Nobuo Ito

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy

The clinicopathologic features of two Japanese sisters with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) are described. Neither patient had a history of hypertension, and both experienced cerebrovascular events before reaching their forties. Severe degenerative changes in the lumbar spine and knee joints were seen on radiographs. MRI showed extensive cerebral white matter lesions, which revealed remarkable arteriosclerotic changes on autopsy.

Vagus nerve and celiac ganglion lesions in generalized amyloidosis: A correlative study of familial amyloid polyneuropathy and AL-amyloidosis

To clarify the cause of gastrointestinal disorders in systemic amyloidosis we made pathologic and morphometric studies of vagus nerves, celiac ganglia, stomach and rectum in three autopsied cases with type 1 familial amyloid polyneuropathy (FAP) and two with nonhereditary generalized amyloidosis (AL-amyloidosis). The gastric and rectal walls in all cases were affected in the same way by amyloid deposition. On the other hand, there was a great difference between the two diseases in the severity of vagus nerve and celiac ganglion lesions: the vagus nerves in FAP showed very extensive endoneurial deposition of amyloid with severe loss of myelinated nerve fibers, but in AL-amyloidosis there was no loss of myelinated nerve fibers and only slight amyloid deposition in the endoneurium. Similarly, in the celiac ganglion, intraganglionic deposition of amyloid was prominent in FAP and slight in AL-amyloidosis. It is known that bowel symptoms frequently occur in type I FAP and are less prominent in AL-amyloidosis. This study demonstrated that the gastrointestinal autonomic nerves were more markedly disturbed by amyloid in the former than in the latter, and disorder in neural control of the digestive tract may be responsible for the bowel symptoms in systemic amyloidosis, especially in type I FAP.

Extensive loss of arterial medial smooth muscle cells and mural extracellular matrix in cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL)

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a distinctive clinicopathologic entity characterized by young adult‐onset non‐hypertensive vasculopathic encephalopathy accompanied by alopecia and disco‐vertebral degeneration. CARASIL arteriopathy is histopathologically characterized by intense arteriosclerosis without the deposition of granular osmiophilic materials. Until now, the obliterative arteriosclerosis is the presumptive cause of subcortical ischemia in CARASIL; however, a detailed vascular pathology leading to diffuse leukoencephalopathy remains unclear. In this study, we examined two autopsied CARASIL brains in comparison with an autopsy case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Intensity of arterial sclerotic changes of CARASIL was evaluated by sclerotic index analysis. Immunohistochemical investigations were performed using a battery of primary antibodies, which recognized vascular cellular and extracellular components. As a result, sclerotic changes were disclosed to be mild and infrequent in CARASIL, in contrast to CADASIL that showed severe obliterative arterial changes. In CARASIL, conversely, most of the arteries were centrifugally enlarged and some were collapsed. We further revealed that arterial medial smooth muscle cells (SMCs) in patients with CARASIL were extensively lost, even in arteries without sclerotic changes. Arterial adventitia in CARASIL was conspicuously thin and immunoreactivities for type I, III, and VI collagens and fibronectin were appreciably weak in this region, indicating a reduction in the mural extracellular matrix (ECM). Because of the medial and adventitial degeneration, CARASIL brains likely receive marked fluctuations in blood flow because of deviations in the structural and functional basis of autoregulation mechanisms. We thus consider that diffuse leukoencephalopathy in CARASIL may be caused by arterial medial SMC loss with mural ECM reduction. We speculate that the abnormalities in the ECM are causatively related to the SMC degeneration, since the ECM is a crucial signal determining the biophysiological properties of arterial SMCs.

Cerebral arterial pathology of CADASIL and CARASIL (Maeda syndrome).

Two familial cerebro‐vascular diseases characterized by different cerebral arterial pathologies and presenting in non‐hypertensive young and middle‐aged adults are described. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by the deposition of smudged periodic acid–Schiff (PAS)‐positive granules known as granular osmiophilic materials (GOM) in the media of small arteries and arterioles. The medial smooth muscle cells are completely lost, and intense adventitial fibrosis is present. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), or Maeda syndrome, is characterized by intense arteriolosclerosis without GOM deposition. Fibrous intimal proliferation, hyaline degeneration of the media, thickening and splitting of the internal elastic lamina, and concentric narrowing of the lumen are characteristic features. In PAS preparation, small arteries are occasionally stained homogeneously due to exudative changes, but never exhibit granular appearance in CARASIL (Maeda syndrome). Each of the small arterial changes is intense in the cerebral medullary and leptomeningeal arteries, leading to multifocal, confluent, or diffuse ischemic changes in the cerebrum. The authors suggest that CARASIL be referred to as ‘Maeda syndrome’ or ‘CARASIL (Maeda syndrome)’ to avoid confusion with CADASIL.

Hepatotoxic action of a poisonous mushroom, Amanita abrupta in mice and its toxic component

An aqueous extract of a poisonous mushroom, Amanita abrupta was injected intraperitoneally into male ICR mice and the acute effects on the liver were studied. Contents of serum glucose and liver glycogen decreased to 60% and 10% of the control levels, respectively, 6 h after injection. Activities of serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase increased to 3- and 8-fold, respectively, 12 h after injection, and the elevated activities were maintained up to 24 h. Activities of the hepatic drug metabolizing enzymes were also reduced 15 h after injection. Histological examination demonstrated massive liver cell necrosis and disappearance of glycogen granules in the liver of the treated animals. Two amino acids, L-2-amino-4-pentynoic acid and L-2-amino-4,5-hexadienoic acid were identified in the mushroom extract. The former caused similar biochemical effects to those of the mushroom extract.

MR imaging of primary leiomyosarcoma of the thyroid gland

Primary leiomyosarcoma of the thyroid gland is extremely rare and radiological information on this tumor is scant. We presented radiological findings on primary thyroid leiomyosarcoma in a 66-year-old woman in which anaplastic carcinoma was suspected based on clinical and cytological features and discussed the radiological clues to distinguish between the two diseases. Ultrasonography showed an ill-defined hypoechoic mass without halo in the left lobe and the isthmus of the thyroid gland. Computed tomography depicted a low-density mass with calcification and necrosis, which invaded the thyroid cartilage. No lymphadenopathy was seen. The tumor was demonstrated as an isointense mass on T1-weighted MR images and a mass of intermediate signal on T2-weighted images. The tumor showed a fair enhancement on gadolinium-enhanced T1-weighted images. Although the radiological picture was nonspecific, primary thyroid leiomyosarcoma appeared less invasive and far less frequent in developing nodal metastasis than anaplastic carcinoma in light of the literature.

A case of anaplastic lymphoma kinase (ALK)-positive ciliated muconodular papillary tumor (CMPT) of the lung

Ciliated muconodular papillary tumor (CMPT) is a rare papillary tumor that arises in the peripheral lung fields and is associated with the proliferation of ciliate d and goblet cells and increased mucin production. We report a case of CMPT involving the rearrangement of the anaplastic lymphoma kinase (ALK) gene. The patient was an 84‐year‐old Japanese female who had exhibited a small nodular shadow on chest computed tomography during a regular checkup 10 years ago. She underwent a partial resection of segment S10 of the right lung. The cut surface of the surgical specimen revealed a well‐circumscribed, jelly‐like mass measuring 8 × 8 × 10 mm. Histologically, the tumor was composed of a mixture of ciliated, goblet, and basal cells arranged in a papillary pattern together with pools of mucin. A diagnosis of CMPT was made. The lung tumor cells were subjected to fluorescent in situ hybridization and highly sensitive immunohistochemical staining for the ALK protein, both of which produced positive results. CMPT usually follows a favorable course, but the exact nature of this tumor; i.e., whether it is benign or malignant, has not been established. This is the first reported case of an ALK‐positive CMPT.

Bronchogenic cyst of the shoulder

An 8‐month‐old girl presented with a painless mass on her left shoulder that was noticed by her mother. Ultrasonography and magnetic resonance imaging (MRI) showed a well‐defined subcutaneous cystic mass. The excised cyst was lined with ciliated pseudostratified columnar epithelium with occasional goblet cells and diagnosed as a bronchogenic cyst. She made a good recovery.

The importance of cellular adhesion for mesangial cell proliferation in serum sickness nephritis of the rat: A co‐culture study of glomerular macrophages and mesangial cells

The role of cell‐cell contact on activating mesangial cell proliferation by nephritic macrophage was investigated. Nephritic glomerular macrophages were obtained from serum sickness nephritis (SSN) rat kidneys at 14 days after the cessation of sensitization, when proliferating cells were most increased in the glomeruli in the course of the SSN. The effect of the nephritic macrophages on mesangial cell proliferation was greater than that of control by co‐culture allowing cellular contact. However, nephritic macrophages did not enhance mesangial cell proliferation by co‐culture without direct contact even though the nephritic macrophages were activated with lipopolysaccharides. Conditioned medium from co‐culture of the nephritic macrophages and mesangial cells did not enhance mesangial cell proliferation. Anti‐intercellular adhesion molecules (ICAM)‐1 antibody inhibited mesangial cell proliferation by direct co‐culture dose‐dependently. From these results, cellular contact was important for stimulation of mesangial cell proliferation by macrophages and ICAM‐1 participated in these interactions.

Spinal cord vascular and leptomeningeal amyloid beta-protein deposition in a case with cerebral amyloid angiopathy.

SummaryCerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid fibrils on leptomeningeal and cortical blood vessels, and the incidence of this disorder increases with age. However, this form of vascular amyloid deposition rarely involves tissues outside of the brain. A 71-year-old woman first developed some deterioration in memory, and soon afterwards suffered from recurrent episodes of subcortical hemorrhage. Histopathological examination of this case revealed typical pathology of Alzheimers disease with an extensive appearance of β-protein type CAA, and additionally, the spinal leptomeningeal vessels and the pia-arachnoid membranes were also affected by amyloid β-protein deposits. The spinal cord involvement associated with CAA and Alzheimers disease is unusual, and the present case provides additional important information on the pathogenesis of disorders with β-protein deposition including Alzheimers disease.