Effect of free fatty acids on binding of drugs by bovine serum albumin, by human serum albumin and by rabbit serum.
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Association between serum interleukin-6 and serum 3,5,3'-triiodothyronine in nonthyroidal illness.
Increased serum concentrations of FFA, bilirubin, and carboxyl-methyl-propyl-furanpropionic acid, accumulating in chronic renal failure in direct relationship with serum creatinine, have all been implicated in the pathogenesis of the low T3 syndrome during illness. Cytokines may also be involved in the sick euthyroid syndrome. In contrast to interleukin-1 (IL-1) and tumor necrosis factor-alpha, IL-6 is usually detectable in serum during illness and acts as a systemic hormone. We studied the association between serum T3 and IL-6 in consecutive hospital admissions with a wide variety of medical conditions. Patients were divided into group A (T3, > or = 1.30 nmol/L; T4, > or = 75 nmol/L; n = 41), group B (T3, < 1.30 nmol/L; T4, > or = 75 nmol/L; n = 46), and group C (T3, < 1.30 nmol/L; T4, < 75 nmol/L; n = 13). Serum IL-6 levels in groups C and B were higher than those in group A (median values 59, 39, and 9 U/mL, respectively; P < 0.01). Serum creatinine and bilirubin/albumin ratios were similar in the three groups, but the FFA/albumin ratio in group C was higher than in group A (P < 0.05). When all patients were analyzed together, serum T3 was negatively correlated to serum IL-6 (r = -0.56; P < 0.001), bilirubin/albumin ratio (r = -0.29; P = 0.004), and FFA/albumin ratio (r = -0.21; P = 0.03), but not with creatinine (r = -0.16; P = 0.11). Stepwise multiple regression resulted in the following equation: serum T3 = 2.13-0.18ln(IL-6)-0.15ln(creatinine)-0.094ln(bilirubin /albumin) (r = 0.61). The variability in serum T3 was accounted for 28% by ln(IL-6), 5% by ln(creatinine), and 4% by ln(bilirubin/albumin). FFA/albumin did not contribute in this respect. We conclude that the low T3 syndrome in nonthyroidial illness is associated with high serum IL-6 levels. However, even when IL-6 is assumed to play a causative role, the variation of serum T3 in NTI-patients remains largely unexplained.
Adult↗
Serum fluoride and serum osteocalcin levels in response to a novel sustained-release monofluorophosphate preparation: comparison with plain monofluorophosphate.
In a previous study we found that sustained-release monofluorophosphate (MFP-SR), a novel, sustained-release MFP preparation, acutely maintained the basal therapeutic serum fluoride levels without causing the high serum peak levels associated with plain MFP administration. The objective of the present study was to determine (a) whether chronic MFP-SR administration would provide therapeutic serum fluoride levels, and (b) whether treatment with this new preparation would result in an increase in bone formation similar to that achieved with plain MFP. Bone formation was assessed by serum osteocalcin (OC) determination. We studied 17 postmenopausal women older than 60 years and suffering from primary osteoporosis. All had received a minimum of 6 months of continuous treatment with plain MFP at a dose of 152 mg/day (76 mg b.i.d.). Upon entering the study, the subjects were randomized, in a double-masked protocol, to receive either MFP-SR (76 mg b.i.d.) (n = 9) or placebo (n = 8) for 2 months, after which all subjects returned to the original plain MFP regimen. Serum fluoride and serum OC levels were determined monthly for 3 months. At the beginning of the study serum fluoride levels were in the accepted therapeutic range (5-10 microM) in all patients. Serum fluoride levels were maintained in the patients switched to MFP-SR. In contrast, serum fluoride levels decreased significantly (p < 0.005) in the placebo-treated control subjects and returned to therapeutic levels upon switching back to plain MFP. Similarly, serum OC levels remained elevated in the subjects switched to MFP-SR but dropped significantly (p < 0.001) in the placebo-treated group. Our results demonstrate that chronic MFP-SR administration, at a dose of 152 mg/day, results in maintenance of therapeutic serum fluoride levels and in stimulation of bone formation. Because we have previously reported that high, supratherapeutic post-absorptive serum fluoride levels are avoided by MFP-SR administration, this novel preparation may prevent side effects associated with plain MFP by reducing the amount of fluoride deposited in bone.
Aged↗
Threshold value of serum 25-hydroxyvitamin D concentration in relation to elevated serum parathyroid hormone concentrations in elderly Japanese women.
This study was designed to determine the threshold value for 25-hydroxyvitamin D [25(OH)D] concentration in relation to elevated serum parathyroid hormone (PTH) concentrations in elderly Japanese women. The subjects were 582 noninstitutionalized, ambulant women who lived in a community in Japan. Serum 25(OH)D concentrations were determined using the Nichols Advantage chemiluminescent assay, and serum intact PTH concentrations were determined with a two-site immunoradiometric assay. Demographic characteristics, calcium intake, and serum 1,25(OH)(2)D levels were also determined. The average age, body mass index (BMI), and calcium intake of the subjects were 74.5 years (SD 4.5), 23.3 kg/m(2) (SD 3.4), and 579 mg/day (SD 248), respectively. The serum log-transformed intact PTH concentration was significantly predicted by the serum 25(OH)D concentration (r = -0.147, P = 0.0004), but not by age, BMI, the serum log-transformed 1,25(OH)(2)D concentration, or the log-transformed calcium intake. Analysis of variance with Dunnett's multiple comparisons showed that mean serum intact PTH concentrations with serum 25(OH)D concentrations less than 30 nmol/l (mean intact PTH = 5.89 pmol/l, P < 0.0001) and in the range 30-39 nmol/l (mean intact PTH = 4.54 pmol/l, P = 0.0067) were significantly higher than mean intact PTH concentrations for serum 25(OH)D concentrations greater than 50 nmol/l (mean intact PTH = 3.65 pmol/l, the baseline level), but the mean serum intact PTH concentration for 25(OH)D concentrations in the range 40-49 nmol/l (mean intact PTH = 3.70 pmol/l, P = 0.9975) was not. We conclude that serum 25(OH)D for ambulant elderly Japanese women should be maintained at 40 nmol/l or higher.
Aged↗
Effect of long-term treatment with omeprazole on serum gastrin and serum group A and C pepsinogens in patients with reflux esophagitis.
Twenty-nine nongastrectomized and three partially gastrectomized patients with chronic reflux esophagitis resistant to 12 weeks' treatment with histamine H2-receptor antagonists were treated with a daily oral dose of 20-40 mg of omeprazole for 12-30 months. Basal serum gastrin, serum pepsinogen A, and serum pepsinogen C concentrations were monitored at regular intervals. Serum gastrin levels significantly (P less than 0.01) increased threefold to fourfold during the first 1-2 months of the study when all patients ingested 40 mg of omeprazole daily. Dose reduction to 20 mg did not significantly decrease gastrin levels. Serum gastrin levels showed a trend to further increase after the first 3 months of treatment, reaching statistically significant differences for values from the 3-12-month period (P less than 0.05) and from the 3-24-month period (P less than 0.005). Women and patients with high basal serum gastrin levels before omeprazole treatment were more likely to achieve higher serum gastrin levels during omeprazole treatment. Serum pepsinogen A and C levels were significantly (P less than 0.01) increased at all time intervals during long-term treatment with omeprazole. No significant tendency toward higher serum pepsinogen C levels in time was observed. However, serum pepsinogen A levels and the ratio of pepsinogen A to pepsinogen C further increased significantly (P less than or equal to 0.05) during the initial 3-12-month period. However, this trend was not observed anymore afterward. Antrectomized patients did not show increases in serum gastrin and serum pepsinogen A and C levels, suggesting that hypergastrinemia may be involved in the observed hyperpepsinogenemia.
Aged↗
Effects of pregnancy and delivery on serum prolyl endopeptidase (PEP) activity: alterations in serum PEP are related to increased anxiety in the early puerperium and to postpartum depression.
BACKGROUND: There is now some evidence that anxiety or anxiety disorders are related to increased activity of serum prolyl endopeptidase (PEP) and that major depression is related to lower serum PEP. The aims of the present study were to examine (i) the effects of pregnancy and delivery on serum PEP and (ii) the relationships between serum PEP and postpartum depression, anxiety in the early puerperium and a past history of depression. METHODS: Serum PEP activity was measured in 11 healthy nonpregnant and in 98 pregnant women 3 days before delivery and 1 and 3 days after delivery. On the same occasions, pregnant females completed the Spielberger State Anxiety Inventory (STAI) and were divided into high and low anxiety responders, as defined by changes in the STAI. The presence of a previous depression and postpartum depression within 3 months of delivery was assessed by means of DSM-IV criteria. RESULTS: Serum PEP activity was significantly higher 1 and 3 days after delivery than before. Women with a past history of depression as well as anxiety responders had significantly increased serum PEP activity over nonpregnant women and puerperae with a negative history and anxiety nonresponders, respectively. Parturients who developed a postpartum major, but not minor, depression had significantly lower serum PEP than parturients without postpartum depression. The results were controlled for maternal and labor variables, such as type of analgesia and delivery, induction of labor, breast feeding, parity, and duration of pregnancy and labor. CONCLUSIONS: Our results show that, in puerperae, increased serum PEP is related to increased state anxiety in the early puerperium and that lowered serum PEP is related to a subsequent postpartum major depression. INTERPRETATION: The results suggest that increased serum PEP may be related to postpartum anxious blues and that lowered serum PEP may predispose toward postpartum major depression.
Adult↗
Decrease in serum ALT and increase in serum HCV RNA during pregnancy in women with chronic hepatitis C.
BACKGROUND/AIMS: The natural history of chronic hepatitis C infection during pregnancy has not been clearly established, and thus our aim was to assess serum alanine aminotransferase levels and serum HCV RNA levels during pregnancy. METHODS: Twenty-six pregnant women with chronic hepatitis C were studied. Serum alanine aminotransferase was assessed within the 3 months before, monthly during and within the 3 months after pregnancy. In 12 women, serum HCV RNA levels were quantified by the branched DNA assay. Twenty-six age-matched non-pregnant women with chronic hepatitis C were followed up for 1 year, and used as a comparison group. RESULTS: During pregnancy, serum alanine aminotransferase levels decreased in the second and third trimesters. The third trimester levels were significantly lower than serum alanine aminotransferase levels before pregnancy (p=0.0001). Seventy-seven percent of the pregnant women with increased pre-pregnancy levels had normalization of serum alanine aminotransferase levels. In the second or third trimesters, serum HCV RNA levels increased. The third trimester serum HCV RNA levels were significantly higher than levels before pregnancy (p=0.01). No significant change in serum alanine aminotransferase or HCV RNA levels was observed in the control group. CONCLUSION: In pregnant women with chronic hepatitis C, serum alanine aminotransferase levels decrease, and serum HCV RNA levels increase during the second and third trimesters.
Adult↗
Clinical significance of elevated serum interferon- inducible protein-10 levels in hepatitis C virus carriers with persistently normal serum transaminase levels.
The aim of this study was to assess the immunological profile in hepatitis C virus carriers with persistently normal serum transaminase levels. Forty-two serum HCV RNA positive patients with persistently normal serum transaminase levels (22 natural 'asymptomatic HCV carriers' and 20 biochemical responders to IFN therapy) and 23 complete responders to IFN therapy were enrolled. The HCV genotypes and serum HCV RNA levels were determined before IFN therapy in treatment responders, and at entry in the others. The serum levels of IFN-inducible protein-10 (IP-10) (a protein mainly induced by IFN-gamma), interleukin (IL)-10, and IL-4 were measured in all patients while the serum transaminase levels were normal. The serum transaminase levels and platelet counts were then monitored for the next 4 years and the changes in liver fibrosis were assessed. The serum levels of IP-10 in infected and biochemically normal patients were significantly higher than the levels in complete responders to therapy, whereas the serum levels of IL-10 and IL-4 did not vary significantly among the different groups. During the 4-year follow-up period, 10/20 (50%) biochemical responders and 12/22 (55%) asymptomatic carriers had an elevation of the serum transaminase levels. A significant (P=0.0370) increase in platelet count after 4 years and improvement in liver fibrosis were noted in treatment responders but not in infected patients. The weak but significant residual immune response as reflected by the increased serum IP-10 level may underlie the outcome of HCV carriers with persistently normal serum transaminase levels.
Alanine Transaminase↗
Relationship of serum antioxidant vitamins to serum creatinine in the US population.
Several small clinical studies have reported that serum vitamin A levels were higher but serum vitamin C levels were lower among patients with end-stage renal disease. However, the relationship of antioxidant vitamins to renal function has not been studied in the general population. We examined the relationship of serum antioxidant vitamin levels to serum creatinine levels and risk for hypercreatininemia in a representative sample of 6,629 non-Hispanic whites, 4,411 non-Hispanic blacks, and 4,480 Mexican Americans aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey. Serum antioxidant vitamins were measured by isocratic high-performance liquid chromatography, and serum creatinine levels, by the modified kinetic Jaffé method. Serum vitamin A level was positively and significantly associated with serum creatinine level, whereas serum vitamin C level was inversely and significantly associated with serum creatinine level. A one-SD higher level of serum vitamin A (16.9 microg/dL) was associated with a 2.53-fold (95% confidence interval, 1.96 to 3.27; P < 0.001), 2.07-fold (95% confidence interval, 1.84 to 2.33; P < 0.001), and 2.76-fold (95% confidence interval, 1.74 to 4.37; P < 0.001) greater risk for hypercreatininemia among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans, respectively. A one-SD higher serum vitamin C level (0.45 mg/dL) was associated with a 22% (95% confidence interval, 0.06 to 0.35; P = 0.01) and 42% (95% confidence interval, 0.08 to 0.62; P = 0.02) lower risk for hypercreatininemia in non-Hispanic whites and Mexican Americans. Our study provides useful information to support the hypothesis that antioxidant vitamins may have an important role in the pathogenesis of chronic renal failure.
Adult↗
Influence of serum paraoxonase polymorphism on serum lipids and apolipoproteins.
One hundred and sixty-three healthy Chinese subjects of both sexes were studied for serum paraoxonase (PON) polymorphism, and levels of lipids and apolipoproteins in order to examine effects of PON alleles on these parameters. The level of serum triglyceride was significantly higher in high activity allele (PON*B) compared with that in low activity allele (PON*A) in both sexes (P less than 0.01). The subjects with PON A had significantly higher LDL cholesterol (P less than 0.05) and lower Apo A-II and ApoB levels. The influence of serum paraoxonase on serum lipids was estimated further by Spearman's rank correlation. In the males, there was a significant negative correlation of serum paraoxonase activity with total (P less than 0.05) and LDL (P less than 0.01) cholesterol levels, and positive correlation with HDL cholesterol and Apo A-II levels (P less than 0.05). Serum paraoxonase activity had a high positive correlation with serum triglyceride levels in both sexes (P less than 0.001). Serum ApoB level had a positive correlation with the enzyme activity only in females (P less than 0.01). The allelic effect of PON on these parameters was studied by multiple regression analysis. The high activity allele (PON*B) was associated with higher serum triglyceride level (P less than 0.001) and ApoB (P less than 0.001), while it had lowering influence on total cholesterol (P less than 0.05) and LDL cholesterol (P less than 0.005) in men. The average allelic effect of PON was found to be about 22% for serum triglycerides, 11% for LDL cholesterol, 14% for Apo A-II and 19% for Apo B in the present study. This study suggests a possible significant role of serum paraoxonase alleles in the metabolism of serum lipids and apolipoproteins.
Adult↗
Prediction of serum IgG1 concentration in Holstein calves using serum gamma glutamyltransferase activity.
We examined the relationship between serum gamma glutamyltransferase (GGT) activity and serum gamma immunoglobulin G (IgG1) concentration in Holstein calves. Blood samples were collected from calves aged 1 to 3 days. A follow-up sample was obtained from each calf 2, 7, or 15 days after the initial sampling. Serum GGT activity and IgG1 concentration were measured. Regression models were used to predict IgG1 concentration as a function of age and serum GGT activity measured 2, 7, or 15 days later. Serum GGT activity and calf age at the time of the second sample were directly related to serum IgG1 concentration in the initial sample in calves aged 3 to 17 days (r = .54) and in calves aged 3 to 10 days (r = .63). Models were used to estimate the serum GGT activity equivalent to a serum IgG1 concentration of 1,000 mg/dL. One-day-old calves should have serum GGT activities > 200 IU/L. Four-day-old calves should have serum GGT activities > 100 IU/L. One-week-old calves should have serum GGT activities > 75 IU/L. Calves with serum GGT activities < 50 IU/L should be classified as having failure of passive transfer.
Aging↗
Assessment of the contribution of alpha 1-acid glycoprotein to the serum binding of basic drugs using serum treated with sulphosalicylic acid and DEAE-cellulose.
Treatment of human serum with DEAE-cellulose in acid conditions almost completely removed alpha 1-acid glycoprotein (alpha 1-AG) with little change in the concentration of albumin and beta-lipoprotein, while treatment with sulphosalicylic acid removed almost all the proteins except alpha 1-AG. The binding of various drugs to serum treated as above was measured by equilibrium dialysis and the contribution of alpha 1-AG to drug binding by human serum was assessed. Sulphosalicylic acid-treated serum exhibited a saturable binding for propranolol, which was considered to be due to the binding to alpha 1-AG while DEAE-cellulose-treated serum mostly exhibited non-saturable binding, for which albumin and beta-lipoprotein may be responsible. With this treated serum, alpha 1-AG was estimated to contribute approximately 40% to the binding of therapeutic concentrations of propranolol, 15% to that of imipramine and 15-20% to that of desipramine, respectively, in serum samples pooled from healthy adults. However, no contribution of alpha 1-AG was observed in the binding of salicylic acid to the serum. Dissociation constants of the propranolol binding to the high affinity site in control serum, sulphosalicylic acid-treated serum and purified alpha 1-AG showed similar values (3.7-6.7 microM). These results suggest that treatment of serum with sulphosalicylic acid and DEAE cellulose is useful in assessing the contribution of alpha 1-AG to the serum binding of basic drugs.
Benzenesulfonates↗
Bone mineralisation in premature infants cannot be predicted from serum alkaline phosphatase or serum phosphate.
BACKGROUND: The bone mineral content of premature infants at term is lower than in mature infants at the same postconceptional age. Serum alkaline phosphatase and serum phosphate are often used as indicators of bone mineralisation. OBJECTIVE: To analyse the association between bone mineral content and serum alkaline phosphatase and serum phosphate. METHODS: Serum alkaline phosphatase and phosphate were measured at weekly intervals during admission in 108 premature infants of gestational age below 32 weeks (mean (SD) gestational age 29 (2) weeks; mean (SD) birth weight 1129 (279) g). Bone mineral content was measured at term (mean gestational age 41 weeks) by dual energy x ray absorptiometry and corrected for body size. RESULTS: Serum alkaline phosphatase was significantly negatively associated with serum phosphate (p < 0.001). Bone mineral content was not associated with mean serum alkaline phosphatase (p = 0.8), peak serum alkaline phosphatase (p = 0.5), or mean serum phosphate (p = 0.2) at term. CONCLUSION: Routine measurements of serum alkaline phosphatase and serum phosphate are of no use in predicting bone mineralisation outcome in premature infants.
Absorptiometry, Photon↗
The relationship between serum cholesterol and serum thyroid hormones in male patients with suspected hypothyroidism.
The relationship between serum cholesterol, thyrotropin, thyroxine and triiodothyronine was investigated in 456 male patients with suspected hypothyroidism. The correlation between serum cholesterol and serum thyroxine (r = 0.0572) and between serum cholesterol and serum triiodothyronine (r = 0.1136) were not significant but the correlation between serum cholesterol and TSH (r = 0.0376) was significant (P < 0.001). The mean serum cholesterol was only significantly increased in the patient groups with a serum TSH greater than 20 mU/L. In 26 patients treated for hypothyroidism with thyroxine replacement there was a significant correlation between the decrease in serum cholesterol and the decrease in serum TSH (r = 0.5334, P < 0.01) but there was poor correlation between the decrease in cholesterol and either the increase in serum triiodothyronine or the increase in serum thyroxine.
Aged↗
Insulin-like growth factor binding proteins in maternal serum throughout gestation and in the puerperium: effects of a pregnancy-associated serum protease activity.
The cDNAs encoding three major insulin-like growth factor-binding proteins (IGFBPs) have been cloned and sequenced. We have examined, by Western ligand blotting, the profiles of these binding proteins in human female serum in the normal menstrual cycle, throughout pregnancy, and during the postpartum period. There was no change in the serum profile of any of the binding proteins in early pregnancy compared to that in the secretory phase of the menstrual cycle. However, there was a marked decrease in circulating levels of the main serum IGFBP, IGFBP-3, after 6 weeks of gestation, continuing progressively to term and returning to nonpregnant levels by 5 days postpartum. IGFBP-2 decreased steadily throughout gestation. In contrast, IGFBP-1 levels were found to rise by the second trimester. Endoglycosidase-F digestion did not enhance detection of IGFBP-3 by ligand blotting. Immunoprecipitations with two separate antibodies against IGFBP-3 and IGFBP-2, followed by Western ligand blotting, confirmed the marked decrease in IGFBP-3 levels after 6 weeks of gestation and the more gradual decrease in IGFBP-2. In contrast, immunoprecipitations with IGFBP-1 monoclonal antibodies confirmed the increase in IGFBP-1 during gestation. Endogenous serum IGFs were separated from serum IGFBPs by acid chromatography, and an 80% decrease in total IGF-binding activity in the IGFBP fraction of chromatographed pregnancy vs. nonpregnancy serum was detected by charcoal absorption assay. Furthermore, immunoprecipitations of IGF affinity cross-linked IGFBP fractions with IGFBP-3-specific antiserum confirmed a marked diminution of IGFBP-3 in pregnancy compared to nonpregnancy serum, and revealed, only in pregnancy serum, the concomitant appearance of a band with a mol wt of 34K and three less intense bands with mol wt between 20-26K on sodium dodecyl sulfate gels. Incubation of nonpregnancy serum with 6-week pregnancy serum at 37 C for 5 h, followed by Western ligand blotting, showed only a slight reduction in the amount of IGFBP-3 in the mixture compared to that in controls. However, incubation of term pregnancy with nonpregnancy serum at 37 C for 5 h revealed a marked reduction of IGFBP-3 in the mixture. When iodinated recombinant IGFBP-3 was incubated with term pregnancy serum under the same conditions, the appearance of a 29K protein was identified by gel electrophoresis and autoradiography, along with three less intense bands with mol wt between 17-22K.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
The relationship between serum GH and serum IGF-I in acromegaly is gender-specific.
In patients with acromegaly, there is a linear association between log10 serum GH and IGF-I. Healthy females secrete three times more GH than males but have broadly similar serum IGF-I levels, and in adult GH deficiency, the dose of exogenous GH required to achieve a given serum IGF-I is significantly greater in females than males. We report the influence of gender on the relationship between serum GH and IGF-I in subjects with active acromegaly. A single, fasted, serum sample was obtained from 153 subjects with active disease (87 males; median age, 47.8 yr; range, 20-82 yr) in whom serum IGF-I was at least 30% above the upper limit of an age-related reference range after washout from medical therapy. A linear correlation between serum IGF-I and log10 serum GH was observed (r = 0.53; P < 0.0001), but this relationship was significantly influenced by gender. For a given serum GH value, females were estimated to have serum IGF-I values 82 ng/ml less than males [P < 0.02; 95% confidence interval (CI), 15.2-149]. In females receiving oral E, mean serum IGF-I for a given GH value was 130 ng/ml lower than in males (P = 0.01; 95% CI, 29.8-230.2) but only 60 ng/ml less than the remaining 45 females (NS; P = 0.2). This study demonstrates a gender difference in the relationship between serum GH and IGF-I in patients with active acromegaly consistent with relative GH resistance observed in normal and GHD females, which may, in part, be mediated by E. This observation has important implications for the use of IGF-I as a measure of disease activity.
Acromegaly↗
Kinetics of cell spreading in the presence of different concentrations of serum or fibronectin-depleted serum.
A morphometric assay has been used to show that speed of cell spreading is sensitive to the level of serum in the surrounding growth medium. There was an inverse relationship between serum concentration and speed of spreading; as serum concentration was increased from 0.1% to 100% cells took progressively longer to become fully spread. The time taken to achieve complete spreading in serum concentrations of 0.1, 1.0, 10 and 100% serum was 45, 60, 105 and 240 min, respectively. At serum concentrations of 3% and above, fibronectin depletion had no effect on rates of spreading. Only at concentrations below 3% was there an effect of fibronectin depletion and although cells became fully spread in the depleted serum they took longer to do so in comparison to native serum. It is suggested that plasma fibronectin plays no role in serum-stimulated spreading at serum concentrations of 3% and above since at these concentrations rates of spreading are identical whether fibronectin is present or not. At concentrations of 3% and above spreading is mediated by the 70K spreading factor. At serum concentrations below 3% both fibronectin and 70K factor are effective. The reason for the lack of effect of fibronectin at higher serum concentrations is an inhibition by albumin and other plasma proteins. In contrast, 70K factor is not affected by exogenous protein concentration. The effect of exogenous protein concentration on cell adhesion is discussed in terms of cell migration between compartments that have different extracellular protein concentrations.
Animals↗
Inhibitory effects of human serum on human fetal skin fibroblast migration: migration-inhibitory activity and substances in serum, and its age-related changes.
In order to clarify the environmental factors modulating cell migration, we investigated the effects of human serum on cell migration, and found that serum from adult donors strongly (by 48%) suppressed the migration of human fetal skin fibroblasts into a denuded area in a cell monolayer. Human serum from old donors inhibited cell migration more strongly than that from adult donors. Next, we investigated the properties of migration-inhibitory activity of human serum and serum proteins in order to identify migration-inhibitory substances. Human serum from adult donors strongly suppressed the migration of human fetal skin fibroblasts, although it stimulated cell proliferation more strongly than fetal bovine serum (FBS), indicating that the inhibitory effects of human serum on cell migration was not due to its toxic effects. The inhibition of cell migration by human serum was concentration dependent. It was demonstrated that the inhibition did not depend on the inhibitory effects of human serum on collagen synthesis. The migration-inhibitory activity was seen in fractions over 100 kDa, as determined by an ultrafiltration membrane, and no inhibitory activity was observed in fractions under 100 kDa. On the other hand, it was not detected either in fractions over 100 kDa or under 100 kDa in FBS. Among the over 100 kDa human serum proteins examined, gamma-globulin, alpha2-macroglobulin, and low density lipoprotein (LDL) suppressed fibroblast migration in a concentration-dependent manner. However, among the three, cell migration-inhibiting activity of gamma-globulin almost disappeared when cell migration was conducted in 10% FBS-supplemented medium. These results indicated that alplha2-macroglobulin and LDL were candidate substances for cell migration-inhibiting activity in human serum.
Adult↗