Superposition of motor programs—I. Rhythmic forearm movements in man

The so-called invariant characteristics of the elbow muscles are described. An invariant characteristic is a curve on a plot of elbow static moment vs angle. An invariant characteristic shows the elbow displacements in response to different amplitudes of load change when the subject is told not to compensate, or not to intervene voluntary to correct the deflection of the arm. If an inclination of the invariant characteristic is known, the degree of central tonic coactivation of antagonistic motoneurones can be estimated. The idea was utilized when analysing rhythmic movements (2–6 Hz) of the forearm that were carried out against a spring resistance (2–10 Nm). When the spring was suddenly switched off, the deflection of forearm rose. The subject was told not to correct the deflection and not to interrupt the swingings. The mean changes of both muscle torque and joint angle were determined in the experiments so that it was possible to estimate the inclination of the invariant characteristic used at a given frequency. Judging by the results, central tonic coactivation of elbow flexors and extensors occurs and increases to maximum as the frequency of movement increases. In addition, the reciprocal activation of antagonistic muscles is well known to occur upon execution of this movement.It can be concluded that both the reciprocal and the unidirectional central commands to antagonistic motoneurones occur simultaneously. The functional significance, as well as a scheme of superposition, of these motor commands are discussed. It is suggested that the commands are universal, i.e. the nervous system operates by using them during the performance of any movement.     

Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene.

Mutations in the human phenylalanine hydroxylase gene producing phenylketonuria or hyperphenylalaninemia have now been identified in many patients from various ethnic groups. These mutations all exhibit a high degree of association with specific restriction fragment-length polymorphism haplotypes at the PAH locus. About 50 of these mutations are single-base substitutions, including six nonsense mutations and eight splicing mutations, with the remainder being missense mutations. One splicing mutation results in a 3 amino acid in-frame insertion. Two or 3 large deletions, 2 single codon deletions, and 2 single base deletions have been found. Twelve of the missense mutations apparently result from the methylation and subsequent deamination of highly mutagenic CpG dinucleotides. Recurrent mutation has been observed at several of these sites, producing associations with different haplotypes in different populations. About half of all missense mutations have been examined by in vitro expression analysis, and a significant correlation has been observed between residual PAH activity and disease phenotype. Since continuing advances in molecular methodologies have dramatically accelerated the rate in which new mutations are being identified and characterized, this register of mutations will be updated periodically.     

Temporal and spatial localization of three germline-specific proteins in medaka.

We show that germline-specific proteins, olvas (vasa), nanos, and tdrd1 (tudor), alter their localization in the cytoplasm during germline development in the medaka (Oryzias latipes). By immunohistochemical analysis, these three germline-specific proteins were detectable on granule-like structures in the cytoplasm of migrating primordial germ cells. In the germ cells of the gonadal primordia, these granules formed a hollow area lacking these three protein components. During the sexual differentiation of the female gonads, the granules were found to be reduced in size in the germ cells undergoing cystic division and they showed a perinuclear localization in the oocytes. However, the germ cells in the male gonads retained their hollow granules during this early sex differentiation stage. We further demonstrate the differential localization of olvas, nanos, and tdrd1 on these granules during medaka germline development.     

Familial eosinophilia: Clinical and laboratory results on a U.S. Kindred

We describe a five-generation kindred with familial eosinophilia (FE; MIM131400), characterized by the occurrence of sustained eosinophilia of unidentifiable cause in multiple relatives. The inheritance pattern is consistent with an autosomal dominant pattern. Among 52 related subjects studied, 19 were affected and 33 were unaffected. Ten unaffected spouses were also evaluated. Four subjects with sustained eosinophilia were diagnosed with cardiac abnormalities and two of them also had neurologic symptoms. In comparison with the unaffected or spouses, evaluation of complete blood counts showed that the affected relatives had, as expected, significantly higher white cell (P < 0.005) and absolute eosinophil counts (P < 0.001) and lower red cell counts (P < 0.05). Evaluation of serum cytokine levels (IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GMCSF) and serology for parasitic helminth infection demonstrated no differences between the affected and unaffected individuals; no individuals studied had serologic evidence for parasitic infection. There were also no differences in anti-nuclear antibody, serum cobalamin (vitamin B₁₂) level, immunoglobulin level, leukocyte alkaline phosphatase, rheumatoid factor, HLA analysis, and stool findings for ova and parasites. Among eight affected persons who had peripheral blood or bone marrow karyotype analysis, two carried the same chromosome abnormality, a pericentric inversion of chromosome 10, inv (10) (p11.2q21.2). A gene mapping study is currently underway to study the underlying genetic mechanism(s) of this syndrome. Am. J. Med. Genet. 76:229–237, 1998. © 1998 Wiley-Liss, Inc.     

肠产毒性大肠埃希菌定植因子研究进展

肠产毒性大肠埃希菌定植因子为近几年发现的一种重要的细菌致病菌毛,它能使大肠杆菌粘附于宿主肠牯膜而不被肠蠕动和肠分泌液所清除,再通过其分泌肠毒素导致婴幼儿和旅行者腹泻。菌毛亚单位的保守区域、抗原决定簇组成、定植因子质粒与毒力编码基因的联系,对研制广谱重组菌毛疫苗具有重要指导意义。本文综述了近几年来有关定植因子菌毛的研究进展,以及与各类肠毒素编码质粒的相关性和疫苗研究概况。     

Superposition of motor programs—II. Rapid forearm flexion in man

A man carried out a rapid change of forearm position while overcoming the resistance of a spring. The spring was suddenly switched off in some experiments either prior to or after the initiation of movement. In these cases another final position of the forearm was achieved providing that the subject had been told not to correct voluntarily the mistake. A similar effect was observed when the subject made the same movements without any external load while the spring was unexpectedly switched on in some experiments. The so-called invariant characteristics of the elbow muscles (static muscle torque versus angle) were determined. It has been found earlier that the nervous system accomplishes movements by means of the invariant characteristics. If the slope of the invariant characteristics is known, the degree of central coactivation of antagonistic motoneurones can be estimated. Judging by the data obtained, there is considerable, although not maximal, central coactivation of antagonistic motoneurones during this type of movement. The reciprocal activation is also known to be utilized during this movement. Thus, a superposition of two central commands takes place. The functional significance, as well as a scheme, of the superposition are discussed.The data obtained give additional support to the hypothesis that the reciprocal and the joint central control of antagonistic motoneurones are universal commands that are used for the construction of any motor program.     

Characterization of CD44 expressed on alveolar macrophages in patients with diffuse panbronchiolitis.

Interleukin (IL)-8 may play an important role in neutrophil infiltration in the airways of patients with diffuse panbronchiolitis (DPB). Furthermore, alveolar macrophages could produce IL-8 subsequent to CD44-hyaluronic acid (HA) interaction. The purpose of this study was to evaluate the contribution of CD44 expressed on alveolar macrophages to the pathogenesis of DPB. We examined the concentration of soluble CD44 (sCD44) in bronchoalveolar lavage fluid (BALF) and CD44 expression on macrophages in BALF from patients with DPB before and after low-dose, long-term macrolide therapy. We also assessed the HA-binding ability of alveolar macrophages as a functional analysis of the CD44 molecule. The sCD44 concentration in BALF was significantly lower in patients with DPB than in healthy volunteers. Percentages of alveolar macrophages expressing low CD44 (CD44 low(+)) and HA-nonbinding alveolar macrophages were higher in patients with DPB compared with healthy volunteers. Furthermore, macrolide therapy normalized CD44 expression and HA-binding ability of macrophages in BALF from DPB patients. Our findings suggest that alveolar macrophage dysfunction could result from abnormalities of CD44 expression in patients with DPB and that these events could contribute to the pathogenesis of DPB.     

宫颈癌及其前期病变HPV感染与基因型分布

目的了解宫颈癌及宫颈上皮内瘤变CIN患者的HPV的感染和其基因分型及主要感染型别情况。方法应用型特异PCR检测宫颈癌及其前病变的患者的HPV感染及其主要基因分型情况的分析。结果在本研究宫颈癌及宫颈上皮内瘤变患者中,宫颈癌的HPV感染率为91．0％,CINⅠ／Ⅱ／Ⅲ的HPV感染率为73．3％,主要高危型HPV基因型别依次为HPV16、HPV18、HPV58、HPV33。结论在宫颈上皮内瘤变患者中感染主要高危型HPV基因型别依次为HPV16、HPV18、HPV58、HPV33、HPV16在宫颈癌和CIN中的构成比随着宫颈病变的增加而明显增加。     

Mitogenesis, micronuclei, and carcinogenesis in the rat liver: some basic inconsistencies.

The rodent liver carcinogen, mitogen, and peroxisome proliferator, methylclofenapate (MCP), has been investigated as a chemical mitogen for use in the rat liver micronucleus assay. A series of experiments comparing MCP with the potent mitogen 4-acetylaminofluorene (4AAF) and with 2/3 partial hepatectomy showed unexpected differences between the three treatment regimes as monitored by the expression of micronucleated hepatocytes (MH) in livers initiated with N-nitrosodimethylamine (NDMA). These differences were observed in both the profile of MH induction, as a function of time after mitogenic stimulation, and in the magnitude of response. There was no correlation between the magnitude of MH induction and the degree of mitogenesis triggering the MH induction. It is concluded that the yield of MH observed in a rat liver micronucleus assay is not a simple function of the level of DNA damage induced by the initiating agent (here NDMA). This indicates the need for caution in the interpretation of data obtained in the liver micronucleus assay for chemicals of unknown carcinogenicity. The use of acridine orange as a fluorescent stain for use with isolated hepatocytes is described.     

Blind source separation to enhance spectral and non-linear features of magnetoencephalogram recordings. Application to Alzheimer's disease

This work studied whether a blind source separation (BSS) and component selection procedure could increase the differences between Alzheimer's disease (AD) patients and control subjects’ spectral and non-linear features of magnetoencephalogram (MEG) recordings. MEGs were acquired with a 148-channel whole-head magnetometer from 62 subjects (36 AD patients and 26 controls), who were divided randomly into training and test sets. MEGs were decomposed using the algorithm for multiple unknown signals extraction (AMUSE). The extracted AMUSE components were characterised with two spectral – median frequency and spectral entropy (SpecEn) – and two non-linear features: Lempel-Ziv complexity (LZC) and sample entropy (SampEn). One-way analysis of variance with age as a covariate was applied to the training set to decide which components had the most significant differences between groups. Then, partial reconstructions of the MEGs were computed with these significant components. In the test set, the accuracy and area under the ROC curve (AUC) associated with each partial reconstruction of the MEGs were compared with the case where no BSS-preprocessing was applied. This preprocessing increased the AUCs between 0.013 and 0.227, while the accuracy for SpecEn, LZC and SampEn rose between 6.4% and 22.6%, improving the separation between AD patients and control subjects.     

Inhibitory Effects of Scutellaria Barbata D. Don. and Euonymus Alatus Sieb. on Aromatase Activity of Human Leiomyomal Cells

It is now well documented that a large proportion of breast tumors express their own aromatase. This intratumoral aromatase produces estrogen in situ and therefore may contribute significantly to the amount of estrogen to which the cell is exposed. Thus it is not only important that aromatase inhibitors potently inhibit the peripheral production of estrogen and eliminate the external supply of estrogen to the tumor cell, but that they in addition potently inhibit intratumoral aromatase and prevent the tumor cell from making its own estrogen within the cell. To study the inhibition of intracellular aromatase, we have examined the aromatase‐inhibiting potency of the Scutellaria barbata D. Don. (SB) and Euonymus alatus Sieb. (EA) in myometrial and leiomyomal cells which contain aromatase. We have also used human placental tissues. Although SB and EA are approximately equipotent in a cell‐free aromatase system (human placental microsomes), EA is consistently 10–30 times more potent than SB in inhibiting intracellular aromatase in myometrial and leiomyomal cells. To provide insights into the effect of SB and EA on aromatase activity in leiomyomal cells, we examined the cell lines, which is induced to differentiate toward the more transformed cell phenotype by 12‐tetradecanoylphorbal‐13‐acetate (TPA) as a protein kinase C activator and transforming growth factor‐β1 (TGF‐β1). Enzyme activity was inhibited in a time‐and dose‐dependent fashion by SB and EA and by either 1–50 nM TPA or 0.01–0.5 ng/ml TGF‐β1, with maximal responses after 2–3 h exposure.     

草药瑞香狼毒丙酮提取物与低剂量卡马西平或丙戊酸镁配伍的抗惊厥研究

目的:探讨草药瑞香狼毒丙酮提取物(AESC)与西药卡马西平(CBZ)、丙戊酸镁(VPM)配伍使用后抗癫痫效果,并与西药单药进行比较。方法:观察AESC和CBZ、VPM不同的配伍方式和剂量,对大鼠癫痫模型、小鼠电休克惊厥模型、小鼠戊四唑惊厥模型和小鼠印防已毒素惊厥模型的作用,并观察AESC对健康自愿受试者CBZ和VPM血药浓度的影响。结果:AESC 500 mg/kg与CBZ 30 mg/kg及VPM 68 mg/kg配伍后对上述三种模型的抗惊厥效应明显优于单用CBZ、VPM组(P<0.01)。结论:采用AESC与小剂量抗惊厥西药CBZ或VPM合理配伍使用可提高抗惊厥效应及减少抗惊厥西药剂量,从而减少西药剂量相关的副作用,具有抗惊厥效应好、抗癎谱广、减少副作用等优点。