Heavy-ion-induced mutations in the gpt delta transgenic mouse: comparison of mutation spectra induced by heavy-ion,X-ray,and gamma-ray radiation

Heavy-ion radiation accounts for the major component of absorbed cosmic radiation and is thus regarded as a significant risk during long-term manned space missions. To evaluate the genetic damage induced by heavy particle radiation, gpt delta transgenic mice were exposed to carbon particle irradiation and the induced mutations were compared with those induced by reference radiations, i.e., X-rays and gamma-rays. In the transgenic mouse model, deletions and point mutations were individually identified as Spi(-) and gpt mutations, respectively. Two days after 10 Gy of whole-body irradiation, the mutant frequencies (MFs) of Spi(-) and gpt were determined. Carbon particle irradiation significantly increased Spi(-) MF in the liver, spleen, and kidney but not in the testis, suggesting an organ-specific induction of mutations by heavy-ion irradiation. In the liver, the potency of inducing Spi(-) mutation was highest for carbon particles (3.3-fold increase) followed by X-rays (2.1-fold increase) and gamma-rays (1.3-fold increase), while the potency of inducing gpt mutations was highest for gamma-rays (3.3-fold increase) followed by X-rays (2.1-fold increase) and carbon particles (1.6-fold increase). DNA sequence analysis revealed that carbon particles induced deletions that were mainly more than 1,000 base pairs in size, whereas gamma-rays induced deletions of less than 100 base pairs and base substitutions. X-rays induced various-sized deletions and base substitutions. These results suggest that heavy-ion beam irradiation is effective at inducing deletions via DNA double-strand breaks but less effective than X-ray and gamma-ray irradiation at producing oxidative DNA damage by free radicals.     

内隐记忆的研究证据及临床意义

内隐记忆 (ｉｍｐｌｉｃｉｔｍｅｍｏｒｙ)一词最初由Ｇｒａｆ与Ｓｃｈａｃｔｅｒ于 1985年提出 ,指对特定的过去经验进行有意识或外显的回忆测验中表现出来的对先前获得信息的无意识提取 ,也就是说 ,在有意或无意间获得的信息、技能或习惯 ,虽不能有意识地回忆和再认 ,但会影响类似作业的成效和行为的有效性。这一概念的提出扩大了记忆研究的内涵 ,因此迅速成为记忆研究的热点之一。目前内隐记忆的研究在测量方法与理论解释方面都取得了一些进展 ,大量证据表明它与外显记忆存在质的不同 ,是一个相对独立的记忆系统。不过现存的问题也很多 ,…     

HSP70在米非司酮引产胎儿肝、肾、脑组织中的表达

目的对米非司酮引产胎儿肝、肾、脑组织进行热休克蛋白70的检测,探讨米非司酮对胎儿损伤的可能性.方法米非司酮引产胎儿17例,水囊引产胎儿5例, 采用免疫组化方法,检测HSP70在胎儿肝肾脑组织中的表达.结果实验组中HSP70均呈阳性表达,且有不同程度的表达,对照组均呈阴性表达.结论米非司酮可不同程度造成胎儿肝、肾、脑组织损伤.     

Short term status epilepticus in rats causes specific behavioral impairments related to substantia nigra necrosis

Summary Status epilepticus (SE) was induced for 40 min by flurothyl in well oxygenated rats. This insult resulted in selective destruction of up to 65% of the substantia nigra pars reticulata. We investigated the short and long term behavioral effects of this damage. No deficits were observed in sensorimotor reactivity, locomotor coordination, spontaneous or apomorphine-stimulated locomotor activity in the rats with induced epilepsy. However, these rats exhibited a long-lasting enhancement of amphetamine-stimulated locomotor activity. We propose that this selective impairment is caused by the necrosis of the pars reticulata. This damage might lead to deficient regulation either of mesostriatal dopamine neurons innervating nc. accumbens, or of neurons in the mesencephalic reticular formation mediating the locomotor response initiated in the nc. accumbens.     

Eccentric muscle damage: mechanisms of early reduction of force

Pain and weakness are prominent symptoms which occur after a delay in muscles which have been stretched during contraction (eccentric contraction). These symptoms are particularly severe when the exercise is unaccustomed and when the stretch occurs in muscles on the descending limb of the force–length relation, i.e. at long muscle lengths. It is known that sarcomeres are potentially unstable on the descending limb and it has been proposed by Morgan that uncontrolled elongation of some sarcomeres occurs during eccentric contractions on the descending limb. In this article, the evidence that this mechanism leads to the reduced force is considered. If overextended sarcomeres persist after the eccentric exercise it will cause a shift in the peak of the force–length curve. There is also evidence that in some types of muscle, excitation–contraction coupling is impaired and contributes to the muscle weakness. Cytoskeletal proteins stabilize the sarcomeric structure and may be injured either by the overextended sarcomeres or by activation of proteases. The potential of these mechanisms to contribute to the effects of muscle training and to the symptoms of muscle disease, such as muscular dystrophy, is considered.     

Ultrastructure of the neuroglial fatty metamorphosis (virchow) in the perinatal period

Summary The ultrastructure of neuroglial fatty metamorphosis (GFM) has been investigated in the telencephalic white matter of 12 premature and mature infants (gestational age 22–40 weeks; survival 0–96 days). GFM was found in all cases apart from a 22-week-old fetus, and involves predominantly astrocytic cells (68.8%), then glioblasts (43.5%), but only 7.4% of oligodendrocytes. GFM, therefore, seems to be independent of the myelination process and indicates the vulnerability of the immature neuroglial population in the metabolic and circulatory disorders of the perinatal period. Since GFM is found in almost all children dying within the early postnatal period, this subtle alteration reflects a special form of minimal brain damage. The relationship between GFM, astrocytic hypertrophy and periventricular leucomalacia and their role in the telencephalic leucoencephalopathy are discussed.

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Zusammenfassung Die Gliazellverfettung im unreifen Großhirn-Marklager wurde bei 12 Kindern ultrastrukturell untersucht (Gestationsalter 22–40 Wochen; Überlebenszeit 0–96 Tage). Die fettige Metamorphose der Neuroglia (Virchow) fand sich in allen Fällen, ausgenommen den 22 Wochen alten Feten, und betrifft vorwiegend junge Astrozyten (68,8%), ferner zu 43,5% unreife Vorstufen, jedoch nur zu 7.4% die (z.Z. der Geburt erst in Erscheinung tretende) Oligodendroglia. Die Fett-Metamorphose der unreifen Glia stellt einen sensiblen Indikator für metabolisch-zirkulatorische Störungen der Perinatalperiode dar und erfolgt unabhängig von dem Prozeß der Markscheidenbildung. Zusammen mit einer oft auffälligen Astroglia-Proliferation ist die intracytoplasmatische Akkumulation nicht membrangebundener Lipide Ausdruck einer temporären Differenzierungsstörung der unreifen Neuroglia. Die resultierende Reifungsdissoziation mit Unterdrückung der oligodendrozytären Zellinie führt zur retardierten Markscheidenbildung und dem Bild der telencephalen Leucoencephalopathie.

     

Expression and localization of heat shock proteins in rat basophilic leukemia cells: differential modulation by degranulation,thermal or oxidative stress

BACKGROUND: Rat basophilic leukemia (RBL-2H3) cells are well characterized in terms of morphological and biochemical changes upon activation, and have been extensively used as a model system for studying the mechanisms of the immediate hypersensitivity reaction. To investigate whether overexpression of heat shock/stress proteins (HSP) is involved in the mast cell-dependent reactivity, we examined the adaptive responses of RBL-2H3 cells to classical stress conditions such as heat shock or oxidative injury produced by an aqueous extract of tobacco smoke. METHODS: HSP were determined by flow cytometry and immunocytochemistry. Degranulation was confirmed as the release of beta-hexosaminidase, determined spectrophotometrically, and by electron microscopy experiments. RESULTS: We found that RBL-2H3 cells respond to heat shock or oxidative injury by the synthesis of both the inducible 72 kDa HSP (Hsp70), and the oxidation-specific 32 kDa heme oxygenase (HO)-1. Heat shock induced mainly Hsp70 in a cell growth-dependent manner, whereas oxidative stress induced mainly HO-1 in a cell growth-independent manner. However, heat shock or oxidative stress had no significant effects on degranulation. CONCLUSION: Stress-mediated synthesis of HSP was not associated with RBL-2H3 degranulation and likewise, degranulation did not induce HSP.     

Frequent cellular senescence in small bile ducts in primary biliary cirrhosis: a possible role in bile duct loss

The pathogenesis of progressive bile duct loss in primary biliary cirrhosis remains unclear. In this study, the involvement of cellular senescence of biliary epithelial cells was examined in liver tissue samples from patients with primary biliary cirrhosis (n = 33), and compared with control diseased and normal livers (n = 83). In addition, cellular senescence was induced by oxidative stress in cultured mouse biliary epithelial cells. Biliary epithelial cells in small bile ducts in primary biliary cirrhosis, especially those in patients presenting with chronic non-suppurative cholangitis, frequently expressed senescence-associated beta-galactosidase, and senescence-associated p16(INK4) and p21(WAF1/CIP). In contrast, senescence-associated markers were rarely expressed in small bile ducts in control livers. The infiltration of myeloperoxidase-positive inflammatory cells into biliary epithelial cell layers was closely associated with the cellular senescence of biliary epithelial cells in early-stage PBC. Cellular senescence of cultured mouse biliary epithelial cells was induced by treatment with H2O2 via the p38MAPK-dependent pathway and nitric oxide-augmented H2O2-induced cellular senescence. Oxidative stress- and nitric oxide-mediated cellular senescence may be involved in bile duct lesions, which are followed by progressive bile duct loss in primary biliary cirrhosis.