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Graaff Esther de; Rouillard Patricia; J.Willems Patrick; P.T.Smits Arie; Rousseau Francois; A.Oostra Ben 《Human molecular genetics》1995,4(1):45-49
The fragile X syndrome is the most frequent cause of inheritedmental retardation. The molecular mechanism of the disorderis based on the expansion of a CGG repeat in the 5' UTR of theFMR1 gene In the majority of fragile X patients. The instabilityof this CGG repeat containing region is not restricted to theCGG repeat Itself but expands to the flanking region as well.We describe four unrelated fragile X patients that are mosaicfor both a full mutation and a small deletion in the CGG repeatcontaining region. Sequence analysis of the regions surroundingthe deletions showed that both the (CGG)n repeat and some flankingsequences were missing in all four patients. The 5' breakpointsof the deletions were found to be located between 7553bp proximal to the CGG repeat. This suggests the presence ofa hot spot region for deletions in the CGG repeat region ofthe FMR1 gene and emphasizes the instability of this regionIn the presence of an expanded CGG repeat. 相似文献
43.
Using data from 1982 and 1984, we examined how Medicare's prospective payment system affected hospitals. The study showed that hospitals paid through the prospective payment system had significantly lower increases in Medicare costs and greater declines in Medicare use than did other hospitals. Unlike these other hospitals, for which Medicare costs approximately equaled Medicare revenues, hospitals receiving prospective payment kept Medicare costs from rising as fast as Medicare revenues, earning the profit that the prospective payment system allowed. The opportunity to earn a profit led hospitals to slow increases in Medicare costs, regardless of the level of revenue constraint. However, the more the prospective payment system constrained hospitals' revenues, the more hospitals slowed increases in Medicare costs. In the most constrained hospitals, slower increases in Medicare costs were accompanied by slower increases in total hospital spending. The least constrained hospitals slowed Medicare cost increases the least and did not show their overall spending. These hospitals nevertheless increased their profit margins the most, since the prospective payment system's federal rate paid them the highest rates relative to base-year costs. Since federal rates produced extra profits, not extra cost containment, their appropriateness is questionable. The prospective payment system should be modified to eliminate windfalls while continuing to promote cost containment. 相似文献
44.
The relationship between sensation seeking and the orienting reflex (OR) using skin conductance change is investigated in two experiments. In Experiment I, high sensation seekers gave a greater initial OR In novel visual stimuli while not differing in habituation on subsequent trials. In Experiment II. the paradigm was extended to include auditory as well as visual stimuli. Again, high sensation seekers were found to be more arousable with respect to initial ORs while not differing in habituation rates. The results suggest that sensation seekers may be characterized as having strong excitatory CNS processes. In Experiment II, anxiety (trait and state) was also related to the OR. There were no effects due to trait anxiety but state anxiety did yield significant differences. The more highly anxious (state) subjects had weaker initial ORs than lows in both novel tones, but not to repeated tones. The findings with state anxiety are consistent with findings by others using anxiety neurotics as subjects. 相似文献
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Liver specimens from 1-day-old ducklings infected in ovo with maternally transmitted duck hepatitis B virus (DHBV) were examined by electron microscopy. Complete and incomplete DHBV particles were located within hypertrophied cisternae of the endoplasmic reticulum of the hepatocytes. The complete viral particles found intracellularly have inner cores with a diameter ranging from 35 to 37.5 nm and an outer coat or envelope. The whole particle measures approximately 45-65 nm in diameter. Naked core particles were located in the nuclei, free in the cytoplasm, and also near or on the cisternal membrane of the endoplasmic reticulum on the cytoplasmic face. Duck hepatitis B virions appear to share morphological characteristics with the viral coat and core of human hepatitis B virus (HBV). Electron microscopy suggested that the core particles of DHBV migrate from the nucleus into the cytoplasm through the nuclear pores. The complete viral particles are probably formed by protrusion of the core particles through the endoplasmic reticulum and by simultaneous encapsulation with a coat derived from the endoplasmic reticulum. 相似文献
47.
In vivo inhibition of lipopolysaccharide-induced lethality and tumor necrosis factor synthesis by Rhodobacter sphaeroides diphosphoryl lipid A is dependent on corticosterone induction. 下载免费PDF全文
Diphosphoryl lipid A from the lipopolysaccharide (LPS) of Rhodobacter sphaeroides (Rs-DPLA) has been demonstrated to block in mice and guinea pigs the increase in the serum tumor necrosis factor (TNF) response induced by highly purified deep rough chemotype LPS from Escherichia coli D31m4 (ReLPS). The present study was designed to determine the role of corticosterone induction by Rs-DPLA and its effect on TNF regulation and survival in lethal endotoxin shock models and to evaluate the ability of Rs-DPLA to induce endotoxin tolerance. Administration of a 100-fold excess of Rs-DPLA 1 h prior to ReLPS administration inhibited the characteristic peak in serum TNF levels induced by LPS. Inhibition was apparent in normal and D-galactosamine (GalN)-sensitized mice and occurred at the pretranslational level, as splenic TNF and interleukin-1 beta mRNAs were present in lower amounts in LPS-stimulated mice pretreated with Rs-DPLA. Consistent with its effects in reducing serum TNF levels, Rs-DPLA pretreatment protected GalN-sensitized mice from a lethal ReLPS challenge. In contrast, Rs-DPLA did not inhibit the increase in the serum TNF response or protect against a lethal ReLPS challenge in parallel experiments with adrenalectomized (Adrex) mice, for which the 50% lethal dose of ReLPS was comparable to that for GalN-sensitized mice. Furthermore, Rs-DPLA appeared to prime Adrex animals and increase the magnitude of the serum TNF response to a suboptimal LPS stimulus. Priming by Rs-DPLA, however, was not observed in normal or GalN-sensitized mice. Although Rs-DPLA by itself was nontoxic and unable to elevate serum TNF levels in any of the models investigated, it did induce a significant increase in the serum corticosterone response and was capable of inducing endotoxin tolerance in normal mice. The inability of Rs-DPLA to protect Adrex mice from a lethal ReLPS stimulus or to inhibit the increase in the serum TNF response suggests that the protective effect of Rs-DPLA in normal or GalN-sensitized animals occurs through corticosterone induction. These results support the concept that endogenous glucocorticoids can modulate the endotoxic effects of LPS by inhibiting the synthesis of inflammatory cytokines. 相似文献
48.
F A Jakobiec B D Zuckerman A J Berlin P Odell D W MacRae R J Tuthill 《American journal of ophthalmology》1985,100(1):100-113
In one patient, an epithelioid cell nevus of the conjunctiva contained numerous large, unpigmented, mononucleated, binucleated, and multinucleated benign-appearing nevus cells with abundant cytoplasm and frequent intranuclear vacuoles. Despite their overall size, the cells manifested a low nuclear-cytoplasmic ratio. After a partial excision of the lesion, the remainder spontaneously regressed during a two-year period. Another patient's lesion was dominated by a proliferation of spindle nevus cells developing in a long-standing epibulbar nevus. The spindle cells were moderately pigmented, frequently located within walls of epithelial inclusion cysts, and had benign cytologic features. Finally, in a third patient with the cutaneous B-K mole syndrome, a dysplastic conjunctival nevus developed that featured intraepithelial, atypical melanocytic proliferation with superficial colonization of the substantia propria. This portion coexisted with a deeper, preexistent lesion in the substantia propria that was comprised of orderly nests of unpigmented cuboidal nevus cells surrounded by pigmented, spindle-shaped blue nevus cells--a so-called "mixed nevus." 相似文献
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