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Serum thyrotropin concentrations are more highly correlated with serum triiodothyronine concentrations than with serum thyroxine concentrations in thyroid hormone-infused thyroidectomized rats.

To assess the relative role of circulating T4 and T3 in the regulation of serum TSH, we have measured serum T4, T3, and TSH concentrations in normal and thyroidectomized rats, some of which were chronically infused with T3 or T4. Serum T3, T4, and TSH concentrations were measured 7 and 14 days after surgery. Some groups of infused rats were mildly hypothyroid, as judged by elevated serum TSH concentrations. At both 7 and 14 days, there was a significant inverse correlation between serum T3 and serum TSH concentrations (day 7, r = 0.65, P less than 0.01; day 14, r = 0.71, P less than 0.01). The coefficients for the inverse correlations between serum T4 and TSH concentrations were 0.37 on day 7 (P less than 0.05) and 0.37 (P less than 0.05) on day 14. Linear regression analysis was performed using TSH as the dependent variable for outcome and serum T3 and T4 concentrations as the independent predictor variables. This analysis revealed that after controlling for T3, TSH and T4 were no longer significantly correlated (P = 0.14). The correlation between T3 and TSH remained highly significant. These results suggest that in the euthyroid and mildly hypothyroid rat, serum T3 has a greater inhibitory effect on TSH secretion than does serum T4.

Animals↗

Improved sensitivity of serum thyrotropin measurements. Studies on serum sex hormone-binding globulin in patients with reduced serum thyrotropin.

Most serum TSH assays have a working sensitivity (i.e. the lowest TSH value with an inter-assay coefficient of variation below 10%) around 0.15-0.4 mU/l, which also is the critical area for cut off for further thyroid profile testing when serum TSH is used as a "first line test". A new assay (BeriLux hTSH) based on chemiluminescence was evaluated, and demonstrated a theoretical sensitivity (mean + 2 SD of the zero standard) of 0.005 mU/l and a working sensitivity as low as 0.04 mU/l. Reference range was 0.18-2.60 mU/l (N = 33). Sixty-eight percent (13/19) of hyperthyroid patients had serum TSH less than 0.005 mU/l, all had serum TSH less than 0.037 mU/l. We studied two groups of patients with normal free T4 and T3 indices but serum TSH less than 0.15 mU/l as measured by an immunoradiometric assay. Thirty-five percent (7/20) of patients with nontoxic goitre and 5% (1/20) of L-T4 treated patients had serum TSH less than 0.005 mU/l; and in 60% (11/20) and 30% (6/20), respectively, the levels overlapped the total range for hyperthyroidism. Serum levels of sex hormone-binding globulin expressed as percent of the reference median for the relevant sex (SHBG%) were elevated in both groups of patients (p less than 0.01). Approximately 50% of those with serum TSH overlapping the hyperthyroid range had serum SHBG% levels above reference range. In conclusion, this assay seems superior to most previously reported assays concerning working sensitivity, but it still leaves us with a group of clinically euthyroid patients who has unmeasurably low serum TSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Total serum protein, serum protein fractions and serum immunoglobulins in colostrum-fed and colostrum-deprived calves.

Total serum protein levels, serum protein fraction levels, and specific serum immunoglobulin class or subclass levels were measured in colostrum-fed (CF) and colostrum-deprived (CD) calves during the first 144 hours after birth. Total serum protein values increased at 24 hours in the CF group and then decreased slightly at 144 hours. The increase in total serum protei5) in beta1-, beta2-, and gamma-globulins. The beta2- and gamma-globulin levels decreased by 144 hours, while the serum level of beta1-globulin continued to increase. The CD calves exhibited a significant decrease (P less than 0.05) in total serum protein at 24 hours, folhours, the level of beta1-globulin inlowed by a significant increase (P less than 0.05) at 144 hours. At 24 hours, the level of beta1-globulin decreased slightly, and the level of beta2- and gamma-globulins increased slightly. At 144 creased, and the level of gamma-globulin decreased. The beta2-globulin level did not change. At birth, immunoglobulin (Ig) M was detected in 5 of the 10 calves, IgG1 in 6 of the 10 calves, and IgG2 in 3 of the 10 calves. By 24 hours after birth, all CF calves had detectable levels of IgM, IgG1, and IgG2, and there were significant increases (P less than 0.01) in the mean serum levels of all 3 immunoglobulins. By 144 hours after birth, the serum levels of IgM, IgG1, and IgG2 decreased to various degrees. At 24 hours, the IgM level had not increased in CD calves; however, the level of IgG2 appeared to increase slightly, and the mean IgG1 level increased by approximately 50%. By 144 hours after birth, there was a significant increase (P less than 0.01) in the mean level of serum IgM. The level of IgG, also appeared to increase substantially, while the level of IgG2 appeared to increase slightly.

Animals↗

[Relationships between serum lipid peroxide level (serum TBA level) and smoking, alcohol drinking, food frequency, serum vitamin C and E in subjects with multiphasic screening].

Relationships between serum thiobarbituric acid (TBA) level and smoking, alcohol drinking, differences in food intake with alcohol drinking, serum vitamin C (VC) and E (VE) were studied in 283 non-treated men (aged 20-69 years) who visited a human dock conducted in an urban area of Hyogo prefecture in 1989-1991 (annually May-July). The results were as follows: 1. An effect of smoking on serum TBA level was not observed. 2. The subjects were divided into three groups according to weekly sake intake levels, i.e., non-drinkers including ex-drinkers (ND), mild drinkers (MD, weekly sake intake: < or = 1260 ml), and heavy drinkers (HD, > 1260 ml). The serum TBA level of HD, but not of MD, was significantly higher than that of ND. 3. Serum TBA level had significant positive correlations with age, GPT, gamma-GTP, TC (total cholesterol), TG (triglycerides), PL (phospholipids), total serum lipids (TLP, i.e., TC+TG+PL), VE, eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6), but had no significant correlations with VC and VE/TLP. 4. The subjects (N+M) D, which included ND and MD, and those of HD were divided respectively into three groups according to weekly food intake levels, i.e., non-intake group (NF), low frequent intake group (LF, 1-3 days/week), and high frequent intake group (HF, > or = 4 days/week). The fish intake level of HD was significantly higher than that of (N+M) D, while the intake levels of vegetables, fruits and soft drinks of HD were significantly lower than those of (N+M) D. 5. Serum TBA level, GOT, GPT, gamma-GTP, TG, PL, TLP, VE, EPA and DHA of HD were significantly higher than those of (N+M) D. On the other hand, VC of HD was significantly lower than that of (N+M) D. 6. When the subjects of (N+M) D were divided into three groups according to weekly fish intake levels as mentioned above, serum TBA level, EPA and DHA of HF in (N+M) D were significantly higher than those of NF in (N+M) D. 7. Serum TBA level of HD in non-fish intake group was significantly higher than that of (N+M) D in the same group. These results suggest that increased serum TBA level in HD is closely related to the increased intake frequency of fish in addition to the effect of alcohol drinking.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Two pathways for serum regulation of the c-fos serum response element require specific sequence elements and a minimal domain of serum response factor.

The c-fos serum response element (SRE) is necessary and sufficient for induction of the c-fos gene in response to serum and growth factors. This activation is dependent upon serum response factor (SRF), a transcriptional activator which binds the SRE. A factor, p62TCF, which binds in conjunction with SRF to the SRE and which is activated by mitogen-activated protein kinase, has also been implicated in c-fos regulation. By using a reporter gene system with weak SRE mutations that is dependent upon overexpression of SRF for serum induction, we have found that there are at least two pathways for serum induction that converge on the SRE. Loss of TCF binding by mutations in SRF and the SRE did not reduce serum induction of the reporter genes. We have found a pathway for serum induction that is sensitive to mutations in the A/T-containing central sequence of the SRE and which is independent of TCF. When this pathway was mutated, activation was dependent upon TCF binding, demonstrating that TCF can also function in serum induction. Both of the signalling pathways required a minimal domain of SRF. This domain, spanning SRF's DNA binding domain, was sufficient for serum induction when fused to a heterologous transcriptional activation domain.

Amino Acid Sequence↗

Regression of transplanted lymphomas induced in vivo by means of normal guinea pig serum. II. Studies on the nature of the active serum constituent: histological mechanism of the regression: tests for effects of guinea pig serum on lymphoma cells in vitro: discussion.

In an extension of the experimental studies recorded in an associated paper; attempts were made to isolate and characterize the constituent of guinea pig serum responsible for inducing regression of transplanted lymphomas in vivo. The active material was precipitated readily from the whole serum, along with some of the globulins, by means of ammonium sulfate in concentrations of 2.0 molar or greater; it withstood heating at 56 degrees C. for 20 or 30 minutes, but was inactivated upon heating at 66 degrees C. for similar periods; it was completely inactivated by chymotrypsin in concentrations of 1 or 2 mg./cc. during 6 hours at 37 degrees C. Furthermore, the inhibitory effects of small amounts of the guinea pig serum in vivo were enhanced upon admixture with immune sera prepared by injecting the lymphosarcoma cells into rabbits. The facts as a whole suggest that the active material is a protein, and that it may be one or another of the components of complement; yet they do not suffice to establish its identity. Microscopic studies showed that the cells of subcutaneous lymphomas rapidly died and were resorbed following injections of relatively large amounts of guinea pig serum intraperitoneally into mice carrying them, while similar changes followed more gradually after repeated injections of smaller amounts of guinea pig serum. No changes referable to the guinea pig serum were seen in the normal tissues or organs of mice receiving it. Mouse lymphoma cells, suspended artificially as individuals in a physiological saline solution, regularly remained viable following incubation in vitro in mixture with guinea pig serum during 6 hours at 37 degrees C. The finding provides strong evidence that the regression of lymphomas that follows injection of guinea pig serum in vivo is brought about through some reaction in which the guinea pig serum and the host both participate. Some of the implications of the findings are discussed.

Animals↗

Serum antibodies to H+,K+-ATPase, serum pepsinogen A and Helicobacter pylori in relation to gastric mucosa morphology in patients with low or low-normal concentrations of serum cobalamins.

OBJECTIVES: To compare the diagnostic performance of serum antibodies to H+,K+-ATPase (EC 3.6.1.36), serum pepsinogen A (EC 3.4.23.1) and the Schilling test in diagnosing chronic atrophic body gastritis; to study the interrelationships between H+,K+-ATPase antibodies, serology for Helicobacter pylori, and gastric morphology. DESIGN: Patients with suspected cobalamin deficiency and serum cobalamin < 200 micromol/l were investigated using upper gastrointestinal endoscopy, the Schilling test and serum tests for H+,K+-ATPase antibodies, pepsinogen A, and H. pylori. SETTING: The Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. PATIENTS: Ninety seven consecutively referred patients. MAIN OUTCOME MEASURES: Sensitivity and specificity of assays for serum H+,K+-ATPase antibodies, serum pepsinogen A, and the Schilling test. RESULTS: Assays of serum antibodies to H+,K+-ATPase and of serum pepsinogen A displayed equal diagnostic sensitivity for atrophic gastritis (around 0.90 for the severe forms) and higher than that for the Schilling test (0.65). The diagnostic specificity for pepsinogen A (1.0) was higher than for H+,K+-ATPase antibodies (about 0.80). The prevalence of antral gastritis and positivity for H. pylori antibodies declined with the transition of body gastritis into severe atrophy, while the prevalence of H+,K+-ATPase antibodies increased. CONCLUSION: Pepsinogen A is preferable to serum H+,K+-ATPase antibodies in the diagnosis of gastric body mucosal atrophy. The formation of H+,K+-ATPase antibodies does not seem to be a primary event in the development of gastric body muscosal atrophy.

Adult↗

The interaction of naturally elaborated blebs from serum-susceptible and serum-resistant strains of Neisseria gonorrhoeae with normal human serum.

We studied the interaction of normal human serum immunoglobulins with outer-membrane bleb antigens of Neisseria gonorrhoeae. Gonococcal 68,000 Dalton and Lip (H.8 antigen) outer-membrane proteins were recognized by normal human serum immunoglobulins in blebs from serum-resistant strains, but not in blebs from serum-susceptible strains. The addition of blebs from a serum-resistant strain to bactericidal assays resulted in significantly greater inhibition of serum killing than the addition of blebs from a serum-susceptible strain. Our results indicate that blebs from two serum-resistant gonococcal strains have an enhanced ability to bind and remove cell-targeted bactericidal factors, and that outer-membrane blebbing may contribute to serum resistance.

Antibodies, Bacterial↗

Evaluation of some serum erythropoietin concentration procedures using serum-containing and serum-free in vitro bioassays.

Studies are reported which were designed to further refine a serum-free culture method to assess the erythropoietic response of fetal mouse liver cells. The objective was to employ such a serum-free system with deproteinized serum concentrates as the test materials in a potentially highly specific assay for erythropoietin (Ep). A serum-free culture method is described which permits responses to Ep (125I-deoxyuridine incorporation) closely comparable to those observed in cultures containing optimal concentrations of sera. Mean recoveries of Ep were acceptable in each of three variations of a serum concentration procedure. However, no correlations were evident between Ep titers in whole sera and those in the concentrates (assayed in both serum-free and serum-containing cultures) with deproteinization and/or concentration procedures involving serum acidification and exposure to boiling water temperature.

Biological Assay↗

An enzyme-linked immunoassay for ferritin in human serum and rat plasma and the influence of the iron in serum ferritin on serum iron measurement, during acute hepatitis.

To measure human serum ferritin and rat plasma ferritin a non-competitive enzyme-linked immunoassay has been developed using horseradish peroxidase as the enzyme. In this assay it proved necessary to use heated rat plasma to obtain reproducible ferritin values. The heating procedure caused a loss of 38% of the plasma ferritin. Rat plasma ferritin values have been corrected for this loss. The standard deviation, from duplicate normal human and rat samples is 10 ng ferritin/ml serum and 69 ng/ml plasma, respectively. (The mean ferritin concentrations are: in human sera, 82 ng/ml and in rat plasma 762 ng/ml.) Mean recovery of added liver ferritin in the human serum is 104% +/- 4% (+/-S.E.M') and in the rat plasma 101% +/- 3% (+/- S.E.M.). Normal ferritin concentrations varied in the human material between 30 ng/ml and 300 ng/ml serum, and in the rat plasma between 500 ng/ml and 1300 ng/ml. During increased body iron and acute hepatitis the ferritin concentrations, in patients as well as in rats, exceeded the upper limit of the normal values in most cases. During human hepatitis high serum ferritin levels combined with high serum iron levels were measured. The high serum iron concentrations could not be explained by the high serum ferritin concentrations, even if the iron content of the ferritin is supposed to be high.

Acute Disease↗

A contraceptive vaginal ring releasing ethinyl estradiol and the progestin ST-1435: bleeding control, serum steroid concentrations, serum lipids and serum chemistry.

Four women used vaginal rings releasing the synthetic progestin ST-1435 and ethinyl estradiol for at least three 21-day cycles with a 7-day treatment-free period between intervals of use. Patterns of bleeding were evaluated and serum concentrations of ST-1435, estradiol, progesterone and ethinyl estradiol were measured by radioimmunoassay. Total serum cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and serum chemistry were determined before ring use and during the first and third treatment cycles. The women experienced no difficulties in using the vaginal ring and all continued to use the ring after the first three cycles. Bleeding control was good and hormonal side effects were minimal. Serum steroid concentrations were: ST-1435, 289 +/- 117 pmol/l (mean +/- SD); ethinyl estradiol, 172 +/- 108 pmol/l; and estradiol, 184 +/- 107 pmol/l. Concentrations of serum progesterone were low, indicating complete suppression of ovulation during treatment. Total serum cholesterol increased slightly during use of ring. However, this increase could be accounted for by an increase in serum HDL-cholesterol. Liver function tests were in the normal range during ring use and values of serum chemistry showed no significant changes. This contraceptive vaginal ring presents a good method of contraception, showing good bleeding control and no harmful metabolic effects.

Adult↗

Serum lipid levels in relation to serum thyroid-stimulating hormone and the effect of thyroxine treatment on serum lipid levels in subjects with subclinical hypothyroidism: the Tromsø Study.

OBJECTIVE: To evaluate the relation between serum thyroid-stimulating hormone (TSH) and lipids. DESIGN: Cross-sectional epidemiological study, nested case-control study, and a placebo-controlled double-blind intervention study. METHODS: In the 5th Tromsø study serum TSH, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured. Subjects with subclinical hypothyroidism (SHT) and a matching control group were re-examined and apolipoprotein A1 (Apo A1) and apolipoprotein B (Apo B) were also measured. Subjects with SHT were included in an intervention study with thyroxine supplementation for 1 year. RESULTS: A total of 5143 subjects from the 5th Tromsø study were included. A significant and positive correlation between serum TSH levels and serum TC and LDL-C levels were found in both genders. However, in the females this did not reach statistical significance after adjusting for age and BMI. The serum LDL-C were significantly higher and the Apo A1 levels significantly lower in 84 SHT subjects compared with 145 controls, and in the SHT females the TC levels were also significantly elevated. In the intervention study (32 subjects given thyroxine and 32 subjects given placebo), we observed a significant reduction in the Apo B levels after thyroxine medication. In those that at the end of the study had serum TSH levels in the range 0.2-2.0 mIU L(-1), the serum TC and LDL-C levels were also significantly reduced. CONCLUSIONS: There is a positive association between serum TSH levels and TC and LDL-C levels. These lipid levels are reduced with thyroxine treatment in subjects with SHT.

Adult↗

Increased serum prolactin in diabetic ketoacidosis; correlation between serum sodium and serum prolacting concentration.

In 8 patients with diabetic ketoacidosis, serum prolactin was measured and found to be elevated (24.8 +/- 10.2 ng/ml, mean +/- SEM). After correction of the ketoacidosis, the prolactin level decreased to 10.9 +/- 6.4 ng/ml (normal range men 4.9 +/-0.8, women 5.1 +/- 1.6 ng/ml). The scatter of prolactin values was wide. A study of the correlation between the serum prolactin values and chemical parameters that are altered in diabetic ketoacidosis was therefore undertaken. Serum prolactin values did not correlate well with the serum bicarbonate concentration or serum osmolality. However, a significant negative correlation between log serum prolactin concentration and serum sodium concentration was demonstrated (r = -0.61, P less than 0.01). It is suggested that serum prolactin may possible participate in sodium retention in man as has been demonstrated in studies on animals.

Adult↗

High and low litter size trait and its relationship with serum and urine progesterone, serum zinc, and serum phosphorus in New Zealand white rabbits and improvement for the low litter size trait.

A number of does was classified according to their initial litter size to high (> 6 bunnies, group 1) and low (< 5 bunnies, group 2) in New Zealand White rabbits. Incidence of low litter size in the herd in the present study was 23%. The number of matings/conception, total mortality, corpora lutea/foetus, number and percentage of resorbed foeti were markedly higher in group 2 than in group 1. The litter weight, number of foetuses, implantation sites, and corpora lutea in group 2 showed a marked decrease over group 1. Serum and urine progesterone levels in pregnant rabbits of group 2 were significantly (P < 0.01) lower than in group 1, however, non-efficacious progesterone levels were significantly (P < 0.01) lower in group 2. The zinc content in serum, foetal dry weight and uterine horn dry weight, and serum inorganic phosphate in group 2 were significantly (P > 0.01) lower than in group 1. The litter size was significantly (P < 0.01) correlated with zinc and inorganic phosphate in group 2, while it was correlated with serum and urine progesterone in the two groups. The correlation coefficients were significant (P < 0.01) between urine progesterone and serum zinc and between serum progesterone and inorganic phosphate more frequently in group 2 during the gestation period than in group 1. The treatment of group 2 does with calcium carbonate, sodium phosphate dibasic, and zinc acetate in drinking water improved the serum progesterone, urine progesterone, and non-efficacious progesterone in addition to serum zinc and inorganic phosphate, which led to improvement of the number of matings/conception, litter size and litter weight, and lowered total mortality.

Animals↗

Maximal serum stimulation of the c-fos serum response element requires both the serum response factor and a novel binding factor, SRE-binding protein.

We have previously reported on the presence of a CArG motif at -100 in the Rous sarcoma virus long terminal repeat which binds an avian nuclear protein termed enhancer factor III (EFIII) (A. Boulden and L. Sealy, Virology 174:204-216, 1990). By all analyses, EFIII protein appears to be the avian homolog of the serum response factor (SRF). In this study, we identify a second CArG motif (EFIIIB) in the Rous sarcoma virus long terminal repeat enhancer at -162 and show only slightly lower binding affinity of the EFIII/SRF protein for this element in comparison with c-fos serum response element (SRE) and EFIII DNAs. Although all three elements bind the SRF with similar affinities, serum induction mediated by the c-fos SRE greatly exceeds that effected by the EFIII or EFIIIB sequence. We postulated that this difference in serum inducibility might result from binding of factors other than the SRF which occurs on the c-fos SRE but not on EFIII and EFIIIB sequences. Upon closer inspection of nuclear proteins which bind the c-fos SRE in chicken embryo fibroblast and NIH 3T3 nuclear extracts, we discovered another binding factor, SRE-binding protein (SRE BP), which fails to recognize EFIII DNA with high affinity. Competition analyses, methylation interference, and site-directed mutagenesis have determined that the SRE BP binding element overlaps and lies immediately 3' to the CArG box of the c-fos SRE. Mutation of the c-fos SRE so that it no longer binds SRE BP reduces serum inducibility to 33% of the wild-type level. Conversely, mutation of the EFIII sequence so that it binds SRE BP with high affinity results in a 400% increase in serum induction, with maximal stimulation equaling that of the c-fos SRE. We conclude that binding of both SRE BP and SRF is required for maximal serum induction. The SRE BP binding site coincides with the recently reported binding site for rNF-IL6 on the c-fos SRE. Nonetheless, we show that SRE BP is distinct from rNF-IL6, and identification of this novel factor is being pursued.

3T3 Cells↗