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1.
T Tyni T Kivel? M Lappi P Summanen E Nikoskelainen H Pihko 《Canadian Metallurgical Quarterly》1998,105(5):810-824
OBJECTIVE: The purpose of the study was to determine the nature and course of ophthalmic abnormalities in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, a recently discovered disorder of mitochondrial fatty acid beta-oxidation. STUDY DESIGN: The study design was a cohort (case series). PARTICIPANTS: A retrospective review of the records of 15 children who had died during their first 2 years was performed. Also performed were a longitudinal reanalysis and cross-sectional clinical examination of four long-term survivors aged 5 to 31 years. MAIN OUTCOME MEASURES: Visual acuity, refraction, visual fields, ophthalmoscopy, fluorescein angiography, biometry, corneal topography, electroretinography (ERG), visual-evoked potentials (VEPs), color vision, and dark adaptation were measured. RESULTS: In seven children, ophthalmoscopic findings were within normal limits at 3 days to 13 months of age (median, 4.8 months). In 11 children, a granular retinal pigment epithelium (RPE), with or without pigment clumping in the macula, was seen at 4 months to 5 years of age (median, 9 months). Two long-term survivors, 16 and 31 years of age, eventually had circumscribed atrophy of the choroid, RPE, and retina, which coincided with a posterior staphyloma type 1. They had progressive axial myopia starting at 6 and 12 years of age and later paracentral scotomas leading to poor central vision. They suffered from early difficulty with mesopic vision, glare, and a severe generalized color vision deficiency that started as a tritanomaly. A third survivor was mildly myopic at 5 years of age. All four surviving patients had visually insignificant, flake-like supranuclear opacities in the lens. The ERG initially was normal but deteriorated during the first decade and later was unrecordable. The VEP responses remained fairly normal. Initially, angiography showed no blockade of the choroidal fluorescence because of the thin RPE. Filling of choroidal vessels was delayed, and the choriocapillaris and, later, larger choroidal vessels in the posterior pole became nonperfused. CONCLUSIONS: In LCHAD deficiency, the fundus is normal at birth (stage 1). Soon, however, pigment dispersion occurs in the RPE (stage 2), followed by circumscribed chorioretinal atrophy, occlusion of choroidal vessels, and deterioration of central vision, often with relative sparing of the peripheral fundus (stage 3). Finally, posterior staphylomas and central scotomas may develop (stage 4). Developmental cataract, progressive myopia, and deterioration of visual fields and color vision are new findings in LCHAD deficiency. The chorioretinopathy and abnormal ERG precede the development of myopia and posterior staphyloma, which, in turn, coincide with the loss of macular vision. The authors postulate that the RPE or choriocapillaris is primarily affected. Awareness of the characteristic ocular features is important because of an opportunity for dietary treatment, genetic counseling, and prenatal diagnosis. 相似文献
2.
2-Pentynoyl-CoA is a mechanism-based inactivator of the flavoprotein short-chain acyl-CoA dehydrogenase from pig liver. Inactivation is associated with the formation of an intermediate absorbing at 800 nm and results in the incorporation of 0.86 +/- 0.13 molecules of radiolabeled inhibitor per subunit. A rapid procedure was devised to isolate the labeled peptide. A glutamate residue was identified as the target of 2-pentynoyl-CoA treatment and proved homologous to the proposed catalytic base, GLU376, in the corresponding medium-chain acyl-CoA dehydrogenase sequence. These results are discussed in terms of the lack of conservation of this glutamate residue in the acyl-CoA dehydrogenase enzyme family. 相似文献
3.
Pregnancy complications are frequent in long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
Hemofiltrate C-C chemokine (HCC)-1 is a recently cloned C-C chemokine that is structurally similar to macrophage inflammatory protein (MIP)-1alpha. Unlike most chemokines, it is constitutively secreted by tissues and is present at high concentrations in normal human plasma. Also atypical for chemokines, HCC-1 is reported not to be chemotactic for leukocytes. In this paper, we have investigated the chemokine receptor usage and downstream signaling pathways of HCC-1. Cross-desensitization experiments using THP-1 cells suggested that HCC-1 and MIP-1alpha activated the same receptor. Experiments using a panel of cloned chemokine receptors revealed that HCC-1 specifically activated C-C chemokine receptor (CCR)1, but not closely related receptors, including CCR5. HCC-1 competed with MIP-1alpha for binding to CCR1-transfected cells, but with a markedly reduced affinity (IC50 = 93 nM versus 1.3 nM for MIP-1alpha). Similarly, HCC-1 was less potent than MIP-1alpha in inducing inhibition of adenylyl cyclase in CCR1-transfected cells. HCC-1 induced chemotaxis of freshly isolated human monocytes, THP-1 cells, and CCR1-transfected cells, and the optimal concentration for cell migration (100 nM) was approximately 100-fold lower than that of MIP-1alpha (1 nM). These data demonstrate that HCC-1 is a chemoattractant and identify CCR1 as a functional HCC-1 receptor on human monocytes. 相似文献
4.
Delta 4-3-Ketosteroid-5 beta-reductase (5 beta-reductase) precedes 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) in steroid hormone metabolism. Both enzymes are members of the aldo-keto reductase (AKR) superfamily and possess catalytic tetrads differing by a single amino acid. In 3 alpha-HSD, the tetrad consists of Tyr55, Lys84, Asp50, and His117, but a glutamic acid replaces His117 in 5 beta-reductase. By introducing the H117E point mutation into 3 alpha-HSD, we engineered 5 beta-reductase activity into the dehydrogenase. Homogeneous H117E 3 alpha-HSD reduced the double bond in testosterone to form 5 beta-dihydrotestosterone with kcat = 0.25 min-1 and Km = 19.0 microM and reduced the double bond in progesterone to generate 5 beta-dihydroprogesterone with kcat = 0.97 min-1 and Km = 33.0 microM. These kinetic parameters were similar to those reported for homogeneous rat liver 5 beta-reductase [Okuda, A., and Okuda, R. (1984) J. Biol. Chem. 259, 7519-7524]. The H117E mutant also reduced 5beta-dihydrosteroids to 5 beta, 3 alpha-tetrahydrosteroids with a 600-1000-fold decrease in kcat/Km versus wild-type 3 alpha-HSD. The ratio of 5 beta-reductase:3 alpha-HSD activity in the H117E mutant was approximately 1:1. Although the H117A mutant reduced Delta 4-3-ketosteroids, the 3 alpha-HSD activity predominated because the 5 beta-dihydrosteroids were rapidly converted to the 5 beta,3 alpha-tetrahydrosteroids. The pH-rate profiles for carbon-carbon double-bond and ketone reduction catalyzed by the H117E mutant were superimposable, suggesting a common titratable group (pKb = 6.3) for both reactions. In wild-type 3 alpha-HSD, the titratable group responsible for 3-ketosteroid reduction has a pKb = 6.9 and is assignable to Tyr55. The pH-rate profiles for 3-ketosteroid reduction by the H117A mutant were pH-independent. Our data indicate that Tyr55 functions as a general acid for both 3 alpha-HSD and 5 beta-reductase activities. We suggest that a protonated Glu117 increases the acidity of Tyr55 to promote acid-catalyzed enolization of the Delta 4-3-ketosteroid substrate. Further, the identity of amino acid 117 determines whether an AKR can function as a 5 beta-reductase by reorienting the substrate relative to the nicotinamide cofactor. This study provides functional evidence that utilization of modified catalytic residues on an identical protein scaffold is important for evolution of enzymatic activities within the same metabolic pathway. 相似文献
5.
LL Jiang A Kobayashi H Matsuura H Fukushima T Hashimoto 《Canadian Metallurgical Quarterly》1996,120(3):624-632
Human medium-chain enoyl-CoA hydratase was purified from liver, because we noticed the presence of a high medium-chain enoyl-CoA hydratase activity in human skin fibroblasts catalyzed by an enzyme different from the known enzymes catalyzing the enoyl-CoA hydratase reaction. Two enzyme preparations were obtained. One of them, preparation I, consisted of 46-kDa polypeptide, and its molecular mass was estimated to be 86 kDa. The other, preparation II, consisted of a major 77-kDa polypeptide and minor smaller polypeptides including 46-kDa polypeptide. The molecular mass of preparation II was 154 kDa. Both enzyme preparations catalyzed reversible dehydration of medium-chain D-3-hydroxyacyl-CoA to 2-trans-enoyl-CoA, but did not react with L-3-hydroxyacyl-CoA. Catalytic properties and immunochemical reactivities of these enzyme preparations were nearly the same. The cross-reactive material to the antibody was confirmed to be in peroxisomes by immunohistochemical study of cultured human skin fibroblasts. 相似文献
6.
Y Kuwano H Fujikawa A Watanabe K Shimodaira A Sekizawa H Saito T Yanaihara 《Canadian Metallurgical Quarterly》1997,44(6):847-853
In spite of improvements in single or double lung transplantation (LT) technique, complications after LT are not uncommon; the most frequent ale anastomotic complications, infections and rejection (acute or chronic). Early detection of complications of LT allows the optimal therapeutic option to be taken, yielding decreased morbidity and mortality. In some cases, CT plays a key role in early detection of several complications of LT that may not be depicted with other diagnostic modalities, so that knowledge of their CT features is important. In this pictorial review, the authors describe the spectrum of CT features of the complications of LT (including reimplantation response, mechanical problems, acute and chronic rejection, infection, lymphoproliferative disorders, recurrence of the initial disease and complications involving the pleura and the anastomotic sites). In addition, the authors analyze the value of CT compared to that of the other available modalities for the detection of complications of LT. 相似文献
7.
3Beta-hydroxysteroid dehydrogenase/steroid delta5-isomerase (3beta-HSD/isomerase) was expressed by baculovirus in Spodoptera fungiperda (Sf9) insect cells from cDNA sequences encoding the human wild-type I (placental) enzyme and the human type I mutant- Y253F. The wild-type and Y253F enzymes were each purified as a single, homogeneous protein from a suspension of the Sf9 cells. Ultraviolet (UV) spectral analyses showed that the wild-type enzyme induced changes in the UV spectrum of the competitive isomerase inhibitor, 19-nortestosterone, and the Y253F mutant did not. The wild-type isomerase required activation by coenzyme to produce the spectral shift. Activation of isomerase by NADH produced a greater change in the 19-nortestosterone spectrum than activation by NAD+. These observations provide direct evidence that Tyr253 functions as the general acid (proton donor) in the isomerase reaction mechanism. Furthermore, the coenzyme-activation profiles support our proposed two-step enzyme mechanism in which NADH produced by the 3beta-HSD activity induces the enzyme to assume the isomerase conformation. 相似文献
8.
A large public service organization was concerned with protection of its customers against hazards associated with furniture tipping in public use concourses. Because no injury experience was available for analysis, hazard patterns for tipping accidents were developed from an observational study of public interaction with the furniture. For each hazard pattern, anthropometric models were used to find the probability of the furniture being safe from tipping, for different age and gender combinations. A safety criterion was developed from this modeling, and used to change the weights of some furniture items to resist tipping. These modifications have now been implemented and are in widespread use. Implications for broader application of these models to the development of valid tipping standards for furniture are discussed. 相似文献
9.
Three cases of multiple false-positive drug tests are described. Postmortem urine specimens were screened using the enzyme-multiplied immunoassay technique. All patients had proteinuria and lactic aciduria. These false-positive reactions were due to the presence of lactate dehydrogenase (LDH), lactic acid, and protein. This finding was confirmed by creating a multiple false-positive sample with a solution of LDH and lactate in 5% bovine serum albumin at pH 6. 相似文献
10.
K Matsuura A Hara M Kato Y Deyashiki Y Miyabe S Ishikura T Sugiyama Y Katagiri 《Canadian Metallurgical Quarterly》1998,285(3):1096-1103
The NADP+-dependent dehydrogenase activity of a predominant isoenzyme of human liver 3alpha-hydroxysteroid dehydrogenase was activated by antihyperlipidemic drugs, such as bezafibrate and clinofibrate, and by clofibric acid and fenofibric acid (active metabolites of clofibrate and fenofibrate, respectively). The optimal pH of the activation by the drugs was about 7.5, and the concentrations giving maximum stimulation (1.8- to 2.4-fold) were 100, 50, 400 and 50 microM for bezafibrate, clinofibrate, clofibric acid and fenofibric acid, respectively. Clofibrate and fenofibrate acted as weak inhibitors, and the clofibric acid derivatives that lack the chloro group, methyl group on the alpha-carbon or carboxyl group greatly decreased the stimulatory effects. The activation by the drugs increased both Km and kcat (turnover number) values for the coenzyme and substrates. Kinetic analysis with respect to NADP+ showed that bezafibrate, clinofibrate, clofibric acid and fenofibric acid were nonessential activators showing dissociation constants of 32, 6, 103 and 11 microM, respectively. The combined activators experiments with one of the above drugs and sulfobromophthalein, a known activator specific for this enzyme, and comparison of their effects on the activities of mutant enzymes (with Met replacing Lys-270 or Arg-276) indicated that sulfobromophthalein and the drugs bind to an identical site on the enzyme. These results suggest that the long-term therapy with the antihyperlipidemic drugs influences the metabolism of steroid hormones, bile acids and several ketone-containing drugs mediated by the enzyme. 相似文献
11.
F Haeseleer J Huang L Lebioda JC Saari K Palczewski 《Canadian Metallurgical Quarterly》1998,273(34):21790-21799
The reduction of all-trans-retinal in photoreceptor outer segments is the first step in the regeneration of bleached visual pigments. We report here the cloning of a dehydrogenase, retSDR1, that belongs to the short-chain dehydrogenase/reductase superfamily and localizes predominantly in cone photoreceptors. retSDR1 expressed in insect cells displayed substrate specificities of the photoreceptor all-trans-retinol dehydrogenase. Homology modeling of retSDR1 using the carbonyl reductase structure as a scaffold predicted a classical Rossmann fold for the nucleotide binding, and an N-terminal extension that could facilitate binding of the enzyme to the cell membranes. The presence of retSDR1 in a subset of inner retinal neurons and in other tissues suggests that the enzyme may also be involved in retinol metabolism outside of photoreceptors. 相似文献
12.
SJ Kish I Lopes-Cendes M Guttman Y Furukawa M Pandolfo GA Rouleau BM Ross M Nance L Schut L Ang L DiStefano 《Canadian Metallurgical Quarterly》1998,55(10):1299-1304
BACKGROUND: Although the abnormal gene products responsible for several hereditary neurodegenerative disorders caused by repeat CAG trinucleotides have been identified, the mechanism by which the proteins containing the expanded polyglutamine domains cause cell death is unknown. The observation that several of the mutant proteins interact in vitro with the key glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) suggests that interaction between the different gene products and GAPDH might damage brain neurons. OBJECTIVE: To measure the activity of GAPDH in postmortem brain of patients with CAG repeat disorders. PATIENTS AND METHODS: Activity of GAPDH was measured in morphologically affected and unaffected brain areas of patients with 4 different CAG repeat disorders (Huntington disease, spinocerebellar ataxia 1 [SCA1], SCA2, and SCA3-Machado-Joseph disease), in brains of patients with Friedreich ataxia (a GAA repeat disorder) and Alzheimer disease, and in brains of matched control subjects. RESULTS: Brain GAPDH activity was normal in all groups with the exception of a slight but statistically significant region-specific reduction in the patients with Huntington disease (caudate nucleus, -12%) and Alzheimer disease (temporal cortex, -19%). CONCLUSION: The presence of the polyglutamine-containing proteins in CAG repeat disorders does not result in substantial irreversible inactivation or in increased activity of GAPDH in human brain. 相似文献
13.
JP Berchtold 《Canadian Metallurgical Quarterly》1976,282(16):1533-1536
Sections of Rat and Amphibian adrenocortical tissue fixed in a mixture of 1% formaldehyde and 0.25% glutaraldehyde, are incubated in a medium containing namely a 3 beta-hydroxysteroid (substrate), NAD, potassium ferricyanide (hydrogen acceptor) and copper sulfate. A hyaloplasmic copper ferrocyanide precipitate is observed in the immediate vicinity of the smooth endoplasmic reticulum membranes, or in close contact with them. This reaction, which does not occur in media lacking the substrate or containing cyanoketone, is a result of 3 beta-hydroxysteroid dehydrogenase activity. Problems concerning the precise localization of this enzyme are discussed. 相似文献
14.
3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase (3alpha-HSD/CR) from Comamonas testosteroni, a bacterium that is able to grow on steroids as the sole carbon source, catalyzes the oxidoreduction at position 3 of a variety of C19-27 steroids and the carbonyl reduction of a variety of nonsteroidal aldehydes and ketones. The gene of this steroid-inducible 3alpha-HSD/CR was cloned by screening a C. testosteroni gene bank with a homologous DNA probe that was obtained by polymerase chain reaction with two degenerative primers based on the N-terminal sequence of the purified enzyme. The 3alpha-HSD/CR gene is 774 base pairs long, and the deduced amino acid sequence comprises 258 residues with a calculated molecular mass of 26.4 kDa. A homology search revealed that amino acid sequences highly conserved in the short-chain dehydrogenase/reductase (SDR) superfamily are present in 3alpha-HSD/CR. Two consensus sequences of the SDR superfamily were found, an N-terminal Gly-X-X-X-Gly-X-Gly cofactor-binding motif and a Tyr-X-X-X-Lys segment (residues 155-159 in the 3alpha-HSD/CR sequence) essential for catalytic activity of SDR proteins. 3alpha-HSD/CR was overexpressed and purified to homogeneity, and its activity was determined for steroid and nonsteroidal carbonyl substrates. These results suggest that inducible 3alpha-HSD/CR from C. testosteroni is a novel member of the SDR superfamily. 相似文献
15.
G Duester 《Canadian Metallurgical Quarterly》1996,35(38):12221-12227
The effects of vitamin A (retinol) on growth and development are mediated by the active metabolite retinoic acid which controls a nuclear receptor signaling pathway. While elegant work on the retinoic acid receptor family has focused attention upon how the receptor controls this pathway, there now exists a relatively large gap in our understanding of how retinol is activated to form the ligand. During vertebrate embryogenesis and in adult organs retinoic acid is detected in a distinct spatiotemporal pattern, suggesting that it is produced from retinol in a regulated fashion. Enzymes involved in retinol and retinal metabolism are likely candidates for regulators of tissue retinoic acid levels. Members of the alcohol dehydrogenase and short-chain dehydrogenase/reductase enzyme families catalyze the reversible interconversion of retinol and retinal, the rate-limiting step, whereas members of the aldehyde dehydrogenase and cytochrome P450 enzyme families catalyze the irreversible oxidation of retinal to retinoic acid. The identification of enzymes likely to catalyze retinol oxidation in vivo has been particularly controversial, and this is made even more difficult by the reversible nature of this reaction. Taking into account enzymatic properties and coenzyme preferences, a case can be made that class IV alcohol dehydrogenase catalyzes retinol oxidation to provide retinal for retinoic acid synthesis, whereas microsomal retinol dehydrogenase (a short-chain dehydrogenase/reductase) catalyzes the reduction of retinal to retinol to promote retinoid storage. Further studies on these enzyme families will allow this layer of control in the retinoid signaling pathway to be understood. 相似文献
16.
17.
Eicosapentaenoic acid (EPA, 20:5n-3) is less efficiently accumulated in tissue triacylglycerols (TAGs) during fish oil feeding than docosahexaneoic acid (DHA, 22:6n-3) or docosapentaenoic acid (DPA, 22:5n-3), and EPA is preferentially released from the TAG of isolated adipocytes in vitro and adipose tissue in vivo during fasting compared with DHA or DPA. It is not known if this preferential release occurs in vivo under nonfasting conditions or if it is limited to adipose tissue. Accordingly, we have carried out experiments to study the turnover of EPA, DHA, and DPA in the TAG of adipose tissue, liver, and skeletal muscle. Weanling rats were fed diets containing fish oil for 6 weeks and then switched to diets containing only corn oil as the dietary fat for 8 weeks. The fatty acid composition and mass in epididymal fat pads, omental fat, liver, and soleus muscle TAGs were determined weekly for the first 10 weeks and at weeks 12 and 14. Subsequent to the change to the corn oil diet, EPA (20:5n-3), DPA (22:5n-3), and DHA (22:6n-3), which had accumulated during fish oil feeding, were lost from the tissue TAG pools of each tissue examined. After 8 weeks on the corn oil diet, less than 10% of the accumulated EPA, DPA, and DHA remained in the liver and muscle. The loss of EPA, DPA, and DHA from epididymal fat pad was slower. In each tissue, EPA was lost more rapidly than DPA or DHA. This selective loss of EPA relative to DHA or DPA may explain the previously reported underrepresentation of EPA compared with DHA or DPA in tissue TAG. 相似文献
18.
E Fujii H Iwase I Ishii-Karakasa Y Yajima K Hotta 《Canadian Metallurgical Quarterly》1995,210(3):852-857
2-Keto-3-deoxygluconic acid (3-DGA) is produced from 3-deoxyglucosone (3-DG:a highly reactive glycation intermediate) through oxidation by the enzyme oxoaldehyde dehydrogenase (OAD) in animals. We developed a specific assay method for 3-DGA using high-performance liquid chromatography [Fujii, E. et al. (1994) J. Chromatogr. B 660, 265-270] and measured it in the hemolysate and plasma of diabetic patients and healthy subjects. Both human erythrocytes and plasma contained considerable amounts of 3-DGA. However, human erythrocyte contained about 30-50 times higher 3-DGA than human plasma did and also had the same ability to convert 3-DG to 3-DGA as OAD had. Erythrocyte 3-DGA levels of diabetic patients were 990 +/- 370 nmol/gHb (n = 57, Mean +/- SD) and were significantly higher compared with healthy subjects (527 +/- 194 nmol/gHb, n = 7, p < 0.01). In all diabetic patients and healthy subjects (n = 64), there was only one patient who had a very low level of erythrocyte 3-DGA and lacked the ability to convert 3-DG to 3-DGA. When erythrocytes were incubated at 37 degrees C for 8 hours in phosphate buffer containing 0.35 mM 3-DG, 3-DG was easily taken into the erythrocytes and was converted to 3-DGA. Our results suggest the contribution of OAD not only to the prevention of glycation of hemoglobin but also to that of blood vessels by scavenging plasma 3-DG into erythrocytes. 相似文献
19.
Sugar-3-phosphates are related to aspects of diabetes which depend on protein glycosylation events. Sorbitol-3-phosphate and fructose-3-phosphate occur in normal and diabetic individuals, and glucose-3-phosphate is a potential intermediate in their biosynthesis. Almost nothing is known about enzyme pathways for their metabolic turnover. We have found that part of the phosphohydrolytic activity on glucose-3-phosphate in rat liver supernatants corresponds to a specific, Mg(2+)-dependent, glucose-3-phosphatase much less or not active on other phosphate esters, including glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, fructose-6-phosphate and p-nitrophenyl-phosphate. This finding opens a route to a better understanding of the metabolism and role of sugar-3-phosphates. 相似文献
20.
RA Fleming GA Milano MH Gaspard PJ Bargnoux A Thyss R Plagne N Renée M Schneider F Demard 《Canadian Metallurgical Quarterly》1993,(5):740-744
Dihydropyrimidine dehydrogenase (DPD) is the major catabolic enzyme of pyrimidines and fluoropyrimidines. The clinical course of 2 patients with suspected DPD deficiency is described. Both patients had significantly delayed clearance of fluorouracil (5-FU), elevated plasma uracil concentrations, and subsequent lethal toxicity. The prevalence of DPD deficiency in the general population is unknown, but given the large number of cancer patients treated with 5-FU, it may be of great clinical significance. Lymphocytes have been previously shown to be a useful marker of systemic DPD activity. Because DPD activity has not been previously reported in a large population of cancer patients using 5-FU as the substrate, we determined DPD activity in lymphocytes from 66 patients with cancer. DPD activity was determined by a sensitive high performance liquid chromatography method. The mean DPD activity (S.D.) in 66 patients with head and neck cancer was 0.189 (0.071) nomol/min/mg protein with wide interpatient variability (range 0.058-0.357). DPD activity was not correlated to age (r = -0.164, P = 0.188). The mean DPD activity in men [0.192 (0.074)] was not significantly different from that in women [0.172 (0.057); t-test P = 0.418]. Likewise, there was no statistical difference in DPD activity in patients who had not received prior chemotherapy [0.195 (0.066)] to patients receiving one or more cycles of chemotherapy [0.186 (0.074); t-test P = 0.638]. 相似文献