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Association of increased bronchoalveolar lavage fluid albumin and serum beta 2-microglobulin with pulmonary complications after allogeneic bone marrow transplantation.

The aim of this prospective study was to identify markers in bronchoalveolar lavage fluid (BAL fluid) and serum predictive for the development of pulmonary complications in the early phase (< 50 days) post-BMT. Concentrations of BAL fluid albumin (alb) and serum beta 2-microglobulin (S-beta 2m,) were determined 10 days before BMT (BAL-B, baseline) and on day 1 post-BMT (BAL-1) in 20 patients who subsequently developed pulmonary complications (group 1) and in 66 patients who remained free of complications for a minimum of 12 months (group 2). Median BAL fluid alb concentrations were significantly (P < 0.05) higher in group 1 patients as compared to group 2 patients at BAL-B (40 vs 28 mg/l) and at BAL-1 (30 vs 15 mg/l). S-beta 2m at BAL-1 was also significantly elevated in group 1 patients (median 1.3 mg/l) compared to group 2 patients (median 1.15 mg/l). Using cut-off values for BAL fluid alb (> 23 mg/l) and S-beta 2m (> 0.8 mg/l) we identified 12 patients out of 19 who developed subsequent pulmonary complications from 12 out of 62 patients without such complications, 1 day post-BMT.

Adolescent↗

[The changes in retinol-binding protein, N-acetyl-beta-glucosaminidase, albumin and IgG in urine before and after ESWL].

The retinol-binding protein (RBP), N-acetyl-beta-glucosaminidase, (NAG) albumin (alb) and IgG in urine were measured from 67 patients with urinary stone before and after ESWL. The results showed that the amount of alb, IgG and RBP in urine was obviously increased for the patients with renal, upper ureteral or lower ureteral stone associated with hydronephrosis. ESWL may injure the glomerule and tubules by direct or indirect action. 2 weeks after ESWL, the alb, IgG and RBP in urine returned to normal in 56.8%, 70.3% and 51.4% of cases respectively. Therefore we suggest that retreatment should be put off as late as 2 weeks after the first ESWL. However, it is not limited for retreatment of lower ureteral stones without hydro nephrosis.

Acetylglucosaminidase↗

Nitric oxide dose-response study in the isolated perfused rat kidney after inhibition of endothelium-derived relaxing factor synthesis: the role of serum albumin.

The dose-response relationship of steady-state nitric oxide (NO) administration on renal vascular resistance in isolated rat kidneys (IPRK) perfused at constant pressure was investigated after inhibition of NO synthesis with NG-monomethyl-L-arginine (L-NMMA). To study the influence of biological thiols on renovascular NO effects, experiments were carried out with Krebs-Henseleit (KH) perfusate solutions alone, and in combination with bovine serum albumin (KH-ALB). Steady-state administration of NO by gassing the perfusate with 0 to 340 ppm NO led to graded decreases in renovascular tone. The minimal effective NO perfusate concentration in the absence of endogenous NO synthesis was about 6 to 8 nM, whereas a near-maximal effect was observed with approximately 200 nM. The presence of albumin reduced the speed of onset of renal vasodilation and the maximal effect at a given concentration of NO. After termination of NO administration, NO-induced vasodilation persisted in KH-ALB perfused kidneys for 30 min, whereas KH-perfused kidneys showed a rapid reconstriction. These findings suggest that the prolonged, potent renal vasodilation was caused by a reaction of bovine serum albumin (BSA) with oxides of nitrogen to form S-nitroso-BSA. Nitrosothiol levels in the KH-ALB perfusate were found to be proportional to the concentration of NO administered. The above-mentioned findings, confirmed in identical experiments with diethylamine NONOate, a novel NO-liberating substance, support the biological importance of S-nitrosothiols (RS-NO) in the action and metabolism of endothelium-derived relaxing factor (EDRF) in the IPRK.

Animals↗

Autocrine mitogen IgEGF cooperates with c-myc or with the Hcs locus during hepatocarcinogenesis in transgenic mice.

Hepatocarcinogenesis is deterministic in transgenic mice expressing in the liver gene construct Alb-DS4 that encodes autocrine growth factor IgEGF (D Stern et al. (1987), Science 235: 321-324), causing their death within 7.1 months. Hepatic expression of construct AAT-myc encoding murine c-myc causes liver cancer in 44% of the mice at 14.8 months. Cooperation of these genes was evident in CD2F1 transgenics bearing Alb-DS4 plus AAT-myc, in which accelerated hepatocellular carcinoma (HCC) formation caused death of all mice within 4.4 months. Alb-DS4 also cooperates with the Hcs locus, which in C3H/HeJ mice mediates high susceptibility to spontaneous hepatocarcinogenesis, causing accelerated formation of HCC to which mice succumbed at 5.1 months. Thus, genes that predispose to HCC formation cooperate in transgenic mice and their interaction is a key to understand mechanisms that cause liver cancer.

Animals↗

[Relationship between syndrome differentiation and blood total fibrinolytic activity, superoxide dismutase and albumin in nephrosis syndrome].

Relationship between the Syndrome Differentiation and total fibrinolytic activity (TFA), superoxide dismutase (SOD), serum albumin (Alb) was observed in 118 pediatric patients with nephrosis syndrome. The results suggested that there was significant difference between Damp-Heat type and Spleen Deficiency type in terms of blood TFA, SOD and serum Alb. Very significant positive correlation was found between serum Alb and TFA, P < 0.01. The level of TFA in pediatric patients with edema was significantly lower than that in normal children, the more the degree of edema, the more the level of TFA activity. It was shown that there would be possibility to find intrinsic connection between Syndrome Differentiation and laboratory findings.

Adolescent↗

[Relationship between nutritional depletion and cell-mediated immune function in active pulmonary tuberculosis].

A survey on the nutritional status and cell-mediated immune function of 47 hospitalized patients with active pulmonary tuberculosis and healthy controls was conducted. In the patients group: 1) Anthropometric measurements, such as %ideal body weight (%IBW), %arm circumference (%AC), %arm muscle circumference (%AMC) and %triceps skin fold (%TSF), were significantly reduced. 2) Visceral proteins including serum albumin (Alb), transferrin (Tf), prealbumin (PA) and retinol binding protein (RBP) were significantly reduced. 3) The imbalance of plasma amino acids, which was characterized by the depression of Fischer ratio, a molar ratio of branched chain amino acids (BCAA) to aromatic amino acids (AAA), was observed. Fischer ratio was significantly correlated with anthropometric measurements (%IBW, %AC and %AMC). Delayed-type hypersensitivity to DNCB (2,4-dinitrochlorobenzene) and lymphocyte transformation to phytohemagglutinin (PHA) and concanavalin A (Con A) were significantly impaired in the patients group, whereas NK cell activity was higher than that of controls. Alb, PA, RBP and Fischer ratio were significantly lower in the patients with reduced DNCB reaction than in those with normal responses. Lymphocyte transformation was significantly correlated with Fischer ratio, and NK cell activity was significantly correlated with Alb, PA, RBP. These data may suggest that the imbalance of plasma amino acids represented by the reduction of Fischer ratio and the depletion of visceral proteins are closely related to the impairment of lymphocyte function in the patients with active pulmonary tuberculosis.

Adult↗

[Concentration of serum proteins and blood group substances in human saliva 2. Individual differences in serum protein concentration in saliva with special reference to age estimation].

Factors related to the concentrations of IgA, IgG and albumin (Alb) in human saliva were studied. Saliva specimens that were strongly positive for the occult blood test contained much more Alb than negative specimens. The concentrations of IgA and IgG in the saliva specimens showed no clear associations with the results of the occult blood test. Although associations were found among the concentrations of individual proteins (IgA, IgG and Alb) in saliva specimens, no association was found between the concentration of these proteins and the DMF (decayed, missing and filled teeth) and PMA (papillary, marginal and attached gingival) indexes. The concentrations and ratios of these proteins were almost the same in saliva specimens from both sexes. The ratios of IgA/Alb and IgG/Alb among those aged less than 20 years old were significantly lower than in older subjects (probability < 0.001). We also found relatively low IgA/Alb value among those 45 years old or older. The ratios of these proteins in saliva stains did not change remarkably after storage for 18 weeks.

Adult↗

Serum interleukin-1 and granulocyte-macrophage colony-stimulating factor levels in protein malnourished patients during acute infection.

OBJECTIVE: To investigate the response of serum interleukin-1 (IL-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) to infection of malnourished patients. DESIGN: Prospective observational study. SETTING: Paediatric clinics of Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey. SUBJECTS: 13 protein-depleted (kwashiorkor marasmic kwashiorkor), 15 marasmic nutritionally repleted kwashiorkor (NRK), and 12 well-nourished control subjects. INTERVENTIONS: Clinical and laboratory data, and serum IL-1 and GM-CSF levels during acute infections were examined. MAIN OUTCOME MEASURES: White blood cell count, pc of circulating neutrophils (%PNL), serum total protein, albumin (ALB), IL-1 and GM-CSF levels. RESULTS: Fever, pcPNL, serum IL-1 and GM-CSF levels of kwashiorkor patients were lower than those of marasmic and control patients (p < 0.005). Fever, neutrophil pc(PNLpc), serum IL-1 and GM-CSF levels of NRK patients during further acute infection were not significantly different from those of marasmic and control patients, but higher than those of the kwashiorkor patients. Although there were positive correlations between serum IL-1 and ALB levels (r = 0.922, p < 0.001), and between serum GM-CSF and ALB levels (r0.730, p = 0.005) in the kwashiorkor group, there were not significant correlations between the same parameters in the other groups (r < 0.5, p > 0.05). And also, although there was not significant correlations between PNL% and IL-1 levels in the kwashiorkor group (r0.312, p = 0.299), there were significant positive correlations between the same parameters in the other groups (r < 0.5, p > 0.05). However, significant positive correlations were found between fever and IL-1 levels, and between IL-1 and GM-CSF levels in all groups (r > 0.5, p < 0.05). CONCLUSION: The responses of serum IL-1 and GM-CSF to acute infection of kwashiorkor patients are defective, and nutritional-repletion therapies restore the production of these cytokines.

Acute Disease↗

Oxidative metabolism of polymorphonuclear leukocytes in continuous ambulatory peritoneal dialysis.

OBJECTIVE: To evaluate the oxidative metabolism of polymorphonuclear leukocytes (PMNL) in continuous ambulatory peritoneal dialysis (CAPD) patients compared with those of hemodialysis (HD) patients, chronic renal failure (CRF) patients not yet on dialysis, and healthy controls; and to discover factors contributing to the oxidative function in CAPD patients. PATIENTS: Thirty-five CAPD, 22 HD, 11 CRF patients were assessed; all were free from infections at the time of examination. Thirty-one healthy volunteers served as controls. METHODS: The oxidative metabolism was estimated by the production of superoxide anion, which was detected by luminol-dependent zymosan stimulated chemiluminescence (CL) with whole blood assessment. The volume of superoxide production equivalent to 1 mL of circulating blood (T-CL), that equivalent to 10(4) neutrophils (CL/N) and the velocity of superoxide production (V-CL), were measured as parameters for the oxidative function of PMNL. RESULTS: There were no differences in all CL parameters between CAPD and HD patients. T-CL and CL/N of dialysis patients were equal to controls but those of CRF patients were significantly decreased. V-CL of dialysis patients, as well as CRF patients, was smaller than that of controls but the difference was not significant. Among nutritional status, degree of anemia, dialytic efficacy and duration of dialysis in CAPD patients, only serum albumin concentration (Alb) correlated well to all CL parameters. Hypoalbuminemic patients (Alb < 3.6 g/dL, n = 20) had significantly decreased T-CL and CL/N compared to normoalbuminemic patients (Alb > or = 3.6 g/dL, n = 15), and decreased CL/N and V-CL compared to controls. No differences in CL parameters were observed between the patients with a history of peritonitis (n = 15) and without a history of peritonitis (n = 20). CONCLUSIONS: Oxidative metabolism of PMNL in CAPD patients was maintained with respect to superoxide productive volume, while the oxidative velocity was relatively impaired. Furthermore, it seems that albumin has a great influence on the oxidative metabolism of PMNL in CAPD patients.

Adolescent↗

Different urinary albumin responses to submaximal exercise by normoalbuminuric diabetic children and controls.

It is not clear if exercise could be useful to identify diabetic patients at risk for the development of nephropathy. We evaluated the responses of blood pressure (BP) and urinary albumin (Alb) and retinol-binding protein (RBP) excretion to standardized sub-maximal exercise in 17 normoalbuminuric normotensive children with IDDM and 17 matched normal subjects. RBP was used as an index of tubular function. Standardization of exercise load was based on heart rate (HR) which was maintained at 70% of the maximum calculated to age. A step exercise test lasted for 35 min; baseline BP and HR were taken at midtime and during cooling down. Pre- and postexercise urines were obtained for Alb, RBP and creatinine determinations. Both groups showed a significantly increased systolic BP at the midpoint but the percent variations were not different. HR responses did not differ and demonstrated the exercise effectiveness. Great variability in Alb excretion was observed within the normal range for both groups. The baseline Alb/creatine ration was not significantly different between normal and diabetic subjects, but became different following exercise (6.6 +/- 4.1 vs 17.7 +/- 18.7 mg/g. P < 0.05). While this ratio decreased in the control group (14.8 +/- 11.1 to 6.6 +/- mg/g, P < 0.02), it increased (9.0 +/- 7.1 to 17.7 +/- 18.7 mg/g, P = 0.05) in diabetic patients. Percent variations in the two groups occurred in opposite directions and were significantly different. RBP/creatinine followed the same pattern within each group; normals showed a tendency to a decrease (0.058 +/- 0.064 to 0.030 +/- 0.039 microgram/g, P = 0.05) and diabetic patients to an increase (0.116 +/- 0.125 to 0.247 +/- 0.247 microgram/g, P = 0.06). We conclude that there was a variable proteinuric response to exercise among diabetic subjects with normal renal function as evaluated by albumin excretion. A subset of IDDM patients responded abnormally to the exercise stress, increasing albumin excretion to levels compatible with microalbuminuria. Whether this heterogeneity reflects individual risk for diabetic renal disease require further investigation.

Adolescent↗

[Blood amino acid levels in sarin poisoning patients].

Since plasma is generally employed for amino acid analysis, we compared amino acid levels in plasma with those in serum for healthy individuals and examined the influence of separation and storage conditions on the stability of the samples. Then, we determined the amino acid levels of frozen serum samples obtained from sarin poisoned patients. A. Comparison of Amino Acid Levels in Plasma and Those in Serum Blood was collected from 5 healthy individuals. Then, heparinated plasma and serum were separated by centrifugation immediately after blood collection. Serum was also separated by centrifugation after standing whole blood at room temperature for 1 hour. Frozen plasma and serum were store at -40 degrees C for 5 months. All were subjected to analysis in an amino acid analyzer. It was found that the cystine (Cys) and 3-methyl-histidine (3-M-His) levels in serum and plasma were affected when stored in a frozen state, that the aspartate (Asp) level was changed according to the method of collecting serum, and that the taurine (Tau) and ornithine (Orn) levels were affected by standing blood. B. Analysis of Blood Taken from Sarin Poisoned Patients Twelve sarin poisoned patients were selected as subjects, and serum cholinesterase (Ch-E) and serum albumin (Alb) levels were determined. Amino acid analysis was conducted using an amino acid analyzer. Serum samples which had been obtained from the 6 patients and frozen and stored at -40 degrees C from 5 months were used for amino acid analysis. As a result, the serum Ch-E level decreased and the Alb level tended to rise. Since the Ch-E/Alb ratio was reduced in the sarin poisoned patients, it is considered useful for discrimination from liver cirrhosis in which both Ch-E and Alb levels decreased. Amino acid levels in the serum obtained from the sarin poisoned patients were compared with those of healthy individuals, both of which had been stored under the same conditions. There were significant differences in Asp, glutamate (Glu), phenylalanine (Phe), 3-M-His, glutamine (Gln), and Cys levels. The Glu, Phe, and Gln levels were not affected by storage of serum in a frozen state, while the Glu and Phe levels were elevated and the Gln level was reduced. Although Cys exhibited lower values in frozen serum samples, the Cys level was elevated with a rise in the serum Ch-E levels. Therefore, we deduced that Cys metabolism disorders also occur in sarin poisoning. As stated above, the Glu and Phe levels were elevated and the Gln and Cys levels were reduced, suggesting the presence of abnormal amino acid metabolism, in patients with sarin-poisoning.

Adolescent↗

[The effect of dialysis solutions containing amino acids on the nutritional status of patients treated with continuous ambulatory peritoneal dialysis].

BACKGROUND: In the patient population which is subjected to haemodialysis or peritoneal dialysis is a high prevalence of protein-energy malnutrition which independently on the causal factor causes a deterioration of their prognosis. To influence protein nutrition in patients on peritoneal dialysis Nutrineal was developed, i.e., a dialysis solution using as an osmotic agent a 1.1% amino acid mixture instead of glucose used as a rule. The objective of the present study was to evaluate the effect of its administration on some nutritional indicators in patients treated by continuous ambulatory peritoneal dialysis (CAPD) and to assess its tolerance. METHODS AND RESULTS: The authors investigated eight patients aged 45.5 years (29-78 years, median, minimal and maximal value), treated for 19.9 (5-42) months by CAPD. For a period of four weeks Nutrineal was administered once a day instead of glucose based solution to patients without diseases complicating nutrition, with a serum albumin concentration (ALB) below 35 (20-34) g/l. Before treatment and after its termination an anthropometric examination was made, the rate of protein catabolism was examined (PCR), plasma concentrations of total proteins were assessed, as well as ALB, transferrin (TRF) and 14 free amino acids substituted by the dialysis solution. For statistical comparison the paired Wilcoxon test was used. As compared with the baseline value of 0.83 g/kg/24 h after treatment a significant increase of PCR was recorded--to 0.96 g/kg/24 h (p < 0.05) as well as a significant increase of the urea concentration from 18.4 (10.9-34.8) mmol/l to 26.7 (19.6-33) mmol/l (p < 0.05). The value of phosphorus declined significantly from 2.25 (1.6-2.6) to 1.9 (0.9-2.5) mmol/l (p < 0.05). No significant difference was recorded in the anthropometric findings and in concentrations of total proteins, ALB, TRF and amino acids. CONCLUSIONS: Four weeks administration of a solution with amino acids raised significantly the PCR which may be indirect evidence of an anabolic effect and it reduced plasma phosphates which participate in uraemic toxicity. The solution was well tolerated by the patients. Final evaluation of the values of the solution containing amino acids calls for long-term and controlled studies.

Adult↗

Contribution of acute-phase proteins and cardiovascular risk factors to erythrocyte aggregation in normolipidemic and hyperlipidemic individuals.

BACKGROUND: Numerous studies have demonstrated that elevated concentrations of acute-phase proteins affect red blood cell (RBC) aggregation. Plasma lipids and lipoproteins were also shown to be correlated with RBC aggregation in hypercholesterolemia. However, whether acute-phase proteins promote RBC hyperaggregation in hyperlipidemic patients is unknown. The main objective of the study was to identify the impact of acute-phase proteins such as fibrinogen (Fib), haptoglobin (Hp), ceruloplasmin (Cp), alpha1-acid glycoprotein (AGP), alpha1-antitrypsin (AT), immunoglobulin G (IgG), and albumin (Alb) on RBC aggregation in 35 hyperlipidemic patients. The influence of these proteins in 32 normolipidemic subjects was also determined. METHODS AND RESULTS: RBC aggregation parameters reflecting the kinetics of rouleau formation and the adhesive strength between RBCs were measured by laser reflectometry. Multivariate forward stepwise linear regression analyses were performed to study the relationship between RBC aggregation and these acute-phase proteins, total cholesterol (TC), triglycerides (TG), high (HDL-C) and low (LDL-C) density lipoprotein cholesterol, age, gender, body mass index (BMI), mean blood pressure (Mpresure), and smoking habit. The kinetics of rouleau formation was positively correlated with the linear combination of IgG and Hp (r=0.76, p <0.0001) in hyperlipidemic patients, whereas IgG, smoking, AGP and gender were significant independent predictors in healthy subjects (r=0.79, p <0.0001). The correlations obtained for the models predicting the adhesive strength between RBCs were 0.69 in patients (Alb, HDL-C, IgG, p <0.002) and 0.71 in healthy individuals (AGP, BMI, p <0.0001). CONCLUSION: This study suggests that acute-phase proteins such as IgG, Hp, AGP and Alb influence significantly and in an independent way the level of RBC aggregation. The close association between RBC aggregation and cardiovascular risk factors further strengthens its clinical importance.

Acute-Phase Proteins↗

In vitro laser welding of amniotic membranes.

OBJECTIVE: To test in vitro the feasibility of welding amniotic membranes using Nd:YAG laser energy. STUDY DESIGN: Fresh fetal membranes from term pregnancies were washed and cut into 1 cm2 pieces. Pooled cryoprecipitate (CPT), 50% albumin (Alb), or polytetrafluoroethilene (e-PTFE) were used as solder medium. The optimal settings of the laser were determined. Results were assessed quantitatively and semi-quantitatively using Pearson Chi-square analysis. RESULTS: Laser welding of amniotic membranes was successful in 82.6% of experiments with e-PTFE and in 10.7% of experiments with CPT (P < 0.001). The strength of the welding was also significantly better with e-PTFE (P < 0.001). Optimal results were obtained using 1-7 Watts and 0.1-1 seconds. Laser welding was unsuccessful in 100% of experiments with Alb. CONCLUSIONS: Laser welding of fetal membranes can be accomplished with e-PTFE and to a lesser degree with the CPT using Nd:YAG energy under low wattage-high exposure settings. Further studies are underway to test other grafting or soldering materials.

Extraembryonic Membranes↗

Extracellular matrix in tooth cementum and mantle dentin: localization of osteopontin and other noncollagenous proteins, plasma proteins, and glycoconjugates by electron microscopy.

BACKGROUND: Noncollagenous proteins (NCPs) are considered to have multiple functions related to the formation, turnover, and repair of the collagen-based mineralized tissues. Collectively, they comprise a class of generally acidic, mineral-binding proteins showing extensive posttranslational modifications, including glycosylation, phosphorylation, and sulfation. METHODS. We have used colloidal-gold immunocytochemistry and lectin-gold cytochemistry, together with transmission electron microscopy, to examine the organic matrix composition of tooth cementum and the subjacent mantle dentin in rodent molar teeth. Molars were processed for immunocytochemistry using antibodies against osteopontin (OPN), osteocalcin (OC), bone sialoprotein (BSP), bone acidic glycoprotein-75 (BAG-75), albumin (ALB), and alpha 2HS-glycoprotein (alpha 2HS-GP), or for glycoconjugate cytochemistry using lectin-gold complexes. RESULTS: Ultrastructurally, at the advancing root edge in developing molars, OPN and BSP initially were associated with small calcification foci in the mantle dentin. With progressing mineralization, OC and alpha 2HS-GP appeared diffusely distributed throughout the calcified mantle dentin, and diminished as a gradient toward the circumpulpal dentin. Immediately following disruption of Hertwig's epithelial root sheath, cementum deposition commenced at the root surface occasionally with the appearance of a cement line rich in OPN. Cementum matrix proper contained abundant OPN, BSP, OC, and alpha 2HS-GP, but no or little BAG-75 or ALB. Protein immunolabeling, as well as lectin labeling for beta-D-galactose and N-acetyl-neuraminic acid and/or N-glycolyl-neuraminic acid, both being prominent sugars of certain NCPs, was primarily concentrated between, and at the surface of, collagen fibrils in acellular extrinsic fiber cementum. OPN, BSP, OC, and alpha 2HS-GP were also prominent components of cellular cementum and of Sharpey's fibers. In cellular cementum, laminae limitantes sometimes present delimiting cementocyte lacunae and cell process-containing canaliculi were also rich in OPN. Along the root surface, occasional cementoblasts exhibited intracellular labeling for OPN over the Golgi apparatus and secretory granules. CONCLUSIONS: We have identified OPN, BSP, OC, and alpha 2HS-GP as being prominent organic constituents of both mantle dentin and acellular and cellular cementum, and, have elucidated the details of their distribution at the ultrastructural level. The temporal appearance and spatial distribution of these organic moieties in the teeth root are similar to those seen during bone formation and are consistent with proposals that certain NCPs may be involved in regulating calcification and/or participating in cell-matrix and matrix-matrix/mineral adhesion events.

Animals↗

Adsorption of proteins onto poly(ether urethane) with a phosphorylcholine moiety and influence of preadsorbed phospholipid.

In a previous report we demonstrated that the blood compatibility of poly(ether urethane) (PEU) was improved by grafting phosphorylcholine (PC) groups on the surface. The improved blood compatibility was indicated by decreased platelet adsorption/activation and reduced thrombin formation at the polymer surface in experiments in which the surfaces were contacted with platelet-rich plasma in vitro. In the present study, we investigated the effect of grafted PC groups at a PEU surface on protein and phospholipid adsorption. Adsorption of human fibrinogen (Fg), human serum albumin (Alb), human high-molecular-weight kininogen (HMWK), and dioleoyl phosphatidylcholine (DOPC) vesicles was measured by ellipsometry. For this purpose, thin PEU films were cast on silicon wafers. The polymer film was photochemically modified with a PC-containing aryl azide. The presence of PC groups on the polymer surface was demonstrated by ESCA (Electron Spectroscopy for Chemical Analysis). The hydrophilicity of the polymer surface increased by the surface modification, as indicated by a decrease of the contact angle from 59 degrees before to 43 degrees after modification. Our data show that the presence of PC groups has little effect on the adsorption of proteins to a PEU surface. The highest adsorption was observed for Fg (0.49 microgram/cm2 on PC-modified PEU and 0.50 microgram/cm2 on PEU), followed by HMWK (0.28 microgram/cm2 on both PC-modified PEU and PEU), and Alb (0.16 microgram/cm2 on PC-modified PEU and 0.18 microgram/cm2 on PEU). Protein adsorption was further studied on a "biomembrane-like" DOPC bilayer formed on hydrophilic silicon. We found no protein adsorption on this DOPC bilayer. The adsorption of small unilamellar DOPC vesicles on the polymer surfaces amounted to about 0.06 microgram/cm2 (corresponding to circa 30% of monolayer coverage) and was similar for PC-modified PEU and PEU. Despite this partial surface coverage, preadsorbed DOPC on the polymer surface diminished the subsequent adsorption of proteins considerably. These results show that the mere presence of phosphorylcholine groups on a PEU surface is insufficient to suppress protein adsorption. The highly ordered structure of natural phospholipid bilayers seems to be required to suppress protein adsorption effectively.

Adsorption↗

Selection of phenotypically distinct NK1.1+ T cells upon antigen expression in the thymus or in the liver.

Unlike the main TCR alphabeta T cell lineage in which deletion occurs at the CD4+ CD8+ double-positive (DP) stage upon TCR engagement by antigen in the thymus, some T cells appear to require such engagement for their selection, either in the thymus or extrathymically. We used a transgenic TCR (tgTCR) model which, as we previously showed, led to selection upon expression of the corresponding antigen H-2Kb (Kb) in the thymus, of tgTCR/CD3(lo) CD4- CD8- double-negative (DN) thymocytes that expressed the NK1.1 marker (NK T cells) (Curnow, S. J., et al., Immunity 1995. 3: 427). We now report that antigen expression on medullary epithelial cells of the thymus failed to select the NK T cells, whereas its expression on thymocytes did, although tgTCR DP thymocyte development was affected under both conditions. Antigen expression on hepatocytes (Alb-Kb mice) did not perturb tgTCR DP thymocyte development. No enrichment in tgTCR NK T cells was detected in the periphery, except for the liver of the Alb-Kb/tgTCR mice. When reconstitution of thymectomized and irradiated H-2k hosts expressing or not Kb was performed with bone marrow from tgTCR H-2k mice, an enrichment in tgTCR+ NK T cells was found in the liver, but not in the spleen, of the hosts which expressed Kb, either selectively on hepatocytes or ubiquitously. Surprisingly, the majority of the hepatic tgTCR+ NK T cells also expressed the CD8 alpha/beta heterodimer. These results indicate that thymus-independent NK T cells with unique phenotypic characteristics can be selected upon antigen encounter in the liver.

Animals↗

Human yolk sac tumor serially transplanted in nude mice: its morphologic and functional properties.

Three human yolk sac tumors (TE, OE, and TT-1) were serially transplanted into nude mice. The histology of the transplanted tumors is moderately different from that of the original tumor; the transplants had mainly a tubular structure with an inconspicuous endodermal sinus structure due to a decreased mesenchymal element surrounding the vascular core. Ultrastructural features of the transplanted tumor cells, however, were identical to those of the original tumor. Immunochemical survey of the blood plasma of nude mice bearing these tumors demonstrated the production of adult type human plasma proteins including prealbumin, albumin (Alb), alpha 1-antitrypsin (alpha AT), transferrin (Tf), hemopexin, and alpha 1-fetoprotein (AFP). The types of adult plasma proteins that were produced varied, depending on the tumor line but were the same between serial passages within the same tumor line. The intracellular localization of AFP, alpha AT, Tf, and Alb was also investigated by immunoelectron microscopy. Plasma proteins of the adult type and AFP were localized mainly within the membrane systems of the endoplasmic reticulum and Golgi complex and occasionally on the microvilli. These results suggest that transplanted human yolk sac tumors have almost all of the protein-producing function possessed by their normal counterparts.

Animals↗