Determination of a cleavage site of presenilin 2 protein in stably transfected SH-SY5Y human neuroblastoma cell lines

Mutations in the presenilin 1 (PS1) and presenilin 2 (PS2) genes are associated with early-onset autosomal dominant familial Alzheimer's disease, and the gene products are endoproteolytically processed to yield N-terminal fragments (NTF) and C-terminal fragments (CTF). We have studied the cleavage site of the PS2 protein in stably transfected human neuroblastoma cells. The 23 kD PS2-CTF was isolated by a combination of anion exchange chromatography and affinity chromatography and directly sequenced. The N-terminus of the PS2-CTF started at residue 307, which indicated that the cleavage occurs between Lys306 and Leu307 in the proximal portion of the large hydrophilic loop. This site is close to the cleavage positions observed in the PS1 protein.     

Abnormal development and differentiation of macrophages and dendritic cells in viable motheaten mutant mice deficient in haematopoietic cell phosphatase

In mice homozygous for the 'viable motheaten' (mev) mutation, numbers of macrophage progenitor cells, particularly monocytes, were markedly increased in the bone marrow and spleen. Increased mobilization of these precursor cells to peripheral tissues and their differentiation to macrophages were evidenced by striking increases in macrophage numbers. Immunohistochemical double staining of tissue sections and flow cytometry analyses of single cell suspensions from these mice demonstrated CD5 (Ly-1)-positive macrophages in the peritoneal cavity, spleen and other tissues. Ly-1-positive macrophage precursor cells were demonstrated in the peritoneal cavity of the mev mice and developed in the omental milky spots. The development of marginal metallophilic and marginal zone macrophages was poor in the splenic white pulp and related macrophage populations were absent in the other lymphoid tissues. The numbers of epidermal Langerhans cells in the skin and T cell-associated dendritic cells in the thymic medulla, lymph nodes, and the other peripheral lymphoid tissues were decreased. However, increased numbers of dendritic cells accumulated in the lungs, liver, and kidneys. These abnormalities in development and differentiation of macrophages and dendritic cells may be ascribed to the deficiency in haematopoietic cell SHP-1 tyrosine phosphatase or may be a secondary consequence of abnormal microenvironments, (either constitutive or in response to inflammatory stimuli) in the haematopoietic and lymphopoietic organs and tissues of these mice.     

Assessment of Swallowing Ability Scale for oral and oropharyngeal cancer patients

The Swallowing Ability Scale (SAS) has been recently reported by us. This scale is a new method to assess dysphagia after therapy for oral and oropharyngeal cancer. The preliminary results on 23 patients showed that the scale was reliable and sensitive to functional differences across a broad spectrum of oropharyngeal dysphagia after therapy. This paper confirmed the above facts in 73 oral and oropharyngeal cancer patients who were treated in two hospitals between 1995 and 1996. As stated in the previous paper, SAS consists of a 2-step questionnaire: the MTF score and the Dysphagia score. The MTF score is a simple and practical assessment tool consisting of three subscales: 1) Method of intake, 2) Time of intake, and 3) Food. The Dysphagia score is a relevant assessment tool for defining patients' anatomic or physiologic swallowing disorders. In 40 patients with wide resection of the tongue, the Dysphagia score (p < 0.05) and the MTF score (p < 0.01) were significantly decreased. And we found a correlation between the MTF score and the Dysphagia score (r = 0.78, p < 0.001) in 73 patients. The usefulness of the SAS will be further studied for the assessment of rehabilitation to improve postoperative dysphagia.     

Lack of carcinogenicity of medium-viscosity liquid paraffin given in the diet to F344 rats

The carcinogenicity of medium-viscosity liquid paraffin was examined in Fischer 344 rats. Groups of 50 males and 50 females were given the material at dietary doses of 0 (control), 2.5 or 5% for 104 wk. Slight increases in food consumption and body weight were observed in both sexes of the 5% group. However, no significant differences between the control and treated groups were noted with regard to clinical signs, mortality and haematology findings. A variety of tumours developed in all groups, including the control group, but all the neoplastic lesions were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any tumour type was found for either sex in the treated groups. Granulomatous inflammation in the mesenteric lymph nodes, considered to be a reaction to paraffin absorption, was observed with similar incidence and severity in both sexes of the 2.5 and 5% groups. Thus, it is concluded that under the present experimental conditions, the high dose, about 2000-200,000 times higher than the current temporary acceptable daily intake, does not have any carcinogenic potential in F344 rats. Furthermore, granulomatous inflammation observed in mesenteric lymph nodes were not associated with any development of neoplastic lesions.     

Rearrangements of the BCL6 gene and chromosome aberrations affecting 3q27 in 54 patients with non-Hodgkin's lymphoma

Chromosome aberrations affecting 3q27 are among the most frequent non-random abnormalities in non-Hodgkin's lymphomas (NHL), especially the diffuse, large cell type. Recently, an association between BCL6 rearrangement and frequent extranodal lesions, rare bone marrow infiltration and a favorable clinical outcome was reported. We performed molecular studies of the BCL6 gene in 54 patients with NHL. Twelve patients (22%) with rearranged BCL6 genes were selected for histological, clinical, molecular, and cytogenetic studies. Ten of these cases were diffuse, large cell type lymphoma, one a follicular lymphoma, and one a mantle cell lymphoma (MCL). All cases were of the B-cell type and this is the first time a rearranged BCL6 gene has been found in an MCL. Cytogenetic data for 10 cases were available and the partner sites of the 3q27 translocation were determined in 7 of 10 patients. These locations were variable, including 6p21.3, 9p22, and 14q11 in addition to the immunoglobulin loci 14q32 (IGH), 2p12 (IGK), and 22q11 (IGL). The heterogeneity in partner sites is distinct from other lymphoma subgroups and may suggest that the genetic events are not uniform among patients with BCL6 rearrangements.     

Eye-tracking device comparisons of three methods of magnetic resonance image series displays

This study evaluated the effectiveness of three kinds of display methods for magnetic resonance (MR) image interpretation using an eye-tracking device. Seven radiologists interpreted head MR studies by using a single monitor (17-inch, 1,024 X 1,280 bit) in the 4 images/screen display format. Three paging modes were compared: (A) rapid paging only, (B) multiple image series display at the same slice position with consecutive rapid paging, and (C) simultaneous display of multiple series with each image series being browsed independently. Using an eye-mark camera, the radiologist's point of fixation and the duration of fixation were recorded during actual image interpretation. In mode A, the duration of fixation was short, and the points of fixation were distributed randomly over the visual field. In mode B, the points of fixation were clustered chiefly on a specific image series. In mode C, the points of fixation were not clustered on a specified series, but the duration of viewing the T2 series was relatively long. The total tracing area in mode B and C was smaller than that in mode A. Multiple series display, in which selected key series of slices could be viewed effectively, was found to be suitable for MR image interpretation.     

Expression and localization of angiotensin II type 1 receptor mRNA in rat ocular tissues

OBJECTIVE: Hereditary hemorrhagic telangiectasia (HHT) is an inherited abnormality passed down as a dominant autosomal feature. Recurrent epistaxis usually constitutes the major clinical manifestation of this disease. The unsatisfactory results of conservative therapy have stimulated a research interest for the role of laser photocoagulation in telangiectatic vessels associated with this clinical entity. METHOD: The Nd:YAG laser was used to treat a group of 11 individuals suffering from HHT, all of whom had been previously treated using other modalities. RESULTS AND CONCLUSION: The excellent results of Nd:YAG laser irradiation are addressed in view of all treatment modalities proposed for the treatment of recurrent epistaxis in HHT.     

Analysis of amyloid deposition in a transgenic mouse model of homozygous familial amyloidotic polyneuropathy

Amyloid fibrils derived from the Japanese, Portuguese, and Swedish types of familial amyloidotic polyneuropathy all consist of a variant transthyretin (TTR) with a substitution of methionine for valine at position 30 (TTR Met 30). In an attempt to establish an animal model of TTR Met-30-associated homozygous familial amyloidotic polyneuropathy and to study the structural and functional properties of human TTR Met 30, we generated a mouse line carrying a null mutation at the endogenous ttr locus (ttr-/-) and the human mutant ttr gene (6.0-hMet 30) as a transgene. In these mice, human TTR Met-30-derived amyloid deposits were first observed in the esophagus and stomach when the mice were 11 months of age. With advancing age, amyloid deposits extended to various other tissues. Because no significant difference was detected in the onset, progression, and tissue distribution of amyloid deposition between the ttr-/- and ttr+/+ transgenic mice expressing 6.0-hMet 30, endogenous normal mouse TTR probably does not affect the deposition of human TTR Met-30-derived amyloid in mice. TTR is a tetramer composed of four identical subunits that binds thyroxine (T4) and plasma retinol-binding protein. The introduction of 6.0-hMet 30 into the ttr-/- mice significantly increased their depressed serum levels of T4 and retinol-binding protein, suggesting that human TTR Met 30 binds T4 and retinol-binding protein in vivo. The T4-binding ability of human TTR Met 30 was confirmed by the analysis of T4-binding proteins in the sera of ttr-/- transgenic mice expressing 6.0-hMet 30. The T4-binding studies also demonstrated the presence of hybrid tetramers between mouse and human TTR subunits in the ttr+/+ transgenic mice expressing 6.0-hMet 30.