Sialocele (ranula) simulating oral papillomatosis in a domestic (Oryctolagus) rabbit.

A sialocele originating in the duct of the sublingual salivary gland near its opening, close to the lingual frenulum, was observed as a naturally-occurring lesion in a laboratory rabbit. The lesion was assumed during necropsy dissection to be an oral papilloma. Microscopic examination of histologic sections revealed the lesion to have the characteristics of a sialocele (ranula).     

Visual-only assessments of skin lesions on free-ranging common bottlenose dolphins (Tursiops truncatus): Reliability and utility of quantitative tools

Photo analysis offers a simple, noninvasive approach to characterizing and quantifying skin lesions in cetaceans; however, this process involves methodological considerations that have often gone unaddressed or have varied in approach among investigators. Subjectivity associated with classifying skin lesion types of unknown etiology and quantifying measures of skin lesion prevalence and extent from photo data raises questions about observer bias and agreement (i.e., interrater reliability), which are often ignored. The purpose of the present study was to improve upon data quality control and assessment practices when studying skin lesions using only photo data. Specifically, we tested interrater reliability of a skin lesion classification system, compared methods of quantifying skin lesion extent, and determined the validity of the dorsal fin as a proxy for skin lesions on the entire body. Acceptable levels of interrater reliability were achieved for only 7 of 17 defined lesion types, but reliability was high for the two tested measures of lesion extent. Skin lesion extent measured from the dorsal fin alone was not a decent proxy for the whole visible surface; disparities between measures were as high as 43%. We discuss the potential pitfalls discovered and provide recommendations for others attempting similar approaches.     

Decreased cutaneous sensory axon-reflex vasodilatation below the lesion in patients with complete spinal cord injury

The histamine-induced skin flare response has been considered of practical value in determining the level of a spinal cord lesion, but clinical observations have varied widely with regard to the nature and degree of change below the lesion. We have quantified cutaneous sensory axon-reflex vasodilatation in patients with complete spinal cord injury (SCI) above and below the lesion, and compared the findings with normal subjects. Axon-reflex vasodilatation was induced by intradermal histamine injection, and measured by (a) laser Doppler fluxmetry and (b) tracing the surface area of the flare. Axon-reflex vasodilatation was present in all SCI patients above and below the lesion, but was significantly diminished below the lesion by both measures (pflux rise = 0.0008; pflare = 0.023), and in comparison with controls (by 39%). The flux increase was significantly correlated with the area of flare (r = 0.82; p = 0.02). Axon-reflex vasodilatation and visual analogue scale (VAS) pain scores on histamine injection were not significantly different above the lesion in SCI patients from controls. Baseline laser Doppler flux was not different at any test site in SCI and normal subjects. The cutaneous sensory axon-reflex is thus significantly diminished in SCI patients below the level of the lesion, but the underlying mechanism is unclear. A possible explanation under investigation is that increased basal or reflex sympathetic vasoconstriction mediated via the isolated spinal cord may counteract the vasodilatation produced by the cutaneous sensory terminals.     

Cognitive abilities and language comprehension in preschool children with perinatal brain lesion

Perinatal brain lesion is a risk factor for development, making parents of such children particularly worried about consequences it may have on the child's cognitive and language development. Although literature findings on the outcome of perinatal brain lesion are inconsistent, most of the studies have found a positive general outcome, but also subtle deficits that affect the child's academic success. Since language comprehension and cognitive abilities influence learning abilities at school, we wanted to know how six-year olds who were selected based on pathological ultrasonographical findings (ischemic or hemorrhagic brain lesion) would perform on subtests of Wechsler battery (WISC) and language comprehension measures (Reynell Developmental Language Scale and Peabody Picture Vocabulary Test), compared with controls. The second issue we investigated was whether in children who suffered a perinatal brain lesion cognitive abilities predicted the level of language comprehension in the same way as in children without perinatal brain lesion. The relation between cognitive and linguistic abilities is still a controversial one, and a different relation would mean that these two groups of children have different structure of abilities probably due to perinatal brain lesion. Forty children who suffered a perinatal brain lesion and forty age-matched children without perinatal risk factors were examined. Our results showed that the groups differed more in linguistic than in cognitive variables. Also, the two groups showed different relation patterns between cognitive abilities and language comprehension. Cognitive abilities were statistically significantly associated with language comprehension in children who suffered a perinatal brain lesion, while this association was not statistically significant within the control group. Since a number of participants with perinatal brain lesion had language difficulties, it is presumed that they rely on cognitive abilities in order to overcome and compensate for language shortcomings.     

血清胃泌素变化与急性胃粘膜病变关系的研究

对大白鼠血清中胃泌素水平的变化与急性胃粘膜病变的关系进行了初步的研究,结果表明以消炎痛为诱因引起的急性胃粘膜病变大白鼠血清胃泌素水平明显增高。而维酶素可以抑制因消炎痛引起的急性胃粘膜病变时血清胃泌素的释放,对胃粘膜具有保护作用。     

Characterizing rice lesion mimic mutants and identifying a mutant with broad-spectrum resistance to rice blast and bacterial blight

Many plant mutants develop spontaneous lesions that resemble disease symptoms in the absence of pathogen attack. In several pathosystems, lesion mimic mutations have been shown to be involved in programmed cell death, which in some instances leads to enhanced disease resistance to multiple pathogens. We investigated the relationship between spontaneous cell death and disease resistance in rice with nine mutants with a range of lesion mimic phenotypes. All nine mutations are controlled by recessive genes and some of these mutants have stunted growth and other abnormal characteristics. The lesion mimics that appeared on the leaves of these mutants were caused by cell death as measured by trypan blue staining. Activation of six defense-related genes was observed in most of the mutants when the mimic lesions developed. Four mutants exhibited significant enhanced resistance to rice blast. One of the mutants, spl11, confers non-race-specific resistance not only to blast but also to bacterial blight. The level of resistance in the spl11 mutant to the two pathogens correlates with the defense-related gene expression and lesion development on the leaves. The results suggest that some lesion mimic mutations in rice may be involved in disease resistance, and cloning of these genes may provide a clue to developing broad-spectrum resistance to diverse pathogens.     

Metastatic subcutaneous zygomycosis following intravenous and intracerebral inoculation of Absidia corymbifera spores.

A subcutaneous granuloma developed in a C3H mouse ca. 5 months after sequential intravenous and intracerebral inoculation of Absidia corymbifera spores. A. corymbifera was demonstrated microscopically and culturally in the lesion. Infection is believed to have been secondary to fungal infection of the kidney. The histopathological features of the lesion are described.     

Excitotoxin lesion of nucleus basalis causes a specific decrease in Go mRNA in cerebral cortex. Sensitivity to MK-801

Lesions of the ascending cholinergic pathway from nucleus basalis are known to have profound effects on cortical function. In particular, a substantial potentiation of carbachol-stimulated polyphosphoinositide turnover is detected from 1 day after lesion and is maintained for several days before returning to normal by 1 month. In this study the effect of this lesion was investigated on levels of three G-protein alpha-subunit mRNAs. Excitotoxin lesion of the nucleus basalis caused a selective reduction in the levels of Go alpha mRNA in cerebral cortex ipsilateral to the lesion, Gs alpha and Gi alpha mRNA being unaffected. The maximal effect was obtained at 3 days after lesion where levels of Go alpha mRNA were decreased by 40% compared to sham-operated animals. Levels of Go alpha mRNA returned to normal values by 28 days. Treatment with MK-801 caused a significant attenuation of the decrease in Go alpha mRNA, indicating the involvement of NMDA receptors in this response.     

Lesion radioactivity concentration estimation using dual modality gamma ray/X-ray imaging

Although the use of dedicated gamma cameras in scintimammography permits closer access to the breast and improved spatial resolution relative to conventional gamma cameras, the task of quantifying the radiotracer concentration in the lesion relative to that in the surrounding breast tissue remains challenging because of the lesion-depth-dependent effects of attenuation and collimator blur. We are developing a dual modality scanner that combines digital x-ray mammography and a dedicated gamma camera on a common upright gantry. Here we present the results of a phantom study evaluating the use of the dual modality system for quantifying radioactivity in breast lesions. In addition to assessment of lesion activity, lesion volume estimates are necessary to quantify lesion radioactivity concentration. We have used multiple view x-ray imaging as a means of estimating lesion volume. Using phantom experiments, we have empirically derived a formula for correction of the measured z dimension of the lesion. The error obtained in quantification of lesion activity is approximately 10%. Lesion volume can be assessed with an accuracy comparable to that of lesion activity assessment using five x-ray views. These results suggest that the error in lesion concentration assessment is approximately 14%.     

Biochemical reconstitution of abasic DNA lesion replication in Xenopus extracts

Cellular DNA is under constant attack from numerous exogenous and endogenous agents. The resulting DNA lesions, if not repaired timely, could stall DNA replication, leading to genome instability. To better understand the mechanism of DNA lesion replication at the biochemical level, we have attempted to reconstitute this process in Xenopus egg extracts, the only eukaryotic in vitro system that relies solely on cellular proteins for DNA replication. By using a plasmid DNA that carries a site-specific apurinic/apyrimidinic (AP) lesion as template, we have found that DNA replication is stalled one nucleotide before the lesion. The stalling is temporary and the lesion is eventually replicated by both an error-prone mechanism and an error-free mechanism. This is the first biochemical system that recapitulates efficiently and faithfully all major aspects of DNA lesion replication. It has provided the first direct evidence for the existence of an error-free lesion replication mechanism and also demonstrated that the error-prone mechanism is a major contributor to lesion replication.     

Temperature and the formation of radiation-induced chromosome aberrations. II. The temperature dependence of lesion repair and lesion interaction

Dicentric chromosome aberration yields have been measured after single-exposure and split-dose irradiations of human lymphocytes with 150 kV X-rays. Various temperature programmes between 4 and 37 degrees C were applied before, during and after irradiations and in the radiation-free interval. It was found that chromatin lesion repair was completely suppressed at 21 degrees C and below, whereas lesion formation is reduced only below 17 degrees C. The interaction between repairable lesions which leads to exchange-type aberrations is also suppressed by low temperatures. Hypothermic suppression of chromatin lesion repair and interaction is fully reversible at least up to 12 h of maintenance of the 'stored' state of these lesions.     

Site-specific mutagenesis using a gapped duplex vector: a study of translesion synthesis past 8-oxodeoxyguanosine in E. coli

We have constructed a gapped plasmid vector in which a single defined lesion is introduced, site-specifically, within a single-strand region. Efficiency of translesional synthesis is determined by the number of colonies recovered following transformation of E. coli. The nucleotide sequence of progeny plasmids in the gapped region of the vector reflects incorporation of bases opposite and near the lesion. The analysis detects non-mutagenic as well as mutagenic events. This system was used to establish the mutagenic potential of 2'-deoxy-7,8-dihydro-8-oxoguanosine (8-oxodG), a lesion produced by the action of active oxygen species on DNA. The presence of 8-oxodG did not affect the number of transformants recovered. Most transformants (greater than 99%) contained G:C pairs at the site of the lesion; however, a limited number of targeted G----T transversions were observed in the presence and absence of SOS induction. Base substitutions neighboring the lesion, reported for an in vitro system, were not observed. We conclude that the 8-oxodG lesion in DNA is weakly mutagenic in E. coli.     

Translesion synthesis past equine estrogen-derived 2'-deoxyadenosine DNA adducts by human DNA polymerases eta and kappa

Hormone replacement therapy (HRT) increases the risk of developing breast, ovarian, and endometrial cancers. Equilin and equilenin are the major components of the widely prescribed drug used for HRT. 4-Hydroxyequilenin (4-OHEN), a major metabolite of equilin and equilenin, promotes 4-OHEN-modified dC, dA, and dG DNA adducts. These DNA adducts were detected in breast tumor and adjacent normal tissues of several patients receiving HRT. We have recently found that the 4-OHEN-dC DNA adduct is a highly miscoding lesion generating C --> T transitions and C --> G transversions. To explore the mutagenic potential of another major 4-OHEN-dA adduct, site-specifically modified oligodeoxynucleotides containing a single diastereoisomer of 4-OHEN-dA (Pk-1, Pk-2, and Pk-3) were prepared by a postsynthetic method and used as DNA templates for primer extension reactions catalyzed by human DNA polymerase (pol) eta and kappa that are highly expressed in the reproductive organs. Primer extension catalyzed by pol eta or pol kappa occurred rapidly on the unmodified template to form fully extended products. With the major 4-OHEN-dA-modified templates (Pk-2 and Pk-3), primer extension was retarded prior to the lesion and opposite the lesion; a fraction of the primers was extended past the lesion. Steady-state kinetic studies with pol eta and pol kappa indicated that dTMP, the correct base, was preferentially incorporated opposite the 4-OHEN-dA lesion. In addition, pol eta and pol kappa bypassed the lesion by incorporating dAMP and dCMP, respectively, opposite the lesion and extended past the lesion. The relative bypass frequency past the 4-OHEN-dA lesion with pol eta was at least 2 orders of magnitude higher than that observed with pol kappa. The bypass frequency past Pk-2 was more efficient than that past Pk-3. Thus, 4-OHEN-dA is a miscoding lesion generating A --> T transversions and A --> G transitions. The miscoding frequency and specificity of 4-OHEN-dA varied depending on the stereoisomer of the 4-OHEN-dA adduct and DNA polymerase used.     

Varix of the digit

Varix of the digit is a rarely described lesion. Over 3 years, eight patients were diagnosed as having this abnormality. Surgical confirmation of the identity of the lesion was accomplished in six of these patients. Repetitive trauma, mechanical compression, and aging phlebectasia have all been associated with the pathogenesis of a digital varix. Thrombophlebitic and thrombotic changes occurring within the varix may lead to an erroneous assessment and clinical confusion. In such instances, a tourniquet test has been useful in demonstrating the presence of a varix. Excision of a symptomatic lesion has proven to be curative for all six patients. Two patients have been observed for 3 years with little change and no resolution of the varix. It is probable that varix of the digit is a more common lesion than indicated by a review of the literature.     

杏仁中央核损毁对缺钠大鼠钠欲行为启动和表达的影响

目的:探讨杏仁中央核(CeA)损毁对缺钠大鼠钠欲行为启动和表达的影响。方法:将18只成年雄性SD大鼠随机分为3组(n=6):双侧Ce A损毁组、假损毁组和不损毁组,手术恢复后给予大鼠14 d低钠饲料摄食以建立缺钠大鼠模型,运用单笼双瓶选择测试方法观察缺钠大鼠在24 h内5个不同时间段对0.3 mol/L NaCl和自由饮水的摄入情况。应用免疫荧光化学染色方法观察杏仁中央核损毁与否对缺钠或正常大鼠孤束核内醛固酮敏感神经元活动的影响。结果:低钠饮食14 d后,大鼠对0.3 mol/L NaCl 24 h内饮用量和偏爱率比低钠饮食前明显增加(P<0.01);杏仁中央核损毁后缺钠大鼠对0.3 mol/L Na Cl溶液的摄入量和偏爱率显著下降(P<0.01)。杏仁中央核损毁对低钠饮食诱发的大鼠孤束核内醛固酮敏感神经元活动增加没有影响。结论:低钠饮食诱导大鼠钠欲行为表达增加;杏仁中央核损毁压抑缺钠大鼠钠欲行为的表达,而对缺钠大鼠的钠欲行为的启动没有影响。     

Insertional inactivation of genes to isolate mutants of Synechococcus sp. strain PCC 7942: isolation of filamentous strains.

We have developed a simple procedure for generating mutants of the cyanobacterium Synechococcus sp. strain PCC 7942 in which the site of the lesion can be readily identified. This procedure involves transforming Synechococcus sp. strain PCC 7942 with a library of its own DNA that was fully digested with Sau3A and ligated into the plasmid vector pUC8. The homologous integration of the recombinant plasmid into the genome will often result in the disruption of a gene and the loss of gene function. We have used this method to generate many mutants of Synechococcus sp. strain PCC 7942 which grow as multicellular filaments rather than as unicells. Since the gene harboring the lesion was tagged with pUC8, it was easily isolated. In this paper, we discuss the usefulness of this procedure for the generation of mutants, and we characterize one mutant in which the lesion may be in an operon involved in the assembly of lipopolysaccharides.     

Error-free bypass of 2-hydroxyadenine by human DNA polymerase lambda with Proliferating Cell Nuclear Antigen and Replication Protein A in different sequence contexts

1,2-dihydro-2-oxoadenine (2-OH-A), a common DNA lesion produced by reactive oxygen species, is a strong replicative block for several DNA polymerases (DNA pols). We have previously shown that various bases can be misincorporated opposite the 2-OH-A lesion and the type of mispairs varies with either the sequence context or the type of DNA pol tested. Here, we have analysed the ability of the human pol family X member DNA pol λ, to bypass the 2-OH-A lesion. DNA pol λ can perform error-free bypass of 2-OH-A when this lesion is located in a random sequence, whereas in a repeated sequence context, even though bypass was also largely error-free, misincorporation of dGMP could be observed. The fidelity of translesion synthesis of 2-OH-A in a repeated sequence by DNA pol λ was enhanced by the auxiliary proteins Proliferating Cell Nuclear Antigen (PCNA) and Replication Protein A (RP-A). We also found that the DNA pol λ active site residue tyrosine 505 determined the nucleotide selectivity opposite 2-OH-A. Our data show, for the first time, that the 2-OH-A lesion can be efficiently and faithfully bypassed by a human DNA pol λ in combination with PCNA and RP-A.     

An oscillating extracellular voltage gradient reduces the density and influences the orientation of astrocytes in injured mammalian spinal cord

We have studied the cellular basis for recovery from acute spinal cord injury induced by applied electric fields. We have emphasized this recovery is due to the regeneration of spinal axons around and through the lesion, and have begun to evaluate the contribution of other cells to the recovery process. We have imposed a voltage gradient of about 320 μV/mm across puncture wounds to the adult rat spinal cord in order to study the accumulation and orientation of GFAP⁺ astrocytes within and adjacent to the lesion. This electric field was imposed by a miniaturized electronic implant designed to alternate the polarity of the field every 15 minutes. Astrocytes are known to undergo hyperplastic transformation within injured mammalian cords forming a major component of the scar that forms in response to injury. We have made three observations using a new computer based morphometry technique: First, we note a slight shift in the orientation of astrocytes parallel to the long axis of the spinal cord towards an imaginary reference perpendicular to this axis by approximately 10°—but only in undamaged white matter near the lesion. Second, the relative number of astrocytes was markedly, and statistically significantly, reduced within electrically—treated spinal cords, particularly in the lesion. Third, the imposed voltage gradient statistically reduced the numbers of astrocytes possessing oriented cell processes within the injury site compared to adjacent undamaged regions of spinal cord.     

植物类病变突变体的诱发与突变机制

植物类病变突变体（lesion mimic mutant,LMM）是在无明显逆境或病原物侵染时,植物自发地形成类似病斑的一类突变体。它涉及到细胞程序性死亡（programmed cell death,PCD）,往往能提高植物的抗病能力。因此,它对于揭示植物抗病反应机制,增加植物的广谱抗性具有重要意义。现就植物类病变突变体的诱发与表型特点、突变基因的分子定位与克隆及类病变表型的形成机制研究进展作一简要综述,以期为植物细胞程序性死亡机制和抗病分子作用机制研究提供有益的信息。