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61.
62.
Laurence M. Demers Allan Lipton Harold A. Harvey Kathleen B. Kambic Howard Grossberg Carolyn Brady Richard J. Santen 《The Journal of steroid biochemistry and molecular biology》1993,44(4-6):687-691
The pharmacologic inhibition of aromatase activity has been the focus of clinical trials in patients with advanced stage breast cancer. Recent developments with imidazole compounds that inhibit aromatase activity suggest their clinical use as potent inhibitors of estrogen biosynthesis in postmenopausal breast cancer patients. In this Phase I, open-label, dose-range finding study, we examined the inhibitory potency of CGS 20267 on blood and urine levels of estradiol, estrone and estrone sulfate in 8 patients with metastatic breast cancer. Studies included evaluation of adrenal and thyroid function to look for evidence of general hydroxylase inhibition at dose levels effective for aromatase blockade. Patients were administered CGS 20267 at doses of 0.1 and 0.25 mg, once a day in ascending doses over a 12-week period. Preliminary data reveal that CGS 20267 elicits a striking suppression in plasma estradiol, estrone and estrone sulphate which was observed in some patients as quickly as within 24 h of the first dose. Estrogen suppression of over 90% was achieved within 2 weeks of therapy. No alterations in either baseline or ACTH (cortrosyn) stimulated cortisol and aldosterone levels were observed through the 12 weeks of therapy. In addition, 24 h urine sodium and potassium values were not appreciably altered during therapy. We conclude that CGS 20267 is a potent, specific inhibitor of estrogen biosynthesis in postmenopausal patients with metastatic breast cancer and effectively reduces blood and urine estrogens to undetectable levels. 相似文献
63.
Jerome J. Howard 《Journal of Insect Behavior》1993,6(4):441-453
Patterns of resource fidelity, switching, and variation in individual diet were examined in the polyphagous grasshopper Taeniopoda equesforaging in experimental cages over an 11-day period. Ten novel dicots were provided in the cages, but grasshoppers fed primarily on kale (Brassica oleraceavar. acephala),lobelia (Lobelia erinus),pansy (Viola x wittrockiana),and dry bermuda grass (Cynodon dactylon).Grasshoppers showed significant fidelity to a single plant within a meal but tended to eat less of the same plant in the next meal and, in the case of pansy, on the next day. Grasshoppers switched nonrandomly, suggesting that compensatory feeding on complementary resources may have occurred. There was no evidence that behavioral interactions among individuals increased switching rate or lowered fidelity. Overall patterns of resource use varied significantly among grasshoppers during the study, despite frequent switching among resources and a significant tendency to aggregate while feeding. All individuals were polyphagous but differed in relative consumption of available plants. The results suggest that individual grasshoppers express different feeding patterns that are consistent over time and that variation in diet among individual observed in the field may be more than simple sampling error. 相似文献
64.
65.
We quantified patterns of vegetation removal and light availability above Atta colombica nests on Barro Colorado Island, Panama. Ants cleared vegetation less than 1 cm in diameter from an area of 77 m2, and up to 3 m above ground level. Overall light availability 1.5 m above ground level was 49 percent greater at ant nest sites than at sites in undisturbed understory. These higher light levels fell within the range known to enhance growth of both shade tolerant and pioneer species. 相似文献
66.
67.
Francisco Berguido Michelle Kagey Charles F. Howard Jr. Susan R. Stapleton 《Primates; journal of primatology》1995,36(3):423-429
Members of the monkey speciesMacaca nigra spontaneously develop impairments in insulin secretion and glucose clearance, and eventually become overtly diabetic. Changes
in certain metabolic signals such as clearance of glucose and insulin increment secreted in an intravenous glucose tolerance
test have allowed the identification of four stages in the progression from non-diabetes to diabetes in monkeys — non-diabetic,
hormonally impaired, borderline diabetic, and diabetic. Recently, another metabolic stage, hyperinsulinemic, was also identified
in these animals. In recent years, other factors besides those listed above have been implicated to be correlated with the
metabolic progression from a nondiabetic to a diabetic state. One of these factors, is insulin like growth factor I (IGF-I).
In diabetic humans who are in poor metabolic control, and in rats with streptozotocin induced ketotic diabetes, serum levels
of IGF-I are lowered by as much as 40–50% of control non-diabetics. If indeed decreased IGF-I levels are correlated with the
onset of diabetes then changes in IGF-I concentrations prior to the clinically diagnosed disease state would be expected.
Using serum samples collected from different animals in a colony ofMacaca nigra in a variety of metabolic states, we have found that IGF-I and insulin levels decrease in each defined metabolic state as
the animals progress from nondiabetic to diabetic. Since IGF-I and insulin levels decrease in a similar fashion in the progression
of this disease then this maybe indicative of the coordinate expression of these two factors. 相似文献
68.
Phillip A Patten Russell J Howard Willem PC Stemmer 《Current opinion in biotechnology》1997,8(6):724-733
DNA shuffling is a practical process for directed molecular evolution which uses recombination to dramatically accelerate the rate at which one can evolve genes. Single and multigene traits that require many mutations for improved phenotypes can be evolved rapidly. DNA shuffling technology has been significantly enhanced in the past year, extending its range of applications to small molecule pharmaceuticals, pharmaceutical proteins, gene therapy vehicles and transgenes, vaccines and evolved viruses for vaccines, and laboratory animal models. 相似文献
69.
Data on cyanobacteria (blue-green algae) are generallycollected on a reactive basis, frequently in responseto bloom events. Such data presents a biased andincomplete snapshot of water quality. This paper looksat two typical data sets for UK waters showing thatwhile statistics may be used to describe the data theyare of limited use in forecasting. Suggestions ofappropriate tests for small and sparse data sets aremade. 相似文献
70.
Meiheng Yang Howard Allen Hisao Fukushima Richard A. DiCioccio 《Glycoconjugate journal》1984,1(1):15-19
Fucosidosis is an autosomal recessive lysosomal storage disease resulting from the absence of -l-fucosidase activity. Two natural missense mutations (G197A) and (A860G) within the -l-fucosidase gene have been reported to be homozygous in four patients with fucosidosis. Expression of wild-type and mutated -l-fucosidase cDNAs in COS-1 cells revealed complete deficiency of -l-fucosidase for the G197A transition and a normal level of enzyme for A860G. We therefore conclude that the change of G197A is responsible for fucosidosis in the patients while A860G is a normal polymorphic variant of -l-fucosidase. 相似文献