Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells

RBP-J is a key mediator of Notch signaling that regulates cell fate determination in various lineages. To investigate the function of Notch-RBP-J in mature B cell differentiation, we generated mice that selectively lacked B cell RBP-J expression using conditional mutagenesis. Absence of RBP-J led to the loss of marginal zone B (MZB) cells with a concomitant increase in follicular B cells; in contrast, B1 cells in the peritoneal cavity were unaffected. Lack of RBP-J caused no defects in B cells maintenance, survival, plasma cell differentiation or activation. It is therefore likely that Notch-RBP-J signaling regulates the lineage commitment of mature B cells into follicular versus MZB cells. In addition, in mice with RBP-J-deficient B cells, had no obvious changes in immunoglobulin production in response to Ficoll, lipopolysaccharide or chicken gammaglobulin. In contrast, these mice exhibited increased mortality rates after blood-borne bacterial infection, which indicates that MZB cells play pivotal roles in the clearance of these bacteria.     

激活AMPA受体抑制大鼠骶髓后连合核神经元NMDA反应──制霉菌素穿孔法膜片钳研究

在急性分离的大鼠骶髓后连合核神经元上，采用制霉菌素穿孔法膜片钳技术，研究ＡＭＰＡ受体和ＮＭＤＡ受体的相互作用．结果显示，激活ＡＭＰＡ受体可逆性地抑制ＮＭＤＡ反应，该效应依赖于细胞外钙离子．而且，通过ＡＭＰＡ受体通道内流的钙离子单独即足以抑制ＮＭＤＡ受体介导的反应．本结果证明，钙离子可透性ＡＭＰＡ受体可能参与了脊髓伤害性信息的调控．该过程可能与针刺镇痛的机制有关．     

Genomic imprinting and its relevance to genetic diseases

Summary Genomic imprinting is a biological phenomenon determined by an evolutionally acquired, underlying system that may control harmonious development and growth in mammals. It is also relevant to some genetic disorders in man. In this article, lines of biological evidence of imprinting, characteristics of the mouse and human imprinted genes, and findings and mechanisms on the occurrence of several human imprinting disorders are reviewed.     

Rhythmic motor activity in thin transverse slice preparations of the fetal rat spinal cord

Networks generating locomotor-like rhythmic motor activity are formed during the last week of the fetal period in the rat spinal cord. We investigated the coordinated rhythmic motor activity induced in transverse slice preparations of the lumbar spinal cord taken from fetal rats as early as embryonic day (E) 16.5. In slices as thin as 100 microm, bath-application of 5-hydroxytryptamine (5-HT) induced rhythmic [Ca(2+)](i) elevations in motoneurons labeled with Calcium Green-1 dextran. The rhythmic [Ca(2+)](i) elevations were similar in frequency to that in the intact lumbar spinal cord, although there was no temporal correlation between the activity in the left and right sides of 100-microm slices. Such rhythmic [Ca(2+)](i) elevations were observed in the slices taken from all lumbar segments. Moreover, the rhythmic activity was abolished by simultaneous blockade of glutamate, glycine, and GABA(A) receptors, indicating that synaptic transmission mediated by these receptors is important for the generation of the rhythm in these slices. Synchronous rhythmic activity between the left-right sides was found in slices thicker than 200 microm taken from any segmental level of the lumbar spinal cord. In these preparations, commissural neurons were activated synchronously with ipsilateral motoneurons. These results indicate that the neuronal networks sufficient to generate coordinated rhythmic activity are contained in one-half of a single lumbar segment at E16.5. Such spinal cord slices are a promising experimental model to investigate the neuronal mechanisms and the development of rhythm generation in the spinal cord.     

OSTEOCLAST-LIKE GIANT CELL TUMOR OF THE LIVER

A 66-year-old male with osteoclast-like giant cell tumor of the liver that arose in the non-cirrhotlc liver is presented. The liver tests were almost normal, and plasma levels of alpha-fetoprotein and carcinoembryonic antigen were within normal limits. The findings of liver scan by ^99mTc phytate, celiac angiography, and CT scans are described for the first time for this rare neoplasm, showing a large, unresectable liver tumor. Histologically, the tumor mainly consisted of osteoclast-like giant cells and mononuclear cells, which were focally arranged in a vaguely trabecular pattern and sarcomatous pattern. By an electromicroscopic study, however, no definitive evidence was obtained whether it arose from epithelial cells or nonepithellal cells. Various clinicopathological features were described and compared with previously reported cases including two cases arising in the liver.     

Isolation of vaccine-derived type 1 polioviruses displaying similar properties to virulent wild strain Mahoney from sewage in Japan

Type 1, 2, and 3 vaccine-derived polioviruses were isolated from a sewage disposal plant located downstream of the Oyabe River in Toyama Prefecture, Japan, between October 1993 and September 1995. Neurovirulence was analyzed in 13 type 1 vaccine-derived strains, using mutant analysis by polymerase chain reaction and restriction enzyme cleavage (MAPREC). Nine strains (69%) were estimated to have marked neurovirulence. Some of the neutralizing antigenic sites, temperature sensitivity, and plaque-forming ability of two virulent vaccine-derived poliovirus strains were similar to Mahoney strain. The neutralizing activity of human sera obtained after oral poliomyelitis vaccine (OPV) administration against one of the virulent vaccine-derived polioviruses was examined. Although all human sera showed sufficient neutralizing activity for the prevention of poliomyelitis by vaccine-derived poliovirus strains, a lower titer than that against Sabin type 1 strain was observed. Vaccination against virulent vaccine-derived poliovirus will be effective. However, the environmental presence of viruses that have properties similar to those Mahoney strain is a threat. The introduction of inactivated poliovirus vaccine (IPV), and well-maintained herd immunity, together with reinforced environmental surveillance is important for the final phase of the polio eradication program by the World Health Organization (WHO).     

Novel Fluorinated Hybrid Polymer by Radical Polyaddition of Bis(α‐trifluoromethyl‐β,β‐difluorovinyl) Terephthalate onto Dialkoxydialkylsilanes

To develop the radical polyaddition of bisperfluoroisopropenyl esters, the reactions of bis(α‐trifluoromethyl‐β,β‐difluorovinyl) terephthalate [CF₂?C(CF₃)OCOC₆H₄COOC(CF₃)?CF₂] (BFP) with dialkoxydialkylsilane were examined to prepare fluorinated hybrid polymers bearing dialkylsilyl groups in the main chain. Prior to polyaddition, the radical addition reaction of 2‐benzoyloxypentafluoropropene [CF₂?C(CF₃)OCOC₆H₅] (BPFP) has been investigated to afford the results that diethoxydimethylsilane (DEOMS) or dimethoxydimethylsilane with BPFP initiated by oxo radical are the best combination for the preparation of polymers. The mechanism of the addition reaction was proposed. Radical polyaddition of BFP with DEOMS initiated by benzoyl peroxide or di‐tert‐butyl peroxide has yielded polymers of up to molecular weight 1 × 10⁶ with rather broad molecular weight distribution. A mechanism for the polyaddition reaction is proposed based on the radical addition reaction between BPFP and DEOMS. The step‐growth polymerization is initiated by hydrogen abstraction of DEOMS to add a perfluoroisopropenyl group, followed by a 1,7‐shift of the radical in the intermediate. The relationship between addition reaction mechanism and polyaddition mechanism was also discussed.

     

The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis

PTEN is an important tumor suppressor gene. Hereditary mutation of PTEN causes tumor-susceptibility diseases such as Cowden disease. We used the Cre-loxP system to generate an endothelial cell-specific mutation of Pten (Tie2CrePten) in mice. Tie2CrePten(flox/+) mice displayed enhanced tumorigenesis due to an increase in angiogenesis driven by vascular growth factors. This effect was partially dependent on the PI3K subunits p85alpha and p110gamma. In vitro, Tie2CrePten(flox/+) endothelial cells showed enhanced proliferation/migration. Tie2CrePten(flox/flox) mice died before embryonic day 11.5 (E11.5) due to bleeding and cardiac failure caused by impaired recruitment of pericytes and vascular smooth muscle cells to blood vessels, and of cardiomyocytes to the endocardium. These phenotypes depend strongly on p110gamma rather than on p85alpha and were associated with decreased expression of Ang-1, VCAM-1, connexin 40, and ephrinB2 but increased expression of Ang-2, VEGF-A, VEGFR1, and VEGFR2. Pten is thus indispensable for normal cardiovascular morphogenesis and post-natal angiogenesis, including tumor angiogenesis.