nascent lesions into classical demyelinated plaques. The findings also support experimental evidence that recurrent demyelination of the same area of white matter may be one of the factors underlying failed remyelination in multiple sclerosis.

Multiple sclerosis: remyelination of nascent lesions.

The relationship between plaque pathology and disease duration was examined in 15 patients with multiple sclerosis who died early in the course of their illness. Myelin-stained sections revealed that most plaques examined in patients who died during the first month of their illness showed evidence of ongoing myelin destruction accompanied by a loss of oligodendrocytes. Plaques containing large numbers of oligodendrocytes were not observed in these patients, but were relatively common in patients who died more than 1 month after clinical onset. Remyelination affecting more than 10% of the plaque area was observed in 3 of 82 plaques in 5 patients who died within 10 weeks of clinical onset, in 38 of 105 plaques in 5 patients who died 3 to 10 months after clinical onset, and in 19 of 92 plaques in 5 patients who died 18 months or longer after clinical onset. The study provides new evidence that both oligodendrocytes and myelin are destroyed in new lesions, that this activity ceases completely in many lesions within a few weeks, and that remyelination frequently ensues following repopulation of the plaque by oligodendrocytes. The findings suggest that new lesions normally remyelinate unless interrupted by recurrent activity and that remyelinated shadow plaques are the outcome of a single previous episode of focal demyelination.

Interaction of astrocytes and newly formed oligodendrocytes in resolving multiple sclerosis lesions.

Cells resembling oligodendrocytes are sometimes seen within reactive astrocytes in fresh lesions in multiple sclerosis. Using immunostained paraffin and epoxy sections of fresh plaques obtained at autopsy from a series of cases of short clinical duration, it was found that small cells with round nuclei are commonly observed within reactive astrocytes in some hypercellular plaques and that these cells are phenotypically undifferentiated oligodendrocytes, i.e., nonmyelinating cells expressing intensely the oligodendrocyte determinants 2',3'-cyclic nucleotide 3'-phosphohydrolase and the carbohydrate epitope present on the family of cell adhesion molecules recognized by monoclonal antibody HNK-1. They also stain positively for IgG. This unusual astrocyte-oligodendrocyte interaction, which appears to be restricted to nonmyelinating oligodendrocytes in lesions of several weeks' to several months' duration, has not been described during normal oligodendrocyte differentiation or in experimental central remyelinating lesions. It bears some resemblance, however, to a pattern of slow oligodendrocyte destruction seen previously in organotypic perinatal central nervous tissue cultures exposed to multiple sclerosis serum. It is concluded that the evolution of some multiple sclerosis lesions early in the course of the disease is associated with abnormal binding and/or destruction of newly generated oligodendrocytes by reactive astrocytes. These observations raise new questions concerning mechanisms underlying failed remyelination in multiple sclerosis, including the novel possibility of an immune response directed against a developmentally restricted oligodendrocyte antigen.

Sera from MS patients and normal controls opsonize myelin.

Fc receptor-dependent myelin phagocytosis has been proposed as a mechanism of demyelination in multiple sclerosis (MS). The object of this study was to determine whether MS patients' sera are more opsonic for myelin than normal controls' sera. Opsonization was tested by culturing thioglycollate elicited murine peritoneal macrophages with 125I-labelled, serum-sensitized bovine central myelin. The two groups of sera were found to opsonize myelin equally well after 30 and 120 min incubations. We conclude that MS patients' sera are not more opsonic for myelin than sera from normal controls.

Multiple sclerosis. Oligodendrocyte proliferation and differentiation in fresh lesions.

Fresh lesions in the brain and spinal cord of patients with multiple sclerosis who died shortly after the onset of symptoms were examined immunocytochemically for myelin and oligodendrocyte antigens that are known to be sequentially expressed during normal development. Cells with oligodendrocyte-like morphology that appear in large numbers throughout fresh lesions after acute myelin breakdown and before new myelin formation were found to express galactocerebroside, carbonic anhydrase, and 2',3'-cyclic nucleotide 3'-phosphohydrolase but not myelin-associated glycoprotein or myelin basic protein. They also exhibit intense surface reactivity for a carbohydrate epitope associated with the family of cell adhesion molecules recognized by the monoclonal antibody HNK-1. With the onset of remyelination and the appearance of myelin-associated glycoprotein, myelin basic proteins, CNP, and the HNK-1 epitope is newly formed myelin sheaths, perikaryon CNP and HNK-1 reactivity diminished. A possible oligodendrocyte precursor cell in the form of a large HNK-1 positive glial fibrillary acidic protein negative glial cell was observed among interfascicular oligodendrocytes in white matter bordering these hypercellular plaques. Because a similar progression in the expression of CNP and the HNK-1 epitope occurs during normal oligodendrocyte differentiation, these observations are additional evidence that extensive oligodendrocyte regeneration occurs in some plaques early in the course of the disease. The finding of large numbers of immature oligodendrocytes, presumably expressing many developmentally restricted antigens not normally present in the mature nervous system, in plaques at a particular stage in their evolution may be important in understanding why remyelination eventually fails in multiple sclerosis.

Opsonization of normal myelin by anti-myelin antibodies and normal serum.

Fc receptor-dependent myelin phagocytosis has been proposed as a possible important effector mechanism in several immune-mediated demyelinating diseases. The present study was designed to determine whether myelin is opsonizable by anti-myelin antibodies. Thioglycolate-elicited mouse peritoneal macrophages were cultured with 125I-labelled bovine central myelin pretreated with normal or immune serum. Serum opsonic activity was determined by a kinetic study comparing macrophage uptake of opsonized and untreated 125I-myelin. Heat-stable and heat-labile myelin opsonins were detected in normal rabbit serum. Myelin was also opsonized by normal rabbit gamma globulin and by heat-inactivated normal mouse, human, and guinea pig serum. Increased opsonic activity was detected in rabbit anti-myelin antiserum and the gamma globulin fraction prepared from this serum, in anti-myelin basic protein and anti-galactocerebroside antiserum but not in anti-myelin-associated glycoprotein antiserum or in serum from rabbits injected with Freund's adjuvant alone. One out of three anti-sheep red blood cell antisera tested also showed increased myelin opsonic activity. It is concluded that anti-myelin antibodies can promote opsonic phagocytosis, and that normal serum and normal serum gamma globulin also opsonize myelin.

The distribution of myelin-associated glycoprotein and myelin basic protein in actively demyelinating multiple sclerosis lesions.

Active plaques from 4 patients with multiple sclerosis were examined for myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) using the peroxidase-antiperoxidase (PAP) immunocytochemical procedure applied to paraffin sections. MBP loss was intimately related to the presence of infiltrating macrophages which appeared to remove MBP-positive fragments directly off intact myelin sheaths. Phagocytosis of MAG-positive myelin sheaths was also observed. These findings support previous morphological studies that suggest that phagocytosis by macrophages of myelin attached to axons is an important mechanism of demyelination in multiple sclerosis.

Continual breakdown and regeneration of myelin in progressive multiple sclerosis plaques.

Plaques with lipid macrophages and macrophages containing undigested myelin fragments from five multiple sclerosis patients were studied by light microscopy of epoxy-embedded tissue (five cases) and electron microscopy (one case). Cell counts determined electron microscopically revealed that oligodendrocytes were reduced in number in areas of commencing myelin breakdown. The major mechanism of myelin destruction was phagocytosis by macrophages of intact myelin sheaths in the presence of very small numbers of lymphocytes and plasma cells. When plaques were orientated to allow examination of whole myelin internodes, it was found that most lesions, including lesions known to have been present for less than ten months, contained remyelinating internodes, sometimes in numbers large enough to form shadow plaques. It is concluded that the two processes of sometimes massive remyelination and active demyelination frequently coexist in "fatty" subacute plaques filled with lipid-containing macrophages, and that myelin breakdown at the edges of progressive lesions includes destruction of remyelinating internodes.