Scanning electron microscopy of the three different types of cementum in the molar teeth of the guinea pig

The aim of this study was to observe the three-dimensional distribution and structural characteristics of the three different types of cementum in the molar teeth of guinea pig by means of scanning electron microscopy. Twenty-five 4-week-old male guinea pigs were used in this study. Using decalcified and undecalcified specimens with or without NaOH maceration, we examined the mandibles, maxillae and extracted molars by scanning electron microscopy. Guinea pig molars consist of two longitudinal, deeply folded lamina cores covered by enamel on all surfaces, except the buccal surface of the upper molars and the lingual surface of the lower molars. In the regions without enamel, we observed continuous thin belt-like layers of conventional acellular cementum on the dentin surface. On the enamel-covered surfaces, two different types of coronal cementum were found: small circular islands of coronal cementum called cementum pearls, which were distributed widely at almost regular intervals on the peripheral enamel surface from the apical fifth to the occlusal surface; and cartilage-like cementum, which occupied almost all of the occlusal half of the two longitudinally folded grooves. The present study demonstrated the unique distribution pattern of the three different types of cementum in guinea pig molars. These cementum types may contribute to the requirements for many different functions such as mastication, anchorage and continuous tooth eruption.     

Active c-jun N-terminal kinase induces caspase cleavage of tau and additional phosphorylation by GSK-3beta is required for tau aggregation

Neurofibrillary tangles (NFTs), comprising human intracellular microtubule-associated protein tau, are one of the hallmarks of tauopathies, including Alzheimer's disease. Recently, a report that caspase-cleaved tau is present in NFTs has led to the hypothesis that the mechanisms underlying NFT formation may involve the apoptosis cascade. Here, we show that adenoviral infection of tau into COS-7 cells induces activation of c-jun N-terminal kinase (JNK), followed by excessive phosphorylation of tau and its cleavage by caspase. However, JNK activation alone was insufficient to induce sodium dodecyl sulfate (SDS)-insoluble tau aggregation and additional phosphorylation by GSK-3β was required. In SH-SY5Y neuroblastoma cells, overexpression of active JNK and GSK-3β increased caspase-3 activation and cytotoxicity more than overexpression of tau alone. Taken together, these results indicate that, although JNK activation may be a primary inducing factor, further phosphorylation of tau is required for neuronal death and NFT formation in neurodegenerative diseases, including those characterized by tauopathy.     

Molecular chaperone-mediated tau protein metabolism counteracts the formation of granular tau oligomers in human brain

Intracellular accumulation of filamentous tau proteins is a defining feature of neurodegenerative diseases termed tauopathies. The pathogenesis of tauopathies remains largely unknown. Molecular chaperones such as heat shock proteins (HSPs), however, have been implicated in tauopathies as well as in other neurodegenerative diseases characterized by the accumulation of insoluble protein aggregates. To search for in vivo evidence of chaperone-related tau protein metabolism, we analyzed human brains with varying degrees of neurofibrillary tangle (NFT) pathology, as defined by Braak NFT staging. Quantitative analysis of soluble protein levels revealed significant positive correlations between tau and Hsp90, Hsp40, Hsp27, alpha-crystallin, and CHIP. An inverse correlation was observed between the levels of HSPs in each specimen and the levels of granular tau oligomers, the latter of which were isolated from brain as intermediates of tau filaments. We speculate that HSPs function as regulators of soluble tau protein levels, and, once the capacity of this chaperone system is saturated, granular tau oligomers form virtually unabated. This is expressed pathologically as an early sign of NFT formation. The molecular basis of chaperone-mediated protection against neurodegeneration might lead to the development of therapeutics for tauopathies. (c) 2007 Wiley-Liss, Inc.     

Assembly of two distinct dimers and higher-order oligomers from full-length tau

Abnormal accumulation of tau as filamentous structures is a neuropathological hallmark of neurodegenerative diseases referred to as tauopathies. Little is known about the role of native cysteine residues in tau assembly because their substitution with other amino acids has no effect on tau filament morphology. To understand the process involved in tau oligomerization, we analysed both heparin-induced assembly of different forms of recombinant human tau and assembly of tau from COS-7 cells transiently expressing different human tau constructs. Here, we demonstrated that tau assembly involves two distinct dimers (cysteine-dependent and cysteine-independent) that differ in resistance to reduction. During assembly, an increase of cysteine-dependent tau oligomer was observed prior to detection of increased thioflavin T fluorescence signals. The latter event was accompanied by an increase of cysteine-independent dimer. Fewer higher-order oligomers and aggregates were assembled from four-repeat tau containing two amino-terminus inserts that have either the C291A/C322A mutation (cysless-4R2N) or a hexapeptide deletion at residues 306-311 (DeltaPHF6-4R2N) compared with those assembled from wild-type tau. Assembly of distinct types of dimers was also observed in lysates from COS-7 cells expressing wild-type 4R2N and brain extracts from mice expressing P301L mutant tau. In contrast, COS-7 cells expressing cysless- or DeltaPHF6-4R2N tau contained very little cysteine-dependent dimer. Together, the results indicate that intermolecular disulfide crosslinking along with PHF6 hexapeptide facilitates tau oligomerization and that this event is accompanied by cysteine-independent intermolecular bridging of microtubule-binding domain, leading to assembly of higher-order oligomers. The levels of these dimers may be used to gauge the potential for tau assembly.     

Triple-phase computed tomography during arterial portography with bolus tracking for hepatic tumors

Purpose  

The purpose of this study was to assess the usefulness of triple-phase computed tomography during arterial portography (CTAP) using a bolus-tracking technique.     

Cor triatriatum sinister disclosed after diagnosis of acute myocardial infarction

We present a case of cor triatriatum sinister diagnosed occasionally after acute anterior myocardial infarction. For management of the acute myocardial infarction (AMI), urgent reperfusion therapy was successfully performed through the left anterior descending coronary artery. Thereafter, no complication associated with AMI occurred. Cor triatriatum sinister was diagnosed and assessed later by means of several modalities. Finally, medical observation was indicated for this patient. This case illustrates the importance of awareness of this congenital disease in an adult when echocardiography shows an abnormal linear echo in the mid portion of the left atrium.     

Anti-tumor effect of chemically synthesized sulfolipids based on sea urchin's natural sulfonoquinovosylmonoacylglycerols.

We recently reported that 3'-sulfonoquinovosyl-1'-monoacylglycerol (designated A-5) extracted from sea urchin intestine was effective in suppressing the growth of solid tumors. Although the major fatty acid component of A-5 was a saturated C(16) acid, there were five other fatty acids, 14:0, 18:0, 14:1, 16:1, and 18:1, which constitute minor components of A-5. Therefore, it remains unclear as to which of these six fatty acid components of A-5 has the anti-tumor effect. In this study, we synthesized sulfolipids each containing only one of these six fatty acids and tested their cytotoxicity against tumor cells and in vivo anti-tumor effects on nude-mice bearing solid tumors of human lung adenocarcinoma cell line A-549. The IC(50) values of all products against tumor cells were more than 10(-5) M, suggesting weak cytotoxic activity compared with other chemotherapeutic compounds for cancer. On the other hand, in vivo anti-tumor assay showed that sulfoquinovosylmonoacylglycerols (SQMG) composed of 14:1 and 18:1 (designated SQMG(14:1) and SQMG(18:1), respectively) were significantly effective in suppressing the growth of solid tumors. Our data suggested that these two SQMGs had a substantial anti-tumor effect in vivo, and they are of interest as candidate drugs for anti-cancer treatment.