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More than 25 clinical settings in amyloidosis have been acknowledged in which a peculiar criminal protein, a precursor protein, has been identified. As of now, however, the mechanism of amyloidogenesis, by which a precursor protein is transformed irreversibly into an amyloid protein, remains to be clarified. We speculated that a study of the molecular conformation of beta 2-microglobulin (beta 2 m), a precursor protein in dialysis-related amyloidosis (DRA), might provide a typic model of amyloidogenesis in other precursor proteins. Therefore, we investigated the misfolding of beta 2 m in DRA using a specific monoclonal antibody against C-terminal peptide 92-99 of beta 2 m. Our study indicated the possibility that the monoclonal antibody specific for C-terminal 92-99 of beta 2 m can detect a pre-amyloid state in amyloidogenesis in vivo, which might take place in the extravascular space.

We studied cerebral blood flow and oxygen metabolism in 6 patients with pure akinesia (PA), 8 patients with progressive supranuclear palsy (PSP), 16 patients with Parkinson's disease (PD), and 10 normal control subjects using positron emission tomography (PET). Regions of interest were studied in the cerebral cortex (the frontal, temporal, parietal, and occipital lobe), thalamus, cerebellar hemispheres, cerebellar vermis, and brainstem. In patients with PA, regional cerebral blood flow (CBF) was significantly decreased in the frontal cortex, thalamus, and brainstem compared with normal control subjects. PSP patients showed significantly decreased CBF in the entire cerebral cortex, thalamus, cerebellar hemispheres, and brainstem and regional cerebral oxygen metabolic rate (CMRO2) in the frontal cortex, thalamus, and brainstem, whereas patients with PD were revealed to be normal in both CBF and CMRO2 values. In conclusion, a part of patients with PA may be in the early stage of PSP or may be atypical presentations of PSP whose symptom is only akinesia judging from the followings. 1) PET findings demonstrated a close similarity between PA and PSP; a pattern of CBF and CMRO2 decrement especially in the frontal cortex, thalamus and brainstem. 2) Patients with PA were shown to have similar pathological changes to PSP in recent studies. 3) Several authors reported that some PSP cases could show only akinesia initially, later developing dementia, supranuclear ophthalmoplegia, pseundobulbar palsy, and nuchal rigidity during their illnesses.

We studied cerebral blood flow, oxygen metabolism and their relation to clinical symptoms in 45 patients with spinocerebellar degeneration (SCD) and 12 normal control subjects using positron emission tomography (PET). Regions of interest were acquired for the cerebellar hemispheres, cerebellar vermis, brainstem, thalami, and cerebral cortices. PET studies in these patients revealed that regional cerebral blood flow (CBF), regional cerebral oxygen metabolic rate (CMRO2), CBF/mean CBF of each cerebral cortex (CBF/mCBF) and CMRO2/mean CMRO2 of each cerebral cortex (CMRO2/mCMRO2) in the cerebellar hemispheres, cerebellar vermis, and brainstem showed a significant decrease in comparison with the normal control subjects, while in the cerebral cortices and thalami, SCD patients showed normal values. CBF/mCBF and CMRO2/mCMRO2 were significantly decreased in patients with olivopontocerebellar atrophy (OPCA) and Menzel type of hereditary ataxia (Menzel type) in the cerebellar hemispheres, cerebellar vermis, and brainstem, whereas patients with late cortical cerebellar atrophy (LCCA) and Holmes type of hereditary ataxia (Holmes type) revealed a significant decrease of CBF/mCBF and CMRO2/mCMRO2 in the cerebellar hemispheres and cerebellar vermis, but not in the brainstem. Patients with OPCA showed a significant decrease of CBF in the cerebellar hemispheres, cerebellar vermis, brainstem and that of CMRO2 in the cerebellar hemispheres and cerebellar vermis. Patients with LCCA showed a significant decrease of CBF in the right cerebellar hemisphere and cerebellar vermis. However, a significant reduction of CBF and CMRO2 was not observed in patients with Menzel type or Holmes type in these regions. In patients with LCCA and Holmes type, the severity of upper limb ataxia and dysdiadochokinesis were significantly correlated with CBF/mCBF and CMRO2/mCMRO2 in the cerebellar hemispheres and brainstem.(ABSTRACT TRUNCATED AT 250 WORDS)