Clinical study of childhood acute disseminated encephalomyelitis,multiple sclerosis,and acute transverse myelitis in Fukuoka Prefecture,Japan

Acute disseminated encephalomyelitis (ADEM) has recently been studied in several countries owing to the development and wide spread use of imaging technology, but few epidemiological studies of childhood ADEM have been undertaken in Asian countries. To perform a comprehensive survey of ADEM and related diseases in Japanese children, we conducted a multicenter, population-based study on childhood ADEM, multiple sclerosis, and acute isolated transverse myelitis in Fukuoka Prefecture, Japan. We identified 26 children with ADEM, 8 with multiple sclerosis, and 4 with acute transverse myelitis during 5 years between September 1998 and August 2003. The incidence of childhood ADEM under the age of 15 years was 0.64 per 100,000 person-years, mean age at onset was 5.7 years, and male–female ratio was 2.3:1. The prevalence of childhood multiple sclerosis was 1.3 per 100,000 persons. The mean age at onset of multiple sclerosis, 9.3 years, was significantly higher than that of ADEM. Nineteen (73%) and four (15%) patients with ADEM experienced antecedent infectious illnesses and vaccinations, respectively, within 1 month before the onset. Clinical and radiological findings of ADEM revealed that the frequency of seizures, mean white blood cell counts in cerebrospinal fluid, and the frequency of subcortical lesions in Fukuoka study, seemed to be higher than those in previous non-Asian studies. These findings suggest that there are ethnic or geographical differences in the incidence and clinical features of ADEM, and that there might be potent genetic or environmental risk factors for ADEM distinct from those for multiple sclerosis.     

Role of multinuclear cells in granulation tissue in osteomyelitis: immunohistochemistry in 66 patients

We investigated the origin of multinuclear cells (MNCs) in the granulation tissue in osteomyelitis by immunohistochemical techniques in 66 patients. 12 samples were analyzed for the presence of CD68, cathepsin K, CD11b and tartrate-resistant acid phosphatase (TRAP) activity. Many MNCs were present in the granulation tissue adjacent to a sequestrum. MNCs in contact with the sequestrum were also noted, however, no osteoblasts were found. Immunohistochemically, CD68, cathepsin K and TRAP were strongly expressed in most of the MNCs, while CD11b positive cells were not found. MNCs remote from and in contact with the sequestrum showed the same immunohistochemical features which are characteristic of osteoclasts. Further, MNCs in contact with the sequestrum had originally developed in the granulation tissue and directly infiltrated towards the sequestrum without cell-to-cell interaction with osteoblasts.     

Delayed paraplegia caused by the gradual collapse of an infected vertebra

A case of delayed paraplegia caused by a gradual and progressive collapse of a vertebra after healing of pyogenic spondylitis is reported. A 73-year-old man was treated for a hematogenously seeded pyogenic spondylitis of the first lumbar vertebra. Magnetic resonance imaging showed a high signal intensity of the involved vertebra and adjacent discs and a paravertebral abscess without disc space narrowing. Eight months after healing of the infection, the patient had muscle weakness and paresthesia of the lower extremities, which gradually increased. The plane radiographs revealed a kyphotic deformity of 36 degrees with a collapse of the first lumbar vertebra.     

Suppression by interferon-γ of tumor cell-induced increase in mesothelial permeability

The effect of interferon- (IFN-) on the interaction between tumor cells and mesothelial cell layers was studied from the aspect of changes in mesothelial permeability. Mesothelial permeability was assessed as the percentage diffusion of radiolabeled albumin across the mesothelial cell sheets on Matrigel-coated filter cup assemblies. When lined gastric carcinoma cells (KATO-III) were seeded on the confluent mesothelial cell layers, the fine cobblestone appearance of the cell sheet was disrupted and mesothelial permeability significantly increased. The increase in permeability was suppressed by the addition of as little as 1 U/ml of IFN-. The effect of IFN- was observed when either the conditioned medium of tumor cells alone or the IFN--resistant tumor cells, K-562, was placed onto the mesothelium. The cobblestone appearance of the cell sheet was relatively well preserved in the presence of IFN-. In contrast, IFN- did not suppress tumor-induced mesothelial permeability. These results suggest that IFN- has the potential to protect the human mesothelial cell layers against tumor cells.     

Proinflammatory cytokine (TNFalpha/IL-1alpha) induction of human osteoclast formation

TNFalpha and IL-1alpha are potent stimulators of bone resorption in vivo and in vitro. Recently, it has been demonstrated that these two cytokines directly induce osteoclastogenesis in mouse marrow cultures. This study determined whether TNFalpha (+/- IL-1alpha) is also capable of inducing human osteoclastogenesis. The CD14(+) monocyte fraction of human peripheral mononuclear cells was cultured with TNFalpha +/- IL-1alpha in the presence of M-CSF. TNFalpha induced the formation of multinucleated cells (MNCs) which were positive for TRAP, VNR and cathepsin K and showed evidence of resorption pit formation. IL-1alpha stimulated TNFalpha-induced lacunar resorption two- to four-fold. Osteoprotegerin, the decoy receptor for RANKL, did not inhibit this process. Anti-human IL-1alpha neutralizing antibodies significantly inhibited resorption without inhibiting the formation of TRAP(+)/VNR(+) MNCs. These results suggest that, in the presence of M-CSF, TNFalpha is sufficient for inducing human osteoclast differentiation from circulating precursors by a process which is distinct from the RANK/RANKL signalling pathway.     

Immunoglobulin analysis of anti-streptolysin-O antibody

The immunoglobulin characteristics of human serum ASLO antibody were examined using Sephadex gel filtration column chromatography. IgM associated ASLO antibody was found in certain sera.

IgM ASLO antibody appeared in sera from individuals suspected of having had their initial streptococcal infection, and was detected only in sera from children having ASLO titres below 2 Todd unit (T.u.) at first, and having acquired titres of around 333 T.u. after 3 months.

IgM ASLO antibody was never found in sera from children who were not at the initial streptococcal infection stage. In addition IgM ASLO antibody was not detected in the sera of children having ASLO titres of over 500 units, even if they were at the initial streptococcal infection stage.

No adult sera were shown to have IgM ASLO antibody regardless of their ASLO titres.