Early development of four Diphyllobothrium species in the final host

The early development of four Diphyllobothrium species, D. latum, D. dendriticum, D. ditremum, and D. vogeli, are described. D. latum sheds the entire larval body easily and shows a high shedding rate of 82.1% on average. On the other hand, D. dendriticum exhibits a different developmental pattern, with a low shedding rate of 8.7% in the hamster and a high shedding rate of 34.9% in the rat. D. ditremum is difficult to recover from hamsters but shows a high shedding rate of 42.9%. D. vogeli shows a constant recovery rate of 38.3% without shedding. The species specificity of these four diphyllobothriids is discussed briefly in relation to the early developmental pattern and the growth rate.     

Malgun (clear) cell change in Helicobacter pylori gastritis reflects epithelial genomic damage and repair

Cancers may develop in the background of genomic instability with accumulated mutations. Helicobacter pylori gastritis is characterized by acute foveolitis of the proliferative zone, which is found in any stage of the gastritis as long as the infection persists. Because acute foveolitis targets specifically the proliferative zone of pits, the proliferating epithelial cells are under severe and persistent mutagenic pressure. In H. pylori gastritis, a characteristic morphological change of epithelial cells, the malgun (clear) cell change is frequently present in association with acute foveolitis. Malgun cells have enlarged euchromatic nuclei and abundant cytoplasm. The expression of proliferating cell nuclear antigen and cytokeratin 8 are typically up-regulated in them indicating that they are mitotically and metabolically active. Here, we report evidence for DNA damage and repair in malgun cells. Significant double-strand DNA breaks were shown by the consistent terminal dUTP nick-end labeling in the nuclei of malgun cells. Proteins related to DNA damage and repair, such as Ku, poly(ADP-ribosyl) polymerase, OGG1, and MSH2 were selectively up-regulated in malgun cells. Inducible nitric oxide synthase was also up-regulated. There were occasional bcl2- and p53-expressing cells suggesting that further steps of carcinogenesis took place at the single cell level. Our results suggest that the malgun cell change represents a characteristic morphological sign of cellular genomic damage and repair, and may be implicated in an early stage of carcinogenesis. It is suggested that acute foveolitis of the proliferative zone is a major pathogenetic step of gastric carcinogenesis in H. pylori gastritis.     

Stromal cells direct local differentiation of regulatory dendritic cells

CD11c(hi) dendritic cells (DC) play an essential role during the initiation of cell-mediated immunity. Recently, CD11c(lo)CD45RB(hi) DC with regulatory properties have been described. However, the origins of regulatory DC are poorly understood. Here, we show that spleen-derived stromal cells promote selective development of CD11c(lo)CD45RB(+) IL-10-producing regulatory DC from lineage-negative c-kit(+) progenitor cells. These DC have the capacity to suppress T cell responses and induce IL-10-producing regulatory T cells in vitro and to induce antigen-specific tolerance in vivo. Furthermore, stromal cells from mice infected with Leishmania donovani more effectively supported differentiation of these highly potent regulatory DC. The ability of tissue stromal cells to direct the development of DC with a regulatory phenotype thus provides a new mechanism for local immune regulation.     

Age-related changes in gene expression patterns of matrix metalloproteinases and their collagenous substrates in mandibular condylar cartilage in rats

Matrix metalloproteinases (MMPs) have been implicated in physiological cartilage matrix remodelling as well as in pathological and invasive extracellular matrix remodelling of tissue. Age-related changes in the gene expression patterns of MMPs in mandibular condylar cartilages (MCCs) were analysed. We examined the gene expression patterns of Mmp-8 and -13 and their substrates, Col1a1, Col2a1 and Col10a1, in MCC of growing and ageing rats. Temporomandibular joints of male Wistar rats aged 4, 8, 16 and 32 weeks were subjected to in situ hybridization analysis. Histologically, MMCs showed characteristics of growth plate cartilage at ages 4 and 8 weeks, and more closely resembled articular cartilage thereafter. Mmp-8 was expressed in the cells in all cartilaginous cell layers at ages 4 and 8 weeks, and then was localized only in the mature cells at ages 16 and 32 weeks. Whereas Mmp-13 expression was limited to the lowermost hypertrophic chondrocytes in the growth stage, mature chondrocytes instead of hypertrophic chondrocytes expressed Mmp-13 in adult non-hypertrophic MCC. Because Mmp-8 and -13 expression overlapped with Col2a1 and Col10a1, chondrocytes could play a pivotal role in degradation as well as production of the cartilaginous matrix in MCC.     

Effects of FK506 on rat thymic epithelial cells; immunohistochemical study.

The effects of FK506, a new immunosuppressive agent, on the rat thymus were investigated using the immunoperoxidase technique and flow cytofluorometry using monoclonal antibodies. Flow cytometric analysis of the thymus revealed that the proportion of cells labelled positively with OX7 (Thy-1 antigen), OX8 (CD8, T cytotoxic/suppressor cells) and W3/25 (CD4, T helper cells and macrophages) increased following treatment, with FK506, 1 mg/kg body weight for 14 days. A marked reduction of the thymic medulla following treatment was clearly demonstrated by staining with OX18 (MHC class I) and OX6 (MHC class II). Changes produced by FK506 were also observed in the cortical area of the thymus, being especially marked in the subcapsular area and around the blood vessels by staining with OX6, PKK-1 (alpha-cytokeratin), AB-1040 (type IV collagen), and AB-1220 (laminin). Eventually FK506 treatment resulted in patchy reduction of OX-6, PKK-1, AB-1040 and AB-1220 positive area in the cortex. This evidence suggests that FK506 may impair the thymic microenvironment and subsequently disturb the thymocyte maturation.     

Lack of association between DNA base excision repair gene XRCC1 Gln399Arg polymorphism and risk of malignant lymphoma in Japan

Growing evidence suggests that the polymorphism of DNA base excision repair gene XRCC1 Arg399Gln is associated with altered DNA repair proficiency and subsequent cancer susceptibility; however, no evidence is available for malignant lymphoma. We therefore conducted a case-control study (372 cases, 500 controls) to evaluate links with malignant lymphoma risk in Japan. The risk was evaluated in terms of odds ratio (OR) and 95% confidence interval (CI) adjusted for age and sex in an unconditional logistic regression model. There was no statistical risk change with the Arg/Gln (adjusted OR 0.89; 0.65-1.23, P = 0.492) or the Gln/Gln (0.57; 0.27-1.17, P = 0.127) compared with the Arg/Arg of the XRCC1 Arg399Gln polymorphism. The results were unchanged in analyses according to histological subtype (diffuse large lymphoma, follicular lymphoma, low-grade lymphoma of mucosa-associated lymphoid tissue, and others). These data suggest that XRCC1 Gln399Arg polymorphism plays a limited role in lymphomagenesis. Further study on the interaction between the polymorphism and environmental exposure is required.     

Voxel-based morphometry of human brain with age and cerebrovascular risk factors

The objectives of this study were to evaluate the correlations of the volumes of the gray matter and white matter with age, and the correlations of the tissue probabilities of the gray matter and white matter with age and several cerebrovascular risk factors. We obtained magnetic resonance (MR) images of the brain and clinical information from 769 normal Japanese subjects. We processed the MR images automatically by correcting for inter-individual differences in brain size and shape, and by segmenting the MR images into the gray matter and white matter. Volumetry of the brain revealed a significant negative correlation between the gray matter volume and age, which was not observed between white matter volume and age. Voxel-based morphometry showed that age, systolic blood pressure, and alcohol drinking correlated with the regional tissue probabilities of the gray matter and white matter.     

Improvement of blood compatibility on cellulose dialysis membrane. 2. Blood compatibility of phospholipid polymer grafted cellulose membrane.

The blood compatibility of a cellulose haemodialysis membrane whose surface was grafted with a methacrylate having a phospholipid polar group, 2-methacryloyloxyethyl phosphorylcholine, was evaluated with attention to platelet adhesion to the membrane surface and complement activation induced by the membrane. When the original cellulose membrane came in contact with platelet-rich plasma for 30 min, numerous platelets adhered to the surface and aggregated. On the other hand, the membrane grafted with 2-methacryloyloxyethyl phosphorylcholine effectively suppressed platelet adhesion and activation. This effect became more pronounced with increasing surface distribution. Especially, the 2-methacryloyloxyethyl phosphorylcholine grafted membranes, whose distribution exceeded 0.27, completely inhibited platelet adhesion, even when the contact time was 180 min. Moreover, the complement activation was also reduced with increased 2-methacryloyloxyethyl phosphorylcholine distribution on the surface of the membrane.     

Analgesic action of loperamide,an opioid agonist,and its blocking action on voltage-dependent Ca2+ channels

We investigated the relationship between the antinociceptive effect of the opiate agonist loperamide at the spinal level and its inhibitory effect on calcium influx. Intrathecal administration of loperamide showed a significant antinociceptive effect in the formalin test, which was not prevented by naloxone. On the other hand, no significant effects were observed by nicardipine, an L-type specific blocker, or by BAY K8644, an L-type specific agonist, suggesting no significant role of L-type calcium channels in nociceptive signal transduction. Loperamide suppressed the calcium influx in dorsal root ganglion neurons. As the antinociceptive effect of loperamide was not affected by naloxone or other calcium channel blocking toxins, and loperamide showed a direct inhibitory effect on calcium-influx, the analgesic effect of intrathecally injected loperamide might be due to its blockade of the voltage-dependent calcium channels at the terminals of the primary afferent fibers.     

Review: extracellular matrix regulates tooth morphogenesis

Mineralized tissues are unique in that they use proteins to attract and organize calcium and phosphate ions into a structured mineral phase, thus precise knowledge of the expression and extracellular distribution of matrix proteins is very important to understand their function. Tooth development is regulated by sequential and reciprocal interactions between neural crest-derived mesenchymal cells and the oral environment. However, the precise molecular mechanisms that mediate interactions between epithelium and mesenchymal cells are not clear, although basement membrane (BM) components have been shown to play important roles in these regulatory events. In addition, the extracellular matrix layer, whose main components are laminin, collagen IV, nidogen, and sulfated proteoglycan, and the BM layer are both considered to be involved with cell proliferation and differentiation. During tooth morphogenesis, extracellular matrices are dramatically changed. Further, the BM components, laminin and collagen IV support dental epithelium; however, in the late stage, they begin the processes of enamel matrix secretion and calcification, after which the BM structure between the dental epithelium and mesenchyme disappears. In addition, tooth abnormalities associated with several kinds of human diseases that cause mutations in the extracellular matrix, as well as the molecular mechanisms of the basement membrane and enamel matrix during tooth morphogenesis, are not clearly understood. In our review, we discuss the role of the extracellular matrix, with focus on the BM and enamel matrix during tooth morphogenesis.