Flat adenoma and flat mucosal carcinoma (IIb type)— A new precursor of colorectal carcinoma?

Two flat adenomas and a flat mucosal carcinoma of the colon were reported in patients with synchronous and metachronous colonic carcinomas. These lesions were almost flat and were not detected by preoperative endoscopic examinations. Colonoscopists should be aware of the presence of flat adenomas, which can be easily missed, and recognize them as lesions that play an important role in the "adenoma-carcinoma sequence."     

Progressive cerebellar ataxia with diencephalic symptoms (Toyokura)--a case report]

We reported a 16-year-old boy suffering from dwarfism, diabetes insipidus and progressive cerebellar ataxia. The disease entity here reported was originally reported by Toyokura et al. in 1967, under the title of "progressive cerebellar ataxia with diencephalic symptoms". Ten similar cases have been reported in literature so far, all of which were Japanese except for two sibling cases reported by Robinson et al. The topographic distribution of the lesion in this disorder, however, had been conjectured to be at spinocerebellar tract and diencephalon only on a clinical ground. By applying the modern techniques of neuroimaging, electrophysiological and endocrinological test in our patient, the authors were able to demonstrate the lesion of the disorder more precisely. CT and MRI of the head revealed degenerative changes in deeper structures of the bilateral cerebellar hemispheres. ABR abnormality suggested the presence of a wide lesion in the brain stem. Pituitary hormones (GH and ACTH) sufficiently responded to the loading of hypothalamic hormones such as growth hormone releasing factor and corticotropin releasing factor, in spite of poor responses of GH under the insulin stimulation or sleep. These clinical and laboratory findings suggested that the patient has a systemic degenerative disease which preferentially involves hypothalamus, brain stem and cerebellum.     

SOLITARY GASTRIC POLYPS IN THE FUNDIC GLAND AREA A Histochemical Study

Six solitary gastric polyps in the acid-secreting fundic mucosa were histo-chemically investigated using the mucin histochemistry, immunoperoxidase method, and silver methods for endocrine cells. Histologically, the polyps were grouped into three types : they largely consisted of either hyperplastic foveolar cells (group 1), normal-appearing fundic gland cells with mild cystic changes (group 2) or hyperplastic fundic gland cells with cystic dilatation (group 3). The presence of parietal cells and mucous neck cells was confirmed in all polyps by the immunoperoxidase method using parietal cell autoantibody and the paradoxical Concanavalin A staining, respectively. Regarding the endocrine component, somatostatin-containing cells, Grimelius-positive argyrophil cells, and Fontana-Masson-positive enterochromaffin cells were scattered in the fundic gland area of the polyps as well as in the surrounding normal-appearing fundic mucosa. Gastrin-containing cells were absent. In one of the group 2 polyps and both group 3 polyps, a varying number of glicentin-containing cells were found among the fundic gland components : In one polyp in group 3, glucagon immunoreactivity was detected in the glicentin-containing cells. These findings suggest that some of the polyps express characteristics of the fetal fundic mucosa, since glicentin and glucagon immunoreactivities in normal human stomach have been detected exclusively in the fetal fundus. ACTA PATHOL. JPN. 35: 831–840, 1985.     

Presence of natural killer-cell clones with variable proliferative capacity in chronic active Epstein-Barr virus infection

Chronic active Epstein-Barr virus infection (CAEBV) is a syndrome that takes diverse clinical courses and is often associated with lymphoproliferative disorders of T/natural killer (NK)-cell lineage. We describe a patient with CAEBV associated with persistent pharyngeal ulcer, and with subsequent nasal T/NK-cell lymphoma in her neck lymph nodes and nasopharynx. Immunophenotyping of lymphoid cells showed that the lineage of Epstein-Barr virus (EBV)-positive cells in the patient was of NK-cell origin. By means of high-dose recombinant interleukin-2, we established an EBV-positive cell line of NK-cell lineage from her peripheral blood. Southern blot analysis for the number of terminal repeat sequences of EBV detected three NK-cell clones in the patient's lymph node. One of these clones was identical to the established cell line but was not observed in the pharyngeal ulcer, while the other two clones were present in the pharyngeal ulcer. These results suggest that the patient had expansion of the three NK-cell clones, one of which had proliferative capacity in vitro and was involved in the formation of the lymphoma. Moreover, the results suggest that the proliferative capacity of EBV-positive cells can be variable even in a single patient, and this variability may explain the clinical diversity in CAEBV.     

Reduced-intensity unrelated cord blood transplantation for patients with advanced malignant lymphoma.

We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.     

Gaps and fragmentation of the superficial cortex in the abdominal and pelvic lymph nodes of elderly Japanese

Gaps and fragmentation of the superficial lymph node cortex are considered to provide intranodal shunt flow between the afferent and efferent vessels. Using serial sections of 205 nodes obtained from 27 donated cadavers more than 70 years of age, we examined the histological architecture of the abdominal and pelvic nodes in elderly Japanese. Secondary follicles were rare in the specimens. Cortex gaps were, to a greater or lesser degree, found in all nodes. We classified these nodes into three types according to how often the gap occurred. Type 1 nodes, with a relatively complete shield for the afferent lymph, were most frequently found in gastric nodes, whereas type 3 nodes, with numerous gaps, were often observed in the colic, para-aortic and pelvic nodes. The type 3 nodes showed a specific architecture characterized by a fragmented superficial cortex, three-dimensionally assembled cords and a common sinus between them. Primary follicles were located in the assembled cord structures as well as at the superficial cortex. Irrespective of the type, B and T lymphocyte areas were intermingled in the cortex-like areas. The present results reveal region-specific histological heterogeneity in aged human visceral nodes. Due to increased surface areas, the type 3 architecture seemed to accelerate systemic immunity rather than act as a local barrier in the para-aortic and pelvic nodes, which are located centrally along the lymphatic drainage routes. However, thick trabeculae often seemed to develop in the type 3 sinus to decrease nodal function with aging.     

Effect of Enamel Prism Decussation and Chemical Composition on the Biomechanical Behavior of Dental Tissue: A Theoretical Approach to Determine the Loading Conditions to Which Modern Human Teeth are Adapted

This theoretical study explored whether the directions of loads to which modern human molars are commonly subjected to are reflected in the biomechanical behavior of the tissue itself. A detailed finite element model of a piece of decussating enamel (M³ paracone) was created, taking into account differences in crystal orientation between the prism head and the interprismatic matrix, and was tested under differently angled mediolateral loads (i.e., mimicking various stages of the chewing cycle). Second, although teeth are highly mineralized, they also contain organic material and water, while in modern humans, there are systematic differences in chemical composition from the outer enamel surface to the dentinoenamel junction. To test the biomechanical effects of this gradient in mineralization a second set of models with gradually changing properties was created and subjected to the same loads. Chemically heterogeneous enamel yielded overall lower stress levels than homogenous enamel, especially at extreme loading angles. However, the general trends regarding the increase in tensile stresses at more oblique angles, and the number of nodes exhibiting tension, were comparable between the different set‐ups. The findings support suggestions that (a) the biomechanical behavior of dental tissue is the combined result of micromorphology and chemical composition and (b) that the range of loading directions, to which teeth are normally subjected to, can be inferred from dental microanatomy. For (palaeo)biological applications, the findings suggest that the absolute strength of teeth (e.g., bite force) cannot be predicted with certainty, whereas kinematic parameters of the masticatory apparatus can. Anat Rec, 2007. © 2008 Wiley‐Liss, Inc.     

Biological activities of Bacteroides forsythus lipoproteins and their possible pathological roles in periodontal disease

Bacteroides forsythus is a gram-negative, anaerobic, fusiform bacterium and is considered to be an etiological agent in periodontal disease. A lipoprotein fraction prepared from B. forsythus cells by Triton X-114 phase separation (BfLP) activated human gingival fibroblasts and a human monocytic cell line, THP-1, to induce interleukin-6 production and tumor necrosis factor alpha production. BfLP was found to be capable of inducing nuclear factor-kappaB translocation in human gingival fibroblasts and THP-1 cells. By using Chinese hamster ovary K1 cells transfected with Toll-like receptor genes together with a nuclear factor-kappaB-dependent CD25 reporter plasmid, it was found that signaling by BfLP was mediated by Toll-like receptor 2 but not by CD14 or Toll-like receptor 4. BfLP induced apoptotic cell death in human gingival fibroblasts, KB cells (an oral epithelial cell line), HL-60 cells (a human myeloid leukemia cell line), and THP-1 cells but not in MOLT4 cells (a T-cell leukemia cell line). Caspase-8, an initiator caspase in apoptosis, was found to be activated in these cells in response to BfLP stimulation. Thus, this study suggested that BfLP plays some etiological roles in oral infections, especially periodontal disease, by induction of cell activation or apoptosis.     

Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo

Notch receptors and their ligands contribute to many developmental systems, but it is not apparent how they function after birth, as their null mutants develop severe defects during embryogenesis. Here we used the Cre-loxP system to delete the Delta-like 1 gene (Dll1) after birth and demonstrated the complete disappearance of splenic marginal zone B cells in Dll1-null mice. In contrast, T cell development was unaffected. These results demonstrated that Dll1 was dispensable as a ligand for Notch1 at the branch point of T cell-B cell development but was essential for the generation of marginal zone B cells. Thus, Notch signaling is essential for lymphocyte development in vivo, but there is a redundancy of Notch-Notch ligand signaling that can drive T cell development within the thymus.     

Association of Actinobacillus actinomycetemcomitans leukotoxin with nucleic acids on the bacterial cell surface.

Actinobacillus actinomycetemcomitans, a periodontopathic gram-negative bacterium, produces a leukotoxin that is a member of the RTX cytotoxin family. Although genes may function in toxin secretion, the leukotoxin is not secreted extracellularly but remains associated with the bacterial cell surface. We report here that this toxin-cell surface association is mediated by nucleic acids and directly demonstrate that the extracellular secretion of toxin occurs in growing cultures with increased ionic strength of medium. All examinations were performed with freshly harvested A. actinomycetemcomitans 301-b from anaerobic fructose-limited chemostat cultures. The occurrence of cell surface-localized DNA was shown by directly digesting whole cells with the restriction endonuclease EcoRI or HindIII, which yielded many DNA fragments. The cell surface DNA constituted about 20% of the total cellular DNA. The leukotoxin was released from the whole cells by digestion with DNase I as well as restriction endonucleases. Because the leukotoxin binds ionically to DNA, it is dependent on the ionic strength of buffers or media. Accordingly, the toxin was released from cells suspended in saline at pH 7.5 in the presence of increasing amounts of MgCl2 (0 to 10 mM) or NaCl (0 to 50 mM). Moreover, a considerable quantity of leukotoxin was detected in the culture supernatant of fructose-limited chemostat cultures when sodium succinate solution was pumped into the steady state as an additional salt (30 and then 50 mM). This toxin-DNA association was also found in well-characterized strains including not only the leukotoxin-producing ATCC 29522 but also the toxin production-variable ATCC 29523 and the non-leukotoxin-producing ATCC 33384 when these strains were grown in the chemostat culture.