Latency of EEG attenuation ("blocking") in relation to age and reaction time in normal children

Blocking latency of the EEG (BL) and reaction time (RT) were investigated in 53 normal boys aged 88–207 months. The purpose was to discover whether changes in BL which have been reported to occur during growth in children parallel the well known decrease in RT that accompanies development. EEGs were recorded (1) during an experiment in which the tracings were attenuated by short, high intensity flashes of white light, and, (2) while the subjects performed an auditory reaction task in which they responded to a tone that occurred without warning by closing a switch as quickly as possible. As expected, findings showed an inverse relationship between RT and age of substantial magnitude (r= ?.822). By contrast, no relationship was apparent between BL and age in the group tested. This finding, together with the fact that the correlation between BL and RT was not significantly different from zero, suggested that BL and RT follow different developmental courses and may be measures of essentially independent systems in children 7 years and older.     

Burkitt's lymphoma in Africa, a review of the epidemiology and etiology

Burkitt's lymphoma (BL) was first described in Eastern Africa, initially thought to be a sarcoma of the jaw. Shortly it became well known that this was a distinct form of Non Hodgkin's lymphoma. The disease has given insight in all aspects of cancer research and care. Its peculiar epidemiology has led to the discovery of Epstein Barr virus (EBV) and its importance in the cause of several viral illnesses and malignancies. The highest incidence and mortality rates of BL are seen in Eastern Africa. BL affects mainly children, and boys are more susceptible than girls. Evidence for a causal relationship between EBV and BL in the endemic form is fairly strong. Frequency of association between EBV and BL varies between different patient groups and different parts of the world. EBV may play a role in the pathogenesis of BL by deregulation of the oncogene c-MYC by chromosomal translocation. Although several studies suggest an association between malaria and BL, there has never been a conclusive population study in support of a direct role of malaria in causation of BL. The emergence of HIV and a distinct subtype of BL in HIV infected have brought a new dimension to the disease particularly in areas where both HIV and BL are endemic. BL has been reported as a common neoplasmin HIV infected patients, but not in other forms of immuno-depression, and the occurrence of BL seems to be higher amongst HIV positive adults, while the evidence of an association amongst children is still disputed. The role of other possible risk factors such as low socio-economical status, exposure to a plant species common in Africa called Euphorbiaceae, exposure to pesticies and to other infections such as schistosomiasis and arbovirus (an RNA virus transmitted by insect vectors) remain to be elucidated.     

Carboxyphenyl chloroanthranilic acid (CCA) in the modulation of immune response in mice

A study to elucidate the immunopharmacological mechanisms of carboxyphenyl chloroanthranilic acid (CCA) was carried out, employing as a parameter the rosette formation of mouse spleen and thymus cells with red blood cells of sheep. The immunopharmacological properties of CCA and levamisole (LMS) were compared. In C57BL/6 mice, the immune response was either suppressed or enhanced by LMS, whereas CCA caused a suppression of rosette formation. Both drugs enhanced response in adult thymectomized C57BL/6 mice. LMS induced Thy-1 positive rosette-forming cells after adult thymectomy in C57BL/6 mice, whereas CCA did not. CCA was significantly effective in restoring the impaired immune response in C57BL/6 mice pretreated with immunosuppressants. The effect of LMS or CCA on the immune response varied among six different mouse strains (C57BL/6, BALB/c, C3H/He, DBA/2, (NZB X NZW) F1 and BXSB). The results suggest that both drugs have immunomodulation or immunonormalization properties.     

Antibody Response and Acquired Tolerance of A/J Mice: Age- and Immunogen-Related Isotype Differences

In earlier work we have observed strain- and age-related diversity of immunological ageing in inbred mice pretreated with tolerogen or left without pretreatment and then immunized. Different isotypes show different age- and strain-related changes. Here, we extend this isotype analysis from C57BL/6 and SJL to A/J. By comparison with the first two of these, animals of strain A/J show very little age-related change, as judged by indirect plaque-forming response. We have found that in A/J, as in SJL and C57BL/6 mice, age-related changes are isotype-dependent. The age-related changes in isotype predominance and magnitude differ for different determinants. They depend on the structural relation between the tolerance-inducing or -sensitizing macromolecule and the immunogen.     

Lymphocyte population kinetics during the development of the immune system. B cell persistence and life-span can be determined by the host environment

We have investigated the kinetic behaviour of LPS reactive Bcells during the development of the immune system. By studyingthe persistence of LPS reactive spleen cells transferred fromadult C57BL/6 donor mice into histocompatible C57BL/10 Sc.CrLPS non-responder mice we have confirmed that B cell populationsobtained from adult donor mice decay rapidly after transferinto adult recipients. In contrast, the same cell populationsafter transfer into neonatal reclpients are able to divide andmaintain their numbers for {small tilde}2-5 weeks in the host'sspleen. In fact, comparison of hosts at different ages showthat with the increasing age of the host the fate of donor Bcells evolves to mimic the behaviour observed upon transferinto adult recipients. Kinetic studies of LPS reactive spleencells obtained from newborn (2 weeks old) C57BL/6 donors aftertransfer into adult C57BL/10 Sc.Cr mice have shown that youngdonor cells were able to keep at constant numbers in the adultenvironment for the first {small tilde}10–15 days aftertransfer and to decay afterwards in the host's spleen at thesame rate as observed upon transfer of spleen cells from adultdonors into adult hosts. These studies provide the first evidencefor the different kinetic behaviour of lymphoid B cell populationsin developing and mature immune systems, confirm that cell persistencecorrelates with cell activation and division, and show thatB cell life-span is also dependent on the host environment.     

Using Blended Learning to Implement Evidence‐Based Psychotherapies

Historically, clinicians have learned about evidence‐based psychotherapies (EBPs) by reading therapy manuals and/or attending clinical training workshops. However, researchers agree that such methods alone are insufficient to support the implementation of EBPs. This article explores the concept of blended learning (BL) and its potential for facilitating the implementation of EBPs. Blended learning refers to integration of multiple methods of information delivery into a single learning system. Implementation of EBPs describes a specific set of activities that are designed to promote the uptake and sustained adoption of a psychotherapeutic approach, strategy, or technique that has demonstrable empirical support. This article reviews the most common methods by which EBPs are currently disseminated and implemented, defines the concept of BL, and presents some examples of different elements that can be combined into a BL system. Three models of BL are presented and illustrations of these BL formulations are provided using examples from the extant literature. This article concludes with a summary and recommendations for future research.     

Characterization of Clostridium butyricum neurotoxin associated with food-borne botulism

The neurotoxin of Clostridium butyricum strain LCL155 (BuNT/LCL155) associated with type E food-borne botulism showed antigenic and biological properties different from those of C. botulinum type E (BoNT/E) andC. butyricum strain BL5262 (BuNT/BL5262). The specific toxicity of BuNT/LCL155 was found to be about 10% those of BoNT/E and BuNT/BL5262. Immunological analysis with monoclonal antibodies against BoNT/E showed that the heavy chain of BuNT/LCL155 differs partially from those of BoNT/E and BuNT/BL5262. Binding experiments with rat brain synaptic membrane revealed that BuNT/LCL155 possesses a binding activity lower than either BoNT/E or BuNT/BL5262. There was no difference in the catalytic activity of the three neurotoxins, which had been determined with a recombinant of the intracellular target protein SNAP-25. These data suggest that the BuNT/LCL155 shares the receptor-recognition site structurally different from BoNT/E and BuNT/BL5262, perhaps causing a decreased specific toxicity.     

V genes of the primary antibody response of C57BL/10 mice to the hapten phenyloxazolone

The mRNA of ten monoclonal phenyloxazolone (phOx) antibodies originating from the primary (day 7) response of C57BL/10 mice were partially sequenced. The sequences were analyzed together with those of two previously published antibodies. The C57BL response does not have a predominant subset of antibodies like the BALB/c response has (VH-Ox1/V kappa-Ox1 JK5). Probably, C57BL mice lack the VH-Ox1 gene and, as a consequence, their V kappa-Ox1 gene does not have a main role in the anti-phOx response. Five V kappa and six VH genes were found to participate. All five V kappa genes or their "alleles" had previously been found from the BALB/c response to 2-phenyloxazolone (phOx). On the other hand, the two strains use different VH genes for the anti-phOx response. Most C57BL antibodies were coded by VH genes of group 1 which has only minor role in the BALB/c response. The remaining VH genes were from group 7. Our data show that one V kappa segment (e.g. V kappa-Ox1) can code for anti-phOx antibodies with several, even widely different, VH genes. On the other hand, they emphasize the role of certain VH/VL gene combinations for the anti-phOx specificity. Thus, VH genes of group 7 were found to code for anti-phOx antibodies only together with the V kappa 45.1 gene.     

Different serotypes of B-tropic murine leukemia viruses and association with endogenous ecotropic viral loci

We have previously presented evidence suggesting that the B-tropic viruses isolated from C57BL mice are generated through recombination of the endogenous N-tropic virus with an endogenous xenotropic virus. To further study the origin of B-tropic viruses and to genetically map the determinants of N/B-tropism, we have isolated 22 new N- and 13-tropic viruses from several strains of mice and have characterized their gene products serologically. For comparison, we have characterized an additional 14 N- and B-tropic viruses obtained from other sources. All of the N-tropic viruses had AKR-like p12s and p30s which competed in a radioimmunoassay specific for endogenous N-tropic p30s. Eight of nine 13-tropic viruses from three different substrains of C57BL mice had xenotropic-type p12s demonstrating that recombination involved the gag gene region. In contrast, 8 of 8 B-tropic viruses from BALB/c mice were characterized by AKR-like p12s. All 23 of the B-tropic viruses in the study have p30s that fail to compete in the specific p30 assay. These results demonstrate that there is strain specificity in the type of recombination resulting in generation of B-tropic viruses, although in both cases the p30 region is involved. The influence of the endogenous N-tropic viral locus on the type of B-tropic viruses is indicated by the observation that 3 of 4 13-tropic viruses isolated from C57BL/6 mice carrying the C3H ecotropic viral locus resembled the BALB/c 13-tropics, rather than the C57BL B-tropic viruses.     

广泛性子宫颈切除术后子宫载荷对子宫韧带和阴道影响的有限元仿真

目的 应用有限元法分析广泛性子宫颈切除术后不同子宫载荷(腹压和子宫重量)时子宫阔、圆韧带和阴道的应力分布和变形情况,获得子宫韧带和阴道对子宫载荷变化的敏感度。方法 建立后位子宫、韧带和阴道三维几何模型并导入ABAQUS软件,然后设置约束、施加载荷,计算各部位的应力和变形。结果 广泛性子宫颈切除术后阔、圆韧带的应力和位移均有不同程度增大;阔、圆韧带和阴道的应力和变形均随子宫载荷的增大而增大,阔韧带的变形和应力主要分布于中下部(腹压变化)或中上部(子宫重量变化),圆韧带的应力与变形主要分布于中下部,阴道的应力与变形主要分布于中上部;腹压与子宫重量单独变化或同时变化时,阴道所受应力及对载荷变化的敏感度最大,阔韧带变形及对载荷变化的敏感度最大,总的应力和变形排序因载荷情况不同而略有差异,并且子宫重量比腹压对韧带和阴道的影响程度显著。结论 研究结果与临床资料相符,可为临床手术方案优化和发病机制探索提供指导。     

Basal lamina at the site of spinal cord injury in normal, immunotolerant and immunosuppressed rats

The cut ends of a rat spinal cord are capped with basal lamina (BL) within 20 days. This BL may block regenerating axons. BL at the transection site in rats made immunologically unresponsive to central nervous system antigens is not significantly different from that of control rats, but rats treated with cyclophosphamide show a less complete BL cap during the first 25 days. This may account for the increased axonal regeneration found in cyclophosphamide-treated rats.     

化疗治愈荷瘤小鼠模型的建立及氟尿嘧啶抑瘤作用的免疫机制

目的:建立荷瘤野生型C57BL/6小鼠及C57BL/6裸鼠模型,探讨5-氟尿嘧啶(5-FU)抑瘤作用的免疫机制。方法:给正常野生型C57BL/6小鼠皮下接种小鼠淋巴瘤EL4细胞,建立荷EL4肿瘤的小鼠模型。接种瘤细胞后12d,荷瘤小鼠腹腔单次注射不同剂量的5-FU,找出5-FU可发挥最大的抑瘤作用、并能致使荷瘤小鼠肿瘤消退不再复发的最小使用剂量。遗传背景相同的野生型C57BL/6小鼠及C57BL/6裸鼠同时皮下接种小鼠淋巴瘤EL4细胞,建立两种荷瘤小鼠模型。接种瘤细胞后12d,两种荷瘤小鼠腹腔内同时注射可使野生型C57BL/6荷瘤小鼠肿瘤消退不再复发5-FU的最低剂量,以正常野生型C57BL/6小鼠为对照,观察5-FU对T淋巴细胞缺陷裸鼠的抑瘤作用。结果:以75mg/kg5-FU治疗1周后,两种荷瘤小鼠的肿瘤以相同的速率缩小直至消失。但在5-FU治疗2周后,T淋巴细胞缺陷的C57BL/6裸鼠肿瘤复发,而免疫功能正常的野生型C57BL/6小鼠肿瘤治愈。结论:单一剂量的5-FU对荷淋巴瘤EL4小鼠具有明显的近期治疗效果,5-FU抑瘤作用的发挥不需要T细胞参与;但5-FU抗肿瘤作用的远期疗效与机体T淋巴细胞功能密切相关。     

Behavioral Differences among C57BL/6 Substrains: Implications for Transgenic and Knockout Studies

Separate breeding colonies of C57BL/6 (“B6”) mice maintained at the Jackson Laboratories (“J”) and NIH (“N”) have led to the emergence of two distinct substrains of C57BL/6 mice: C57BL/6J and C57BL/6N. Molecular genetic studies indicate simple sequence-length polymorphisms, single-nucleotide polymorphisms, and copy-number variants among B6 substrains that may contribute to phenotypic differences. We examined differences in motor coordination, pain sensitivity, and conditional fear in the C57BL/6J strain and three N strains: C57BL/6NCrl (Charles River), C57BL/6NTac (Taconic), and C57BL/6NHsd (Harlan Sprague Dawley). Male C57BL/6J mice demonstrated enhanced motor coordination, as measured by the rotarod assay, markedly enhanced pain sensitivity in two assays of acute thermal nociception (e.g., tail withdrawal and hot plate), and a reduced level of conditional fear. The tail withdrawal result was confirmed in a separate laboratory. We also provide a table reviewing previously reported behavioral differences among various B6 substrains and discuss the significance of environmental differences due to obtaining mice form different vendors. These data may be seen as a potential problem and as a potential opportunity. Great care must be taken when working with mice engineered by using B6 embryonic stem cell lines because control groups, backcrosses, and intercrosses could inadvertently introduce behaviorally significant polymorphic alleles or environmental confounds. On the other hand, deliberate crosses between B6 substrains may provide an opportunity to map polymorphic loci that contribute to variability in a trait on largely homogenous backgrounds, which has the potential to improve mapping resolution and aid in the selection of candidate genes.     

Differences in expression of toll-like receptors and their reactivities in dendritic cells in BALB/c and C57BL/6 mice

We have previously reported that differences in early production of interleukin 12 (IL-12) by dendritic cells (DC) underlies the difference between the susceptibilities to Listeria monocytogenes of C57BL/6 and BALB/c mice. To elucidate mechanisms for the different abilities of DC to produce cytokine in C57BL/6 and BALB/c mice, we examined Toll-like receptor (TLR) expression by DC and their responses in vitro to known microbial ligands for TLRs. We found that DC isolated from the spleens of naive C57BL/6 mice preferentially expressed TLR9 mRNA, whereas DC from naive BALB/c mice strongly expressed TLR2, -4, -5, and -6 mRNAs. C57BL/6 DC produced a higher level of IL-12p40 in response to the ligands for TLR4 (lipopolysaccharide), TLR2 (lipoprotein), and TLR9 (CpG), whereas BALB/c DC responded to these ligands by producing a larger amount of monocyte chemoattractant protein 1. C57BL/6 DC expressed higher levels of CD40 and Stat4 than BALB/c DC did, suggesting that naive C57BL/6 mice contained more-mature subsets of DC than naive BALB/c mice. Differences in reactivities of DC to microbial molecules through TLRs may be associated with susceptibility and resistance to Listeria infection in BALB/c and C57BL/6 mice.     

Isolation and characterization of a unique C57BL B-tropic virus

A unique B-tropic virus (CS43) has been isolated from a C57BL mouse. This virus differs from those we have previously characterized and from several isolates we have obtained from normal and leukemic C57BL mice. Unlike other C57BL B-tropic viruses, CS43 does not have a p12 polypeptide homologous to that of the class II xenotropic virus, but does have a p12 homologous to that of AKR MuLV (class I). In common with the other C57BL B-tropic isolates, CS43 has an altered major core protein (p30), which competes only weakly in a class-specific assay that distinguishes ecotropic MuLV p30s from those of xenotropic origin. The data are compatible with a unique recombinational event in the generation of this isolate, which should prove useful in studying the origin of B-tropic viruses and the properties that determine N/B tropism.     

Basal lamina of rat myocardium. Its fate after death of cardiac myocytes

As part of a study of the interactions between myocardial cells and extracellular matrix during healing of necrotic lesions, we have examined the fate of myocyte basal lamina (BL) after injury with ischemia, freeze-thawing, or isoproterenol. Using light and electron microscopy, and antibodies to three BL-associated antigens, we found that the BL of necrotic myocytes remained largely intact and continued to delineate the myocyte compartment from connective tissue space. Inflammatory cells entered the myocyte compartment through holes in the acellular BL and removed cell debris. The holes may have been produced by inflammatory cells and/or by the stretching force of the beating heart. After removal of debris, some BL sheaths of necrotic myocytes collapsed, resulting in spatial approximation of vessels. Interstitial cells deposited collagen and elastic fibers in the connective tissue space and within portions of the myocyte compartment. The acellular myocyte BL, collapsed or not, retained normal antigen staining for type IV collagen, laminin, and heparan sulfate for about 10 days, then showed diminished staining in patchy areas. These areas may correspond to BL disruption and degradation in conjunction with fibrosis, although a substantial amount of acellular BL remained in situ and became embedded in scar tissue. At least two types of granulo-vesicular bodies, measuring 25 to 60 and 60 to 160 nm respectively, were associated with the acellular BL; these were of unknown origin and function. The study shows that the fate of acellular BL in injured myocardium is similar to the fate of BL in other injured tissues; however, the appearance of holes in acellular BL, within hours after injury, is unusual and may enhance scar tissue formation. Whether the acellular BL contributes to regeneration of myocardium, as do acellular BLs in other injured tissues, remains to be determined.     

Bright light effects on body temperature, alertness, EEG and behavior.

The immediate psychophysiological and behavioral effects of photic stimulation on humans [bright light (BL) of 5K lux or dim light (DL) of 50 lux] were assessed in male subjects (N = 43) under four different conditions. For one condition the same subjects (N = 16) received alternating 90-min blocks of BL and DL during the nighttime h (2300-0800 h) under sustained wakefulness conditions. A second condition was similar to the first except that subjects (N = 8) received photic stimulation during the daytime hours. For the third and fourth conditions different subjects received either continuous BL (N = 10) or continuous DL (N = 9) during the nighttime hours. For the nighttime alternating condition body temperature decreased under DL but either increased or maintained under BL. For the continuous light condition, body temperature dropped sharply across the night under DL but dropped only slightly under BL. Sleepiness was considerably greater under DL than under BL, and the difference became larger as the night progressed. Similarly, alertness, measured by EEG beta activity, was greater under BL, and nighttime performance on behavioral tasks was also generally better. There were no differential effects between BL and DL on any measure during the daytime. These data indicate that light exerts a powerful, immediate effect on physiology and behavior in addition to its powerful influence on circadian organization.     

Closely similar values obtained when the ME7 strain of scrapie agent was titrated in parallel by two individuals in separate laboratories using two sublines of C57BL mice

A single C57BL mouse-brain infected with the ME7 strain of mouse-passaged scrapie agent was used to carry out four parallel infectivity titrations in mice. These were carried out by two individuals in two laboratories using two sublines of C57BL mice. The titre values obtained by the four assays were very similar, and showed no significant differences between the two different operatives, the two different laboratories or the two different sublines of C57BL mice. The data confirm the validity of comparing these types of transmission data generated in different laboratories when a common methodology is used.