Developmental switch from GABA to glycine release in single central synaptic terminals

Early in postnatal development, inhibitory inputs to rat lateral superior olive (LSO) neurons change from releasing predominantly GABA to releasing predominantly glycine into the synapse. Here we show that spontaneous miniature inhibitory postsynaptic currents (mIPSCs) also change from GABAergic to glycinergic over the first two postnatal weeks. Many 'mixed' mIPSCs, resulting from co-release of glycine and GABA from the same vesicles, are seen during this transition. Immunohistochemistry showed that a large number of terminals contained both GABA and glycine at postnatal day 8 (P8). By P14, both the content of GABA in these mixed terminals and the contribution of GABA to the mixed mIPSCs had decreased. The content of glycine in terminals increased over the same period. Our results indicate that switching from GABAergic to glycinergic inputs to the LSO may occur at the level of a single presynaptic terminal. This demonstrates a new form of developmental plasticity at the level of a single central synapse.     

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).     

Comparison of isolation of Haemophilus vaginalis (Corynebacterium vaginale) from peptone-starch-dextrose agar and Columbia colistin-nalidoxic acid agar.

A total of 447 cervical or vaginal specimens were inoculated in parallel onto peptone-starch-dextrose (PSD) and Columbia colistin (10 mg/ml)-nalidixic acid (15 mug/ml) (CNA) agar and were incubated for 48 h at 35 degrees C in an atmosphere with 2 to 10% CO2. One hundred (22.4%) of the cultures were positive for Haemophilus vaginalis. Forty-eight of the isolates were recovered from both PSD and Columbia CNA agar, five from PSD only, and 47 from Columbia CNA agar only (P less than 0.001). On Columbia CNA agar, 76 of the isolates were detected after 24 h of incubation, and the remainder were detected within 4 days of incubation.     

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.     

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.     

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.     

Wegener's granulomatosis. Associated with diffuse pulmonary hemorrhage.

The authors report a case of Wegener's granulomatosis with the unusual manifestation of diffuse pulmonary hemorrhage. A 58-year-old man complained of bloody sputum and fever. Chest X-ray films showed multiple nodular shadows in both lung fields. He was diagnosed as having Wegener's granulomatosis by transbronchial lung biopsy, which revealed necrotizing granulomatous inflammation with necrotizing vasculitis. Despite treatment with cyclophosphamide and prednisolone, his condition rapidly deteriorated. An extensive diffuse alveolar shadow appeared in both lung fields in chest X-ray films, anemia became worse, and he died of respiratory failure. Autopsy revealed diffuse alveolar hemorrhage with necrotizing capillaritis in addition to the typical pathological findings in Wegener's granulomatosis. The capillaritis was characterized by neutrophilic infiltration of alveolar septa, and fibrin thrombi in alveolar capillaries. Diffuse pulmonary hemorrhage is uncommon in Wegener's granulomatosis. However, once diffuse pulmonary hemorrhage occurs, the respiratory condition rapidly deteriorates and is life-threatening. Therefore, accurate diagnosis and appropriate treatment are required.