Light-evoked expansion of subretinal space volume in the retina of the frog.

The retina of the frog was superfused with a Ringer solution containing impermeant "probe" cations and anions. Light-evoked concentration changes in these probe ions were measured in the subretinal space (SRS) with ion-selective microelectrodes. A decrease in probe ion concentration was found, and several observations suggest that this is caused by a light-evoked expansion of the SRS. The probe ion decrease was not seen in the isolated retina; thus, the pigment epithelial (PE) cells are important for its generation. Pharmacological studies suggest that K+ channels in the PE cells are important--perhaps the PE cells shrink in response to the light-evoked decrease in SRS [K+]. The light-evoked decrease of SRS volume may be important in the understanding of SRS solute concentrations, retina-PE adhesivity, photoreceptor-PE cell interactions, and the interphotoreceptor matrix.     

Efficacy of sonothrombolysis in a rat model of embolic ischemic stroke

The key goal in the treatment of acute ischemic stroke is fast vessel recanalization. Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is efficient in humans but mean time for recanalization is within hours. Ultrasound bio-effects has been shown to facilitate rt-PA mediated thrombolysis in peripheral arteries. We used an embolic stroke model in the rat. In all rats we induced an ischemic stroke by a selective occlusion of the middle cerebral artery with whole blood clots. From an entire collective of 54 rats 47 completed the protocol (n = 7 died early). Four different groups (no treatment n = 6; full dose rt-PA treatment only [10 mg/kg per body weight] n = 14, half dose rt-PA treatment plus ultrasound n = 10, and full dose rt-PA treatment plus ultrasound n = 17) were investigated. We found a significant reduction of absolute as well as relative infarct volume in the full dose rt-PA plus ultrasound group (81+/-72 mm(3); P< 0.05) in comparison to untreated rats (253+/-159 mm(3); P < 0.05) as well as in comparison to rats treated with full dose rt-PA only (167+/-91 mm(3); P < 0.05). There were five intracranial bleedings giving a bleeding rate of 9.3%. In summary: ultrasound treatment in addition to rt-PA is more effective than single rt-PA treatment in reducing infarct volume and safe with regard to bleeding.     

Preferential synthesis of IgE reaginic antibodies in rats immunized with alum-adsorbed antigens.

The reaginic antibody response to alum-precipitated ovalbumin (OA) and the dialyzed water-soluble extracts of ragweed (DWSR) and Alternaria tenuis (DWST) in several strains of rats appeared to be wholly an IgE response. There was no evidence of a heat-stable (IgGa) antibody to OA, DWSR and DWST in the sera of the rats immunized with these antigens suspended in alum. Wistar-Furth and Lew inbred and hooded outbred rats produced comparable amounts of reaginic antibody after immunization with DWST, but BN inbred rats failed to generate a reaginic response to this antigen. The amount of antigen-induced histamine release from rat peritoneal mast cells did not always correlate with the level of circulating IgE-specific antibody.     

Effects of omalizumab and budesonide on markers of inflammation in human bronchial epithelial cells.

BACKGROUND: Many patients with asthma have an IgE-mediated allergic component to the disease. Omalizumab, a monoclonal anti-IgE antibody, has demonstrated clinical efficacy in patients with allergic asthma. The effects of omalizumab on inflammation in asthma are not completely understood. OBJECTIVES: To evaluate the effects of omalizumab on allergen- and growth factor-stimulated proinflammatory cytokine and nitric oxide (NO) production in human bronchial epithelial cells (BECs) and to compare them to the effects of budesonide, a corticosteroid with known anti-inflammatory properties. METHODS: Human BECs were stimulated in duplicate with interleukin 1beta (IL-1beta), 100 U/mL; ragweed, 10 microg/mL; dust mite, 1000 AU; and epithelial growth factor, 40 ng/mL; and either 10(-7) M budesonide or 0.1 microg/mL of omalizumab in a 4% dust mite atopic serum medium for 6 and 24 hours in 5% carbon dioxide at 37 degrees C. Tumor necrosis factor alpha and transforming growth factor betaexpression and production and IL-4, IL-13, and NO production were assayed using gene-specific messenger RNA or sensitive enzyme-linked immunosorbent assays. RESULTS: Omalizumab inhibited the expression and of production proinflammatory cytokines and growth factor in antigen-stimulated BECs at 6 and 24 hours. Production of NO was inhibited at 6 hours and increased at 24 hours by omalizumab and budesonide. CONCLUSIONS: The effects of omalizumab were similar to those of budesonide. These results, consistent with previously reported evidence of anti-inflammatory effects of omalizumab, demonstrate that omalizumab may reduce airway inflammation and probably contributes to decreased airway remodeling in patients with asthma.     

The extracellular matrix of pulmonary scar carcinomas is suggestive of a desmoplastic origin.

Pulmonary scar carcinomas and noncarcinomatous apical scars were subjected to collagen extraction, ultrastructural, and immunocytochemical studies designed to investigate the nature of their extracellular matrix. These studies revealed marked differences in both cellular and biochemical composition of scar carcinomas, compared with apical scars. Myofibroblasts, identified by antimyosin antibodies and confirmed by electron microscopy, constituted over 90% of the stromal cells of the scar carcinomas, compared with 0-10% in the apical scars. Collagen extraction studies revealed both an absolute and relative increase in Type V collagen in the scar carcinomas, compared with that found in the apical scars. The extracellular matrix of the pulmonary scar carcinomas was, however, identical to that of scirrhous carcinomas of the breast. These findings suggest that pulmonary scar carcinomas are probably desmoplastic carcinomas, rather than scar-arising tumors.     

培养细胞整装内质网三维结构的多态性

用高锰酸钾－锇酸固定法制备了５种培养细胞整装内质网标本，并在扫描电镜下对其三维结构进行了观察。观察结果表明内质网是由膜性小管构成的贯穿整个细胞质的管囊网络样膜性区室，并以多种形态深入到细胞伪足及突起中；细胞质中内质网则表现为簇状网络（见于ＧＣＭ３Ｔ３细胞）、多态性多孔扁囊样网络、筛网状网络、条索状网络、大孔条索网状和细孔扁囊样分区网络、不规则管网状和多孔管囊分区网络（见于ＣＶ－１细胞）、细管网络（见于ＣＣＬ１８７和ＣＣＬ２２９细胞）、球囊网络（见于ＣＣＬ１８７和Ａ４３１细胞）和不规则管网状网络（见于Ａ４３１细胞）等。内质网的这种多态性提示它是一种高度可变的结构，其可变性可能与细胞特性、分化程度、细胞功能状态及细胞骨架系统的分布变化等因素有关。     

The influence of normal human ageing on automatic movements

There is evidence that aged normal subjects have more difficulty in achieving automaticity than young subjects. The underlying central neural mechanism for this phenomenon is unclear. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the effect of normal ageing on automaticity. Aged healthy subjects were asked to practice self-initiated, self-paced, memorized sequential finger movements with different complexity until they could perform the tasks automatically. Automaticity was evaluated by having subjects perform a secondary task simultaneously with the sequential movements. Although it took more time, most aged subjects eventually performed the tasks automatically at the same level as the young subjects. Functional MRI results showed that, for both groups, sequential movements activated similar brain regions before and after automaticity was achieved. No additional activity was observed in the automatic condition. While performing automatic movements, aged subjects had greater activity in the bilateral anterior lobe of cerebellum, premotor area, parietal cortex, left prefrontal cortex, anterior cingulate, caudate nucleus and thalamus, and recruited more areas, including the pre-supplementary motor area and the bilateral posterior lobe of cerebellum, compared to young subjects. These results indicate that most healthy aged subjects can perform some complex motor tasks automatically. However, aged subjects appear to require more brain activity to perform automatically at the same level as young subjects. This appears to be the main reason why aged subjects have more difficulty in achieving automaticity.     

Genetically abnormal clones in histologically normal breast tissue.

Breast cancer is believed to develop as multiple genetic abnormalities accumulate, each conferring some growth advantage, but the timing and nature of the earliest steps in this progression are not yet elucidated. Proliferative breast lesions, associated with an increased risk of breast cancer although considered benign, recently were shown to contain clonal genetic abnormalities. Therefore, we hypothesized that clonal genetic abnormalities might be detectable before any phenotypic abnormalities are evident, ie, in histologically normal breast tissue. We examined DNA extracted from 95 normal-appearing breast ducts or terminal ductal-lobular units from 20 individuals at varying degrees of risk (those undergoing reduction mammoplasties, those with atypical hyperplastic proliferative lesions, and those already diagnosed with breast cancer). Using nine microsatellite markers, we sought evidence of genetic instability or of allelic imbalance (most likely representing loss of heterozygosity). We found genetically abnormal clones in 21/95 (22%) seemingly normal samples from 10/20 (50%) women from all three risk groups. In women under age 50, trends toward increased rates of abnormalities were noted with increased cancer risk. The abnormalities identified were more likely to be at sites of known or postulated tumor suppressor genes rather than at random or neutral loci. Our data indicate that genetic abnormalities potentially critical to breast tumorigenesis accumulate before pathological detection even of high-risk lesions and are detectable in tissue that is not only histologically benign but also completely normal.