Triploid origin of the gibel carp as revealed by 5S rDNA localization and chromosome painting

5S ribosomal DNA (rDNA) was isolated and sequenced from the gibel carp Carassius auratus gibelio with 162 chromosomes and crucian carp Carassius auratus with 100 chromosomes, and fluorescent probes for chromosome localization were prepared to ascertain the ploidy origin and evolutionary relationship between the two species. Using fluorescence in-situ hybridization (FISH), major 5S rDNA signals were localized to the short arms of three subtelocentric chromosomes in the gibel carp and to the short arms of two subtelocentrics in the crucian carp. In addition, some minor signals were detected on other chromosomes of both species. Simultaneously, six chromosomes were microdissected from the gibel carp metaphase spreads using glass needles, and the isolated chromosomes were amplified in vitro by degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR). Significantly, when the DOP-PCR-generated probes prepared from each single chromosome were hybridized, three same-sized chromosomes were painted in each gibel carp metaphase, whereas only two painted chromosomes were observed in each crucian carp metaphase spread. The data indicate that gibel carp is of triploid origin in comparison with diploid crucian carp.     

Impaired colour discrimination in Huntington's disease

Colour discrimination and visual contrast perception were investigated in 18 patients with Huntington's disease (HD) and in 18 age- and sex-matched healthy volunteers using the Farnsworth-Munsell 100 Hue test (FM) and stationary contrast targets. The mean total error score (MTES) and the partial scores for the “red-green” and the “blue-yellow” axes in the FM of the patients with HD were significantly elevated as compared to controls (MTES in HD: 113.0 ± 90.8; MTES in controls: 19.2 ± 8.8). The spatial contrast sensitivity in HD patients was normal. The colour perception dysfunction indicates that the visual system is affected in HD. The visual disorder may be related to an imbalance of certain neurotransmitters in the visual system of HD patients. Possible anatomical sites of the dysfunction responsible for colour discrimination abnormalities could be the retinal cone system and/or impaired parvocellular central visual pathways in HD.     

High serum levels of tumour necrosis factor‐α and interleukin‐8 in severe asthma: markers of systemic inflammation?

BACKGROUND: Severe asthma is characterized by elevated levels of pro-inflammatory cytokines and neutrophilic inflammation in the airways. Blood cytokines, markers of 'systemic' inflammation, may be a feature of amplified inflammation in severe asthma. OBJECTIVE: To detect differences in IL-8, TNF-alpha, IL-16 and IL-13 levels in the serum(s) of stable severe and mild-moderate asthmatics related to blood leucocytes proportion, airway calibre and exhaled nitric oxide (NO) levels. METHODS: We assessed cytokine serum levels by ELISA and blood leucocyte counts by an alkaline peroxidase method in 20 healthy controls, 22 mild-moderate [forced expiratory volume in 1 s (FEV1)(%pred): 89+/-3] and 14 severe asthmatics [FEV1(%pred): 49+/-2]. RESULTS: IL-8 and TNF-alpha levels were higher in severe asthmatics than in mild-moderate asthmatics or in controls (P<0.05). No differences in IL-16 and IL-13 levels were detected. Severe asthmatics showed higher circulating neutrophil and eosinophil number than controls (P<0.05). In severe asthmatics, exhaled NO levels were superior than in controls (P<0.05), but inferior than in mild-moderate asthmatics (P<0.05). We found positive correlation between TNF-alpha levels and exhaled NO (r=0.67; P=0.01) or circulating neutrophil counts (r=0.57; P=0.03) in severe asthmatics. CONCLUSION: sTNF-alpha and sIL-8 are markers of 'systemic' inflammation in severe asthmatics, in conjunction with augmented circulating neutrophils, suggesting the involvement of neutrophil-derived cytokine pattern in severe asthma.     

Neurokinin A with K channel blockade potentiates contraction to electrical stimulation in human bronchus

This study investigated the effects of neurokinin A (NKA) on cholinergic neural responses in human bronchus. NKA (0.1 nM) did not alter the contractile response to submaximal electrical field stimulation. However, K⁺ channel blockade with 4-aminopyridine (4-AP) (0.1 mM) potentiated the response to electrical field stimulation (to 182 ± 25% of control, n = 4, P < 0.05) and subsequent addition of NKA in the presence of 4-AP produced further potentiation (to 123 ± 6% of the response to 4-AP n = 4, P < 0.05). Neither 4-AP (0.01 or 0.1 mM) nor NKA in the presence of 4-AP potentiated the actions of exogenous acetylcholine but in these experiments 4-AP itself produced a marked direct contractile response. Thus NKA in the presence of K⁺ channel blockade potentiates cholinergic neural response in human bronchus and this occurs at a prejunctional site.     

Persistent Hypotension Associated with Hypermedullipinemia: A New Syndrome

A new syndrome is described in a patient with advanced renal insufficiency. This consists of severe and persistent hypotension causing weakness but associated with a clear mental status. Also present is evidence for decreased vascular reactivity. The hypotension was not orthostatic. The hypotension was associated with a circulating vasodepressor substance having the characteristics of medullipin I. The medullipin appears to have been derived from the remaining right kidney. Hypotension existed despite the presence of major prohypertensive mechanisms, including an endstage kidney, hyperreninemia and hyperaldosteronemia. It is likely that hypotension due to hypermedullipinemia is an entity occurring in the human being.     

1,3-Dipropyl-8-cyclopentylxanthine attenuates the NMDA response to hypoxia in the rat hippocampus

Excitatory amino acids may cause neuronal damage and death in cerebral hypoxia and ischemia, through the activation of different subtypes of glutamate receptors, in particular of the (NMDA) receptor. In the present work, the effect of hypoxia on the component of the field excitatory postsynaptic potential (fepsp) mediated by the NMDA receptor was studied in the hippocampal CA1 area of the rat. A period of 15 min of hypoxia induced virtual abolition of the NMDA receptor-mediated fepsp and a 94.8 ± 0.7% maximal decrease in the fepsp. A period of 3 min of hypoxia induced a 89.3 ± 12.3% maximal decrease in the NMDA receptor-mediated component of the fepsp and only a 50.8 ± 11.5% maximal decrease in the fepsp. Both periods of hypoxia thus induced a more pronounced depression of the NMDA receptor-mediated component of the fepsp than of the fepsp. We found that 48.5 ± 9.1% decrease (about half of the total decrease) in the NMDA receptor-mediated fepsp, and 51.6 ± 19.6% decrease (approximately all decrease) in the fepsp induced by hypoxia (3 min) were reversed in the presence of the selective adenosine A₁ receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (50 nM), and thus likely to be mediated by endogenous adenosine, through the activation of adenosine A₁ receptors. On the other hand, under the conditions we assumed to be normoxic in our slices, DPCPX (50 nM) induced a much larger increase in the amplitude of the NMDA receptor-mediated fepsp compared to the increase in the fepsp, which suggest that endogenous adenosine is inhibiting predominantly the NMDA receptor-mediated fepsp under these conditions. Hypoxia markedly decreases the NMDA receptor-mediated fepsp in the hippocampal CA₁ area. The contribution of endogenous adenosine to the inhibition of the NMDA receptor-mediated fepsp may be fundamental for its neuroprotective effects.     

Allergen activates peripheral blood eosinophil nuclear factor-κB to generate granulocyte macrophage-colony stimulating factor, tumour necrosis factor-α and interleukin-8

BACKGROUND: Allergic inflammation is characterized by the influx and activation of eosinophils. Cytokines generated by both resident and infiltrating cells are responsible for the initiation and maintenance of this pathogenesis. This study focuses on allergen-induced activation of eosinophil NF-kappaB and generation of granulocyte macrophage-colony stimulating factor (GM-CSF), TNF-alpha, and IL-8. METHODS: Peripheral blood eosinophils were enriched to >99.9% by Percoll gradient sedimentation and negative magnetic affinity chromatography. NF-kappaB activation by 10 microg/mL house dust mite (HDM) extract was demonstrated immunocytochemically using a monoclonal antibody against the active form of NF-kappaB (NF-kappaBa). The authenticity of NF-kappaB was confirmed by Western blot. Cytokine production was assessed both by immuno-staining of eosinophils and by assay of cytokines in the cell supernatant. RESULTS: Activation of peripheral blood eosinophils from atopic, but not non-atopic, donors induced activation of NF-kappaB, which peaked at 4 h and was accompanied by a decline in IkappaB-alpha. The activation of authentic NF-kappaB was confirmed in gel shift assays. Supershift assays showed p65 to be the major subunit of eosinophil NF-kappaB. Immunofluorescent confocal microscopy demonstrated localization of NF-kappaBa to the nucleus. Following activation, cytokine immunoreactivity was seen in a fraction of the eosinophils and cytokines were released into the supernatant. The NF-kappaB inhibitors, calpain inhibitor 1 (10 microm), pentoxifylline (0.5 mm), pyrrolidine dithiocarbamate (PDTC, 10 microm) or gliotoxin (1 pg/mL) reduced the generation of GM-CSF, TNF-alpha and IL-8 in parallel with their inhibition of NF-kappaB. CONCLUSIONS: HDM allergen activates human eosinophil NF-kappaB leading to the production of the cytokines GM-CSF, TNF-alpha and IL-8. We speculate that a role for eosinophil NF-kappaB-dependent cytokines is to act as an autocrine loop augmenting the survival of eosinophils in vivo.     

高血压病肠系膜动脉平滑肌细胞端粒酶活性表达的研究

目的 :探讨高血压病动脉平滑肌组织端粒酶活性与高血压的发病关系。方法 :采用PCR -ELISA法检测 30例高血压病患者和 2 0例血压正常者肠系膜动脉平滑肌细胞 (SMC)端粒酶活性。结果 :高血压患者端粒酶阳性表达 2 8例 (93.3% )。血压正常者端粒酶阳性表达 3例 (15 % )。差异非常显著 (P <0 .0 5 )。结论 :高血压病动脉平滑肌细胞端粒酶活性的表达升高 ,可能与高血压发病有关。     

Deep brain stimulation for Parkinson''s disease: electropermeabilization and activation

Deep brain stimulation, DBS, is an accepted technique for the treatment of Parkinson's disease. DBS affects the electrical functions of neurons, but exactly how it alters those functions is not clearly explained. An electrical model is determined to simulate treatment with DBS of the sub thalamic nucleus. This model shows the difference in electrical fields between the inside and the outside the neurons. The generated electrical field near the electrodes is high enough to perform an electropermeabilization of the cell membranes, which most likely blockade normal nerve pulses or reduce the nerve impulse speed. Further away from the electrodes activation of large axons is performed.     

小肠吸收胆固醇的分子生物学研究进展

胆固醇通过分布于十二指肠和近段空肠黏膜上皮细胞刷状缘膜的Niemann—Pick C1样蛋白1摄取，ATP结合盒G5、G8抑制小肠对胆固醇的摄取过程。进入上皮细胞的胆固醇大多数被乙酰辅酶A，胆固醇转乙酰基酶2酯化，随后通过组装形成乳糜微粒，经淋巴管进入血循环；另一部分胆固醇则以未酯化形式直接进入血循环形成高密度脂蛋白颗粒。这些过程受核受体——肝脏X受体的调控。年龄、性别、黏膜屏障和小肠传输速度也影响胆固醇的吸收。