Regression stage senile plaques in the natural course of Alzheimer's disease.

Resolution process of cerebroparenchymal amyloid beta-protein (Abeta) deposition has become of increasing interest in the light of recent advance in the Abeta-vaccination therapy for Alzheimer's disease (AD). However, the neuropathological features of degraded and disappearing senile plaque remain poorly characterized, especially in the natural course of the disease. To clarify the natural removal processes of Abeta burden in the brain with AD, we devised a triple-step staining method: Bodian for dystrophic neurites, anti-glial fibrillary acidic protein for astrocytes, and anti-Abeta. We thus examined 24 autopsied AD brains. A novel form of senile plaques, termed 'remnant plaques', was identified. Remnant plaques were characterized by mesh-like astroglial fibrils within the entire plaque part, Abeta deposit debris exhibiting weak Abeta immunoreactivity, and only a few slender dystrophic neurites. In remnant plaques, amyloid burden was apparently decreased. The density of remnant plaques increased significantly with disease duration. Dual-labelling immunohistochemistry revealed many Abeta-immunoreactive granules in astrocytes and a modest number in microglia, both of which accumulated in senile plaques. We consider amyloid deposits of diffuse and neuritic plaques to be shredded by astrocytic processes from the marginal zone of plaques, and to gradually disintegrate into smaller compartments. Cerebroparenchymal Abeta deposits undergo degradation. After a long-standing resolution process, diffuse and neuritic plaques may finally proceed to remnant plaques. Astrocytes are actively engaged in the natural Abeta clearance mechanism in advanced stage AD brains, which may provide clues for developing new therapeutic strategies for AD.

Iron overload and antioxidative role of perivascular astrocytes in aceruloplasminemia.

Aceruloplasminemia (ACP) is an inherited disorder of iron metabolism caused by the lack of ceruloplasmin activity; the neuropathological hallmarks are excessive iron deposition, neuronal loss, bizarrely deformed astrocytes, and numerous 'grumose or foamy spheroid bodies (GFSBs)'. We histopathologically examined two autopsied ACP brains, and observed for the first time that GFSBs form in clusters at the ends of perivascular astrocytic foot processes. Both the deformed astrocytes and the GFSBs contained ferric iron and were intensely immunolabelled with antibodies against the antioxidant proteins ferritin and manganese superoxide dismutase (Mn SOD). Ceruloplasmin is largely produced by perivascular astrocytes in the central nervous system and exhibits a ferroxidase activity that inhibits iron-associated lipid peroxidation and hydroxyl radical formation; therefore, the lack of ceruloplasmin causes direct oxidative stress on astrocytes. The intense immunolabelling of ferritin and Mn SOD most likely reflects a defensive response to iron-mediated oxidative stress. This study suggests that astrocytes play key roles in iron trafficking and the detoxification of iron-mediated free radicals at the blood-brain barrier and in the parenchyma in ACP brain. The antioxidative ability of astrocytes is one of their essential neuroprotective effects, and the decompensation of this ability may lead to secondary neuronal cell death in ACP.

Chronic exercise accelerates the degeneration-regeneration cycle and downregulates insulin-like growth factor-1 in muscle of mdx mice.

The aim of this study was to examine the effects of chronic running exercise on degenerative-regenerative processes in the hindlimb muscles of dystrophin-deficient mdx mice. The number of large-sized degenerative-regenerative groups (DRGs) was markedly decreased, whereas that of small-sized DRGs was unchanged by exercise. Expression of insulin-like growth factor-1 (Igf1), as well as a myogenic factor MyoD (Myod1), was downregulated in mdx muscles by exercise. The downregulation of Igf1 may well correlate with the decrease in the population of early regenerating fibers, which existed predominantly in DRGs, because IGF-1 was mainly localized in these fibers. Our data indicate that chronic exercise may accelerate the active cycle of degeneration-regeneration in mdx skeletal muscles. This means that mdx skeletal muscles can temporarily cope with work-induced injury by enhancing muscle regeneration and repair, but we speculate that an early decline of IGF-1 will accelerate age-dependent muscle wasting and weakness in the later stage of life in mdx mice.

A case of psychogenic tremor associated with blepharospasm and myoclonus: an analysis with surface electromyogram.

We report a 25-year-old woman with an unusual complex psychogenic movement disorders consisting of blepharospasm, tremor, and myoclonus. The tremor appeared in both arms and legs with resting, kinetic, and postural tremor of a variable amplitude, direction, and frequency. The analysis of the arm tremor with surface electromyogram revealed that it consisted of reciprocal and alternating contraction of the wrist flexor and extensor. No apparent co-activation of agonist-antagonist muscles could be seen at the onset of the tremor at rest or at its appearance while performing diadochokinesis.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome in Nagano, Japan: clinical, radiological, and cytokine studies of 13 patients.

OBJECTIVE: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) has so far been reported almost exclusively from the USA and Europe. We carried out this study to define the clinical characteristics of this syndrome in Japanese patients. METHODS: Prospectively, we identified 13 Japanese patients with RS3PE (5 men and 8 women, age 72.7 +/- 11.8 years (mean +/- SD)) without underlying neoplasm. Their clinical features were summarized, pertinent laboratory data including serum/synovial interleukin-6 (IL-6) concentrations were obtained, and extensive radiologic studies using magnetic resonance imaging and 67gallium-citrate (67Ga) whole body scintigram were performed. RESULTS: All patients suffered from proximal arthralgia/myalgia in addition to typical distal symptoms of RS3PE, and all experienced systemic symptoms such as fever, malaise, and weight loss. In laboratory examinations, anemia and elevated inflammatory markers were often remarkable. Magnetic resonance imaging showed severe tenosynovitis of the hands. 67Ga-scintigram revealed radioisotope accumulation in both proximal and distal joints of the extremities. IL-6 activity was markedly elevated both in the serum (mean 82.4 +/- 62.1 (SD) pg/ml, normal range 0.157-2.94) and in the synovial fluid (mean 3350 +/- 633 (SD) pg/ml). CONCLUSION: Compared with cases reported previously from the USA/Europe, Japanese patients with RS3PE are characterized by more prominent systemic symptoms/signs associated with marked inflammatory responses including elevated IL-6 activity. All patients had proximal as well as distal synovitis which could be demonstrated by 67Ga-scintigram. These clinical features were very similar to those of polymyalgia rheumatica, suggesting that RS3PE and polymyalgia rheumatica are closely related disorders which may have a common pathogenesis.

Prednisolone (30-60 mg/day) for diseases other than AD decreases amyloid beta-peptides in CSF.

The effect of corticosteroid on the concentration of amyloid beta-peptide (Abeta) in human CSF obtained from 16 patients without dementia treated with prednisolone (> or =30 mg daily) was studied. The concentrations of Abetax-40 and Abetax-42 in CSF decreased after treatment was started (p < 0.002). A moderate- or high-dose regimen of prednisolone decreases Abeta production or increases Abeta degradation in the human brain and deserves further study in AD.

[Elderly-onset anticentromere antibody-positive pulmonary-renal syndrome: report of an autopsy case].

We report an autopsy case of elderly-onset anticentromere antibody-positive pulmonary-renal syndrome. An 84-year-old woman was admitted to our hospital with complaints of leg edema and general malaise. Neither skin rush nor arthritis was seen. Because of hematuria, proteinuria with various casts, renal dysfunction and anemia, a clinically diagnosis of rapidly progressive glomerulonephritis was made. Slight pulmonary hypertension was observed in ultrasonic cardiography. Hypocomplementemia was not seen. Tests for MPO- and PR 3-anti-neutrophil cytoplasmic antibodies and anti-glomerular basement membrane antibody were negative, but a high titer of antinuclear antibody with a discrete speckled pattern on immunofluorescent staining was disclosed. Results for anticentromere antibody and anti-Ki antibody were positive, but for anti-Sm antibody and anti-double stranded DNA antibody were both negative. She did not present any clinical features of systemic sclerosis or CREST syndrome. Subsequently, prednisolone was administered, but pulmonary alveolar hemorrhage occurred and the patient died of acute respiratory failure caused by massive pulmonary hemorrhage. Autopsy revealed crescentic glomerulonephritis including glomerular capillaritis and pulmonary capillaritis with positive granular deposits of immunoglobulins and compliment on the glomerular and pulmonary capillary walls. Immunologically mediated crescentic glomerulonephritis and pulmonary capillaritis was then diagnosed histopathologically. The main pathological feature of the case was small-vessel vasculitis with immune-complex deposition. Although this case did not fulfill the clinical criteria for systemic lupus erythematosus (SLE), its histological features resembled those of lupus nephritis and acute lupus pneumonitis. We speculated that anticentromere antibody-positive pulmonary-renal syndrome without any other symptoms or signs of connective tissue disease, such as our case, is a clinical entity distinct from typical SLE or CREST syndrome.

[A case of neurofibromatosis with intrathoracic meningocele presenting respiratory failure caused by pleural effusion].

We reported a 58-year-old man with neurofibromatosis and an intrathoracic meningocele. He was admitted to our hospital because of left-sided chest pain and dyspnea on exertion. He presented with severe kyphoscoliosis and showed a round, well circumscribed mass lesion in the paravertebral region of the left upper lung on a chest roentgenogram. Just before admission, pleural effusion accumulated in the left thoracic cavity, which had caused the respiratory symptoms. The mass was diagnosed as an intrathoracic meningocele by MRI and iotrolan CT myelography. The pleural effusion was transudate fluid and no leakage from the meningocele to pleural cavity was demonstrated. Posterolateral extradural approach with laminectomy was done and dural plasty to close the connection between the meningocele and the subarachnoidal space was carried out. After the operation, both the intrathoracic meningocele and the pleural effusion disappeared with remarkable improvement in the respiratory function. Intrathoracic meningocele is known to be seen in association with neurofibromatosis and scoliosis, but it is very rare to see an intrathoracic meningocele which causes respiratory failure due to massive pleural effusion like this report.

[Selective medical circumflex femoral arteriography in idiopathic ischemic necrosis of the femoral head in adults (author's transl)].

It is generally accepted that the medial circumflex femoral artery nourishes about two-thirds to four-fifths of the femoral head. In order to study the arteries in the idiopathic ischemic necrosis of the femoral head in adults, selective medial circumflex femoral arteriography was performed on 24 affected hips and 14 normal hips. This method enabled the better visualization of the medial circumflex femoral arterial system than the conventional femoral or internal iliac arteriography. The affected hips showed similar vascular patterns compared to normal hips. Anastomoses between the ascending branch or the medial circumflex femoral artery and the gluteal arteries, however, were rarely found in the affected hips. In the affected hips, various pathologic changes were demonstrated angiographically mainly in the portion of the ascending branch and the retinacular arteries. The existence of some degree of vascular insufficiency of the femoral head was assumed. However, complete occlusion of the medial circumflex femoral artery and its main branches that might cause head necrosis was seldom observed.