Inhibitory effect of oral administration of Lactobacillus casei on 3-methylcholanthrene-induced carcinogenesis in mice

The present study was designed to determine whether tumor induction by 3-methylcholanthrene (MC), a carcinogenic hydrocarbon, can be inhibited by oral administration of Lactobacillus casei strain Shirota (LC). C3H/HeN mice were divided into four groups and assigned to the following treatments: treated with MC and given control or LC-containing diet; treated with vehicle only and given control or LC-containing diet. MC (1 mg) was injected intradermally at 7 weeks of age and the tumor incidence was monitored; LC was mixed into a diet at a concentration of 0.05% (w/w) and the diet was fed from the day of MC injection throughout the study. Spleen cells were analyzed for the immune parameters at 12 and 16 weeks after the MC injection. Oral feeding of mice with LC reduced tumor incidence (P < 0.05). MC treatment lowered the in vitro response to concanavalin A (Con A) of spleen cells, the secretion of interleukin-2 in spleen cell culture after stimulation of the cells with Con A and the proportions of CD3⁺, CD4⁺ and CD8⁺ splenic cells. However, the analysis of the spleen cells obtained from the mice treated with MC and given the LC-containing diet revealed that these disrupted host immune parameters were maintained at the level of normal controls. These results suggest that oral feeding of mice with LC inhibits MC-induced tumorigenesis by modulating the disrupted host immune responses during MC carcinogenesis. Received: 14 April 1999     

Presence and course of the incisive canal in the human mandibular interforaminal region: two-dimensional imaging versus anatomical observations

The objective of the present study was to evaluate the presence and course of the incisive canal in the mental interforaminal region of the human mandible and to describe the occurrence of anatomical variations. Mandibles of 50 adult human cadavers were retrieved from the Department of Anatomy of the Faculty of Medicine, Katholieke Universiteit Leuven (Leuven, Belgium). Forty mandibles were edentulous, while 10 mandibles were partially dentate. Intra-oral, panoramic and tomographic imaging of the interforaminal region of the human mandible were performed. Afterwards, mandibles were sawn into vertical sections according to the respective tomographic cross-sections. The latter allowed exploration for the presence and course of an anterior prolongation of the mandibular canal. Measurements of the location of the incisive canal towards the base of the mandible were made using a digital-sliding caliper. Results indicated a well-defined incisive canal [mean (SD) inner diameter 1.8 (0.5 mm)], macroscopically observed in 96% of mandibles. The incisive canal was located on average 9.7 mm (SD 1.8 mm) from the lower cortical border and continued towards the incisor region in a slightly downward direction, with a mean (SD) distance to the lower cortical border of 7.2 (2.1) mm. It was concluded that there is an anterior intraosseous extension of the mandibular canal, denoted as the incisive canal. The latter might be considered as a true anterior extension of the neurovascular bundle. Histological and neurophysiological studies are needed to verify this hypothesis and evaluate its potential clinical implications.

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Electronic Supplementary Material The french version of this article is available in the form of electronic supplementary material and can be obtained by using the Springer Link server located at .D. van Steenberghe is holder of the Prof. P-I. Brånemark Chair in Osseointegration     

Mitochondrial DNA polymorphisms in Yunnan nationalities in China

Nucleotide sequences of the D-loop region of human mitochondrial DNA from four Yunnan nationalities, Dai, Wa, Lahu, and Tibetan, were analyzed. Based on a comparison of 563-bp sequences in 99 people, 66 different sequence types were observed. Of these, 64 were unique to their respective populations, whereas only 2 types were shared between the Lahu and Wa nationalities. The D-loop sequence variation and phylogenetic analysis suggested that the 99 mtDNA lineages were classified into eight clusters in the phylogenetic tree. All lineages that had a 9-bp deletion in the COII/tRNA^Lys intergenic region appeared in one cluster in the D-loop tree, suggesting a single event of the deletion in the Yunnan nationalities studied. Genetic distances, based on net nucleotide diversities between populations including Han Chinese and mainland Japanese, revealed that the Dai, Wa, Lahu, and Han Chinese are closely related to each other, while Tibetan and mainland Japanese formed a single cluster. The bootstrap probabil-ity of separation between the Dai-Wa-Lahu-Chinese clade and the Tibetan-Japanese clade was 99%, indicating that there are at least two different origins among minority groups in Yunnan province. Although the genetic distance between Tibetan and Japanese within the clade is rather long, the results may shed light on the origins of mainland Japanese. Received: December 22, 2000 / Accepted: January 18, 2001     

Miltefosine (Impavido): the first oral treatment against leishmaniasis

Miltefosine is a novel antileishmanial drug that has significant selectivity in both in vitro and in vivo models. Clinical efficacy was demonstrated for the treatment of visceral leishmaniasis with the advantage of oral administration over the currently recommended antileishmanial drugs that require parenteral administration. Miltefosine produces high cure rates also in patients resistant to the standard antimonial therapy.     

Interepithelial cells of the oral mucosa in mice

Summary Non-epithelial mesenchymal and neuroectodermal cells occur between the keratinocytes in the stratified squamous epithelium of the oral mucosa. These cells cannot be classified adequately by light microscopy. In the present study the oral mucosa of the lip, cheek and tongue of 50 mice were studied by light and electron microscopy. 3,025 mononuclear interepithelial cells were documented and analysed.Monocytogenic macrophages, plasma cells and mast cells were not found interepithelially and cannot be regarded as a regular constituent of the epithelium. Only a few neuroectodermal cells — in mice these are exclusively Merkel cells, with no melanocytes — were localized in the epithelium. The majority of the interepithelial cell population is made up of lymphocytes (22.8%) and Langerhans cells (56.8%). They are an integral constituent of the epithelium. Lymphocytes with rounded and indented nuclei can be identified. The larger and dendritic Langerhans cells are a specific cell of squamous epithelium and also occur in the oral mucosa. Not all cells which feature the cytological characteristics of Langerhans cells contain Langerhans or Birbeck granules. Accordingly these granules cannot be considered an exclusive identification characteristic. Two types of Langerhans cells can be differentiated. 80.9% have the more or less typical appearance known from the epidermis and were termed macrophagocytoid Langerhans cells. The nuclei are irregularly indented and moderately heterochromatic. 19.1% possessed conspicuous large, spherical, euchromatic nuclei and an electron-lucent cytoplasm. These were termed reticuloid Langerhans cells. About 20% of the interepithelial cell population could not be identified, neither as typical lymphocytes nor as Langerhans cells. These were small to medium sized cells with deeply indented cerebriform strongly heterochromatic nuclei. They are similar to the Sézary cells or mycosis fungoides cells of epidermotropic human T-cell lymphomas. The lymphocytic nature of these cells has been confirmed. It seems likely that differentiation of lymphocytes to cerebriform cells occurs within the epithelium. It is further discussed whether cerebriform cells are precursors of Langerhans cells, a conclusion suggested morphologically by transitional forms. This would imply that Langerhans cells originate from lymphocytes, and that the cerebriform cell is an intermediate step of differentiation. The microenvironment of the squamous epithelium may play a role in the process of differentiation, which could explain the epitheliotropy of lymphocytes. The possibility is considered that Langerhans cells and interdigitating reticulum cells of the T-cell area of lymph nodes are identical. The close functional cooperation of Langerhans cells, lymphocytes, and interdigitating reticulum cells in immunological defenses against external antigens is discussed.The authors wish to express their sincere appreciation to Miss P. Starck and Miss I. Brandt for invaluable technical assistance in this project.     

Gene conversion-like sequence transfers in a mouse antibody transgene: antigen selection allows sensitive detection of V region interactions based on homology.

Gene conversion is important for antibody diversification in chickens, rabbits and cows. In mice, however, conversion events appear to be infrequent among endogenous antibody genes. DNA sequence transfer events that resemble gene conversions have been reported for a mouse H chain transgene (VVC(mu)) that contains two closely spaced homologous VDJ segments. Surprisingly, these reported VVC(mu) sequence transfers were found frequently among mouse B cells responding to immunization. Transgene sequence transfers could be occurring at high frequency in responding VVC(mu) B cells or could be occurring at lower frequency with subsequent amplification by preferential antigen selection. To distinguish these possibilities, we have analyzed a second transgene (InVVC(mu)) that is identical to VVC(mu) except that the two VDJ regions have been exchanged in position. We find that transgene sequence transfers are much less frequent among responding B cells in InVVC(mu) mice, demonstrating the importance of selection in the frequent transgene conversions observed in VVC(mu) mice. These results suggest that mice, like other species, can use gene conversion to diversify antibodies. Such diversification events are apparently infrequent, however, and might only be detected among endogenous Ig genes with a favorable arrangement of V genes and an antigenic stimulation that selects cells with conversions. For both VVC(mu) and InVVC(mu) mice, conversion-like sequence transfers are strongly correlated with somatic hypermutation. Based on these results, we hypothesize that, in mice, gene conversions represent infrequent alternative reactions of a homology-based DNA repair process that is central in the somatic hypermutational mechanism.     

老年人口腔白色念珠菌的分布与基因分型研究

目的研究健康老年人口腔白色念珠菌的分布、基因型特点及基因型特点与白色念珠菌分布的相关性。方法来自成都地区212例老年人分为4组：A1（男性，有义齿）；A2（男性，无义齿）；B1（女性，有义齿）和B2（女性，无义齿）。CHROMagar Candida^TM鉴定培养基、碳水化合物同化反应鉴定体系（API 20C AUX）和随机扩增片段多态性分析（randomly amplified polymorphic DNA assays，RAPD）鉴定白色念珠菌。RAPD分析健康老年人口腔白色念珠菌分离株的基因型特征。统计学分析比较不同分组健康老年人口腔白色念珠菌基因型之间的差异。结果212例受检个体中检出89株白色念珠菌（42％），A1、A2、B1、B2白色念珠菌检出率分别为56．2％、21．3％、56．6％、38％。A1组与A2组白色念珠菌检出率差异有统计学意义，P〈0．01。以JWFP和NA为随机引物的RAPD分析将白色念珠菌分为5型。RAPD分析基因型构成在A1组与A2组之间比较差异有统计学意义，P〈0．05，A1组主要以A型为主。结论健康老年人口腔白色念珠菌的检出率与义齿修复相关。义齿修复可能促进具有特定基因型特点的白色念珠菌检出率增高。     

抗人白细胞间素-2多克隆及单克隆抗体的生物学特征

利用人工合成的白细胞间素2(IL-2)多肽片段,用中和试验、竞争ELISA和染色IL-2分泌细胞的碱性磷酸酶抗碱性磷酸酶桥联酶标技术,对己制备的抗人IL-2多克隆抗体及单克隆抗体(McAb)的表位特异性、中和活性、亲和常数及杭天然IL-2的反应性进行了全面鉴定。结果表明:利用多种免疫方案、融合前强化加强免疫及多个脾脏混合融合制备策略所获得的McAb,在生物学特征上表现出多样化,即这些McAb的表位特异性、中和活性、亲和力及抗天然IL-2活性各不相同。其中抗IL-2 C末端的McAb为首次报道。这组McAb适用于对IL-2研究的不同目的。     

A B220(-), CD19(-) population of B cells in the peripheral blood of quasimonoclonal mice

We describe a new population of non-naive B cells in the peripheral blood of quasimonoclonal (QM) mice. Surface Ig of switched isotypes is expressed, but not B220 nor CD19. These cells are larger and denser than naive B cells but smaller than blasts or plasma cells; they do not stain with syndecan, a marker for plasma cells. Telomerase, which is usually expressed in B cell blasts, was not present in this population. We sorted the switched, idiotype-positive, B220(-) B cells from the peripheral blood of QM mice and sequenced Ig H chain and lambda L chain cDNA. There were many point mutations but no V gene replacements, gene conversions or other type of diversifications. As they express switched isotypes and have mutated their Ig genes, cells in the B220(-), CD19(-) population must have been in an immune response and we suggest that it includes the memory B cell subset.     

Mechanoreceptor activity from the human face and oral mucosa

Summary The feasibility of adopting the microneurography technique (Vallbo and Hagbarth 1968) as a tool to investigate the mechanoreceptive innervation of peri- and intra-oral tissues was explored. Multi-unit activity and impulses in single nerve fibers were recorded from the infraorbital nerve in healthy volunteers. The innervation territories of individual nerve fascicles were mapped. These varied considerably but most fascicle fields comprised the corner of the mouth. Twenty-four single mechanoreceptive units were recorded. Eighteen innervated the skin of the face, and six innervated the mucous membranes of the lips or cheeks. A majority of the mechanoreceptive afferent units were slowly adapting with small and well defined receptive fields. It is suggested that the various slowly adapting responses may originate from two different types of afferent units. No afferents showed response properties similar to typical Pacinian-corpuscle afferents.