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971.
Although there were no differences in response to an acute injection of pentylenetetrazole (PTZ), there were strain differences in the development of kindled seizures to repeated injections (PTZ; 30 mg/kg 3 times weekly for 13 injections), with Wistar rats reaching stage 4 or 5 of clonic-tonic seizures, but hooded Lister rats reaching only stage 2 or 3 of convulsive waves axially through the body. The strains also reacted differently to a test dose of PTZ (20 mg/kg) one week after the end of kindling, with the Wistar strain showing stage 3 and the Lister strain stage 2 seizures. When the rats were tested 24 h after the end of the kindling injections there was an anxiolytic effect in the social interaction test, in both the low light, familiar and the low light, unfamiliar test conditions that reached significance in the Wistar strain. The Wistar kindled rats showed an anxiolytic effect in the elevated plus-maze test of anxiety when they were tested 24 h after the end of kindling. The anxiolytic effects found 24 h after kindling could not be due to the seizure 24 h earlier, since no changes were found in rats tested 24 h after a single seizure from PTZ (60 mg/kg). When the rats were tested 1 week after the end of kindling there were no changes, compared with vehicle-injected controls, in either test of anxiety. There was no change in benzodiazepine binding in platelets of the kindled Lister rats but there was a significant increase in the kindled Wistar rats 1 week after the end of kindling and also 24 h after a single PTZ seizure. The pattern of increased platelet benzodiazepine binding did not correspond with the time course of rebound anxiolytic effects. However, after kindling it seems that there are long-lasting changes in benzodiazepine binding that are similar to the short-term increases that are found following a single seizure. 相似文献
972.
S Freitag I Le Trong A Chilkoti LA Klumb PS Stayton RE Stenkamp 《Canadian Metallurgical Quarterly》1998,279(1):211-221
Previous thermodynamic and computational studies have pointed to the important energetic role of aromatic contacts in generating the exceptional binding free energy of streptavidin-biotin association. We report here the crystallographic characterization of single site tryptophan mutants in investigating structural consequences of alterations in these aromatic contacts. Four tryptophan residues, Trp79, Trp92, Trp108 and Trp120, play an important role in the hydrophobic binding contributions, which along with a hydrogen bonding network and a flexible binding loop give rise to tight ligand binding (Ka approximately 10(13) M-1). The crystal structures of ligand-free and biotin-bound mutants, W79F, W108F, W120F and W120A, in the resolution range from 1.9 to 2.3 A were determined. Nine data sets for these four different mutants were collected, and structural models were refined to R-values ranging from 0.15 to 0.20. The major question addressed here is how these mutations influence the streptavidin binding site and in particular how they affect the binding mode of biotin in the complex. The overall folding of streptavidin was not significantly altered in any of the tryptophan mutants. With one exception, only minor deviations in the unbound structures were observed. In one crystal form of unbound W79F, there is a coupled shift in the side-chains of Phe29 and Tyr43 toward the mutation site, although in a different crystal form these shifts are not observed. In the bound structures, the orientation of biotin in the binding pocket was not significantly altered in the mutant complex. Compared with the wild-type streptavidin-biotin complex, there were no additional crystallographic water molecules observed for any of the mutants in the binding pocket. These structural studies thus suggest that the thermodynamic alterations can be attributed to the local alterations in binding residue composition, rather than a rearrangement of binding site architectures. 相似文献
973.
SD Ladas H Malamou-Lada G Economou PS Tassios SA Raptis 《Canadian Metallurgical Quarterly》1998,45(21):761-764
BACKGROUND/AIMS: Octreotide is used to arrest peptic ulcer hemorrhage. Since it has anti-secretory properties, it could also be used in Helicobacter pylori eradication therapy, to cure peptic ulcer before discharging patients from hospital. The aim of this pilot study was to determine safety and efficacy of an ultra short quadruple octreotide containing H. pylori eradication therapy in patients with peptic ulcer. METHODOLOGY: Twenty-six consecutive symptomatic H. pylori-positive patients with duodenal (n = 20) or gastric ulcer (n = 6), were treated with a three-day course of octreotide 0.3 mg/day subcutaneously, amoxicillin plus metronidazole 2 g/day orally and colloid bismuth subcitrate 480 mg/day. CLO-test, culture and crush tissue smears were performed on admission to the study, at 4 and 8 weeks post treatment. The effect of octreotide on intragastric pH (n = 10) was also investigated. RESULTS: Octreotide significantly increased the mean 24-hour intragastric pH > 3 over 68.9% of the time (37.1%-99.5%). There were no treatment side effects. Ulcer pain was abolished at between 2-12 days. By intention-to-treat 24/26(92.3%, 95% CI 82%-100%) ulcers had healed at 4 weeks. H. pylori eradication rate at 8 weeks was 88.5% (23/26) (95% CI 76%-100%). CONCLUSIONS: Our ultra-short octreotide containing quadruple therapy is a safe and effective regime in eradicating H. pylori and healing peptic ulcers. It may be a suitable therapy for hospitalized patients with peptic ulcer hemorrhage. 相似文献
974.
E Kalapothakis CL Penaforte RM Le?o JS Cruz VF Prado MN Cordeiro CR Diniz MA Romano-Silva MA Prado MV Gomez PS Beir?o 《Canadian Metallurgical Quarterly》1998,36(12):1971-1980
The cDNAs (Tx3-2 and Pn3A) encoding precursor of toxin Tx3-2 and an isoform called Pn3A have been isolated from a library constructed from stimulated venom glands of the spider Phoneutria nigriventer. The cDNA of Tx3-2 reveals the presence of a signal peptide of 21 amino acids and of an intervening propeptide (with 16 amino acids) preceding the toxin sequence, which was followed by additional amino acid residues at the C-terminus (C-terminal peptide), implying post-translational modifications of the synthesised peptide. The deduced amino acid sequence for the mature toxin confirms the previous sequence published. In addition, by using the whole-cell patch clamp technique, we have determined that purified Tx3-2 decreases L-type currents present in GH3 cells. Finally, the presence of the cDNA Pn3A, with high sequence identity with Tx3-2, reveals the existence of a putative new toxin showing, at the cDNA level, 85.4% identity in its whole segment. 相似文献
975.
We presented an unusual case of cutaneous and bilateral ovarian metastases of malignant melanoma. There was no previously identifiable cutaneous or mucous lesion or teratoid element. Past history revealed that the patient had undergone removal of a blackish, elevated, irregular shaped tumor from the right arm eleven years previously. This lesion was considered to be the primary melanoma; therefore, it was thought to be very unusual as metastasis occurred in both the skin and ovaries after an eleven year disease-free interval. 相似文献
976.
OBJECTIVE: Quantifiable outcome measures for disabling diseases such as osteoarthritis (OA) of the knee are necessary in order to compare the impact of different interventions competing for financial resources. Current subjective and questionnaire data are not satisfactory for such study. In this study, we examine the potential of the direct measurement of ambulatory activity as such a measure. POPULATION: Patients with X-ray evidence of OA of the knee recruited to studies of anti-inflammatory agents (n = 29). Patients with OA of the knee awaiting knee replacement surgery (n = 28). METHODS: Comparison of various standard measures with total energy output data from an activity monitor. RESULTS: Spearman rho correlations of ambulatory energy output (number of steps x average amplitude of steps) correlated with other measures. Correlation with physician's opinion was greater than with patient's opinion (r = 0.4 and 0.2, respectively). There was no correlation with visual analogue pain scale or OA severity index. Correlation with scales of the Nottingham Health Profile questionnaire were not significant either for mobility (r = - 0.15) or for pain (r = - 0.13). There was, however, a significant correlation between poor sleep and increased activity (r = 0.34, P < 0.05). Correlation with Kellgren X-ray grade was significant (r = - 0.45, P = 0.01). Patients recruited to anti-inflammatory studies were 69% more active than those awaiting replacement surgery. CONCLUSION: The monitoring of ambulatory activity shows some construct and discriminant validity, and is worthy of further study. 相似文献
977.
The perirhinal cortex (PRC) plays a major role in memory processes. This role may be influenced by activity in the adjacent entorhinal cortex (EC) and hippocampus (HPC), particularly during the processing of spatial information. In the current experiment we sought to determine whether the cholinergically mediated (type II) theta rhythm, which is a prominent electrophysiological feature of both HPC and EC activity, influenced neuronal firing in the PRC of urethane-anesthetized rats. When the spontaneous firing activity of single units recorded in PRC was related to theta recorded from the hippocampal fissure, it was determined that the firing of 50/163 (31%) PRC neurons exhibited a statistically significant phase relationship (mean phase angle = 188 degrees) to HPC theta. Thirty-three (66%) of these neurons tended to fire near the trough, and 17 near the peak, of this activity. These data indicate that a high proportion of PRC neurons participate in hippocampal-entorhinal theta activity. This activity may support information transmission and storage within and between these structures. 相似文献
978.
PS Smith SM Teutsch PA Shaffer H Rolka B Evatt 《Canadian Metallurgical Quarterly》1996,129(3):424-431
OBJECTIVE: To assess the incremental cost-effectiveness of prophylactic compared with episodic care in boys with severe hemophilia A. SETTING: Eleven U.S. hemophilia treatment centers. METHODS: Charge data from a randomly selected cohort of 70 boys receiving episodic infusions for bleeding events and from all 27 boys receiving infusions prophylactically were collected from documents obtained from the hemophilia treatment centers during a period of approximately 2 years. Published and public sources were used for conversion to cost, lifetime earnings, and earnings losses from disability. A model was constructed for a hypothetical patient from ages 3 to 50 years by means of three infusion scenarios. RESULTS: The cohort receiving prophylactic treatment had fewer bleeding events each year (median, 3 vs 31) but used more concentrate (3323 vs 1015 units/kg per year). Factor VIII concentrate accounted for more than 93% of the cost of both episodic and prophylactic care. Compared with episodic infusion, prophylaxis from ages 3 to 20 years costs $1100 per bleeding event prevented, in comparison with $1380 for prophylaxis from ages 3 to 50 years. The total cost of prophylactic care from ages 3 to 50 years would equal the current total cost of episodic care if the price of the concentrate were decreased by 50%. CONCLUSION: Prophylactic care markedly reduces the number of bleeding events and should prevent joint function impairment, but at substantial cost. 相似文献
979.
PS Cook 《Canadian Metallurgical Quarterly》1996,30(3):405-409
In our laboratory we have developed a relatively simple method for cardiac surgery in rats. The operation is carried out through a small incision in the chest wall using inexpensive equipment. This method allows for the delivery of tissue fragments and cells from a donor rat to an intact or damaged area of ventricular myocardium of a host rat, with easy subsequent localisation of the transplanted/grafted tissue. The rats recover well after the surgery and survive for long periods of time. The technique could also be used for the direct injection of chemicals or molecular probes into the heart. In our experiments we have found that embryonic rat cardiomyocytes that have been transplanted into adult host rat ventricular myocardium using this method survive and develop characteristics typical of heart muscle, thus indicating that using this technique the host heart offers a favourable environment for the transplanted embryonic heart cells. 相似文献
980.
TJ Hiltermann CR de Bruijne J Stolk AH Zwinderman FT Spieksma W Roemer PA Steerenberg PH Fischer L van Bree PS Hiemstra 《Canadian Metallurgical Quarterly》1997,156(6):1765-1772
Asthma is an inflammatory disease of the airways, and exacerbations of this disease have been associated with high levels of air pollution. The objective of this study was to examine whether ambient air pollution and/or allergen exposure induces inflammatory changes in the upper airways of asthmatics. Sixty patients with intermittent to severe persistent asthma visited the Hospital's Out Patient Clinic every 2 wk for a period of 3 mo, and on each visit a nasal lavage was obtained. Associations between nasal inflammatory parameters and seasonal allergens and/or air pollution exposures were analyzed using linear regression analysis. The study ran from July 3 to October 6, 1995, during which period ozone (8-h mean: 80 micrograms/m3) and PM10 (24-h mean: 40 micrograms/m3) were the major air pollutants; the major aeroallergen was mugwort pollen (24-h mean: 27 pollen grains/m3). Effects on both cellular and soluble markers in nasal lavage were demonstrated for both ozone and mugwort pollen, but not for PM10. Ambient ozone exposure was associated with an increase in neutrophils (112% per 100 micrograms/m3 increase in 8-h average ozone concentration), eosinophils (176%), epithelial cells (55%), IL-8 (22%), and eosinophil cationic protein (ECP) (19%). Increases in environmental mugwort pollen counts were associated with an increase in nasal eosinophils (107% per 100 pollen/m3) and ECP (23%), but not with neutrophils, epithelial cells, or lL-8. This study demonstrated that both ambient ozone and allergen exposure are associated with inflammatory responses in the upper airways of subjects with asthma, although the type of inflammation is qualitatively different. 相似文献