Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice

Missense mutations of the tau gene cause autosomal dominant frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), an illness characterized by progressive personality changes, dementia, and parkinsonism. There is prominent frontotemporal lobe atrophy of the brain accompanied by abundant tau accumulation with neurofibrillary tangles and neuronal cell loss. Using a hamster prion protein gene expression vector, we generated several independent lines of transgenic (Tg) mice expressing the longest form of the human four-repeat tau with the R406W mutation associated with FTDP-17. The TgTauR406W 21807 line showed tau accumulation beginning in the hippocampus and amygdala at 6 months of age, which subsequently spread to the cortices and subcortical areas. The accumulated tau was phosphorylated, ubiquitinated, conformationally changed, argyrophilic, and sarcosyl-insoluble. Activation of GSK-3beta and astrocytic induction of mouse tau were observed. Astrogliosis and microgliosis correlated with prominent tau accumulation. Electron microscopic examination revealed the presence of straight filaments. Behavioral tests showed motor disturbances and progressive acquired memory loss between 10 to 12 months of age. These findings suggested that TgTauR406W mice would be a useful model in the study of frontotemporal dementia and other tauopathies such as Alzheimer's disease (AD).     

Effects of ISI and stimulus probability on event-related go/nogo potentials after somatosensory stimulation

The present study investigated the characteristics of the middle-latency negative potential of event-related potentials (ERPs) using somatosensory go/nogo tasks. We manipulated interstimulus interval (ISI) in Experiment 1 and stimulus probability in Experiment 2 and analyzed the subtracted difference waveform resulting from subtraction of the ERP evoked by the go stimulation from that evoked by the nogo stimulation. In Experiment 1, the peak latency of negativity became significantly longer as the ISI increased, but the peak amplitude was unchanged. The reaction time (RT) was longer with increasing ISI. In Experiment 2, manipulation of the stimulus probability yielded an increase in peak amplitude with decreasing probability of the nogo stimulus, but did not affect the latency. The RT increased as the probability of a nogo stimulus rose. Because manipulation of the ISI and stimulus probability elicited different brain activities, we hypothesized that manipulation of the ISI elicited a delay of the stimulus evaluation process including response inhibition, and that stimulus probability significantly affected the strength of the response inhibition process.     

AMYLASE IN THYROID TISSUES FROM NORMAL AND VARIOUS THYROID DISEASES

Amylase activity was measured in thyroid tissues of various thyroid diseases and was analysed electrophoretically. Normal thyroid tissues contained significant amounts of amylase (mean ± SD; 2.71 ± 1.15 lU/g of tissue), and their amylase isozyme was composed of a majority of salivary type isoamylase and other peculiar isoamylase. The statistical decrease of amylase activities in tissues of Graves' disease under hyperthyroldism, thyroid carcinoma, and most of thyroid adenomas were found (Graves' disease; 1.04 ± 0.41, carcinoma; 1.49 ± 1.10, adenoma (except five cases with high activity); 0.88 ± 0.49 IU/g tissue). Five of 18 cases of adenoma showed strikingly higher amylase activity in their tissues. Electrophoretical patterns of amylase isoenzymes in these five adenoma tissue were different from those of normal thyroid tissues. The cellular localization of amylase in the normal thyroid tissues and the adenoma tissues was also demonstrated immunohlstochemically.     

Relationship between muscle fatigue and oxygen uptake during cycle ergometer exercise with different ramp slope increments

Summary The surface electromyogram (EMG) from active muscle and oxygen uptake ( ) were studied simultaneously to examine changes of motor unit (MU) activity during exercise tests with different ramp increments. Six male subjects performed four exhausting cycle exercises with different ramp slopes of 10, 20, 30 and 40 W · min^–1 on different days. The EMG signals taken from the vastus lateralis muscle were stored on a digital data recorder and converted to obtain the integrated EMG (iEMG). The was measured, with 20-s intervals, by the mixing chamber method. A non-linear increase in iEMG against work load was observed for each exercise in all subjects. The break point of the linear relationship of iEMG was determined by the crossing point of the two regression lines (iEMG_bp). Significant differences were obtained in the exercise intensities corresponding to maximal oxygen uptake ( ) and the iEMG_bp between 10 and 30, and 10 and 40 W · min –1 ramp exercises (P < 0.05). However, no significant differences were obtained in and corresponding to the iEMG_bp during the four ramp exercises. With respect to the relationship between and exercise intensity during the ramp increments, the -exercise intensity slope showed significant differences only for the upper half (i.e. above iEMG_bp). These results demonstrated that the and at which a nonlinear increase in iEMG was observed were not varied by the change of ramp slopes but by the exercise intensity corresponding to and the iEMG_bp was varied by the change of ramp slopes. In addition, the significant differences in the exercise intensity slopes for the upper half of the tests would suggest that the recruitment patterns of MU and/or muscle metabolic state might be considerably altered depending upon the ramp slope increments.     

Role of matrix metalloproteinases in failure to re-epithelialize after corneal injury.

Delayed re-epithelialization of the cornea after injury usually precedes stromal ulceration. Previous findings using a rat thermal injury model suggested that re-epithelialization is impeded by products of resident corneal cells, which destroy adhesive structures at the basement membrane zone. In this study, we provide additional evidence for this concept. Failure to re-epithelialize was found to correlate with an increase in the amounts of gelatinolytic matrix metalloproteinases present in the rat cornea. One of these gelatinases, gelatinase B, is synthesized by the resident corneal cells, and inhibitions of its synthesis correlated with inhibition of basement membrane dissolution. The matrix metalloproteinases collagenase and stromelysin are also synthesized by resident corneal cells in thermally injured corneas of rabbits, but the timing of bulk enzyme synthesis correlated more closely with deposition of repair tissue in the stroma than with failure to re-epithelialize. Nevertheless, in human corneas with repair defects, gelatinase B and collagenase are synthesized by cells in the basal layer of the epithelium directly adjacent to the basement membrane, suggesting that both could participate in dissolution of this structure. Importantly, treatment of thermally injured corneas with a synthetic inhibitor of matrix metalloproteinases significantly improved basement membrane integrity. These data support the concept that over-expression of matrix metalloproteinases by resident corneal cells impedes re-epithelialization after some types of corneal injury.     

Fine structure and mineral components of fibrous stonelike masses obtained from the human mesenteries

We investigated the fine structure and mineral components of 29 stonelike masses obtained from the mesenteries of four adult cadavers, using optical microscopy, backscattered electron imaging, scanning electron microscopy, energy-dispersive X-ray microanalysis, and X-ray diffraction. Although the overall appearance of the stonelike masses measuring about 5–20mm in diameter and 0.06–3.1g in dry weight was roughly grouped into smooth bulb- and uneven bulk-shaped types, all the calcified masses basically consisted of core and mantle regions. The smooth bulb-shaped masses had a broad mantle with many concentric rings, whereas the uneven bulk-shaped masses contained a large core. In their core regions, spherulitic and short bundle-shaped deposits composed of needle-shaped apatite crystals were mainly found among loose collagen fibers. Their mantle regions, on the other hand, showed the concentric structures of dense collagen fibers in the intra- and/or extrafibrous calcification with fine sandy grain-shaped deposits. The mineral elements were mainly Ca and P, and the major crystals were hydroxyapatite. Hexahedral whitlockite containing Mg was a minor component. The fiber-rich mantle regions showed lower calcification and lesser crystallization than the fiber-poor core region. When necrotic or some tumor adipose tissues and necrotic lymphoid tissues that might have been caused by some digestive diseases are recognized as foreign matter, their tissues occasionally will be calcified and grow into stonelike masses. These stonelike masses tend to occur more often in women than in men.     

An X-ray diffraction study of the cross-circulated canine heart.

1. The equatorial X-ray diffraction pattern was recorded from a papillary muscle of a cross-circulated canine heart at different phases of the cardiac cycle. The intensity ratio of the 1, 0 and the 1, 1 reflexions (I1, o/I1,1) was 0-79 in the systolic phase and 1-19 in the diastolic phase. 2. Using the intensity ratio obtained, the approximate proportion of the myosin projections present in the vicinity of the thin filaments was calculated. This was 70-71% in the systolic phase and 51-52% in the diastolic phase of the total myosin projections. 3. The peak systolic tension was roughly proportional to the proportion of the projections present in the vicinity of the thin filaments during systole. 4. The projections which stayed in the vicinity of the thin filaments during diastole did not produce significant contractile force.     

Lung carcinoma metastatic to microfollicular adenoma of the thyroid. A case report

A 75-year-old woman with lung adenocarcinoma in whom autopsy revealed metastasis to microfollicular adenoma of the thyroid is described. A thyroid tumor specimen from this patient was initially interpreted as representing primary encapsulated follicular carcinoma of the thyroid associated with a component of poorly differentiated carcinoma of follicular cell origin. The widespread involvement of the lungs and other sites was also interpreted as metastases from the poorly differentiated carcinoma component within the encapsulated follicular carcinoma of the thyroid. Subsequent meticulous histologic examination revealed that the thyroid tumor was a microfollicular adenoma, and that the component of poorly differentiated carcinoma within it was the same as the lung carcinoma. Immunohistochemical investigation revealed that the poorly differentiated carcinoma cells within the thyroid tumor were stained positively with polyclonal and monoclonal antibodies against carcinoembryonic antigen (CEA) and negative for thyroglobulin and calcitonin. The carcinoma cells from the lungs and other sites also showed positive staining for CEA. These findings support the view that the component of poorly differentiated carcinoma was a metastatic lesion from the primary lung carcinoma to the microfollicular adenoma of the thyroid. The present study emphasizes that attention should be directed to thyroid metastasis, even if it is within a thyroid primary neoplasm.