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).     

Clonal expansion of multiphenotypic Epstein-Barr virus-infected lymphocytes in chronic active Epstein-Barr virus infection

Chronic active Epstein-Barr virus (EBV) infection has been recognized as clonal non-neoplastic lymphoproliferative diseases. However, some reports of cases with a multiphenotypic expansion of EBV-infected lymphocytes give rise to questions of how EBV infects multiphenotypic lymphocytes and whether chronic active EBV infection is a truly monoclonal lymphoproliferative disease. We report two patients with chronic active EBV infection who showed expansion of multiphenotypic EBV-infected lymphocytes. EBV DNA was detected in CD4+ and CD8+ T cells and in B cells from pleural fluid of one patient and in T and B cells from a cervical lymph node of the other patient by polymerase chain reaction (PCR). Although real-time PCR showed that there were equally high loads of EBV genomes in CD4+ and CD8+ T cells from the pleural fluid, Southern blot hybridization with terminal repeats of the EBV genome showed a single band of the same molecular weight in three tissue samples from the patient. The results indicated biphenotypic expansions of CD4+ and CD8+ T cells infected with the same clone of EBV. Furthermore, bisulfite PCR analysis showed hypermethylated status in the Cp region in the two patients regardless of their cell populations. There has been a discrepancy between clonality and expansion of multiphenotypic EBV-infected lymphocytes. We speculate that lymphoid progenitor cells that have not differentiated into T and B cell progenitors are infected with EBV, resulting in clonal expansion of EBV-infected multiphenotypic cells.     

Changes in T,B, and NK Lymphocyte Subsets During and After Normal Pregnancy

PROBLEM: Pregnancy affects the maternal immune system and the clinical course of maternal diseases. Here we report the changes in the detailed lymphocyte subsets of helper T cells, suppressor T cells, CD5⁺ B cells, T cell receptor (TCR) αβ-positive T cells (Tαβ cells), TCRαβ-negative T cell (Tγδ cells), and others during and after pregnancy through to one year postpartum, and discuss the significance of the changes. METHOD: The absolute numbers of helper T cells, suppressor T cells, cytotoxic T cells, TCRαβ-negative T cells (Tγδ cells), CD5^— B cells, CD5⁺ B cells, and NK cell subsets were examined by two-color flow cytometry in peripheral blood from 51 healthy non-pregnant women, 106 healthy pregnant women, and 148 healthy postpartum women. RESULTS: In early pregnancy, the numbers of suppressor T cells and NK cells with strong cytotoxicity (NK⁺⁺⁺ cells) increased, and the number of cytotoxic T cells decreased. In late pregnancy, the helper T cell and NK⁺⁺⁺ cell numbers decreased. Tαβ, CD5^— B and CD5⁺ B cells decreased during pregnancy. After delivery, helper T cells and cytotoxic T cells increased from 1 to 4 months postpartum, and suppressor T cells increased at 7 months postpartum. TCRαβ-negative T cells increased at 4 to 10 months postpartum. Both CD5^— and CD5⁺ B cells decreased further at 1 month postpartum, but CD5⁺ B cells increased markedly at 7 to 10 months postpartum. CONCLUSIONS: These data indicate that 1) early increases of suppressor T cells and NK⁺⁺⁺ cells during pregnancy may be related to the mechanism to accept or reject the fetus in early pregnancy, respectively; 2) late decreases of helper T cells and NK⁺⁺⁺ cells may be related to the maintenance of pregnancy: 3) postpartum increases of helper T cells, cytotoxic T cells, TCRαβ-negative T cells (Tγδ cells), and CD5⁺ B cells may be related to the postpartum aggravation of autoimmune diseases; and 4) the immunological effects of pregnancy remains until about 1 year after delivery.     

PCR analysis of the Y chromosome long arm in azoospermic patients: evidence for a second locus required for spermatogenesis

We analyzed DNA from 63 Japanese men with either azoospermiaor severe oligospermia whose Y chromosomes were cytogeneticallynormal. A total of 16 loci were examined: 15 loci on the longarm between DYS7E and DYZ1, and the YRRM1 locus, a candidategene for the azoospermic factor, AZF. One patient with a perlcentricinversion of the Y chromosome was also included. We detectedmicro-deletions in ten individuals. The YRRM1 gene was Involvedin only three of them. The remaining seven patients showed deletionbetween DYS7C and DYS239 in common, indicating the presenceof at least one additional gene, deletion of which causes azoospermia.     

Long term experiment of perfluorochemicals using rabbits

Summary Morphological changes six months to two years after the administration of Perfluorochemicals (PFC) in rabbits injected with a large amount of PFC (67 mg/kg) have already been reported by Ohnishi and Kitazawa (1979, 1980, and 1981). In this paper, the authors report on the persistance of large numbers of foamy cells in the liver, spleen and lymph nodes and many in the kidneys, lung and bone marrow, up to two years after administration. Quantitative analysis of PFC in various organs showed that it was retained. The liver revealed progressive fibrosis surrounding the foamy cells in or around the Glisson's sheath.     

Preparation and physicochemical properties of compression-molded keratin films

The S-sulfo keratin was extracted from wool and was then spray-dried to give S-sulfo keratin powder. Differential scanning calorimetry analysis showed that the glass transition temperature of S-sulfo keratins became lowered with the increase of moisture content, while perfectly dried S-sulfo keratin powder did not give thermal transition in the temperature range 30-130 degrees C. The compression molding of the S-sulfo keratin powder supplemented with one-tenth weight of water afforded a plastic-like transparent proteinous film above the glass transition temperature. The film obtained from the powder without water addition or compression molded below glass transition temperature partly remained powdery. The film compression molded at 120 degrees C gave the maximum ultimate strength and Young's modulus, 27.8 +/- 2.9 and 1218 +/- 80 MPa, respectively. Obtained film was insoluble and slightly swelled in water, but, in the presence of reducing agent, the film significantly swelled at pH 7.0 and even dissolved at pH 9.0, suggesting the relevance of abundant disulfide linkage. The film supported the mammalian cell adhesion and proliferation, demonstrating the biocompatibility of S-sulfo keratin films.     

Preemptive analgesia by zaltoprofen that inhibits bradykinin action and cyclooxygenase in a post-operative pain model

The post-operative pain state results from a barrage of primary afferent inputs exposed to products of tissue damage such as bradykinin and prostaglandins and the central sensitization by the continuing inputs. This provides the rationale for preemptive analgesia, whereby the blockade of primary afferent inputs prior to injury may result in a reduction of post-operative pain. 2-(10,11-dihydro-10-oxo-dibenzo[b,f]thiepin-2-yl) propionic acid (zaltoprofen) is a unique compound that inhibits cyclooxygenase (COX) and exhibits anti-bradykinin activity. The present study evaluated the preemptive analgesic effect of zaltoprofen in a post-operative pain model produced by plantar incision. When orally, but no intrathecally, administered 30 min prior to incision, zaltoprofen significantly increased the withdrawal threshold 2 h and 1-3 days after incision at 10 mg/kg. While the bradykinin B1 antagonist des-Arg10-HOE-140, the selective COX-1 inhibitor SC-560, and the selective COX-2 inhibitor celecoxib did not affect post-operative pain, the B2 antagonist HOE-140 dose-dependently relieved the post-operative pain at 2-200 microg/kg with a time course similar to that of zaltoprofen. The B2 receptor mRNA was expressed in the hindpaw and the expression did not change before and 24 h after surgery. These results suggest that zaltoprofen produces the preemptive analgesic effect peripherally by blocking the B2 pathway.     

Studies on formaldehyde resins, 19. General base catalysis in hydroxymethylation of melamine with formaldehyde

Hydroxymethylation of melamine with formaldehyde to form N-(hydroxymethyl)melamine (2,4-diamino-6-hydroxymethylamino-1,3,5-triazine) was investigated kinetically by the use of hydrogen phosphate/phosphate buffers in aqueous media at pH 11 ? 12. This reaction was found to follow a general base catalysis which results from the kinetic investigation, showing that the reaction takes place by a concerted mechanism involving base, melamine, and formaldehyde. This mechanism differs from that of the base catalyzed hydroxymethylation of phenol or benzamide with formaldehyde, because the acidic phenol and benzamide easily form their conjugate bases by addition of the basic catalyst in a preceding equilibrium step.     

Syntheses of polymeric cobalt dinitrogen complexes and reduction of the coordinated nitrogen

Polymeric cobalt dinitrogen complexes were synthesized by two different methods: by the ligand substitution reaction of polymers 5a – c and 6a – c , containing 4-diphenylphosphinophenylethylene units ( 3 ) or 4-diphenylphosphinomethylphenylethylene units ( 4 ), respectively, with hydridodinitrogentris(triphenylphosphine)cobalt(I) (CoH(N₂)(PPh₃)₃), or by the direct reaction of tris(acetylacetonato)cobalt(III) with triphenylphosphine, the polymers 5a – c or 6a – c , and triisobutylaluminium under nitrogen. The intensity of the v band in the IR spectrum of the polymeric dinitrogen complex was found to be about four times as that of CoH(N₂)(PPh₃)₃. Ammonia was formed after hydrolysis of the complex, which was prepared by mixing a tetrahydrofuran solution of naphthaline, lithium, and titanium tetrachloride with the polymeric dinitrogen complex. The yields of ammonia in the case of the polymeric complexes were high in comparison with that obtained with CoH(N₂)(PPh₃)₃. The highest yields of ammonia were obtained when a mole ratio [P?]/[Co] < 1 ([P?] is the concentration of phosphino groups in the polymer and [Co] is that of Co in CoH(N₂)(PPh₃)₃), a temperature of ?20°C, and a reaction time of 1 h were applied.