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1.
AIMS: To investigate the malignant potential of lichen sclerosus, a study using the cell proliferation marker Ki67 comparing lichen sclerosus with and without associated squamous cell carcinoma was performed. METHODS AND RESULTS: Formalin-fixed, paraffin-embedded slides of 13 cases of lichen sclerosus with associated carcinoma, and 31 cases without associated carcinoma, including 16 random cases, seven with epidermal thickening and eight with epidermal thinning, were examined by the immunoperoxidase technique for Ki67, a cell proliferation marker. Ki67 reactivity was mostly seen in the basal and parabasal cells in both groups of lichen sclerosus and this pattern was similar to normal skin, squamous cell hyperplasia and analogous to that of one form of squamous cell carcinoma. There was a mean of 50 Ki67 positive cells per 100 basal cells in lichen sclerosus with associated squamous cell carcinoma; however, in squamous cell hyperplasia adjacent to carcinoma this rose to 90 Ki67 positive cells per 100 basal cells. In lichen sclerosus without associated carcinoma, the random cases had a count of 53 per 100 basal cells, those with epidermal thickening 53 and those with thinning 42. Non-genital normal skin had a count of 71 per 100 basal cells. CONCLUSION: The lack of qualitative differences of Ki67 expression in normal skin, in lichen sclerosus with and without carcinoma, in squamous cell hyperplasia and in one form of squamous cell carcinoma indicates that these conditions share a common localized pattern of cell proliferation and does not support or deny the malignant potential of lichen sclerosus. The higher Ki67 count in squamous cell hyperplasia adjacent to carcinoma could indicate premalignancy or a reaction to the carcinoma. In patients without carcinoma, the higher Ki67 count in thickened lichen sclerosus compared to thinned suggests that some or all of the cases of thickened lichen sclerosus were lichen sclerosus with squamous cell hyperplasia or that lichen simplex chronicus superimposed on lichen sclerosus has a higher Ki67 expression or that the distinction between squamous cell hyperplasia and lichen simplex chronicus is only one of terminology.  相似文献   

2.
PURPOSE: Recent studies document the value of early combined modality therapy of small cell lung cancer, but also indicate that early thoracic radiation adds to myelosuppression and can complicate further chemotherapy. Other studies indicate that simultaneous use of growth factors with thoracic radiation may be deleterious. However, temporal separation of growth factor use from cytotoxic therapy may allow dose intensity to be maintained/enhanced during combined modality treatment. We sought to integrate filgrastim into a novel chemoradiation regimen for patients with limited small cell lung cancer using an approach that separated growth factor administration from both chemotherapy and thoracic radiation. METHODS AND MATERIALS: Twenty-seven patients with limited disease small cell lung cancer were enrolled in a Phase I trial of cisplatin, ifosfamide/mesna, oral etoposide, and thoracic radiation (1.5 Gy b.i.d. x 30 fractions days 1-19 cycle 1) +/- filgrastim (5 microg/kg/day). Filgrastim was given on days 20-25 of cycle 1 after completion of radiation and following completion of oral etoposide in subsequent cycles. The primary end point was determination of maximum tolerated dose (MTD) of chemotherapy. Serial cohorts were treated with and without filgrastim. RESULTS: Because of dose-limiting thrombocytopenia, primarily, and nonhematologic toxicity, the MTDs with and without filgrastim were identical (cisplatin 20 mg/m2 i.v. and ifosfamide 1200 mg/m2 i.v., both given days 1-3, and etoposide 40 mg/m2 p.o. days 1-14). Filgrastim use shortened the duration of neutropenia at the MTD (median 4 vs. 7 days), but was not associated with a reduction in febrile neutropenia. Although growth factor administration did not allow dose escalation of this regimen, it did allow chemotherapy doses to be maintained at the MTD more frequently through four cycles of therapy. In the 24 evaluable patients, the overall response rate was 100% (71% partial and 29% complete). CONCLUSIONS: Despite careful attention to the timing of growth factor with chemoradiation, the administration of filgrastim with this regimen did not allow dose escalation. As in many other recent studies of hematopoietic growth factors given prophylactically with chemotherapy, the duration of neutropenia at the MTD was shortened and the need for dose reduction throughout treatment was reduced in patients receiving filgrastim at the MTD.  相似文献   

3.
Female amphipods (Crustacea) carry their fertilized eggs in an external brood pouch until the fully formed juveniles emerge (passive brood care). They may also direct specific maternal activities towards the brood (active brood care). We show that Crangonyx pseudogracilis, which typically populates fresh-waters subject to wide fluctuations in temperature and dissolved oxygen, engages in a highly responsive form of active brood care. This involves a flexing motion by the female that expands the brood pouch and increases the suspension of the eggs in the surrounding medium, accompanied by ventilation of the brood pouch and the 'cycling' of eggs therein. Females also selectively eject nonviable eggs from their broods. We investigated the expression of this brood care behaviour in relation to intrinsic and extrinsic factors relevant to the development of broods. The time spent by females in this behaviour initially increased as embryos developed, but decreased once advanced embryos began to self-ventilate and to have a heart pulse. In addition, both increased temperature and decreased oxygen concentration resulted in increased levels of brooding behaviour. We thus propose that this behaviour functions to ameliorate the microclimate of the brood pouch and serves the changing metabolic demand of the brood, as influenced by the interaction of embryonic development with temperature/dissolved oxygen regime. In addition, this behaviour may be a key adaptation facilitating the success of this North American species as an invader of disturbed and polluted freshwaters in Europe and elsewhere. Evidence is emerging that other amphipods associated with harsh environmental conditions also show such active maternal brood care. Copyright 1998 The Association for the Study of Animal Behaviour.  相似文献   

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5.
Spray deposition is a novel manufacturing process which is currently being developed for producing near-net-shape preforms. Spray deposition involves the creation of a spray of droplets by a gas atomizer and the consolidation of these droplets on a substrate to create a preform. In order to maximize the metallurgical benefits of spray deposition, a thorough characterization of momentum and heat transfer in the gas-atomized spray is required. The present paper describes measurements of particle size, gas velocity, particle velocity, and spray temperature in gasatomized Sn-Pb sprays. Measurements were performed on steady-state axisymmetric sprays which were generated using a close-coupled gas atomizer with Sn-5 wt p t Pb and Sn-38 wt p t Pb alloys, atomizer gas flow rates of 2.5 g/s (0.56 MPa) and 3.4 g/s (1.04 MPa), melt flow rates of 35 and 61 g/s, and atomizer-substrate distances of 180 and 360 mm. Gas velocities in the range to 4 m/s were measured using Pitot tube and laser Doppler anemometry (LDA). Droplet velocities in the range 3 to 32 m/s were determined from photographic streak-length measurements and LDA. Oil calorimetry of the spray enthalpy indicated that the spray temperature decreased with increasing axial distance from the gas atomizer, increasing gas flow rate, and decreasing melt flow rate. Formerly Doctoral Student, Department of Metallurgy and Science of Materials, Oxford University  相似文献   

6.
Mathematical models of disease transmission are being used increasingly in the design of population-based vaccination programs. Their use is illustrated in a review of some modeling studies that have implications for the use of measles, mumps, and rubella vaccine. Investigations of vaccination strategy options yield predictions for effectiveness and cost-effectiveness analyses. A quantitative understanding of the factors affecting disease transmission enables the setting of targets for vaccination programs and underpins disease elimination initiatives.  相似文献   

7.
Cystinosis is an autosomal recessive metabolic disease in which the amino acid cystine accumulates in lysosomes due to a defect in lysosomal cystine transport. Cystinosis in infancy is associated with poor growth, muscle wastage, and death at about age 10 due to kidney failure. Treatment with cysteamine and kidney transplantation enables cystinotic girls to reach reproductive age and to be healthy enough to permit pregnancy. It is not known whether exposure to cysteamine will have adverse effects on reproduction in the human. It is also possible that some of the complications seen in cystinotic children could be avoided if a pregnant woman carrying a cystinotic fetus were given cysteamine. However, this treatment is not likely to occur until therapeutic exposures to cysteamine are judged to present no increased risk to the human fetus. As part of a larger investigation assessing the reproductive and developmental safety of cysteamine (as phosphocysteamine) using the rat, the two studies reported herein were performed. The first, a dose-finding study, led to the selection of 150 mg/kg/day as the highest dose of cysteamine used for the second and primary focus of this report. The second study involved the exposure of female rats to cysteamine from premating through day 6.5 postconception and assessment of female fertility and early embryonic development. Cysteamine was administered orally in doses of 0, 37.5, 75, 100, or 150 mg/kg/day. There were no clinical signs of maternal toxicity during the exposures of 2 to 5 weeks before successful mating. Animals in the 150 mg/kg/day group experienced a nonsignificant decrease in body weight gain during pregnancy to day 6.5 postconception, a significant increase in liver and spleen weights, and a significant increase in days to coitus--suggesting that a low level of toxicity was manifested. However, there were no adverse effects on reproductive performance with respect to conception and early embryonic development.  相似文献   

8.
Litter size in mice was studied using a model including ovulation rate, potential embryonic viability, and uterine capacity. Simulated results were compared with experimental results from a selection experiment with mice. The four criteria of selection were selection on number born (LS), selection on an index of ovulation rate and ova success (IX), selection on number born to unilaterally ovariectomized females (UT), and unselected control (LC). Comparisons were made to statistics of the base generation and to responses after 13 generations of selection. Phenotypic and genetic statistics for uterine capacity were generated so that simulations produced the experimental means, standard deviations, and correlations between left and right litter size, as well as responses in number born using the LS, IX, and UT criteria. Statistics for the simulated data generally agreed with observed values. Simulated heritability in the base generation for uterine capacity was .065. Experimental and simulated responses per generation in litter size through 13 generations of selection were .15 and .16, .17 and .18, and .10 and .11 for LS, IX, and UT, respectively. Simulated responses in uterine capacity after 13 generations were 2.19, 1.60, and 3.40 for LS, IX, and UT, respectively. Simulated means for the base generation were 13.22 and 16.30 for ovulation rate and uterine capacity, respectively. Uterine capacity was an important component of the variability in litter size; however, ovulation rate was the more limiting component.  相似文献   

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10.
In this work, a methodology for the optimal design of flow in foundry casting rigging systems is discussed. The methodology is based on a novel, fully analytical design sensitivity formulation for transient, turbulent, free-surface flows. The filling stage of the casting process is modeled by solving the time-averaged form of the Navier-Stokes equations via a turbulent mixing-length model, in conjunction with the volume-of-fluid (VOF) method for modeling the free surface. The design of the runner and gating system of a simple block casting is presented as an example application for using sensitivity information in design. The analytical sensitivity routine is coupled to a numerical optimizer to yield an automated method for optimal design of the casting rigging system. The finite element model of the filling process is verified through physical experimentation. Solutions of glycerol and water are used to perform laminar and turbulent flow filling experiments, which are used to verify independently the VOF algorithm and the adequacy of the mixing-length model. The results show that the numerical model accurately reproduces the main features of the flow, and filling times agree with acceptable accuracy. Finally, the analytical techniques are used to obtain an optimal runner shape, which eliminates air entrainment, and the design is verified experimentally.  相似文献   

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12.
Cadherins and catenins: interactions and functions in embryonic development   总被引:1,自引:0,他引:1  
During the past year, the family of cadherin cell-adhesion molecules has increased in number and diversity. Recent studies have also emphasized how cadherin activity can be regulated by the dynamic association with intracellular components, the catenins, and with extracellular molecules that are linked to different cell-signaling pathways. Finally, the initial steps have been taken towards identifying the function of cadherins in vivo, including their potential roles in early embryonic development.  相似文献   

13.
The bile-esculin test is used to differentiate enterococci and group D streptococci from non-group D viridans group streptococci. The effects on test performance of the concentration of bile salts, inoculum, and duration of incubation were examined with 110 strains of enterococci, 30 strains of Streptococcus bovis, and 110 strains of non-group D viridans group streptococci. Optimal sensitivity (> 99%) and specificity (97%) of the bile-esculin test can be obtained with a bile concentration of 40%, a standardized inoculum of 10(6) CFU, and incubation for 24 h.  相似文献   

14.
Antinociception can be produced at the spinal level by activation of opioidergic, noradrenergic, and serotonergic systems. We tested the antinociceptive effects of combined activation of all three systems. Antinociception was assessed in the rat tail-flick test, and drugs were administered via an intrathecal catheter. Morphine, the norepinephrine uptake inhibitor desipramine, and serotonin produced antinociception of their own. The combination of subthreshold doses of morphine 1 microg and of desipramine 3 microg produced pronounced antinociception that was antagonized by yohimbine. The combination of subthreshold morphine with serotonin 50 microg or desipramine with serotonin caused only small antinociceptive effects. When morphine combined with desipramine was decreased to a subthreshold dose, we observed pronounced antinociception when a subthreshold dose of serotonin was added. A complex interaction can be supposed by results obtained with antagonists. The activation of all three neurotransmitter systems with small doses of agonists may represent an effective principle for pain control at the spinal level. IMPLICATIONS: Pain sensations are modulated at the spinal level by opioids, noradrenergic drugs, and serotonin. Using a rat model, we showed that the concurrent use of drugs from each of these classes produces good pain control at doses that should avoid the side effects associated with larger doses of each individual drug.  相似文献   

15.
Flow stress,subgrain size,and subgrain stability at elevated temperature   总被引:4,自引:0,他引:4  
Well defined subgrain boundaries dominate the microstructural changes occurring during plastic flow of polycrystalline metals at elevated temperature. The quantitative influence of subgrain size on elevated-temperature plastic flow is considered. Based on the results of tests under constant-stress and constant-structure conditions, an equation is developed which predicts the creep rate as a function of subgrain size, stress, diffusion coefficient, and elastic modulus. In general, the subgrain size is a unique function of the current modulus-compensated flow stress, but if fine subgrains can be introduced and stabilized, large increases in creep strength may result. The applicability of the phenomenological relation developed to the behavior of dispersion-strengthened materials (where the second-phase particles may predetermine the effective subgrain size) is discussed. When subgrain effects are included, it is shown that the creep rate is less dependent on stacking fault energy than has been previously thought. This paper is based on a presentation made at a symposium on “Mechanical-Thermal Processing and Dislocation Substructure Strengthening,” held at the Annual Meeting in Las Vegas, Nevada, on February 23, 1976, under the sponsorship of the TMS/IMD Heat Treating Committee.  相似文献   

16.
Dose of acyclovir (ACV) and clinical features of varicella were evaluated in 65 household contacts (0.8-9 y) who received oral ACV (5-80 mg/kg daily in four divided doses) during the latter half of the incubation period of varicella. The severity of the disease was compared with that of 23 children who did not receive ACV. Infection was confirmed by a fluorescent antibody to membrane antigen assay. The antibody titers and the rate of apparent infection increased as the dose of ACV administered decreased. The number of skin lesions in patients who received ACV was significantly reduced when compared to the control group. These data suggest dose-dependence of ACV for modification of varicella during secondary viremia in the incubation of the disease.  相似文献   

17.
Our goal was to evaluate 3 different designs of synthetic corneas in vivo. All devices had a transparent hydrogel center molded to a porous peripheral skirt. Over 30 devices were implanted into rabbits and followed for up to 6 months. The devices were preseeded with rabbit stromal fibroblasts, which enhanced the rate of fibroplasia. The anterior surface of the hydrogel was modified using argon rf plasma treatments. Clinical examinations were performed, and histological analyses were conducted on tissue throughout the time course. Our optimal model ranged from 4.5 to 6 mm and had an extended porous skirt increasing the surface area for fibroplasia and ultimate anchorage of the device. Fibroplasia occurred in this model, and collagen was detected by 28 days. The anterior chamber was normal with no detectable leakage of aqueous humor. Glycosaminoglycans were detected and followed the time course outlined previously when porous material itself was inserted into the stroma. We present the first demonstration that rabbit limbal epithelial cells can migrate onto the synthetic cornea in vivo.  相似文献   

18.
How do group size and recesses affect ability of the most knowledgeable member to influence the group? 199 Ss in groups of 2-5 persons performed with each group having an informed accomplice. 2- and 5-person groups were most accurate, satisfied, and influenced. Recesses decreased the effectiveness of the E's accomplice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

19.
STUDY DESIGN: The effects of orally administered eprosartan on changes induced by angiotensin II in blood pressure, renal hemodynamics, and aldosterone secretion were evaluated in healthy men in this double-blind, randomized, single-dose, placebo-controlled crossover study, which was conducted in three parts. Part 1 (n = 12) assessed the onset and duration of the effect of eprosartan 350 mg or placebo; part 2 (n = 14) assessed the dose-response profile of placebo or 10, 30, 50, 70, 100 or 200 mg eprosartan; and part 3 (n = 5) assessed the duration of the effect of 50, 100, or 350 mg eprosartan. RESULTS: In part 1 of the study; 350 mg eprosartan caused complete inhibition of angiotensin II-induced pressor and renal blood flow hemodynamic effects (effects on effective renal plasma flow [ERPF]) and inhibited angiotensin II-induced stimulation of aldosterone secretion from 1 to 3 hours after administration. Eprosartan, 350 mg, inhibited the effects of exogenous angiotensin II by approximately 50% to 70% from 12 to 15 hours after dosing. Eprosartan had no angiotensin II agonistic activity and produced an increase in ERPF starting at 1 to 4 hours after dosing. In study part 2, at 3 hours after single doses of 10, 30, 50, 70, 100, and 200 mg, eprosartan inhibited angiotensin 11-induced decreases in ERPF by 39.1%, 49.9%, 33.0%, 56.0%, 71.0%, and 85.7%, respectively, compared with placebo. In study part 3, 50, 100, and 350 mg eprosartan produced measurable Inhibition of angiotensin II-induced decreases in ERPF from 12 to 15 hours after administration. In parts 2 and 3, the eprosartan angiotensin II antagonism on blood pressure response and aldosterone secretion mirrored the angiotensin II antagonism on ERPF.  相似文献   

20.
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