scholarly journals Naturally Acquired Passive Protective Activity against Neisseria meningitidis Group C in the Absence of Serum Bactericidal Activity

2004 ◽  
Vol 72 (10) ◽  
pp. 5903-5909 ◽  
Author(s):  
Jo Anne Welsch ◽  
Dan Granoff
Keyword(s):  
Bactericidal Activity ◽  
Geometric Mean ◽  
Antibody Concentration ◽  
Protective Activity ◽  
Serum Samples ◽  
Antibody Avidity ◽  
Serum Bactericidal Activity ◽  
Infant Rat

ABSTRACT The hallmark of immunity to meningococcal disease is a bactericidal titer in serum of ≥1:4 measured with human complement, but this threshold titer may underestimate the extent of protection. We used the infant rat model of meningococcal bacteremia to measure group C passive protective activity in serum samples from 91 unimmunized adults living in California. A total of 35 sera (38.5%) had passive protective activity. Sera with complement-mediated bactericidal titers of ≥1:4 were 3.4-fold more likely to confer protection (89%) than nonbactericidal sera (26%; P < 0.0001). Thus, bactericidal titers of ≥1:4 are a marker of protection, but this threshold lacks sensitivity for predicting protective activity. We investigated the 73 sera with bactericidal titers of <1:4 to determine the basis of protective activity. The 19 sera with protective activity had a higher geometric mean group C anticapsular antibody concentration (0.72 μg/ml) than the 54 sera that lacked protective activity (0.16 μg/ml; P < 0.001). Thus, protective activity in the absence of bactericidal activity was associated with higher concentrations of anticapsular antibodies, but not all sera with anticapsular antibodies conferred protection. Of 18 nonbactericidal sera with anticapsular antibody concentrations between 0.31 and 0.99 μg/ml, the 11 sera that conferred protection had a higher mean antibody avidity constant (21.9 nM−1) than the 7 nonprotective sera (14.6 nM−1; P < 0.03). Thus, in sera with titers of <1:4, protective activity is associated with higher-avidity group C anticapsular antibodies, which are present in concentrations insufficient to elicit complement-mediated bacteriolysis in vitro but sufficient to confer protection in an in vivo bacteremia model.

scholarly journals Specificities and Opsonophagocytic Activities of Antibodies to Pneumococcal Capsular Polysaccharides in Sera of Unimmunized Young Children

2002 ◽  
Vol 9 (5) ◽  
pp. 1032-1038 ◽  
Author(s):  
Anu Soininen ◽  
Maijastiina Karpala ◽  
Sirkka-Liisa Wahlman ◽  
Hannele Lehtonen ◽  
Helena Käyhty
Keyword(s):  
Young Children ◽  
Acute Otitis Media ◽  
Antibody Concentration ◽  
Capsular Polysaccharides ◽  
Serum Samples ◽  
Specific Antibodies ◽  
Functional Activities ◽  
Pneumococcal Carriage

ABSTRACT An enzyme immunoassay (EIA) for antibodies to pneumococcal capsular polysaccharides (Pnc PSs) detects in some cases antibodies that are cross-reactive within different Pnc PSs. Recently, it has been suggested that for detection of only serotype-specific antibodies, EIA can be modified by removing cross-reactive antibodies by absorption with an irrelevant PS, e.g., the type 22F PS. The opsonophagocytosis assay measures the functional activities of antibodies in vitro, and the results of that assay correlate with in vivo protection better than measurement of the antibody concentration by EIA. We compared these different methods for measuring antibodies to type 1, 6B, 11A, 14, 19F, and 23F Pnc PSs in the sera of unimmunized young children who had been monitored for pneumococcal carriage, acute otitis media, and acquisition of antibodies to Pnc PSs from 2 to 24 months of age. Serum samples with antibody increases after contact with a pneumococcus of a homologous serotype contained specific antibodies and often had opsonophagocytic activity (OPA) (20 of 46). In samples with antibody increases from children who had not had contact with a pneumococcus of a homologous serotype, the antibodies found to be type specific by conventional EIA were usually cross-reactive and infrequently had OPA (10 of 68). When type 22F PS absorption was used in the EIA, most of the false antibody increases were eliminated, but most of the true antibody increases were still detected and the association between the antibody concentration detected by EIA and OPA was improved. However, there were serotype-dependent differences in the frequency of OPA. Use of absorption with a heterologous PS in EIA should be encouraged, and both the specificity of EIA and the sensitivity of opsonophagocytic assays should be further evaluated and improved.

scholarly journals Pharmacokinetics of sparfloxacin and serum bactericidal activity against pneumococci.

1996 ◽  
Vol 40 (3) ◽  
pp. 776-779 ◽  
Author(s):  
M Trautmann ◽  
M Ruhnke ◽  
K Borner ◽  
J Wagner ◽  
P Koeppe
Keyword(s):  
Bactericidal Activity ◽  
Geometric Mean ◽  
Clinical Situation ◽  
In Vitro Activity ◽  
Serum Bactericidal Activity ◽  
Time Period ◽  
Quinolone Antibiotics ◽  
Humoral Antibodies ◽  
Bactericidal Activities

Sparfloxacin, a new fluorinated quinolone, exhibits higher in vitro activity against pneumococci than do ciprofloxacin and ofloxacin. Since up to 30% of cases of pneumococcal pneumonia are associated with bacteremia, and since an increasing percentage of pneumococci are resistant against penicillin, we studied the serum bactericidal activity of sparfloxacin against pneumococci in eight healthy, middle-aged volunteers. Pharmacokinetics in serum and urine after a 400-mg oral dose of sparfloxacin were comparable to those described by other authors. Inhibitory and bactericidal activities in serum were measured for four pneumococcal isolates representing penicillin-susceptible (one isolate), intermediately resistant (two isolates), and highly resistant (one isolate) strains. Geometric mean inhibitory titers ranged between 1:2.4 and 1:6.3 and bactericidal titers ranged between 1:1.3 and 1:3.6 during a time period of 1 to 6 h after drug intake. Although such titers were not sufficient to predict a clinical response based on previous pharmacodynamic studies using quinolone antibiotics, data obtained with volunteers may only partially reflect the clinical situation in which a rise of humoral antibodies directed against pneumococcal antigens may help to reinforce the bactericidal action of the antibiotic.

scholarly journals Functional and Transcriptional Adaptations of Blood Monocytes Recruited to the Cystic Fibrosis Airway Microenvironment In Vitro

2021 ◽  
Vol 22 (5) ◽  
pp. 2530
Author(s):  
Bijean D. Ford ◽  
Diego Moncada Giraldo ◽  
Camilla Margaroli ◽  
Vincent D. Giacalone ◽  
Milton R. Brown ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bactericidal Activity ◽  
Scavenger Receptor ◽  
Receptor Expression ◽  
Blood Monocytes ◽  
Bacterial Killing ◽  
Blood Neutrophils ◽  
Vitro Model

Cystic fibrosis (CF) lung disease is dominated by the recruitment of myeloid cells (neutrophils and monocytes) from the blood which fail to clear the lung of colonizing microbes. In prior in vitro studies, we showed that blood neutrophils migrated through the well-differentiated lung epithelium into the CF airway fluid supernatant (ASN) mimic the dysfunction of CF airway neutrophils in vivo, including decreased bactericidal activity despite an increased metabolism. Here, we hypothesized that, in a similar manner to neutrophils, blood monocytes undergo significant adaptations upon recruitment to CFASN. To test this hypothesis, primary human blood monocytes were transmigrated in our in vitro model into the ASN from healthy control (HC) or CF subjects to mimic in vivo recruitment to normal or CF airways, respectively. Surface phenotype, metabolic and bacterial killing activities, and transcriptomic profile by RNA sequencing were quantified post-transmigration. Unlike neutrophils, monocytes were not metabolically activated, nor did they show broad differences in activation and scavenger receptor expression upon recruitment to the CFASN compared to HCASN. However, monocytes recruited to CFASN showed decreased bactericidal activity. RNASeq analysis showed strong effects of transmigration on monocyte RNA profile, with differences between CFASN and HCASN conditions, notably in immune signaling, including lower expression in the former of the antimicrobial factor ISG15, defensin-like chemokine CXCL11, and nitric oxide-producing enzyme NOS3. While monocytes undergo qualitatively different adaptations from those seen in neutrophils upon recruitment to the CF airway microenvironment, their bactericidal activity is also dysregulated, which could explain why they also fail to protect CF airways from infection.

scholarly journals Influence of ionic and non-ionic radiographic contrast media on leukocyte adhesion molecules

2003 ◽  
Vol 12 (5) ◽  
pp. 269-275 ◽  
Author(s):  
Guy L. J. Vermeiren ◽  
Roel Willems ◽  
Marc J. Claeys ◽  
Chris Vrints ◽  
Herman Slegers ◽  
...  
Keyword(s):  
Coronary Angiography ◽  
Contrast Media ◽  
Adhesion Molecules ◽  
Leukocyte Adhesion ◽  
Serum Samples ◽  
Cd11b Expression ◽  
Radiographic Contrast ◽  
Radiographic Contrast Media

Background:Many papers have focused on the importance of granulocytes in the process of reperfusion and ischemia. Most of the clinical studies measured several parameters of this process during and after coronary angiography, without taking into account the effect of the radiographic contrast media (RCM) used during this procedure.Materials and methods:We performed a randomized patient study(n=37)to evaluate the effect of ionic and non-ionic RCM on granulocyte adhesion during coronary angiography. We also evaluated the influence of the ionicity and osmolarity of the different substances on granulocyte adhesion molecules inin vitroexperiments.Results:The osmolarity of patient serum samples increased from 302±1 to 309±1 mOsm/kg(P<0.05)after infusion of RCM. The CD11b expression in the samples of the non-ionic RCM treated group increased from 221±21 MFI to 377±30 MFI(P<0.05)measured as the absolute mean fluorescence intensity (MFI), yet did not alter significantly in the ionic RCM group. In contrast, thein vitroexperiments showed a reduction of the CD11b expression from 360±70 MFI to 149±30 MFI(P<0.05)in the ionic RCM group.Conclusions:The upregulation of adhesion molecules was significantly reducedin vivowith ionic RCM, while ionic substances caused opposite effectsin vitro. This effect should be taken into account when performing leukocyte functional analysis of samples taken during angiography.

scholarly journals Prion Disease Blood Test Using Immunoprecipitation and Improved Quaking-Induced Conversion

mBio ◽  
2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Christina D. Orrú ◽  
Jason M. Wilham ◽  
Lynne D. Raymond ◽  
Franziska Kuhn ◽  
Björn Schroeder ◽  
...  
Keyword(s):  
Real Time ◽  
Blood Test ◽  
Prion Diseases ◽  
Proteinase K ◽  
Transmissible Spongiform Encephalopathies ◽  
Serum Samples ◽  
Spongiform Encephalopathies ◽  
Jakob Disease

ABSTRACT A key challenge in managing transmissible spongiform encephalopathies (TSEs) or prion diseases in medicine, agriculture, and wildlife biology is the development of practical tests for prions that are at or below infectious levels. Of particular interest are tests capable of detecting prions in blood components such as plasma, but blood typically has extremely low prion concentrations and contains inhibitors of the most sensitive prion tests. One of the latter tests is quaking-induced conversion (QuIC), which can be as sensitive as in vivo bioassays, but much more rapid, higher throughput, and less expensive. Now we have integrated antibody 15B3-based immunoprecipitation with QuIC reactions to increase sensitivity and isolate prions from inhibitors such as those in plasma samples. Coupling of immunoprecipitation and an improved real-time QuIC reaction dramatically enhanced detection of variant Creutzfeldt-Jakob disease (vCJD) brain tissue diluted into human plasma. Dilutions of 1014-fold, containing ~2 attogram (ag) per ml of proteinase K-resistant prion protein, were readily detected, indicating ~10,000-fold greater sensitivity for vCJD brain than has previously been reported. We also discriminated between plasma and serum samples from scrapie-infected and uninfected hamsters, even in early preclinical stages. This combined assay, which we call “enhanced QuIC” (eQuIC), markedly improves prospects for routine detection of low levels of prions in tissues, fluids, or environmental samples. IMPORTANCE Transmissible spongiform encephalopathies (TSEs) are largely untreatable and are difficult to diagnose definitively prior to irreversible clinical decline or death. The transmissibility of TSEs within and between species highlights the need for practical tests for even the smallest amounts of infectivity. A few sufficiently sensitive in vitro methods have been reported, but most have major limitations that would preclude their use in routine diagnostic or screening applications. Our new assay improves the outlook for such critical applications. We focused initially on blood plasma because a practical blood test for prions would be especially valuable for TSE diagnostics and risk reduction. Variant Creutzfeldt-Jakob disease (vCJD) in particular has been transmitted between humans via blood transfusions. Enhanced real-time quaking-induced conversion (eRTQ) provides by far the most sensitive detection of vCJD to date. The 15B3 antibody binds prions of multiple species, suggesting that our assay may be useful for clinical and fundamental studies of a variety of TSEs of humans and animals.

scholarly journals Effect of hepatocyte-stimulating factor and glucocorticoids on plasma fibronectin levels

1986 ◽  
Vol 238 (2) ◽  
pp. 365-371 ◽  
Author(s):  
D L Amrani ◽  
D Mauzy-Melitz ◽  
M W Mosesson
Keyword(s):  
Acute Phase Protein ◽  
Plasma Fibronectin ◽  
Phagocytic Cells ◽  
Serum Samples ◽  
Exclusion Chromatography ◽  
A Minor ◽  
Two Peaks ◽  
Stimulating Factor

We evaluated the effects of hepatocyte-stimulating factor (HSF) and a glucocorticoid (dexamethasone) on changes in the levels, in vivo and in vitro, of plasma fibronectin (Fn), a glycoprotein that is synthesized and secreted by hepatocytes. In turpentine-treated chickens, plasma levels of Fn, which peaked at 48 h (whereas fibrinogen levels were maximum at 72 h) rose 200-250% over basal levels, whereas albumin levels decreased by 20-40%. Corticosterone levels in serum samples taken between 5 and 48 h after injection revealed a 124% increase in hormone levels at 24 h in turpentine-treated chickens. We also showed that circulating HSF levels were maximal 8 to 12 h after injection and that HSF activity, as assessed by molecular-exclusion chromatography, was eluted in the 30-45 kDa range. Addition of either serum-derived HSF or dexamethasone (2 nM) to chick hepatocyte cultures resulted in a 130-150% increase in secreted Fn as well as in fibrinogen. When HSF and dexamethasone were added together, a 360-489% increase in the secreted levels of both proteins was found. Chicken mononuclear phagocytic cells treated with lipopolysaccharide secreted an HSF activity that was eluted in two peaks, a minor peak at approximately 70 kDa and a major peak in the 25-40 kDa range. Addition of mononuclear-cell-derived HSF resulted in a greater increase in Fn levels than did the addition of serum HSF. These findings indicate that Fn, like fibrinogen, is an acute-phase protein, the production of which, at least in chickens, is stimulated by HSF and glucocorticoids in an additive manner.

scholarly journals In Vitro ELISA and Cell-Based Assays Confirm the Low Immunogenicity of VNAR Therapeutic Constructs in a Mouse Model of Human RA: An Encouraging Milestone to Further Clinical Drug Development

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Obinna C. Ubah ◽  
Andrew J. Porter ◽  
Caroline J. Barelle
Keyword(s):  
Mouse Model ◽  
Solid Phase ◽  
Molecular Architecture ◽  
Serum Samples ◽  
Complete Control ◽  
Drug Levels ◽  
Trough Serum ◽  
The Impact

Anti-drug antibodies (ADAs), specific for biotherapeutic drugs, are associated with reduced serum drug levels and compromised therapeutic response. The impact of ADA on the bioavailability and clinical efficacy of blockbuster anti-hTNF-α monoclonal antibodies is well recognised, especially for adalimumab and infliximab treatments, with the large and complex molecular architecture of classical immunoglobulin antibody drugs, in part, responsible for the immunogenicity seen in patients. The initial aim of this study was to develop solid-phase enzyme-linked immunosorbent assays (ELISA) and an in vitro cell-based method to accurately detect ADA and estimate its impact on the preclinical in vivo efficacy outcomes of two novel, nonimmunoglobulin VNAR fusion anti-hTNF-α biologics (Quad-X™ and D1-NDure™-C4) and Humira®, a brand of adalimumab. Serum drug levels and the presence of ADA were determined in a transgenic mouse model of polyarthritis (Tg197) when Quad-X™ and Humira® were dosed at 1 mg/kg and D1-NDure™-C4 was dosed at 30 mg/kg. The serum levels of the Quad-X™ and D1-NDure™-C4 modalities were consistently high and comparable across all mice within the same treatment groups. In 1 mg/kg and 3 mg/kg Quad-X™- and 30 mg/kg D1-NDure™-C4-treated mice, an average trough drug serum concentration of 8 μg/mL, 50 μg/mL, and 350 μg/mL, respectively, were estimated. In stark contrast, Humira® trough serum concentrations in the 1 mg/kg treatment group ranged from <0.008 μg/mL to 4 μg/mL with trace levels detected in 7 of the 8 animals treated. Trough serum Humira® and Quad-X™ concentrations in 3 mg/kg treatment samples were comparable; however, the functionality of the detected Humira® serum was significantly compromised due to neutralising ADA. The impact of ADA went beyond the simple and rapid clearance of Humira®, as 7/8 serum samples also showed no detectable capacity to neutralise hTNF-α-mediated cytotoxicity in a murine fibrosarcoma (L929) cell assay. The neutralisation capacity of all the VNAR constructs remained unchanged at the end of the experimental period (10 weeks). The data presented in this manuscript goes some way to explain the exciting outcomes of the previously published preclinical in vivo efficacy data, which showed complete control of disease at Quad-X™ concentrations of 0.5 mg/kg, equivalent to 10x the in vivo potency of Humira®. This independent corroboration also validates the robustness and reliability of the assay techniques reported in this current manuscript, and while it comes with the caveat of a mouse study, it does appear to suggest that these particular VNAR constructs, at least, are of low inherent immunogenicity.

scholarly journals Early Bactericidal Activity and Pharmacokinetics of the Diarylquinoline TMC207 in Treatment of Pulmonary Tuberculosis

2008 ◽  
Vol 52 (8) ◽  
pp. 2831-2835 ◽  
Author(s):  
R. Rustomjee ◽  
A. H. Diacon ◽  
J. Allen ◽  
A. Venter ◽  
C. Reddy ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Bactericidal Activity ◽  
Dose Range ◽  
Study Drug ◽  
First Line ◽  
Serious Adverse Events ◽  
Once Daily ◽  
Smear Positive Pulmonary Tuberculosis

ABSTRACT Tibotec Medicinal Compound 207 (TMC207) is a novel diarylquinoline with a unique mode of action that targets mycobacterial ATP synthase. TMC207 exhibits high in vitro activity against mycobacterial strains either susceptible or resistant to all first-line and many second-line drugs, including fluoroquinolones, and has shown exceptional in vivo activity against several mycobacterial species in different animal models. In this early bactericidal activity study, 75 treatment-naïve patients with smear-positive pulmonary tuberculosis were randomized to once-daily oral TMC207 (25 mg, 100 mg, or 400 mg), 600 mg rifampin (RIF), or 300 mg isoniazid (INH) for 7 days. Sixteen-hour overnight sputum collected at baseline and on each treatment day was plated in serial dilutions on selective agar plates. The bactericidal activity was expressed as the log10 decrease in CFU/ml sputum/day. Pharmacokinetic sampling was performed on day 7 of TMC207 administration up to 24 h postdose. The decreases in log10 CFU counts (± standard deviation) from baseline to day 7 were 0.04 ± 0.46 for 25 mg TMC207 (n = 14), 0.26 ± 0.64 for 100 mg TMC207 (n = 14), 0.77 ± 0.58 for 400 mg TMC207 (n = 14), 1.88 ± 0.74 for INH (n = 11), and 1.70 ± 0.71 for RIF (n = 14). Significant bactericidal activity of 400 mg TMC207 was observed from day 4 onward and was similar in magnitude to those of INH and RIF over the same period. The pharmacokinetics of TMC207 were linear across the dose range. In summary, TMC207 demonstrated bactericidal activity with a delayed onset and was well tolerated, and no study drug-related serious adverse events occurred.

Effect of Sodium-Transport Inhibitors on Bronchial Reactivity in Vivo

1990 ◽  
Vol 79 (4) ◽  
pp. 325-330 ◽  
Author(s):  
Alan J. Knox ◽  
John R. Britton ◽  
Anne E. Tattersfield
Keyword(s):  
Confidence Intervals ◽  
Sodium Transport ◽  
Geometric Mean ◽  
Normal Subjects ◽  
Bronchial Reactivity ◽  
Mean Values ◽  
Doubling Dose ◽  
The Difference

1. We have recently shown that ouabain, an inhibitor of Na+/K+-adenosine triphosphatase, causes contraction of bovine and human airways in vitro, and that amiloride causes relaxation and inhibits receptor-operated contraction in bovine trachealis. 2. To determine whether such drugs alter bronchial reactivity in vivo, we have studied the effect of oral digoxin (an inhibitor of Na+/K+-adenosine triphosphatase) and oral and inhaled amiloride on bronchial reactivity to histamine in three double-blind, placebo-controlled studies. 3. Histamine reactivity was measured as the provocative dose causing a 20% reduction in the forced expiratory volume in 1 s (PD20FEV1) or, when normal subjects were included, the provocative dose causing a 35% reduction in the specific airways conductance (PD35sGaw); the results are given as geometric mean values. 4. In study 1, 13 atopic asthmatic subjects were given 20 mg of oral amiloride or placebo on separate days. Two hours after the drug, the geometric mean PD20FEV1 for histamine was 0.43 μmol after amiloride and 0.54 μmol after placebo (95% confidence intervals for the difference: 0.9 to −0.2 doubling doses of histamine; P = 0.2). 5. In study 2, six normal and 24 atopic asthmatic men inhaled 10 ml of 10−2 mol/l amiloride or diluent control in a crossover study. The mean values of PD35sGaw for histamine immediately after inhalation of amiloride and placebo were 3.0 μmol and 4.3 μmol, respectively, in the normal subjects (95% confidence intervals for the difference: −0.53 to 1.52 doubling doses, P = 0.2), and 0.33 μmol and 0.29 μmol in the asthmatic subjects (95% confidence intervals for the difference: −0.95 to 0.57 doubling doses; P = 0.6). 6. In study 3, 24 atopic asthmatic men were treated for 7 days with placebo or oral digoxin (1.5 mg loading dose plus 0.25 mg twice daily for 6 days). The PD20FEV1 for histamine was measured before, 12 h after the loading dose and on day 7 of treatment. The change in PD20FEV1 did not differ significantly after digoxin and placebo, after either 1 day's treatment [mean (95% confidence intervals) difference: 0.56 doubling dose (−0.37 to 1.5 doubling dose)] or 7 day's treatment [mean (95% confidence intervals) difference: 0.3 doubling dose (−1.23 to 1.8 doubling doses)]. 7. Although our work in vitro has suggested that membrane sodium transport may play an important role in determining airway smooth muscle contractility, we have been unable to demonstrate any effect of the sodium-transport inhibitors amiloride and digoxin on histamine reactivity in these studies.

RATE OF THYROXINE SECRETION BY MALE AND LAYING JAPANESE QUAIL: IDENTIFICATION OF THE RADIOACTIVE THYROXINE DEGRADATION COMPONENT OF THE MULTIPHASIC 131I CURVE

1975 ◽  
Vol 65 (1) ◽  
pp. 65-71 ◽  
Author(s):  
G. A. ROBINSON ◽  
K. H. TAM
Keyword(s):  
Japanese Quail ◽  
Degradation Rate ◽  
The Body ◽  
Secretion Rate ◽  
Distribution Space ◽  
Rapid Loss ◽  
Serum Samples ◽  
Time Period

SUMMARY Counting of radioactivity in Japanese quail in vivo showed a rapid loss of 131I from the body 12–24 h after the i.v. injection of [131I]thyroxine (T4), followed by a period of slow decrease in counting rates to 96 h. From comparison of these [131I]T4 curves with curves for 131iodide-injected birds and from counts on serum and other tissues in vitro it was concluded that, for Japanese quail, the T4 secretion rate should be calculated using serum samples taken during the first 12 h. Using this time period, the parameters measured were: T4 distribution space, laying hens 45·7 and mature cocks 26·3 ml/100 g body weight; fractional degradation rate for T4, hens 5·73 and cocks 3·12/day; serum T4 concentration (Tetrasorb125 method), hens 1·20 ± 0.07 and cocks 1·34 ± 0.05 (s.e.m.)μg/100 ml (n= 16); T4 secretion rate, hens 3·14 and cocks 1·10 μg/100 g/day.

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