Progressive supranuclear palsy presenting as primary lateral sclerosis but lacking parkinsonism, gaze palsy, aphasia, or dementia.

We report an autopsy case of progressive supranuclear palsy (PSP) that clinically showed only slowly progressive and symmetric upper motor neuron syndrome over a disease course of 12 years. A female patient initially exhibited dysarthria at the age of 65, followed by gait disturbance and dysphagia. Neurological examination at age 67 disclosed pseudobulbar palsy, spastic gait, hyperreflexia, and presence of bilateral Hoffmann and Babinski signs. However, muscle atrophy, weakness, evidence of denervation on electromyography, vertical gaze palsy, parkinsonism, gait freezing, aphasia, speech apraxia, or dementia was not noted throughout the course. She was clinically diagnosed as having motor neuron disease consistent with so-called primary lateral sclerosis. Pathological examination disclosed histopathological features of PSP, including argyrophilic and tau-positive tufted astrocytes, neurofibrillary tangles, coiled bodies, and thread-like processes in the motor cortex and superior frontal gyrus, and to a lesser degree, in the basal ganglia and brain stem nuclei. In addition, severe fibrillary gliosis was noted in the precentral gyrus and corticospinal tract, being consistent with upper motor neuron syndrome observed in this case. No TAR-DNA binding protein 43-positive lesion, FUS pathology, Bunina body, or Lewy body-like hyaline inclusion was noted in the motor cortex or lower motor neurons. These findings suggest that when tau pathology is prominent in the motor cortex but is minimal in the basal ganglia and brain stem nuclei, a PSP case can lack all classic clinical features of PSP and show only slowly progressive upper motor syndrome, consistent with clinical picture of primary lateral sclerosis.

Rapid typing of influenza viruses using super high-speed quantitative real-time PCR.

The development of a rapid and sensitive system for detecting influenza viruses is a high priority for controlling future epidemics and pandemics. Quantitative real-time PCR is often used for detecting various kinds of viruses; however, it requires more than 2h per run. Detection assays were performed with super high-speed RT-PCR (SHRT-PCR) developed according to a newly designed heating system. The new method uses a high-speed reaction (18s/cycle; 40 cycles in less than 20min) for typing influenza viruses. The detection limit of SHRT-PCR was 1 copy/reaction and 10(-1) plaque-forming unit/reaction for viruses in culture supernatants during 20min. Using SHRT-PCR, 86 strains of influenza viruses isolated by the Tokyo Metropolitan Institute of Public Health were tested; the results showed 100% sensitivity and specificity for each influenza A and B virus, and swine-origin influenza virus. Twenty-seven swabs collected from the pharyngeal mucosa of outpatients were also tested, showing positive signs for influenza virus on an immunochromatographic assay; the results between SHRT-PCR and immunochromatography exhibited 100% agreement for both positive and negative results. The rapid reaction time and high sensitivity of SHRT-PCR makes this technique well suited for monitoring epidemics and pre-pandemic influenza outbreaks.

Structure and expression of myelin basic protein gene products in Xenopus laevis.

To study roles of the myelin basic protein (mbp) gene products in nervous system development, cDNA cloning and expression analyses were performed in Xenopus laevis. We cloned cDNAs for XMBP.1 and XMBP.2 encoded by xmbp.1 and xmbp.2 genes, respectively. We also identified xmbp.1 gene transcripts encoding three XGolli (X.laevis gene of the oligodendrocyte lineage) proteins, XBG21.1, XJ37.1, and XTP8.1, which are homologues of mouse BG21, J37, and TP8, respectively. In reverse transcription-polymerase chain reaction (RT-PCR) analyses, the XMBP, XJ37, and XTP8 mRNAs were expressed in brain, ovaries, testes, and/or thymus in frogs and in larvae after hatching. In contrast, the XBG21 mRNA was found fairly ubiquitously in adult tissues, unfertilized eggs and embryos throughout the developmental stages examined. Western blot analyses using three different monoclonal antibodies (mAbs) showed that the central and peripheral myelin contained 20kDa and18.5 kDa XMBP variants. In addition, XMBP was found in thymus by Western blotting and in thymocyte cytoplasm immunocytochemically. However, the XGolli protein, most provably XBG21, was detectable only in testes. The results indicate that the structure of xmbp gene products seems highly conserved among amphibians and mammals, although their expression patterns and thus physiological roles may partially differ. This is the first report that systematically describes the mbp gene products in nonmammalian vertebrates.

SMP30 deficiency in mice causes an accumulation of neutral lipids and phospholipids in the liver and shortens the life span.

Senescence marker protein-30 (SMP30) is an androgen-independent factor that decreases with aging. SMP30-deficient (SMP30Y/-) mice are viable and fertile but lower in body weight and shorter in life span than the wild-type. In the electron microscope, hepatocytes from SMP30Y/- but not the wild-type mice at 12 months of age clearly contained many lipid droplets, abnormally enlarged mitochondria with indistinct cristae, and enlarged lysosomes filled with electron-dense bodies. In liver specimens from SMP30Y/- mice, the marked number of lipid droplets visible around the central vein increased notably in size and amount as the animals aged. Biochemical analysis of neutral lipids, total hepatic triglyceride, and cholesterol from SMP30Y/- mice showed approximately 3.6- and 3.3-fold higher levels, respectively, than those from age-matched wild-type mice. Moreover, values for total hepatic phospholipids from SMP30Y/- mice were approximately 3.7-fold higher than those for their wild-type counterparts. By thin-layer chromatography analysis, phosphatidylethanolamine, cardiolipin, phosphatidylcholine, phosphatidylserine, and sphingomyelin accumulations were detected separately in lipid extracts from SMP30Y/- mouse livers and provided results that strongly indicate the profound effect of an SMP30 deficiency on the metabolism of these neutral lipids and phospholipids. Conceivably, this abnormality of lipid metabolism is sufficient to curtail the life span of SMP30-deficient mice.

Developmental expression of XEEL, a novel molecule of the Xenopus oocyte cortical granule lectin family.

We have isolated cDNA clones from a Xenopus laevis embryo library that encode a predicted translation product of 342 amino acids containing a signal sequence for secretion. The predicted protein has 62-70% amino acid identity with the Xenopus oocyte cortical granule lectin (XCGL), the mouse intelectin, the human HL-1/intelectin and HL-2. Onset of gene expression occurs by gastrulation, and the transcripts localize in non-ciliated epidermal cells all over the tailbud embryos. The results suggest that the molecule, designated XEEL ( Xenopus embryonic epidermal lectin), is a novel XCGL family molecule secreted from the embryonic epidermis.