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1.
Despite an urgent medical need, a broadly effective anti-viral therapy for the treatment of infections with hepatitis C viruses (HCVs) has yet to be developed. One of the approaches to anti-HCV drug discovery is the design and development of specific small molecule drugs to inhibit the proteolytic processing of the HCV polyprotein. This proteolytic processing is catalyzed by a chymotrypsin-like serine protease which is located in the N-terminal region of non-structural protein 3 (NS3). This protease domain forms a tight, non-covalent complex with NS4A, a 54 amino acid activator of NS3 protease. The C-terminal two-thirds of the NS3 protein contain a helicase and a nucleic acid-stimulated nucleoside triphosphatase (NTPase) activities which are probably involved in viral replication. This review will focus on the structure and function of the serine protease activity of NS3/4A and the development of inhibitors of this activity.  相似文献   

2.
An HPLC-UV method for the simultaneous identification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in urine is described. It includes a rapid extraction procedure of the 4 analogs from urine using Extrelut 3 columns, derivatization with sodium 1,2-naphthoquinone-4-sulphonate (NQS) to obtain highly chromophoric UV-VIS derivatives, and a final HPLC analysis using an ion-pair reversed-phase technique with eluent monitoring at 480 nm. Structural characterization of the derivatives obtained by mass spectrometry is reported. Recoveries of the amphetamines were in the range 80-85% at concentrations of 300 ng/ml. Practical detection limits were 40-60 ng/ml (S/N ratio = 10) for all derivatives. The chromatographic peaks of the NQS derivatized amphetamines are fairly narrow and well resolved. The method is simple, rapid, quite sensitive, and specific for convenient confirmation of preliminary positive results obtained with immunoassays.  相似文献   

3.
Meningiomas of the lateral ventricles of the brain are rare tumours, accounting for approximately 0.5-5% of all intracranial meningiomas. Their natural history and symptomatology and the possibilities of early diagnosis are presented. The intraventricular location of the slow-growing benign mass provides a compensatory mechanism in the form of reserve space, which contributes to the delay in clinical demonstration of symptoms and signs. This makes the choice of diagnostic procedure an essential problem. CT and MRI are useful in detecting these masses, and magnetic resonance angiography (MRA) has also proved to be of great value in demonstrating the vascular supply of the tumour. This paper deals with two cases. In case 1 CT, MRI and MRA and in case 2 CT examination proved to be very useful. The tumours were removed by a transcortical approach in the posterior area.  相似文献   

4.
Drugs possessing a carboxylate functional group usually form acyl glucuronides as major metabolites. These electrophilic metabolites can undergo several spontaneous reactions, including covalent adduct formation with proteins. The present study examined whether covalent adducts were formed with microtubular protein (MTP, 85%, alpha/beta-tubulin) and whether this influenced its ability to assemble into microtubules. Bovine brain microtubular protein (MTP) was purified by assembly-disassembly cycles and incubated with the nonsteroidal anti-inflammatory drug (NSAID) zomepirac (ZP), its acyl glucuronide (ZAG) and rearrangement isomers (iso-ZAG) at various concentrations for 2 h at room temperature and pH 7.5. Assembly was monitored by change in turbidity (increase in absorbance at 340 nm). Both ZAG and iso-ZAG caused dose-dependent inhibition of assembly (50% inhibition at about 1 mM), while ZP caused modest inhibition (< 50% inhibition at 4 mM). In a slightly different system, incubation of performed microtubules with 4 mM ZAG caused about 35% inhibition of reassembly ability, while modification of MTP under similar conditions resulted in about 85% reduction of assembly ability. Immunoblotting with a ZP antiserum showed that ZAG and iso-ZAG covalently modified MTP in a dose-dependent manner, while ZP itself caused no modification. Tubulin and many minor proteins comprising MTP were modified. ZP-modified tubulin was shown to be present in the cytosol of livers from rats dosed twice daily for 3 days with ZP at 50 mg/kg, using a sandwich ELISA with ZP and tubulin antisera. Whether any perturbation of microtubule assembly occurs in vivo as a result of this in vivo modification is currently under investigation.  相似文献   

5.
Recent studies have provided new insights into the visuomotor functions of the dorsal and ventral regions of the lateral pre-motor cortex. Anatomical and physiological investigations in non-human primates have demonstrated that these regions have differing patterns of cortical connectivity and distinctive neuronal responses. Brain-imaging techniques and lesion studies have begun to probe the functions of homologous regions in humans.  相似文献   

6.
OBJECTIVES: To review the outcome of men with Stage I nonseminomatous germ cell tumors managed with a policy of active surveillance following orchiectomy. METHODS: The clinical records of all men with Stage I nonseminomatous germ cell tumors seen at Royal Prince Alfred Hospital, Australia between 1982 and 1995 were reviewed. Data were obtained concerning the histologic type of tumor, levels of serum tumor markers, relapse and subsequent treatment, and survival. RESULTS: Seventy-seven patients were entered into the active surveillance protocol between 1982 and 1995. With a minimum follow-up of 2 years, 27 (35%) have relapsed, with a median time to relapse of 5 months. Two late relapses occurred at 37 and 57 months after diagnosis. Relapses occurred most commonly in the retroperitoneal lymph nodes, with the lungs the second most common site. Following treatment with chemotherapy and surgery, all patients achieved complete remission, with 1 patient subsequently relapsing and ultimately dying of progressive tumor. One other patient died of acute myeloid leukemia, thought to be secondary to chemotherapy. Overall, 75 patients (97%) remain alive and free of disease. CONCLUSIONS: Active surveillance is a safe and effective approach to the management of Stage I nonseminomatous germ cell tumors. Although most relapses occur within the first 2 years, late relapses may occur.  相似文献   

7.
This special issue of Patient Education and Counseling on genetic education and counseling provides an overview of studies and findings in this field. It features a mixture of papers dealing with five different topics related to several psychosocial aspects of genetic education and counseling. Attention is paid to new issues in counseling for hereditary cancer and Huntington Disease. Articles are presented on information recall of counseled individuals, the use and impact of genetic services on counselees (acceptance of testing; knowledge of inherited cancer susceptibility; risks of genetically testing children). Also topics are addressed with respect to the counselor (neutral attitude; understandable language; information recall; satisfaction with the services provided by the genetic counselor). Furthermore, recommendations are discussed for screening practices for women with a family history of breast cancer, and in addition, the effectiveness of genetic counseling is addressed. In conclusion several suggestions for future research are given.  相似文献   

8.
The effects of permanent forebrain lesions on conditioned taste aversions (CTAs) and conditioned odor aversions (COAs) were examined in 3 experiments. In Experiment 1, lesions of the bed nucleus of the stria terminalis had no influence on CTA or COA acquisition. Although lesions of the lateral hypothalamus induced severe hypodipsia in Experiment 2, they did not prevent the acquisition of CTAs or COAs. Finally, in Experiment 3, lesions of the insular cortex retarded CTA acquisition but had no influence on COA acquisition. The implications of these findings are discussed with regard to the forebrain influence on parabrachial nucleus function during CTA acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

9.
We performed interictal FDG-PET- and MRI-based hippocampal volumetric measurements on 18 adult patients with complex partial epilepsy of temporal lobe origin in whom we had identified their ictal focus by video-telemetry EEG. Sixteen patients (89%) had regional hypometabolism, 11 (61%) had focal 1.5-tesla T2-weighted MRI (two structural abnormalities, nine hippocampal formation [HF] increased T2 signal), and nine (50%) had absolute HF atrophy ipsilateral to the temporal ictal focus. Ten (55%) had abnormal L/R HF ratios, nine ipsilateral to the EEG focus. All patients with abnormal MRI volumetric studies had focal PET abnormalities. Only seven had both abnormal HF volume ratios and T2 MRI (all increased HF T2 signal). There was a significant correlation between hippocampal volume and inferior mesial and lateral temporal lobe cerebral metabolic rate of glucose asymmetry index (p < 0.01), suggesting that hypometabolism may reflect hippocampal atrophy. PET is more sensitive than MRI volumetry in identifying the ictal focus but does not provide additional information when HF atrophy is present.  相似文献   

10.
Childhood amnesia refers to the inability of adults to recall events that occurred during their infancy and early childhood. Although it is generally assumed that children and adolescents also experience childhood amnesia, with limited exceptions, most empirical research on the phenomenon has focused exclusively on adults. Here, we developed a new Timeline procedure to directly compare the early memories reported by children, adolescents, and adults. Overall, the proportion of memories reported before the age of 3 years was greater for the children and adolescents relative to the adults. In addition, the single earliest memory reported by children and adolescents was at a younger age than that reported by adults. In fact, the earliest memories reported by the children and adolescents, but not the adults, were significantly younger than the traditional 3 ?-year-old boundary of childhood amnesia. Regardless of the age of the rememberer, participants' early memories had the same episodic characteristics. We conclude that the boundary and the density of childhood amnesia may increase over the course of human development and that age-related changes in basic memory mechanisms make an important contribution to our understanding of the source of childhood amnesia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

11.
This is a case of true lateral thyroid ectopia, an extremely rare condition. The appearances on sectional imaging are shown.  相似文献   

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14.
Recently, there has been an increase in the interest in various aspects of the biology of small passerine birds. In order to apply many modern neurobiological techniques, it would be useful to be able to surgically inject hormones and drugs directly into passerine brains. We describe a novel and cost-effective stereotaxic-like technique for injecting substances into the lateral ventricles of small passerine birds. The technique is rapid, reducing the period of anesthesia, and reliable. In addition, using this technique, we injected [3H]cysteine (to label newly synthesized proteins) with small doses of colchicine. Colchicine decreased the content of newly synthesized protein in the median eminence, thus suggesting that colchicine inhibited protein transport. The technique should prove useful in a number of neurobiologial applications.  相似文献   

15.
Gap-detection thresholds were determined for 10 younger and 10 older adults (mean age 23 yrs and 68 yrs, respectively) at 2 sensation levels (40 and 60 dB SL) for tone pips with Gaussian amplitude envelopes whose standard deviations were 0.5, 1, 1.5, and 2 msec. Gap-detection thresholds were larger for the older participants under all conditions. For all participants, gap-detection thresholds increased with the standard deviation of the Gaussian amplitude envelope, were relatively independent of sensation level, and were independent of the degree of hearing loss. Because spectral splatter decreases with increasing standard deviation of the Gaussian amplitude envelope, the age-related differences in gap detection cannot be attributed to differences between how young and old listeners are affected by off-frequency cues. Furthermore, the consistent age difference in gap detection at all amplitude envelope standard deviations was shown to be incompatible with the hypothesis that temporal integration time is longer for older listeners. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

16.
NMR spectroscopy and NMR imaging with magnetic field gradients make strange bedfellows, the requirements for one seemingly ruling out the other for human applications. Nevertheless, their stories are intertwined; the advent of high field imaging systems arose because of the desire for human spectroscopy. Localized spectroscopy is possible because of NMR imaging. Both have links to physics at Nottingham, at least in the personalized account that follows. Today, virtually all NMR spectroscopy experiments can be conceived with a localized in vivo spectroscopy counterpart.  相似文献   

17.
The relative contents (RCs) of elements in the human menisci from 23 subjects in the age range between 65 and 93 yr were analyzed by inductively coupled plasma atomic emission spectrometry. The RCs of sulfur, calcium, and phosphorus in menisci increased progressively until the 80s, being the highest in the 80s, and thereafter decreased. The RCs of magnesium in menisci increased progressively until the 90s. Regarding the medial and lateral menisci, higher RCs of magnesium and iron, and a lower RC of phosphorus were found in lateral menisci in comparison with those in medial menisci. There were sexual differences in the RCs of calcium and phosphorus of medial and lateral menisci. The RCs of calcium and phosphorus were about 50% higher in women's menisci than in men's. Histological examinations showed that structureless mucoid masses were observed in the menisci, with very high RCs of calcium and phosphorus being detected.  相似文献   

18.
J. Hassoun and co-workers (1982) described two cases presenting intraventricular tumors of nervous origin, coined by them with the term "central neurocytoma" of the ground of electron microscopic data. As shown by the studies of other authors, central neurocytoma represents a separate morphological entity having light- and electron-microscopic and immunohistochemical characteristic of its own. In the recently published WHO classification of brain tumors (1993) central neurocytoma is entered as a tumor presenting new morphological patterns. Central neurocytoma occurs mainly in young persons, develops in the lateral and third ventricle, comparatively well differentiated from surrounding structures, rich in calcifications, disclosing proper relative specificity during CT scanning and MRI study. Light-microscopically this tumor bears resemblance to, and is erroneously diagnosed as oligodendroglioma or ependymoma. Proceeding from retrospective reassessment of two patients with intraventricular tumors and an additional observation, and on the ground of pertinent literature data, the morphological, clinical and nerve imaging characterization of central neurocytoma is outlined--a tumor met with in the daily routine practice, but usually erroneously interpreted.  相似文献   

19.
We have studied by both qualitative and quantitative methods the subependymal cells in the caudato-pallial angle (CPA) of the lateral ventricle from 1, 2, 6 and 18 month-old rats. We have chosen the CPA, among other zones, because it is an easily delimited glial proliferative zone. The qualitative analysis was carried out using both Klüver-Barrera and Luxol-Fast-Blue stains. The quantitative study was carried out by a semiautomatized image analysis system. Three types of subependymal nuclei were classified by Klüver-Barrera stain, according to the following parameters: staining intensity, morphology and size. Each of the three type groups was found at different frequency depending of rat age. Luxol-Fast-Blue stained mitotic images in metaphase or anaphase: n = 38 in the 1 month, n = 49 in 2 months, n = 12 in the 6 months, and n = 5 in the 18 month-old rats. The quantitative analysis (length, areas and volume of CPA) were in agreement with the above data, showing a more subependymal activity in the 2 month-old animals than in the 1, 6 and 18 month-old rats.  相似文献   

20.
The goat choroid plexus angioarchitecture of the lateral ventricles was studied under the SEM using the method of "microvascular corrosion casts". The whole plexus is semilunar shaped and directed in an antero-posterior, latero-median fashion. In the plexus the lateral extremity is larger than the median one. All the components of the vascular bed (arteries, veins and capillaries) of the choroid plexus have interesting morpho-structural features. In particular, the capillaries are more developed than the other components and they are variously located on both sides of the plexus. The capillary network has a various organization in different zones of each side of the plexus.  相似文献   

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