细胞学联合肿瘤标志物鉴别非典型良恶性胸水

目的探讨细胞学联合癌胚抗原(CEA)、肿瘤抗原19-9(CA19-9)和细胞角蛋白片段(CY-FRA21-1)检测,在鉴别非典型良恶性胸腔积液中的参考价值。方法对200例细胞学发现非典型细胞的胸水用电化学发光法测定其上述3种肿瘤标志物的含量,用t检验对两样本均数进行比较并根据公式计算出3种肿瘤标志物对良恶性胸水诊断的敏感性、特异性和准确性。结果经证实为恶性胸水组的3种肿瘤标志物水平显著高于良性组(P<0.05),CEA的准确性最高;CA19-9的特异性最好,但敏感度低;CY-FRA21-1的准确性与CA19-9相近。结论CEA、CA19-9和CYFRA21-1联合检测,对细胞学鉴别胸腔积液中非典型细胞的性质具有一定的参考价值,对于可疑病例需多次送检,尽可能找到典型的恶性肿瘤细胞,为临床提供准确、及时、可靠的依据。     

A Distributed Model of Carbohydrate Transport and Metabolism in the Liver during Rest and High-Intensity Exercise

A model of reaction and transport in the liver was developed that describes the metabolite concentration and reaction flux dynamics separately within the tissue and blood domains. The blood domain contains equations for convection, axial dispersion, and transport to the surrounding tissue; and the tissue domain consists of reactions representing key carbohydrate metabolic pathways. The model includes the metabolic heterogeneity of the liver by incorporating spatial variation of key enzymatic maximal activities. Simulation results of the overnight fasted, resting state agree closely with experimental values of overall glucose uptake and lactate output by the liver. The incorporation of zonation of glycolytic and gluconeogenic enzyme activities causes the expected increase in glycolysis and decrease in gluconeogenesis along the sinusoid length from periportal to perivenous regions, while fluxes are nearly constant along the sinusoid length in the absence of enzyme zonation. These results confirm that transport limitations are not sufficient to account for the observed tissue heterogeneity of metabolic fluxes. Model results indicate that changes in arterial substrate concentrations and hepatic blood flow rate, which occur in the high-intensity exercise state, are not sufficient to shift the liver metabolism enough to account for the 5-fold increase in hepatic glucose production measured during exercise. Changes in maximal activities, whether caused by exercise-induced changes in insulin, glucagon, or other hormones are shown to be needed to achieve the expected glucose output. This model provides a framework for evaluating the relative importance to hepatic function of various phenomenological changes that occur during exercise. The model can also be used to assess the potential effect of metabolic heterogeneity on metabolism.     

Influence of glucose ingestion by humans during recovery from exercise on substrate utilisation during subsequent exercise in a warm environment

Carbohydrate (CHO) ingestion during short-term recovery from prolonged running has been shown to increase the capacity for subsequent exercise in a warm environment. The aim of this study was to examine the effects of the amount of glucose given during recovery on substrate storage and utilisation during recovery and subsequent exercise in a warm environment. A group of 11 healthy male volunteers took part in two experiments in a controlled warm environment (35°C, 40% relative humidity), 1 week apart. On each occasion the subjects completed two treadmill runs (T1 and T2) at a speed equivalent to 60% of maximal oxygen uptake, for 90 min, until they were fatigued, or until aural temperature (T _aur) reached 39°C. The two runs were separated by a 4 h recovery period (REC), during which subjects consumed 55 g of naturally enriched [U-¹³C]-glucose in the form of a 7.5% carbohydrate-electrolyte solution (CES, mass of solution 667 g) immediately after T1. The subjects then consumed either: the same quantity of CES, or an equivalent volume of an electrolyte placebo, at 60, 120 and 180 min during REC, providing a total of 220 g (C220) or 55 g (C55) of [U-¹³C]-glucose, respectively. Expired gases were collected at 15 min intervals during exercise and 60 min intervals during REC, for determination of total CHO and fat oxidation by indirect respiratory calorimetry, and orally ingested [U-¹³C]-glucose oxidation, estimated from the ¹³C:¹²C ratio of expired CO₂. Substrate metabolism did not differ between conditions during T1. Despite the fact that total CHO (P<0.05) and ingested glucose oxidation (P<0.01) were greater during REC of the C220 condition, glycogen synthesis was estimated to be approximately fivefold greater (P<0.01) than in the C55 condition. During T2 the rate of total CHO oxidation was higher (P<0.01) and total fat oxidation lower (P<0.01) at all times during the C220 compared to the C55 condition. The greater CHO oxidation during C220 appeared to be met from ingested sources, as the rate of [U-¹³C]-glucose oxidation was greater (P<0.01) at all times during T2, compared to C55. Whilst more of the ingested substrate remained unoxidised on completion of T2 during C220, exercise duration was similar in the two experimental conditions, and was limited by thermoregulatory incapacity (T _aur>39°C) rather than substrate availability per se. Electronic Publication     

The effect of glycogen availability on power output and the metabolic response to repeated bouts of maximal,isokinetic exercise in man

The relationship of glycogen availability to performance and blood metabolite accumulation during repeated bouts of maximal exercise was examined in 11 healthy males. Subjects performed four bouts of 30 s maximal, isokinetic cycling exercise at 100 rev · min^–1, each bout being separated by 4 min of recovery. Four days later, all subjects cycled intermittently to exhaustion [mean (SEM) 106 (6) min] at 75% maximum oxygen uptake Subjects were then randomly assigned to an isoenergetic low-carbohydrate (CHO) diet [7.8 (0.6)% total energy intake,n = 6] or an isoenergetic high-CHO diet [81.5 (0.4)%,n = 5], for 3 days. On the following day, all subjects performed 30 min cycling at 75% and, after an interval of 2 h, repeated the four bouts of 30 s maximal exercise. No difference was seen when comparing total work production during each bout of exercise before and after a high-CHO diet. After a low-CHO diet, total work decreased from 449 (20) to 408 (31) J · kg^–1 body mass in bout 1 (P < 0.05), from 372 (15) to 340 (18) J · kg^–1 body mass in bout 2 (P < 0.05), and from 319 (12) to 306 (16) J · kg^t-1 body mass in bout 3 (P < 0.05), but was unchanged in bout 4. Blood lactate and plasma ammonia accumulation during maximal exercise was lower after a low-CHO diet (P < 0.001), but unchanged after a high-CHO diet. In conclusion, muscle glycogen depletion impaired performance during the initial three, but not a fourth bout of maximal, isokinetic cycling exercise. Irrespective of glycogen availability, prolonged submaximal exercise appeared to have no direct effect on subsequent maximal exercise performance.     

Immunization with glycosylated Kb-binding peptides generates carbohydrate-specific,unrestricted cytotoxic T cells

Cytotoxic T cells (CTL) recognize target proteins as short peptides presented by major histocompatibility complex (MHC) class I restriction elements. However, there is also evidence for peptide-independent T cell receptor (TCR) recognition of target proteins and non-protein structures. How such T cell responses are generated is presently unclear. We generated carbohydrate (CHO)-specific, MHC-unrestricted CTL responses by coupling di- and trisaccharides to K^b- or D^b-binding peptides for direct immunization in mice. Four peptides and three CHO have been analyzed with the CHO either in terminal or central positions on the carrier peptide. With two of these glycopeptides, with galabiose (Galα1-4Gal; Gal₂) bound to a homocysteine (via an ethylene spacer arm) in position 4 or 6 in a vesicular stomatitis virus nucleoprotein-derived peptide (RGYVYQGL binding to K^b), CTL were generated which preferentially killed target cells treated with glycopeptide compared to those treated with the core peptide. Polyclonal CTL were also found to kill target cells expressing the same Gal₂ epitope in a glycolipid. By fractionation of CTL, preliminary data indicate that glycopeptide-specific K^b-restricted CTL and unrestricted CHO-specific CTL belong to different T cell populations with regard to TCR expression. The results demonstrate that hapten-specific unrestricted CTL responses can be generated with MHC class I-binding carrier peptides. Different models that might explain the generation of such responses are discussed.     

Terminal modifications of norovirus P domain resulted in a new type of subviral particles, the small P particles

The protruding (P) domain of norovirus VP1 is responsible for immune recognition and host receptor interaction. Our previous studies have demonstrated that a modification of the ends of the P domain affects the conformation and/or function of the P protein. An expression of the P domain with or without the hinge, or with an additional cysteine at either ends of the P protein resulted in P dimers and/or P particles. Here we report a new type of subviral particle, the small P particles, through a further modification, either an addition of the flag tag or a change of the arginine cluster, at the C-terminus of the cysteine-containing P domain. Gel filtration and cryo-EM studies showed that the small P particles are tetrahedrons formed by 6 P dimers or 12 P monomers that is half-size of the P particles. Fitting of the crystal structure of the P domain into the cryo-EM density map of the particle indicated similar conformations of the P dimers as those in P particles. The small P particles bind human HBGAs and are antigenically reactive similar to their parental VLPs and P particles. These data suggest that the C-terminus of the P domain is an important factor in the formation of the P particles. Further elucidation of the mechanism of these modifications in the P particle formation would be important in structure biology and morphogenesis of noroviruses. The small P particles may also be a useful alternative in study of norovirus-host interaction and vaccine development for noroviruses.     

Short-term recovery from prolonged constant pace running in a warm environment: the effectiveness of a carbohydrate-electrolyte solution

Recovery from prolonged exercise involves both rehydration and replenishment of endogenous carbohydrate stores. This study examined the influence of drinking a carbohydrate-electrolyte solution on short-term recovery and subsequent exercise capacity in a warm environment. Thirteen healthy male volunteers completed two trials, at least 7 days apart. On each occasion subjects performed an initial treadmill run at 60% of maximal oxygen uptake (VO_2max), for 90 min or until volitional fatigue (T1), in a warm environment (35 °C, 40% relative humidity, RH). Volitional ingestion of water was permitted during each of the exercise trials. During a subsequent 4-h recovery period (REC) subjects consumed either a 6.9% carbohydrate-electrolyte solution (CES) or a sweetened placebo (P), in a volume equivalent to 140% of body mass loss. Following REC, subjects ran to exhaustion at the same %VO_2max in order to assess their endurance capacity (T2). Mean (SEM) run times during T1 did not differ between the CES [74.8 (4.6) min] and P [72.5 (5.2) min] trials. Body mass was reduced (P < 0.01) by 1.9 (0.2)% (CES) and 1.7 (0.2)% (P), and plasma volume (P < 0.01) by 6.0 (0.9)% (CES) and 5.4 (1.0)% (P) during the T1 trials. During REC 2006 (176) ml and 1830 (165) ml of fluid was ingested, providing 138 (12) g and 0 g of carbohydrate in the CES and P trials, respectively. Prior to T2, plasma volume and net fluid balance were similarly restored [CES +58 (26) g; P −4 (68) g] in both trials. During T2 the exercise duration was longer (P < 0.01) in the CES compared to the P trial [CES 60.9 (5.5) min; P 44.9 (3.0) min]. Thus, provided that an adequate hydration status is maintained, inclusion of carbohydrate within an oral rehydration solution will delay the onset of fatigue during a subsequent bout of prolonged submaximal running in a warm environment. Accepted: 25 February 2000     

Diverticulitis Causing a High Serum Level of Carbohydrate Antigen 19-9: Report of a Case

We report herein a rare case of diverticulitis causing a high serum level of carbohydrate antigen (CA) 19-9. A 52-year-old man was admitted to our hospital with lower abdominal pain. Laboratory data showed evidence of inflammation and a high serum level of CA 19-9 (370 U/ml). Computed tomography demonstrated thickening of the wall of the sigmoid colon. He was diagnosed as having diverticulitis of the sigmoid colon and was treated with antibiotics. Although his symptoms improved, the presence of a malignancy such as colorectal cancer could not be completely ruled out because of the persistently high serum level of CA19-9. A laparotomy was performed and the sigmoid colon was found to be adherent to the bladder. Under a diagnosis of diverticulitis, a sigmoidectomy was performed. Pathological examination revealed diverticulitis of the sigmoid colon, but there was no evidence of malignancy in the resected specimen. The serum CA19-9 level decreased to normal postoperatively and immunohistochemical staining revealed CA19-9 antigen in the cytoplasm of the diverticular epithelium. Therefore, a possible explanation for the high level of this tumor marker was diverticulitis of the sigmoid colon. Received: June 6, 2001 / Accepted: September 11, 2001     

An open label, comparative study of the effects of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol and 100 microg levonorgestrel on hemostatic, lipids, and carbohydrate metabolism variables

In this open label, randomized study we compared the influence of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol (EE) and 100 microg levonorgestrel (20 EE) with a reference preparation containing 30 microg EE and 150 microg levonorgestrel (30 EE) on hemostatic, lipids, and carbohydrate metabolism variables. Data from 48 volunteers were obtained. The direction of the change (increase or decrease) in most of the hemostatic variables were similar in both treatment groups. In particular, prothrombin fragment 1 + 2 increased during treatment, reaching a median percent change of 40% in the 20 EE group and of 17% in the 30 EE group after one year. D-Dimer fibrin split products remained virtually unchanged, with no change at Cycle 13. The median HDL2 cholesterol levels decreased by 26% in the 20 EE group and by 39.8% in 30 EE group (p = 0.0045 for group difference) after one year. The median one year change for LDL cholesterol was 3.23% in the 20 EE group, compared to 25% in the 30 EE group, for VLDL 11.1% compared to 38.8%, respectively, and for total triglycerides 10.0% compared to 37.5%, respectively. The median absolute change for the area under the curve (AUC)(0-3h) for glucose at treatment Cycle 13 was 41.25 mmol/L x min in the 20 EE group and 73.50 mmol/L x min in the 30 EE group. The AUC(0-3h) insulin at treatment Cycle 13 decreased in the 20 EE group by 1635.0 pmolL x min and increased in the 30 EE group by 11797.5 pmolL x min (p = 0.0491 for group difference). Both study treatments were safe and well tolerated by the volunteers.In conclusion, the balanced one-third dose reduction in this new oral contraceptive evoked similar effects on the hemostatic variables, but favorable results for the lipid and carbohydrate profiles.     

Adenocarcinoma of the ileum producing carbohydrate antigen 19-9: Report of a case

We report herein the case of an 81-year-old woman found to have small intestinal carcinoma producing carbohydrate antigen (CA)19-9, in whom recurrence on the abdominal wall was strongly suspected 4 months after resection. She presented to our hospital with acute abdominal pain with severe anemia. Marked serum elevation of CA19-9 to 164.8 U/ml suggested a progression to malignancy. A fluorography using an ileus tube revealed an abnormal mucosal pattern. An exploratory laparotomy showed an incomplete annular constrictive Borrmann type 2 tumor, located approximately 190 cm from Treitz's ligament, without any signs of peritoneal or hepatic metastases. Histological examination confirmed a diagnosis of papillotubular adenocarcinoma without metastases of the regional lymph nodes. CA19-9 antigenicity was detected in the cytoplasm and on the surface of the cancer cells, using the monoclonal CA19-9 antibody, NS19-9. In this report, we demonstrate the CA19-9 productivity and distribution of the cancer tissues in relation to their prognosis. Received: August 17, 1999 / Accepted: March 24, 2000