Cytoskeletal and muscle-like elements in cochlear hair cells

Summary Monospecific antibodies to actin and to tubulin were used as immunofluorescent probes to evaluate the distribution of microtubules and actin filaments in the organ of Corti in mouse and guinea pig. The results indicate that in cochlear receptor cells actin and actin filaments as well as tubulin and microtubules are integral cytoskeletal elements. The presence of actin suggests a possible contractile mechanism within the sensory cilia whereas tubulin is thought to play an important role in the stability of sensory cells. Both proteins are discussed to form structural elements required for the mechano-chemical coupling in hearing.

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Abbreviations ATP adenosin-tri-phosphate - SDS sodium-dodecyl-sulphate - PBS phosphate-buffered saline Dedicated to Professor Dr. A. Herrmann on the occasion of his 80th birthday     

Ischemic rat brain extracts induce human marrow stromal cell growth factor production

Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain.     

A correlative study of the restorative effects of endogenous and exogenous hormones on the Leydig cells, the testis and the epididymis of the regressed hedgehog Effects of hormones on hedgehog Leydig cells

The study of the effects of morphogenesis at puberty on the Leydig cells in the testis of the young hedgehog and of the subsequent changes due to the seasonal varisations, has been done. Furthermore, the restorative changes induced by the exogenous hormones in the Leydig cells and the related sex organs of the regressed hedgehogs have also been studied. It was observed that the Leydig cells from the undifferentiated mesenchyme cell-like nature in the young hedgehog, develop into an adult form possessing large number of lipids, a well-developed Golgi apparatus, complex mitochondria and extensive smooth endoplasmic reticulum. The depletion of the lipids and other regression associated changes are found in the interstitial Leydig cells but not in those situated under tunica albuginea and the latter probably function as lipid storing cells during regression. Pituitary extract, either alone or in combination, but not testosterone, could restore completely the structure of the regressed Leydig cells. Similarly, the restoration of the complete process of spermatogenesis and the structure and function of the epididymis in the regressed hedgehog was found to be dependent upon the synergistic action of both testosterone and the gonadotrophic hormones.     

二乙酰二脱水卫矛醇对小鼠白血病L1210细胞增殖的影响

目的　研究二乙酰二脱水卫矛醇 (1 ,2 :5 ,6 dianhydro 3 ,4 diacetylgalactitol,DADAG)的抗脑白血病作用及机制。方法　用小鼠脑内移植瘤模型、MTT法、DNA掺入法、流式细胞仪和Westernblot法 ,观察DADAG对小鼠脑内移植瘤和体外白血病L1 2 1 0 细胞的作用 ,并探讨作用机制。结果　DADAG对DBA/ 2小鼠脑内移植白血病L1 2 1 0 有明显的抑制作用 ;对体外白血病L1 2 1 0 细胞同样有很强的抗增殖作用 ,其IC50 值为 2 4 6mg·L- 1 。DADAG不可逆地抑制L1 2 1 0 细胞内DNA的生物合成。DADAG 2 4mg·L- 1 处理L1 2 1 0 细胞 6h后 ,细胞发生G2 /M周期阻滞 ,2 4h后达最高峰。细胞周期素B1 蛋白水平在DADAG处理 2 4h后开始下降 ,而磷酸化的细胞周期依赖性激酶CDK1在DADAG处理 6h后开始上调 ,并呈时间依赖性。结论　DADAG的抗脑白血病作用与其抑制白血病细胞的增殖密切相关     

Clinical experience with the use of rhG‐CSF in secondary autoimmune neutropenia

This paper outlines the impact of granulocyte‐colony stimulating factor (G‐CSF) used as a single modality therapy in 17 patients with secondary autoimmune neutropenia (S‐AIN) who had been treated a multiple number of times previously. Fifteen of these patients had demonstrable antineutrophil antibodies and two had cellular S‐AIN with haemopoietic inhibitory T‐cells present in the marrow. Prior to treatment, all had had problems with infection. All patients responded within 7 days of commencement of treatment. Provided G‐CSF neutrophil counts were maintained above 1 × 10⁹/l, no further infections occurred. This was achievable by using G‐CSF administered as infrequently as once every 8 days. Eight of the 17 patients remained on G‐CSF, although five switched to the glycosylated form because of side‐effects. None have developed osteoporosis despite 47.29 patient years of total experience with G‐CSF. In conclusion both glycosylated and nonglycosylated G‐CSF can be used effectively in treating AIN on a long‐term basis.     

rhGM—CSF对小鼠口腔粘膜损伤的防治作用

目的：观察rhGM-CSF对TMX致实验性小鼠口腔粘膜损伤的疗效。方法：按随机分组原则将501只昆明种小白鼠分成8组，分别在相应时间给予不同药物（MTX，CF或rhGM-CSF）的处理因素，于第1－10天光镜下观察小鼠口腔粘膜的病理改变和积分情况。结果：IDMTX致口腔粘膜损伤病变率（45％－63％）和积分率（19．4％－56％）较其它组高，且死亡率很低（小于5％）；IDMTX＋GM0（或GM2）组的口腔粘膜损伤病变率（30．53％和30．99％）和积分率（19．47％和17．25％）比IDMTX组（55．56％和36．31％）明显减少，且溃疡严重程度较轻，二者相差显著（P＜0．01）。结论：IDMTX致小鼠口腔粘膜损伤模型可以用于粘膜损伤的研究；rhGM-CSF可以减少MTX致小鼠口腔粘膜损伤，并促进粘膜损伤恢复。     

Le syndrome de Lazare: une problématique de la rémission. Réflexions autour de la maladie cancéreuse chez l’adulte

Résumé: La rémission du cancer peut être l’occasion pour certains patients d’une réelle détresse émotionnelle ainsi que d’une désadaptation psychologique appelées: syndrome de Lazare. Nous émettons trois hypothèses explicatives quant à la survenue de tels troubles. La première confronte l’issue du cancer aux concepts psychanalytiques de dette et de masochisme. La deuxième envisage les symptômes sous l’angle d’une réaction de sevrage. Et la dernière évoque le contrecoup traumatique des traitements.Dossier: «Cliniques du cancer»     

Changes in immune regulation in response to examination stress in atopic and healthy individuals

BACKGROUND: Stress can aggravate the allergic inflammation, but determinants of disturbed immune regulation are largely unknown. OBJECTIVE: To determine systemic immunological, local inflammatory and functional airway responses to stress in healthy and atopic individuals. METHODS: Forty-one undergraduate students, 22 with allergy of whom 16 had asthma, and 19 healthy controls, were studied in a low-stress period and in association with a large exam. Subjects completed questionnaires on stress and health behaviours, underwent lung function tests, bronchial methacholine challenge, measurements of exhaled nitric oxide and urine cortisol. Blood cells were phenotyped, and cytokines from mononuclear blood cells were analysed. RESULTS: Perceived stress and anxiety increased in both groups during the exam period while cortisol increased only in the atopy group. Cytokine production decreased broadly in response to stress in both groups, which was paralleled by an increase in the proportion of regulatory T cells (CD4(+)CD45RO(+)CD25(bright)). Interestingly, atopic individuals, but not controls, reacted with a decreased T-helper type 1/T-helper type 2 (Th1/Th2) ratio and a decrease in natural killer (NK) cell numbers in response to stress. In control subjects only, exhaled nitric oxide decreased and forced expiratory volume in one second increased during stress. CONCLUSION: Atopic and non-atopic subjects shared some immune changes in response to stress, such as a dramatic decline in cytokines and an increase in the number of regulatory T cells in peripheral blood. However, other stress-induced immune changes were unique to atopic individuals, such as a skewed Th1/Th2 ratio and reduced NK cell numbers, indicating that some pathogenic mechanisms in atopics may be more strongly affected by stress than others.     

B cells as a target of immune modulation

B cells have recently been identified as an integral component of the immune system; they play a part in autoimmunity through antigen presentation, antibody secretion, and complement activation. Animal models of multiple sclerosis (MS) suggest that myelin destruction is partly mediated through B cell activation (and plasmablasts). MS patients with evidence of B cell involvement, as compared to those without, tend to have a worse prognosis. Finally, the significant decrease in new gadolinium-enhancing lesions, new T2 lesions, and relapses in MS patients treated with rituximab (a monoclonal antibody against CD20 on B cells) leads us to the conclusion that B cells play an important role in MS and that immune modulation of these cells may ameliorate the disease. This article will explore the role of B cells in MS and the rationale for the development of B cell–targeted therapeutics. MS is an immune-mediated disease that affects over 2 million people worldwide and is the number one cause of disability in young patients. Most therapeutic targets have focused on T cells; however, recently, the focus has shifted to the role of B cells in the pathogenesis of MS and the potential of B cells as a therapeutic target.     

Involvement of ADAM10 in axonal outgrowth and myelination of the peripheral nerve

The disintegrin and metalloproteinase 10 (ADAM10) is a membrane‐anchored metalloproteinase with both proteolytic and disintegrin characteristics. Here, we investigate the expression, regulation, and functional role of ADAM10 in axonal outgrowth and myelination of the peripheral nerve. Expression pattern analysis of 11 ADAM family members in co‐cultures of rat dorsal root ganglia (DRG) neurons and Schwann cells (SCs) demonstrated the most pronounced mRNA expression for ADAM10. In further studies, ADAM10 was found to be consistently upregulated in DRG‐SC co‐cultures before the induction of myelination. Neurons as well as SCs widely expressed ADAM10 at the protein level. In neurons, the expression of ADAM10 was exclusively limited to the axons before the induction of myelination. Inhibition of ADAM10 activity by the hydroxamate‐based inhibitors GI254023X and GW280264X resulted in a significant decrease in the mean axonal length. These data suggest that ADAM10 represents a prerequisite for myelination, although its activity is not required during the process of myelination itself as demonstrated by expression analysis of myelin protein zero (P0) and Sudan black staining. Hence, during the process of myelin formation, ADAM10 is highly upregulated and appears to be critically involved in axonal outgrowth that is a requirement for myelination in the peripheral nerve. © 2009 Wiley‐Liss, Inc.