Hiroshi Nagura

Neurological Signs and Frontal White Matter Lesions in Vascular Parkinsonism: A Clinicopathologic Study

BACKGROUND AND PURPOSE The clinical characteristics and the pathological lesions of so-called vascular parkinsonism (VP) are still debatable. The purpose of this study was to define the core signs and symptoms and assess the cerebrovascular lesions in pathologically confirmed VP. METHODS In the present study, VP was defined as the presence of parkinsonism and pathological evidence of cerebrovascular lesions but no depigmentation or Lewy bodies at the substantia nigra. We compared the clinical signs and symptoms of 24 VP patients with those of 30 age-matched patients with pathologically confirmed Parkinsons disease. We compared the brain pathology in VP patients with that in 22 age-matched patients with Binswangers disease (BD) who had no parkinsonism according to clinical records. RESULTS VP was characterized clinically by a short-stepped or frozen gait, lead-pipe rigidity, absence of resting tremor, and negative response to levodopa. Half or more of VP patients demonstrated pyramidal tract signs and pseudobulbar palsies. There was no significant difference in the extent of vascular lesions at the basal ganglia between patients with VP and with BD without parkinsonism. The extent of frontal white matter pallor tended to be less broad in VP than in BD without parkinsonism. In VP patients, the number of oligodendrocytes in the frontal white matter was significantly less than that in age-matched normal control subjects and significantly more than in those with BD. CONCLUSIONS The core signs and symptoms of autopsy-proved VP differ from those of typical Parkinsons disease, and most VP patients had diffuse cerebral white matter lesions as well as basal ganglia lesions. VP might be related to frontal white matter lesions.

Urocortin expression in the human central nervous system

Urocortin is a recently identified neuropeptide of the corticotrophin‐releasing factor (CRF) family in the mammalian brain and has been demonstrated to stimulate ACTH secretion from pituitary cells, but its expression in human brain tissue including the hypothalamus has not been examined. In this study, we first examined urocortin expression in the hypothalamus (20 cases) and pituitary stalks (17 cases) of human brain obtained from autopsy using immunohistochemistry and mRNA in situ hybridization.

Double mutations at codon 180 and codon 232 of the PRNP gene in an apparently sporadic case of Creutzfeldt-Jakob disease

Several polymorphisms of the prion protein gene are associated with the occurrence of familial Creutzfeldt-Jakob disease. We described a 84-year-old Japanese man with neuropathologically verified Creutzfeldt-Jakob disease of apparently sporadic type. His clinical presentation was atypical in point of a very late age at onset and absence of periodic synchronous discharge on electroencephalography. The patient carried double hitherto undescribed mutations of the prion protein gene; at codon 180 on one allele and at codon 232 on another. The mutation at codon 180 abolishes the Tth111I cutting site, which may be misunderstood to represent codon 178 mutation on routine restriction fragment length polymorphism study.

Apoptosis and cell proliferation in biliary atresia

Biliary atresia (BA), which is thought to result from progressive destruction of the bile ducts by a necroinflammatory process, is the most common cause of obstructive jaundice in infancy. Abnormalities in the cell turnover of remodelling ductal plates are considered one of the important aetiological factors in this disorder, but little work has been done on this topic. Programmed cell death or apoptosis was therefore examined by TdT‐mediated dUTP biotin nick end labelling (TUNEL) and cell proliferation by Ki67 immunostaining in 34 cases of BA. The results were compared with normal control liver (five cases) and congenital dilatation of the bile ducts (CDB, five cases) in order to study the cell turnover or tissue dynamics of BA. The TUNEL labelling index (LI) in bile ducts (48·9±13·2 per cent) was significantly higher than that of the control normal liver (3·6±2·8 per cent) and of CDB (2·5±5·1 per cent). The Ki67 LI in the bile ducts of BA (15·0±5·57 per cent) was also significantly higher than that of CDB (8·6±5·4 per cent). No significant differences of the TUNEL and Ki67 LIs in hepatocytes were, however, observed between BA, CDB, and normal liver. The TUNEL LI was significantly higher than the Ki67 LI in the bile ducts of BA. BA is therefore associated with increased and disorganized cell turnover of the bile ducts, which is related to malformation of the ductal plate or abnormal bile duct development. Copyright

Endogenous glucocorticoids decrease the acinar cell sensitivity to apoptosis during cerulein pancreatitis in rats

BACKGROUND & AIMS We recently showed that activation of the hypothalamus-pituitary-adrenal axis may mitigate the progress of acute pancreatitis. To clarify the mechanism, the role of endogenous glucocorticoids in pancreatic acinar cell death was examined. METHODS The occurrence of apoptosis was studied in adrenalectomized or sham-operated rats with or without cerulein-induced pancreatitis. The effects of RU38486, a glucocorticoid-receptor antagonist, on the survival of cultured acinar cells (AR42J) were also examined. RESULTS Adrenalectomy caused increases in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) of acinar nuclei depending on the time after adrenalectomy but not of other cell types in the pancreas and in other digestive organs. Electron microscopy showed the characteristic features of apoptosis in the TUNEL-labeled acinar cells. In cerulein pancreatitis of adrenalectomized rats, the TUNEL-labeled acinar nuclei increased remarkably depending on the time after cerulein infusion. Replacement of glucocorticoids blocked the occurrence of apoptosis in these experiments. RU38486 induced dose dependently the apoptosis of AR42J cells. CONCLUSIONS These results provide evidence that endogenous glucocorticoids are an important factor for acinar cell survival. Endogenous glucocorticoids may protect acinar cells by decreasing their sensitivity to the induction of cell death during acute pancreatitis.

Constant and severe involvement of Betz cells in corticobasal degeneration is not consistent with pyramidal signs: A clinicopathological study of ten autopsy cases

This report concerns a clinicopathological study of three additional patients with corticobasal degeneration (CBD), described here for the first time, and a clinicopathological correlation between pyramidal signs and upper motor neuron involvement, in ten autopsy cases of CBD, including seven cases reported by us previously. We investigated pyramidal signs, including hyperreflexia, Babinski sign, and spasticity, and involvement of the primary motor cortex and pyramidal tract, focusing on the astrocytosis of the fifth layer of the primary motor cortex. Pyramidal signs were observed in six (60%) of the ten cases. Hyperreflexia was evident in six patients (60%), with spasticity being observed in three patients (30%). Loss of Betz cells associated with prominent astrocytosis and presence of ballooned neurons in the fifth layer of the primary motor cortex was observed in all ten cases. In all cases, involvement of the pyramidal tract was obvious in the medulla oblongata, without involvement of the pyramidal tract in the midbrain. Constant and severe involvement of the fifth layer of the primary motor cortex, including the Betz cells, has not previously been reported in CBD. We suggest that the pyramidal signs in CBD have been disregarded.

The Immuno-Inflammatory Mechanism for Tissue Injury in Inflammatory Bowel Disease and Helicobacter pylori-Infected Chronic Active Gastritis

The gastrointestinal mucosa is exposed to myriads of infectious and food antigens, and a unique barrier mechanism handles them on the mucosal surface, and specific immune responses to these antigens call on the mucosal immune system in the mucosal tissues to maintain homeostasis of gastrointestinal functions and structure. Abrogation of these mucosal defense mechanisms may lead to alter immunologic homeostasis in the gastrointestinal tract and to induce pathological features of inflammatory bowel disease (IBD) and Helicobacter pylori-infected chronic active gastritis, including chronic active inflammation, mucosal atrophy and tissue injuries. Regardless of the initiating cause of these long-standing chronic active mucosal inflammations, characteristic immuno-inflammatory mechanisms are involved in their pathogenesis, that is, similar and/or different specific prolonged impaired and excessive immuno-inflammatory responses following the abrogation of the mucosal barrier system are present in the diseased mucosa with IBD and H. pylori infection, respectively.

The prophylactic effect of warfarin and aspirin in cerebral ischemia

完成型脳梗塞, RIND, TIAを含む虚血性脳疾患を対象に抗凝固療法とアスピリン治療を行ない, 両者の治療効果と合併症を比較した.9例の心房細動を含む16例には抗凝固療法を行ない, 平均23.8ヵ月間観察し, 52例にはアスピリンを投与し, 平均14.2ヵ月間観察した.結果 : 1) ワーファリン治療群では完成型脳梗塞3例 (年間発症率9.5%), TIA1例認められた.アスピリン治療群では完成型脳梗塞3例 (同, 4.9%), RIND型4例 (同, 6.5%), TIA2例認められた.完成型脳梗塞の発症はアスピリン治療群でやや少ない傾向がみられたが, 脳虚血発作全体の発症率は両治療群間に有意の差はみられなかった.2) 治療期間中の合併症としては, ワーファリン治療群では性器出血1例, アスピリン治療群では脳出血3例, 消化管出血4例の計7例みられた.アスピリン治療における消化管出血には注意する必要がある.