Circadian rhythm of mitotic activity in normal and hyperplastic rat thyroid

1982 ◽  
Vol 100 (1) ◽  
pp. 46-50 ◽  
Author(s):  
D. Wynford-Thomas ◽  
B. M. J. Stringer ◽  
E. D. Williams

Abstract. This study was designed to provide a reliable quantitative assessment of the circadian rhythm of mitotic activity in the follicular cell population of the rat thyroid, and the effect on this rhythm of prolonged stimulation by a raised level of circulating TSH, induced by goitrogen administration. Mitotic activity in groups of control and goitrogen-treated rats was assessed by a stathmokinetic technique during four 4-h periods spaced equally through one 24-h cycle. Particular attention was paid to the method of sampling to eliminate systematic and minimise random errors, and to the assesment of rhythmicity which was carried out by an appropriate statistical method. A highly significant circadian rhythm was found in control animals with a daytime peak (12.00 to 16.00 h). Goitrogen treatment led to a 5- to 6-fold increase in the mean but a loss of detectable rhythmicity. The results show that the presence and timing of this circadian rhythm must be taken into account in future studies of thyroid growth, and they throw some light on the possible mechanisms of its control. Comparison of the rhythm with that of serum TSH reported previously raises the possibility of a dominant control by this hormone even in euthyroid animals and suggests that it may act on cells in the G2 and/or G1/G0 phases of the cell cycle.

1982 ◽  
Vol 101 (4) ◽  
pp. 562-569 ◽  
Author(s):  
D. Wynford-Thomas ◽  
B. M. J. Stringer ◽  
E. D. Williams

Abstract. We have previously shown that administration of goitrogen to the rat leads to a sustained elevation of serum TSH but to only a short-lived burst of mitotic activity in the thyroid, growth eventually ceasing after a few months. This work investigates the possibility that this progressive desensitisation may result simply from continued exposure to high levels of TSH and examines the effect of a period of interruption of goitrogen treatment on the sensitivity of the gland to subsequent TSH stimulation. Rats were treated with the goitrogen aminotriazole (ATA) for an initial period of 80 days to reach the plateau of thyroid growth. ATA was then withdrawn for 25 days and subsequently re-introduced for a further 35 days. Animals were killed in groups of 8 at frequent intervals and the following measurements carried out: — Serum TSH, T3 and T4, thyroid weight, follicular cell number and mitotic activity. The initial period of ATA treatment led to a 5-fold increase in serum TSH, a 10-fold increase in thyroid weight and a 9-fold increase in follicular cell number. Mitotic activity stabilised at a few times control levels. Following withdrawal of ATA, TSH and mitotic activity fell to below normal. Thyroid weight fell by 66% but there was no significant fall in follicular cell number. Re-introduction of ATA simply led to a return of all variables to their previous 'stimulated' levels. There was no second burst of mitotic activity and no renewed thyroid growth. The results show that the desensitisation of follicular cells to the growth-stimulating action of TSH following prolonged stimulation is not reversed by withdrawal of the stimulus, and is therefore unlikely to be mediated by a 'downregulation' at receptor or post-receptor level of the type observed for functional responses in vitro. Other possible mechanisms are discussed.


1987 ◽  
Vol 115 (1) ◽  
pp. 30-36 ◽  
Author(s):  
Kanji Kasagi ◽  
Junji Konishi ◽  
Yasuhiro Iida ◽  
Yasutaka Tokuda ◽  
Keisuke Arai ◽  
...  

Abstract. A sensitive, precise and practical assay for thyroid stimulating antibodies was developed in which poorly differentiated rat thyroid cells (FRTL-5) were exposed to crude immunoglobulin fractions precipitated from serum with 15% polyethylene glycol under hypotonic conditions. After the incubation at 37°C for 2 h, cAMP released into Hank's medium without NaCl was determined by radioimmunoassay. The removal of NaCl from the isotonic Hank's medium greatly enhanced cAMP production in response to both TSH and thyroid stimulating antibodies. The assay was sensitive enough to elicit an approximately 30-fold increase in cAMP at 10 mU/l bovine TSH. Thyroid stimulating activities measured using FRTL-5 cells significantly correlated with those measured using cultured porcine (r = 0.918, N = 72) or human (r = 0.830, N = 23) thyroid cells. Thyroid stimulating activities were detected in all of the 50 patients with hyperthyroid Graves' disease, the 14 patients with recurrent hyperthyroid Graves' disease, and the 25 patients with ophthalmic Graves' disease. Thyroid stimulating activity was also detected in some patients (9/24, 37.5%) with Hashimoto's thyroiditis whose serum TSH concentrations were higher than 30 mU/l. However, it was completely abolished by pre-treatment of the sera with anti-TSH antibodies. Although thyroid stimulating activities were detected in one of the patients with simple goitre (N = 10) and in one with thyroid cancer (N = 10), none of the patients with silent thyroiditis (N = 7), adenomatous goitre (N = 11), and thyroid adenoma (N = 9) were positive for thyroid stimulating antibodies.


1992 ◽  
Vol 127 (1) ◽  
pp. 18-22 ◽  
Author(s):  
Nicola Custro ◽  
Vincenza Scafidi ◽  
Alberto Notarbartolo

To evaluate the 24-h pattern of serum thyrotropin (TSH) in critically ill patients, we measured serum concentrations of TSH in blood samples collected every 2 h for 24 h from nine patients (six with malignancy, two with liver cirrhosis, one with chronic renal failure), who had subnormal levels of both triiodothyronine (T3) and thyroxine (T4), in the absence of history, symptoms or signs of thyroid disease. Analysis of the data, performed using a second-order inferential statistical methodology for rhythmometry (cosinor method), demonstrated that critically ill patients still had daily oscillations of serum TSH which significantly adapted to the function approximating the circadian rhythms (R2 = 74.3%). However, the mean level (mesor) in the rhythm of the patients was found to be significantly lower than that of healthy subjects (0.96 vs 2.18 mU/l); the amplitude of rhythmical daily variations also was lower in patients than in healthy subjects (0.23 vs 0.56 mU/l), even though the amplitude/mesor ratio was similar (23% vs 26%). Lastly, the highest level in the TSH rhythm of the patients was found to be in the late afternoon, in contrast to healthy subjects, who had a TSH surge after midnight. Although these alterations are consistent with the existence of a dysregulation at suprahypophyseal level in critically ill patients, it remains to be established whether the state of low T3 and T4 may be ascribed to anomalous circadian rhythm of TSH.


1982 ◽  
Vol 101 (3) ◽  
pp. 365-370 ◽  
Author(s):  
D. Wynford-Thomas ◽  
B. M. J. Stringer

Abstract. This paper describes the effect of long-term goitrogen-administration on the mast cell population of the rat thyroid. Animals were treated with the goitrogen aminotriazole at a dose sufficient to block thyroid hormone synthesis completely, and compared after 80 days with a control group. Serum TSH was measured by radioimmunoassay, and mast cell number quantified from specially-stained tissue sections using appropriate stereological methods. Goitrogen treatment led to a 9-fold increase in serum TSH and an 8-fold increase in thyroid weight. Mast cell number per unit volume of thyroid decreased, but total numbers per gland increased 4 to 5 fold. There was a significant fall in mean mast cell size. The work demonstrates conclusively that mast cell hyperplasia occurs during goitre formation and provides a method for its quantitative assessment. The possible mechanisms and significance of thyroid mast cell proliferation are discussed.


1982 ◽  
Vol 101 (2) ◽  
pp. 210-216 ◽  
Author(s):  
D. Wynford-Thomas ◽  
B. M. J. Stringer ◽  
E. D. Williams

Abstract. This study was designed to investigate the changes in growth and function which occur in the rat thyroid during prolonged TSH stimulation. Animals maintained on the goitrogen aminotriazole were sacrificed together with controls at frequent intervals over a period of 5 months. The levels of serum T3 and T4 and TSH were measured by radioimmunoassay. Functional activity was assessed by measurement of the thyroid/serum iodide ratio (T/S) and growth by measurement of thyroid weight, follicular cell number and follicular cell mitotic activity. Serum T3 and T4 rapidly fell to undetectable levels within 2 weeks. The level of serum TSH rose to a stable 5-fold maximum after 4 weeks. The T/S ratio followed a closely similar pattern rising to a sustained 7-fold maximum. Thyroid weight and follicular cell number increased rapidly for the first few weeks but the growth rate declined progressively, falling almost to zero after 80 days. Mitotic activity rose dramatically to a 30-fold peak after 7 days but then declined almost to normal after 80 days, consistent with the observed change in cell number. The results thus demonstrate a clear dissociation between the functional and proliferative activity of the thyroid follicular cells during prolonged stimulation by a sustained elevation of serum TSH and point to the existence of specific growth regulating mechanisms which limit the mitotic response.


1974 ◽  
Vol 75 (2) ◽  
pp. 274-285 ◽  
Author(s):  
A. Gordin ◽  
P. Saarinen ◽  
R. Pelkonen ◽  
B.-A. Lamberg

ABSTRACT Serum thyrotrophin (TSH) was determined by the double-antibody radioimmunoassay in 58 patients with primary hypothyroidism and was found to be elevated in all but 2 patients, one of whom had overt and one clinically borderline hypothyroidism. Six (29%) out of 21 subjects with symptomless autoimmune thyroiditis (SAT) had an elevated serum TSH level. There was little correlation between the severity of the disease and the serum TSH values in individual cases. However, the mean serum TSH value in overt hypothyroidism (93.4 μU/ml) was significantly higher than the mean value both in clinically borderline hypothyroidism (34.4 μU/ml) and in SAT (8.8 μU/ml). The response to the thyrotrophin-releasing hormone (TRH) was increased in all 39 patients with overt or borderline hypothyroidism and in 9 (43 %) of the 21 subjects with SAT. The individual TRH response in these two groups showed a marked overlap, but the mean response was significantly higher in overt (149.5 μU/ml) or clinically borderline hypothyroidism (99.9 μU/ml) than in SAT (35.3 μU/ml). Thus a normal basal TSH level in connection with a normal response to TRH excludes primary hypothyroidism, but nevertheless not all patients with elevated TSH values or increased responses to TRH are clinically hypothyroid.


2004 ◽  
Vol 9 (3) ◽  
pp. 233-240 ◽  
Author(s):  
S. Kim

This paper describes a Voronoi analysis method to analyze a soccer game. It is important for us to know the quantitative assessment of contribution done by a player or a team in the game as an individual or collective behavior. The mean numbers of vertices are reported to be 5–6, which is a little less than those of a perfect random system. Voronoi polygons areas can be used in evaluating the dominance of a team over the other. By introducing an excess Voronoi area, we can draw some fruitful results to appraise a player or a team rather quantitatively.


2021 ◽  
pp. 1-6
Author(s):  
Anand K. Bery ◽  
Jayson Lee Azzi ◽  
Andre Le ◽  
Naomi S. Spitale ◽  
Judith Leech ◽  
...  

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to vestibular dysfunction, but no prior studies have investigated the relationship between Persistent Postural Perceptual Dizziness (PPPD), a common cause of chronic dizziness, and OSA. OBJECTIVE AND METHODS: We determined the frequency of OSA in an uncontrolled group of PPPD patients from a tertiary dizziness clinic based on polysomnogram (PSG). We then assessed the sensitivity and specificity of common OSA questionnaires in this population. RESULTS: Twenty-five patients with PPPD underwent PSG (mean age 47, 60% female, mean BMI 29.5). A majority, or 56%, of patients were diagnosed with OSA, and in most, the OSA was severe. OSA patients were older (56 years versus 40 years, p = 0.0006) and had higher BMI (32 versus 26, p = 0.0078), but there was no clear gender bias (56% versus 64% female, p = 1.00). The mean sensitivity and specificity of the STOP BANG questionnaire for detecting OSA was 86% and 55%, respectively. Sensitivity and specificity of the Berlin Questionnaire was 79% and 45%, respectively. CONCLUSIONS: The prevalence of OSA was much higher in our small PPPD group than in the general population. Screening questionnaires appear to demonstrate good sensitivity to detect PPPD patients at risk of OSA in this small study. Future studies should confirm these findings and determine whether treatment of OSA improves symptoms in PPPD.


Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1388
Author(s):  
Ted Friend ◽  
Giulia Corsini ◽  
Vincent Manero ◽  
Raffaella Cocco

The documentation of diurnal patterns in body temperature in lions could be important because disruption of circadian patterns can be a useful measure of distress. This study quantified changes in body temperature of seven African lions (Panthera leo) at 5 min intervals during cold conditions from noon until the ingested body temperature loggers were expelled the next day. Thirteen loggers were fed to 11 lions during their daily noon feeding, while ambient temperatures were also recorded using six data loggers. The lions had continuous access to their dens and exercise pens during the day but were restricted to their heavily bedded dens that also contained a heat lamp from 23:00 until 08:00 the next day. Body temperatures averaged 37.95 ± 0.42 °C at 15:50, and 36.81 ± 0.17 °C at 06:50 the next day, 30 min before the first loggers passed from a lion, and were significantly different (t-test, t = 8.09, df = 6, p < 0.0003). The mean duration for the time of passage was 22 ± 2.69 (h ± SD), so future studies using the noninvasive feeding of temperature loggers need to consider that time frame.


2015 ◽  
Vol 129 (6) ◽  
pp. 600-603 ◽  
Author(s):  
G Chawdhary ◽  
N Liow ◽  
J Democratis ◽  
O Whiteside

AbstractBackground:Necrotising (malignant) otitis externa is a severe infection causing temporal bone osteomyelitis. Although rare, our experience (reported herein) shows local doubling of cases in 2013. Hospital Episodes Statistics data for England over 14 years also indicate increased incidence nationally. Specific learning points in management are also discussed.Methods:A retrospective review was conducted of patients admitted in 2013 to Wexham Park Hospital, Slough, UK (catchment population, 450 000). In addition, the UK Government Hospital Episodes Statistics data were interrogated.Results:There were five cases of necrotising (malignant) otitis externa in 2013, representing a local doubling on previous years. The mean age of patients was 82 years. All cultures grew Pseudomonas aeruginosa; no isolates were antibiotic resistant. All patients responded to systemic anti-pseudomonals on clinical, biochemical and radiological parameters. Hospital Episodes Statistics data showed a six-fold increase in the number of cases from 1999 (n = 67) to 2013 (n = 421).Conclusion:Our experience suggests increasing necrotising (malignant) otitis externa incidence, and retrospective analysis of Hospital Episodes Statistics data supports this observation. Necrotising (malignant) otitis externa poses challenges in management, as exemplified in our cases, requiring a high index of suspicion and early aggressive treatment to achieve cure.


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