bluuebunny/crossref_metadata_2025 huggingface dataset:
Book Review
Authors: Oppenheim Charles
Published: March 2008

Digital Copyright (2nd Edition) Paul Pedley. London, Facet Publishing, 2007, 184 pp. ISBN 978 1 85604 608 4, £34.95, paperback.
Tcf3 is an integral component of the core regulatory circuitry of embryonic stem cells
Authors: Cole Megan F. , Johnstone Sarah E. , Newman Jamie J. , Kagey Michael H. , Young Richard A.
Published: March 2008

Embryonic stem (ES) cells have a unique regulatory circuitry, largely controlled by the transcription factors Oct4, Sox2, and Nanog, which generates a gene expression program necessary for pluripotency and self-renewal. How external signals connect to this regulatory circuitry to influence ES cell fate is not known. We report here that a terminal component of the canonical Wnt pathway in ES cells, the transcription factor T-cell factor-3 (Tcf3), co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog. Thus, Tcf3 is an integral component of the core regulatory circuitry of ES cells, which includes an autoregulatory loop involving the pluripotency regulators. Both Tcf3 depletion and Wnt pathway activation cause increased expression of Oct4, Nanog, and other pluripotency factors and produce ES cells that are refractory to differentiation. Our results suggest that the Wnt pathway, through Tcf3, brings developmental signals directly to the core regulatory circuitry of ES cells to influence the balance between pluripotency and differentiation.
A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial–mesenchymal transition
Authors: Beltran Manuel , Puig Isabel , Peña Cristina , García José Miguel , Álvarez Ana Belén , Peña Raúl , Bonilla Félix , de Herreros Antonio García
Published: March 2008

Expression of Snail1 in epithelial cells triggers an epithelial–mesenchymal transition (EMT). Here, we demonstrate that the synthesis of Zeb2, a transcriptional repressor of E-cadherin, is up-regulated after Snail1-induced EMT. Snail1 does not affect the synthesis of Zeb2 mRNA, but prevents the processing of a large intron located in its 5′-untranslated region (UTR). This intron contains an internal ribosome entry site (IRES) necessary for the expression of Zeb2. Maintenance of 5′-UTR Zeb2 intron is dependent on the expression of a natural antisense transcript (NAT) that overlaps the 5′ splice site in the intron. Ectopic overexpression of this NAT in epithelial cells prevents splicing of the Zeb2 5′-UTR, increases the levels of Zeb2 protein, and consequently down-regulates E-cadherin mRNA and protein. The relevance of these results is demonstrated by the strong association between NAT presence and conservation of the 5′-UTR intron in cells that have undergone EMT or in human tumors with low E-cadherin expression. Therefore, the results presented in this article reveal the existence of a NAT capable of activating Zeb2 expression, explain the mechanism involved in this activation, and demonstrate that this NAT regulates E-cadherin expression.
Coupling meiotic chromosome axis integrity to recombination
Authors: Storlazzi Aurora , Tesse Sophie , Ruprich-Robert Gwenael , Gargano Silvana , Pöggeler Stefanie , Kleckner Nancy , Zickler Denise
Published: March 2008

During meiosis, DNA events of recombination occur in direct physical association with underlying chromosome axes. Meiotic cohesin Rec8 and cohesin-associated Spo76/Pds5 are prominent axis components. Two observations indicate that recombination complexes can direct the local destabilization of underlying chromosome axes. First, in the absence of Rec8, Spo76/Pds5 is lost locally at sites of late-persisting Msh4 foci, with a concomitant tendency for loosening of intersister and interhomolog connectedness at the affected sites. This loss is dependent on initiation of recombination. Second, in wild-type prophase, local separation of sister axes is seen at sites of synaptonemal complex-associated recombination nodules. Additional findings reveal that Rec8 localizes to both axis and bulk chromatin and is required for chromatin compactness. Further, Rec8 is essential for maintenance of sister cohesion, along arms and centromeres, during the pachytene-to-diplotene transition, revealing an intrinsic tendency for destabilization of sister cohesion during this period. This finding shows how the loss of sister connectedness, in arm and/or centric regions, could lead to the segregation defects that are seen in the human “maternal age effect” and how Rec8 could be a target of that effect. Finally, Rec8 plays related, but synergistic roles with Spo76/Pds5, indicating auxiliary roles for meiotic and mitotic cohesion-associated components.
Auxin influx carriers stabilize phyllotactic patterning
Authors: Bainbridge Katherine , Guyomarc’h Soazig , Bayer Emmanuelle , Swarup Ranjan , Bennett Malcolm , Mandel Therese , Kuhlemeier Cris
Published: March 2008

One of the most striking features of plant architecture is the regular arrangement of leaves and flowers around the stem, known as phyllotaxis. Peaks in concentration of the plant hormone auxin, generated by the polar localization of the PIN1 auxin efflux carrier, provide the instructive signal for primordium initiation. This mechanism generates the spacing between neighboring primordia, which results in regular phyllotaxis. Studies of the role of auxin transport in phyllotactic patterning have focused on PIN1-mediated efflux. Recent computer simulations indicate an additional role for transporter-mediated auxin uptake. Mutations in the AUX1 auxin influx carrier have not, however, been reported to cause an aerial phenotype. Here, we study the role of AUX1 and its paralogs LAX1, LAX2, and LAX3. Analysis of the quadruple mutant reveals irregular divergence angles between successive primordia. A highly unusual aspect of the phenotype is the occurrence of clusters of primordia, in violation of classical theory. At the molecular level, the sharp peaks in auxin levels and coordinated PIN polarization are reduced or lost. In addition, the increased penetrance of the phenotype under short-day conditions suggests that the AUX LAX transporters act to buffer the PIN-mediated patterning mechanism against environmental or developmental influences.
SERUM TSH AND THYROID ANTIBODY STUDIES IN ADDISON'S DISEASE
Authors: McHardy‐YOUNG S. , LESSOF M. H. , MAISEY M. N.
Published: March 2008

Thirty‐three patients with Addison's disease have been investigated with particular reference to thyroid function, thyroid antibody status and serum TSH measurements.

Of twenty‐seven patients with idopathic or probably idiopathic Addison's disease, fifteen had antibodies against adrenal tissue and thirteen had thyroid microsomal antibodies. No patient with tuberculous Addison's disease had evidence of thyroid disease or of either adrenal or thyroid antibodies.

The response to injected TSH was usually impaired in patients who had antithyroid antibodies in their serum. This test was cumbersome but appeared to indicate the reserve capacity of the thyroid.

Serum TSH levels were raised in ten of the thirteen patients who had thyroid antibodies, including six whose protein bound‐iodine levels were below 4.0μ/100 ml. Three antibody negative subjects also had an elevated TSH level.

The most sensitive indication of subclinical thyroid disease appeared to be a positive thyroid antibody test. Estimation of the serum TSH level appeared to correlate with more advanced disease and with the earliest evidence of failure of thyroid function.

It is suggested that serum TSH measurements are clinically helpful in patients with positive thyroid antibody testes and in patients with low or low normal proteinbound iodine levels.
KINETIC STUDIES OF CORTISOL AND SYNTHETIC CORTICOSTEROIDS IN MAN
Authors: Fell P. J.
Published: March 2008

Following the rapid intravenous injection of corticosteroids (cortisol, prednisolone, betamethasone and betamethasone‐17‐valerate), the blood levels of each were estimated and the results analysed in a two‐compartment open model. The kinetic analysis revealed differences in distribution and elimination which could have important therapeuticimplications. A theory is presented for the marked differences seen, and the therapeutic importance of these is discussed.
EXCRETION OF 6‐OXYGENATED METABOLITES OF PROGESTERONE AND PREGNANEDIOL DURING PREGNANCY
Authors: JAMES FRANCES , FOTHERBY K. , KLOPPER A.
Published: March 2008

The excretion of preganediola and the 6‐oxygenated metabolites of progesterone was measured during the last 12 weeks of pregnancy in fifty‐five women. There was no significant change in pregnanediol excretion during the last 10 weeks of pregnancy but during this time there was a significant increase in the excretion of the 6‐oxygenated metabolites. There was a significant correlation between the excretion of these latter metabolites and both fetal and placental weights at term. It is suggested that the 6‐oxygenated metabolites may be arising from the fetal 6‐hydroxylation of progesterone. In some patients with severe toxaemia pregnanediol excretion was low although excretion of 6‐oxygenated metabolites was within the normal range.
HUMAN NEUROPHYSINE BLOOD LEVELS UNDER NORMAL, EXPERIMENTAL AND PATHOLOGICAL CONDITIONS
Authors: LEGROS J. J. , FRANCHIMONT P.
Published: March 2008

The first results of serum neurphysine determinations by radioimmunoassay in normal man and in several pathological states are reported.

Under baseline conditions neurophysine levels are higher in women than in men. In women, moreover, they are elevated during pregnancy and decline rapidly postpartum. During labour and suckling there is no significant change in maternal neurophysine. Neonates, and particularly premature infants, have higher serum neurophysine concentrations than adults.

Under certain physiological conditions (water load, dehydration) there is a concordance between serum neurophysine and antidiuresis, whereas these two factors are discordant in states marked by endocrine alterations (anterior pituitary insufficiency, adrenal insufficiency, oestrogen ingestion). A dissociation between neurophysine levels and antidiuresis is also observed during nicotine stimulation by cigarette inhalation. The significance of this dissociation is discussed.

Renal insufficiency whether or not treated by dialysis is accompanied by constatly elevated neurophysine levels, while obesity is sometimes although not always associated with a marked increase in neuropysine. A rise in serum neurophysine is seen only rarely in anterior pituitary insufficiency.
ACTH AND CALCITONIN SECRETING MEDULLARY CARCINOMA OF THE THYROID
Authors: CROUGHS RONALD J. M. , EASTHAM W. NOÉL , HACKENG WILLEM H. L. , SCHOPMAN WILLEM , FELTKAMP‐VROOM THEA M. , DOLMAN ABRAHAM , HENNEMANN GEORG
Published: March 2008

The present report describes the case history of a woman suffering from an ectopic ACTH syndrome due to a medullary carcinoma of the thyroid. Histologic and electron microscopic studies revealed the tumorous nature of the so‐called ‘macrophage‐like’cell; the diagnostic significance of this cell is stressed. It appears that there is a whole spectrum of tumour cells ranging from the typical tumour cell via transitional forms to ‘macrophage‐like’tumour cells.

Tumour tissue was investigated for the presence of calcitonin and ACTH by immunological and biological methods. Tumour tissue sections stained specifically for calcitonin in the immunofluorescence technique; high concentrations of calcitonin could be demonstrated in tumour extracts both by radioimmunoassay and bioassay.

In contrast, the presence of ACTH in tumour tissue could be demonstrated only by radioimmunoassay. The negative results of the bioassay could be attributed to the relative insensitivity of the method used, and a similar explanation may account for the negative results using the immunofluorescence technique. Plasma levels of both calcitonin and ACTH were very high. A final diagnosis of an ACTH and calcitonin secreting medullary carcinoma of the thyroid was made. There is no reason to believe that these polypeptide hormones are produced by different cell types.
THE EFFECT OF CHLORPROMAZINE ON PITUITARY FUNCTION
Authors: SALDANHA V. F. , HAVARD C.W.H. , BIRD R. , GARDNER R.
Published: March 2008

The pituitary‐adrenal response to stress and the production of growth hormone were studied in a group of schizophrenic patients before and after treatment with chlorpromazine in a dose of 300 mg daily for 1 week. Although there was a tendency for the growth hormone levels to be lower after treatment, the mean figures showed no significant differences. The mean plasma corticosteroid response to the stress of hypoglycaemia was only of significant difference at 120 min. Individual cases showed considerable, apparently random, variation.
PLASMA LIPOPROTEEINS IN ADULT DIABETES
Authors: HAYES T. M.
Published: March 2008

The prevalence of hyperlipoproteinaemia was investigated in three groups of diabetics. Of 106 untreated diabetics. Of 106 untreated diabetics 68% had some form of hyperlipoproteinaemia. When the plasma of fifty‐six of these patients was re‐examined after their hyperglycaemia was controlled, then only 22% had an abnormal lipoprotein pattern. A further group of 102 diabetics who had been receiving treatment for between 1 and 34 years and whose hyperglycaemia appeared to be well controlled were also studied and the prevalence of abnormal lipoprotein patterns in this group was 58%. There was no correlation between the age of the patient and the prevalence of hyperlipoproteinaemia but all those studied were over 30 years of age.

There was no evidence that any of the forms of treatment used, diet alone, diet with sulphonylureas, diet with phenformin, or diet and insulin was more successful than any of the others either in reducing the overall prevalence of hyperlipopro‐teinaemia or in treating any particular type of hyperlipoproteinaemia.
TREATMENT OF MENOMETRORRHAGIA WITH AN ANTI‐OESTROGEN
Authors: EL‐SHEIKHA ZAKARIA , KLOPPER ARNOLD , BECK J. SWANSON
Published: March 2008

Six women with menometrorrhagia, two with anovular cycles and four with ovular cycles, have been studied, before, during and after treatment with tamoxifen, a competitive inhibitor of the binding of oestrogen to the endometrium. During treatment the urinary pregnanediol excretion of the women with anovular cycles rose and a modified secretory transformation of the endometrium occurred. Ovulation occurred during treatment in all the patients suffering from ovulatory menorrhagia. Most patients noted a diminution in the amount and duration of bleeding and there was a tendency for the previously irregular bleeding to occur at regular intervals during treatment.
SEMINAL PROSTAGLANDINS AND FERTILITY
Authors: BRUMMER HILARY C. , GILLESPIE ARNOLD
Published: March 2008

The levels of prostaglandins E, A, and 19 hydroxy A in samples of seminal fluid collected from men attending a fertility clinic have been estimated spectrophotometrically and compared with levels found in samples from fertile men undergoing sterilization by vasectomy. Semen taken from oligo or aspermic men and that from men whose wives proved infertile did not contain significantly different amounts of prostaglandin from samples taken from fertile men. However, a smaller scatter of values for PGE content was found in the group where infertility was unexplained. This was significant (P<0.025). It was also found that considerable deterioration of samples occurred on storage.
Plasma testosterone and androstenedione after orchiectomy in prostatic adenocarcinoma
Authors: SCIARRA F. , SORCINI G. , DI SILVERIO F. , GAGLIARDI V.
Published: March 2008

Orchiectomy is often used in the management of metastatic adenocarcinoma of the prostate, an androgen dependent tumour, since it markedly reduces the concentrations of plasma testosterone (to a mean level of 28 ± 16 (SD) ng/100 ml) and temporarily inhibits the growth of the neoplasma.

In some orchiectomized patients, however, the values of plasma testosterone and androstenedione do not drop to these levels, but remain higher, around 137 ± 23 ng/100 ml and 213 ± 39 ng/100 ml respectively.

In these patients, treatment with dexamethasone significantly decreased the levels of testosterone and androstenedione to 22 ± 20 ng/100 ml (P<0.0005) and 43 ± 11 ng/100 ml (P<0.0005) respectively.

It can therefore be assumed that in orchiectomized patients these compounds are produced in the adrenal cortex, which in some cases is stimulated to produce a larger amount of strong androgens such as testosterone and weaker androgens such as androstenedione.

It has also been observed that those patients with an inadequate lowering of plasma testosterone levels after orchiectomy, did not show clinical improvement.

Further studies in a larger number of patients are needed in order to support this finding.
ASSESSMENT OF IN VITRO THYROID FUNCTION TESTS IN 100 CONSECUTIVE PATIENTS REFERRED TO A THYROID CLINIC
Authors: TOFT A. D. , SETH J. , KIRKHAM K. E. , MARSHALL A. , IRVINE W. J.
Published: March 2008

In a series of 100 consecutive patients referred to a thyroid clinic the total serum thyroxine (serum T‐4) measured by competitive protein binding analysis had a much higher diagnostic accuracy than either the serum protein‐bound iodine (PBI) or the triiodothyronine serum uptake (T3 serum uptake) when used alone. In contrast to previous reports, the free thyroxine index (FTI) calculated from the serum PBI and the T3 serum uptake gave disappointing results. The FTI calculated from the serum T‐4 and the T3 serum uptake correlated well with thyroid status, but equally good results were given by the effective thyroxine ratio (ETR) which, although expensive, has the advantage of being a single procedure.

Primary hypothyroidism can be diagnosed with a high degree of accuracy from a single venepuncture by demonstrating a low total serum thyroxine and an elevated plasma thyrotrophin (TSH). There were no false negative results. Fortysix of the fifty euthyroid patients had plasma TSH levels less than 12 μU/ml. The four euthyroid patients with TSH levels greater than 12 μU/ml had evidence of impaired thyroid reserve.
SERUM THYROTROPHIN RESPONSE TO THYROTROPHIN‐RELEASING HORMONE IN NORMAL CHILDREN AND IN PATIENTS WITH SHORT STATURE AND VARIOUS ENDOCRINE OR GENETIC DESEASES
Authors: MALVAUX P. , BECKERS C.
Published: March 2008

The TSH response to TRH has been investigated in a group of forty‐two children, including eight normal controls, eight patients with short stature and without growth hormone deficieny, twelve hypopituitary patients, seven patients with thyroid disorders and seven others with various diseases, including four cases of Turner's syndrome.

All children with short stature and without GH deficiency demonstrate a normal response to TRH. The same conclusion arises from the data obtained in most of the cases with isolated GH deficiency. In one out of three cases of organic hypopituitarism, the maximal TSH response was delayed to 60 min after injection. Patients with Turner's syndrome have a normal response to TRH while the pituitary response was definitely enhanced in one case of pseudohypoparathyroidism.
THE EXCRETION OF 17‐DEOXYCORTICOSTEROIDS BY WOMEN PREGNANT WITH A NORMAL OR AN ANENCEPHALIC FETUS
Authors: DIVER M. J. , CAWOOD MARION L. , HEYS R. F. , OAKEY R. E.
Published: March 2008

The urinary excretion of 17‐deoxycorticosteroids by women with a normal fetus, near term, was 15.8 ± 4.2 mg/day (mean ± SD). In contrast, women pregnant with an anencephalic fetus, non‐pregnant subjects and women taking oral contraceptives containing oestrogen excreted 3.8 ± 1.3 mg/day, 3.1 ± 1.4 mg/day and 2.5 ± 0.7 mg/day, respectively. It is concluded that, in normal pregnancy, the fetal adrenal makes a substantial contribution to the production of urinary 17‐deoxycorticosteroids, or their precursors, near term. Analysis of C21 corti‐costeroids in maternal urine of selected pregnancies may help in the identification of the steroids secreted by the fetus.
ISLETS OF LANGERHANS IN JUVENILE DIABETES MELLITUS
Authors: DONIACH I. , MORGAN A. G.
Published: March 2008

The number of islets per square centimetre section of post‐mortem pancreas was counted and the intensity of β‐cell granulation (Gomori's aldehyde‐fuchsin stain) assessed in thirteen cases of untreated juvenile diabetes and thirteen matched controls, and in thirteen cases of treated juvenile onset diabetes and thirteen matched controls. The morphology of the islets was studied.

In two cases of untreated diabetics the number of islets overlapped with those of the control series. In the remaining eleven, the number was reduced to an average of about one seventh of the controls. β‐Cell granulation was normal in five cases and markedly reduced in the remainder. Eleven of the thirteen treated diabetics showed a similarly marked reduction in number of islets and loss of β‐granulation. In one case the islets showed marked β‐cell hyperplasia with margination of granules. The remaining case showed marked loss of exocrine parenchyma, diffuse fibrosis and crowded surviving islets rich in β‐cells.

Nuclear pleomorphism and hypertrophy of some islets was slightly more marked in untreated juveniles, dying within a few weeks of onset of the disease, than in matched controls. There were no examples of lymphocytic infiltration of islets. Pancreatic fibrosis was seen much more commonly and was more marked in the diabetics than in the controls. The average weight of pancreas was reduced to 32 g in the treated diabetics, the expected weight being 68 g.

It is suggested that the findings support the hypothesis that juvenile diabetes results from failure of islet cell regeneration in response to injury rather than exhaustion atrophy of overstimulated normal β‐cells, and that this is associated with retardation of growth of the exocrine pancreas.
IODINE METABOLISM IN AUTONOMOUS HOT NODULES OF THE THYROID
Authors: KOUTRAS D. A. , LIVADAS D. , RIGOPOULOS G. A. , SFONTOURIS J. , MALAMOS B.
Published: March 2008

The thyroidal iodide clearance rate, the plasma inorganic iodine (PII), the absolute iodine uptake (AIU) by the thyroid, the serum PBI, the intrathyroidal exchangeable iodine pool, the renal iodide clearance rate and the urinary iodine excretion were measured in twenty‐one cases of autonomous hot thyroid nodule with suppression of the normal parenchyma (toxic adenoma, TA), in eight cases of autonomous hot nodule without such suppression (subtoxic adenoma, STA), and in eighteen controls; the 131 I uptake and PB131 I were measured in 390 cases of TA and 111 of STA compared with eighty‐one controls.

The most striking finding was a greatly reduced pool of intrathyroidal exchangeable iodine in the TA group. This explained the high PB131 I values (out of proportion to the degree of hyperthyroidism) and the short biological half‐life of radioiodine within the gland. There was no evidence of iodine deficiency, either from the PII or the urinary iodine measurements. Otherwise the patients with TA showed evidence of mild hyperfunction: increased 131I uptake, AIU and PBI, but with a considerable overlap with the normal range. The patients with STA had, in general, laboratory values intermediate between the TA group and the controls. The intrathyroidal exchangeable iodine pool was not significantly reduced, probably because in STA the normal parenchyma surrounding the nodule was still actively taking part in the exchange, whereas in the TA the normal parenchyma constituted a practically dormant iodine pool.
FAILURE OF TSH RADIOIMMUNOASSAY TO CONSISTENTLY DETECT MILD TSH MEDIATED THYROID STIMULATION
Authors: KOHLER H. , OPL W. , von MÜHLENEN A. , BÜRGI H. , STUDER H. , ORMSTON B. J. , HALL R.
Published: March 2008

The sensitivity of the radioimmunoassay for serum TSH has been tested against a direct method for assessment of thyroid function. Fifteen healthy euthyroid volunteers received an oral dose of 80 μCi 125I in order to label endogenously produced thyroid hormones. Five days later 20 μCi 131I‐T4 were injected intravenously to serve as an internal reference source of T4 deiodination rate. The TSH response to an oral dose of 3 mg TRH given on two consecutive days was evaluated by radioimmunoassay and by determination of urinary 125/131I ratios.

An increase of the urinary 125/131I ratio of the order of 200% (P<0.01 and P= 0.02) indicated an identical stimulation of the thyroid gland on both days. Following the first dose of TRH the serum TSH the serum TSH level rose by an average of 35% (P<0.05) whereas no change of TSH concentration could be detected on the second day of TRH administration. The findings indicate that mild TSH‐mediated stimulation of the thyroid gland may escape detection by radioimmunoassay of serum TSH concentration. Thus, the sole failure of serum TSH levels to rise by a measurable amount does not at present constitute proof for the autoregulatory nature of an observed change of thyroid function.
SERUM TRIIODOTHYRONINE IN HEALTH AND DISEASE
Authors: PATEL Y. C. , BURGER H. G.
Published: March 2008

Using a double antibody radioimmunoassay (RIA) for the measurement of serum triiodothyronine (T3), the present study was undertaken to define the role of this hormone in normal and abnormal thyroid states. Other tests of thyroid function performed included measurement of serum thyroid stimulating hormone (TSH, euthyroid range <0.2‐3.6 μU/ml by RIA) and free thyroxine index (FTI, 4.6‐10.0).

In forty‐six normal subjects (aged 18‐40 years) serum T3 ranged from 75 to 177 with a mean value of 128 ng/100 ml. This differed significantly (P<0.01) from that of the mean T3 level of nine subjects taking oral contraceptives (174 ng/100 ml). The administration of 200 μg i.v. synthetic thyrotrophin releasing hormone to six normal subjects produced a significant serum T3 elevation in all with a mean increase at 120 min of 56%. Serum T3 values in hyperthyroidism were as follows: diffuse goitre (n= 14, mean 600 ng/100 ml, range 290‐1150); multinodular goitre (n= 8, mean 283, range 179‐440); Solitary nodule (n= 4, mean 258, range 195‐305): T3‐toxicosis (n= 2, mean 262). There was no overlap with the normal range. Twenty patients with severe primary hypothyroidism (FTI 0.2‐4.3, serum TSH 83‐1546 μU/ml) had a mean serum T3 level of 42 ng/100 ml. Eighteen patients were studied following drug or radioiodine treatment of thyrotoxicosis. All were clinically euthyroid but had elevated serum TSH (6.0‐84 μU/ml). Serum T3 in this group was normal (87‐185 ng/100 ml) whereas T4 was low in eleven. It is concluded that serum T3 measurements provide a reliable index of thyroid function, facilitate the diagnosis of T3‐toxicosis and correlate with the clinical status during and after treatment of thyrotoxicosis in a more appropriate manner than do T4 measurements which may be misleading.
SUPPRESSION OF PLASMA ACTH LEVELS WITH CORTICOSTEROIDS IN ADDISON'S DISEASE
Authors: HOLDAWAY I. M.
Published: March 2008

Following intravenous injection of a pharmacological dose of dexamethasone, there was a prompt fall in both C‐terminal and N‐terminal plasma immunoreactive ACTH levels in nineteen subjects with Addison's disease. Intravenous infusion of cortisol, sufficient to give physiological plasma levels in three of these subjects, induced a fall in plasma C‐terminal immunoreactive ACTH concentration only when plasma corticosteroid levels exceeded 20–25 μg/IOO ml. Thus although negative feedback control of ACTH secretion was still operative in these subjects, it seems likely that this mechanism of ACTH regulation had diminished sensitivity compared with that found by other workers in normal individuals.
PRODUCTION OF A CORTICOTROPHIN‐LIKE INTERMEDIATE LOBE PEPTIDE AND OF CORTICOTROPHIN BY A BRONCHIAL CARCINOID TUMOUR
Authors: RATCLIFFE J. G. , SCOTT A. P. , BENNETT H. P. J. , LOWRY P. J. , McMARTIN C. , STRONG J. A. , WALBAUM P. R.
Published: March 2008

The isolation and partial characterization of a peptide with C‐terminal corticotrophic immunoactivity from a bronchial carcinoid tumour associated with the ectopic ACTH syndrome is described. It resembles corticotrophin‐like intermediate lobe peptide (CLIP) in amino acid composition and end group analyses. It is suggested that the specific measurement of circulating CLIP may serve as a biochemical marker of tumour activity.
THE TRIIODOTHYRONINE AND THYROXINE RESPONSE TO THYROTROPHIN‐RELEASING HORMONE IN THE ASSESSMENT OF THE PITUITARY‐THYROID AXIS
Authors: LAWTON N. F. , ELLIS S. M. , SUFI S.
Published: March 2008

The thyroidal component of the response to thyrotrophin releasing hormone (TRH) has been studied by measurement of serum triiodothyronine (T3) and thyroxine (T4).

In normal subjects a significant increase in serum T3 followed intravenous administration of TRH 200 μg. A less consistent increase was detected in serum T4 concentration.

Oral TRH at a dose of 40 mg caused a significant rise in serum T4 in normal subjects. The increase in T4 at 24 hr was considered to provide a convenient index of pituitary and thyroidal response.

Fourteen patients with pituitary disease, of whom twelve were euthyroid, were investigated by an oral TRH test. The majority of these patients retain a normal pituitary TSH reserve though a small group can be identified in whom it is diminished.

A significant correlation was obtained between the T4 and TSH response to oral TRH. It is suggested that measurement of serum concentration of thyroid hormone is of value in the assessment of the pituitary response to TRH and the integrity of the pituitary‐thyroid axis.
TRIIODOTHYRONINE
Authors: HOFFENBERG R.
Published: March 2008

After 20 years in the wilderness, 3,5,3′‐triiodo‐l‐thyronine (T3) has come back home, for it is exactly 20 years since Gross & Pitt‐Rivers (1952) first drew attention to its presence in human serum. A few years later Pitt‐Rivers et al. (1955) demonstrated its formation from thyroxine (T4) given to patients with athyreotic myxoedema, and in 1957 Maclagen et al. reported thyrotoxicosis with elevated plasma concentration of T3 and normal concentration of T4‐the first identifiable instance of what is now referred to as ‘T3 toxicosis’. Despite these early suggestions of significant physiological and pathological contributions, T3 was regarded as a minor and unimportant iodinated compound until the development of an improved biochemical assay (Sterling et al., 1969) paved the way for wider recognition of its role in health and disease and stimulated the development of a sensitive and dependable radioimmunoassay. In the past few years information about the action, metabolism and clinical significance of T3 has rapidly accrued; this review attempts to put together some of this new and exciting information. Because methods for the assay of T3 in biological fluids have only recently been introduced, the validity of the various techniques will be considered first.
CIRCULATING LEVELS OF PROLACTIN DURING THE MENSTRUAL CYCLE
Authors: McNEILLY A. S. , CHARD T.
Published: March 2008

In detailed studies on seventeen volunteers, it has been shown that changes in prolactin levels during the menstrual cycle are irregular and inconsistent. Some, but not all, subjects have elevated levels at mid‐cycle, and higher levels in the luteal phase than in the follicular phase. At all stages of the cycle, prolactin levels may show short‐term random fluctuations of as much as 110%. There was no apparent relation between levels of prolactin and those of LH, FSH, oestradiol‐17β or progesterone. It is suggested that if prolactin has any role in the control of the menstrual cycle, then the normal circulating levels are considerably in excess of the threshold requirements for its action.
SUCCESSFUL TREATMENT OF GALACTORRHOEA AND AMENORRHOEA AND SUBSEQUENT RESTORATION OF OVARIAN FUNCTION BY A NEW ERGOT ALKALOID 2‐BROM‐α‐ERGOCRYPTINE
Authors: ROLLAND RUNE , SCHELLEKENS LOUIS A. , LEQUIN RUDOLF M.
Published: March 2008

Three patients with galactorrhoea and menstrual disturbances, due to hyperprolactinaemia and of more than 2 years duration, are described. Administration of 2‐Brom‐α‐ergocryptine effectively lowered the plasma prolactin concentrations in all three patients and restored the normal cyclic ovarian activity. One pregnancy was noticed during therapy. The role of prolactin on ovarian function is discussed. 2‐Brom‐α‐ergocryptine seems to be an effective drug in the long‐term treatment of galactorrhoea associated with menstrual disturbances.
LONG‐TERM ADMINISTRATION OF MEDROXY‐PROGESTERONE ACETATE (MPA) TO ACROMEGALIC PATIENTS
Authors: JOSEFSBERG Z. , LARON Z. , MATHIAS Sh. , KERET R.
Published: March 2008

The long‐term administration of medroxyprogesterone acetate (MPA), 40 mg/day, has not proved to be an effective treatment of acromegaly. It neither stops the growth of the tumour nor adequately suppresses growth hormone secretion and it brings no change in the glucose intolerance and hyperinsulinism.
PLASMA CORTICOTROPHIN LEVELS DURING INSULIN‐HYPOGLYCAEMIA : COMPARISON OF RADIOIMMUNOASSAY AND CYTOCHEMICAL BIOASSAY
Authors: FLEISHER M. R. , GLASS D. , BITENSKY LUCILLE , CHAYEN J. , DALY J. R.
Published: March 2008

Development of a highly sensitive bioassay for ACTH has enabled bioassayable ACTH to be measured in plasma during the course of the insulin hypoglycaemia test for the first time. Comparison with radioimmunoassay (RIA) on the same plasma samples shows that the latter consistently overstimates the true, or biologically active, ACTH level. This overstimate appears to be most marked when ACTH levels are highest and during the fall in plasma levels which occurs following the ACTH peak. This may limit the value of the RIA of ACTH, in some situations.
THE PATHOGENESIS OF GRAVES' DISEASE AND HASHIMOTO'S THYROIDITIS
Authors: VOLPÉ ROBERT , FARID NADIR R. , VON WESTARP CHRISTIAN , ROW VAS V.
Published: March 2008

It is about 150 years since the publication of the original descriptions of the disorder now termed Graves' disease (toxic diffuse goitre, exophthalmic goitre, Von Basedow's disease) (Parry, 1825; Graves, 1835; Von Basedow, 1840) and over 60 years since Hashimoto's thyroiditis (struma lymphomatosa) was first described (Hashimoto, 1912). However, until the past 15 years, there was little understanding of possible pathogenic mechanisms in these disorders. At the present time, notwithstanding several persistent points of contention and gaps in our knowledge, it appears that Grave's disease and Hashimoto's thyroiditis are most probably closely related primary immunological disorders.
THE MEASUREMENT OF TESTOSTERONE IN PLASMA
Authors: WILLIAMS B. M. , WILLIAMS B. M. , HORTH C. E. , PALMER R. F.
Published: March 2008

A simplified radioimmunoassay is described for routine determination of testosterone in plasma, using antiserum to a testosterone‐3‐conjugate, and 3H‐testosterone as the sole radio‐ligand. The method avoids chromatography by using the plasma sex‐steroid binding globulins to effect a partial purification. The radioimmunological method is compared with a specific, chromatographic, competitive protein binding method. Testosterone concentrations in normal subjects are 7.84±2.38 (SD) ng/ml in men, and 0.81±0.17 (SD) ng/ml in women.
DISAPPEARANCE OF LH‐RELEASING HORMONE IN MAN AS DETERMINED BY RADIOIMMUNOASSAY
Authors: ARIMURA AKIRA , KASTIN ABBA J. , GONZALEZ‐BARCENA D. , SILLER JORGE , WEAVER ROBERT E. , SCHALLY ANDREW V.
Published: March 2008

The disappearance of LH‐releasing hormone (LH‐RH) administered i.v. together with inulin was measured by radioimmunoassay. The half‐time disappearance of 3.6 min for LH‐RH was significantly shorter than the half‐time of 14.2 min found for the inulin. On the assumption that diffusion and distribution into the extracellular space and excretion are quantitatively similar for LH‐RH and inulin, the part of the half‐life of LH‐RH due to metabolic breakdown can be calculated to be about 4.8 min. Peak LH and FSH values were found to occur later. The results suggest that most of the immunoreactive LH‐RH is no longer present in the blood at the time of maximal gonadotropin release and that this is because of rapid metabolism as well as diffusion and excretion.
SALIVARY GLAND ENLARGEMENT IN ACROMEGALY
Authors: THOMSON JOHN A. , McCROSSAN JOHN , MASON DAVID K.
Published: March 2008

Three patients with active acromegaly and salivary gland enlargement are described. Detailed studies of flow rate, the biochemistry of the saliva from both the parotid and submandibular salivary glands, sialography and isotope scanning of the glands showed no significant abnormality in function. The literature is reviewed and it would appear that enlargement of the submandibular salivary glands in acromegaly is a relatively common clinical finding although it is not widely known.
EPISODIC SECRETION OF ALDOSTERONE IN PRIMARY ALDOSTERONISM: RELATIONSHIP TO CORTISOL
Authors: VETTER H. , BERGER M. , ARMBRUSTER H. , SIEGENTHALER W. , WERNING C. , VETTER W.
Published: March 2008

Plasma aldosterone, plasma cortisol and plasma renin activity were determined at short time intervals in three supine patients suffering from primary aldosteronism. The patients were studied both under normal conditions and during suppression of ACTH secretion by dexamethasone. Though abnormally high levels were found, aldosterone was secreted episodically in each patient while plasma renin activity was uniformly undetectable. In each patient the secretory episodes of aldosterone were paralleled by those of cortisol indicating that physiological variations in ACTH secretion markedly altered the secretion of aldosterone. The assumption that ACTH played an important role in the regulation of aldosterone secretion in primary aldosteronism was strengthened by the observation that, contrary to normal controls, dexamethasone produced a significant decrease in plasma aldosterone concentrations and that during suppression of ACTH secretion no secretory episodes of aldosterone were observed.
EFFECT OF ORAL THYROTROPHIN‐RELEASING HORMONE ON SERUM THYROXINE IN GROWTH HORMONE DEFICIENT AND NORMAL CHILDREN
Authors: ZUPPINGER K. A. , JOSS E. E. , KÖNIG M. P. , STAUB J. J. , GIRARD J. , EHRENGRUBER H.
Published: March 2008

Oral administration of synthetic TRH in a dose of 80 mg/1.73 m2 at 0 and 12 h to normal and constitutionally small children caused a significant increase of total serum thyroxine (T4) within 6–24 h. The mean maximal T4 increment was + 3.7 ± 1.1 and + 3.8 ± 1.2 μg/dl (mean ± 1 SD) respectively in the two groups. Of seventeen euthyroid GH deficient children, fifteen showed a normal and two patients a slightly subnormal response. Of fifteen hypothyroid GH deficient children nine had a prompt and normal increase of serum T4 indicating primary TRH deficiency. Two had a delayed T4 response and four had no response, even after prolonged stimulation. The localization of the primary defect in these latter subjects with severe hypothyroidism can not be made by measuring T4 only, since the thyroid gland may become unresponsive to TSH after longstanding TSH deficiency. TSH measurements are necessary in these circumstances for a clear localization of the primary defect. One GH deficient patient with hypothalamic TRH deficiency was treated with high oral TRH doses for 7 months and showed no side effects.
THE EFFECT OF YTTRIUM‐90 IMPLANTATION ON ENDOCRINE FUNCTION AND VISUAL FIELDS IN PATIENTS WITH ‘FUNCTIONLESS’ PITUITARY TUMOURS, WITH BIOPSY AND RADIOLOGICAL FINDINGS
Authors: JOPLIN G. F. , JACKSON R. A. , ARNOT R. N. , BURKE C. W. , DOYLE F. H. , HARSOULIS P. , LEWIS P. D. , MACERLEAN D. P. , MARSHALL J. C. , VAN NOORDEN S. , FRASER T. RUSSELL
Published: March 2008

Thirty patients with symptoms from ‘functionless’* pituitary tumours were treated by yttrium‐90 implants, and we report here the effects on symptoms, pituitary function and visual fields. On biopsy, about a third of the tumours showed some hormone granules. In the sixteen fully assessed at 1 year, pituitary function was improved in 25%, unchanged in 62.5%, and reduced in 12.5%. Improvement was confined to those in whom gonadotrophin secretion was the only function impaired pre‐implant.

Visual field defects were present pre‐implant in ten patients (twenty eyes); at 1 year post‐implant these defects had lessened in 80% and deteriorated in only 5% of eyes. Subsequently, within 5 years of the implant the field defects had worsened or recurred in four patients, all with initially extensive suprasellar projection; further treatment was then given. Remineralization of the sella was seen after implantation in seven cases, with reduction in fossa size in five.

Thus pituitary implantation appears to be a practicable and reasonably simple procedure suitable for the treatment of most cases of ‘functionless’ pituitary tumour. The ‘supressive’ doses of irradiation used are adequate to shrink most tumours without loss of pituitary function.
A RAPID 5 HOUR RADIOIMMUNOASSAY OF PROGESTERONE AND OESTRADIOL IN HUMAN PLASMA
Authors: ASO T. , GUERRERO R. , CEKAN Z. , DICZFALUSY E.
Published: March 2008

A rapid 5 h radioimmunoassay method for the determination of progesterone and oestradiol in the plasma of non‐pregnant women is described. Due to the high specificity of the antisera used, it is possible to perform the radioimmunoassay directly on the ether extracts of plasma, without employing chromatographic purification of the steroids.

Evidence is presented indicating that the rapid assay is almost as reliable as the previously described radioimmunoassay method which involves chromatography. The within‐assay and between‐assay coefficients of variation in the progesterone assay were 7.74 and 14.9 and in the oestradiol assay 7.36 and 18.1 respectively. Comparisons between increasing doses of authentic hormone and endogenous hormone extracted from plasma indicated no deviation from parallelism. Progesterone and oestradiol were assayed in 300 plasma samples by the rapid method and by the method involving chromatography. The slopes obtained by a regression analysis were close to unity for both progesterone and oestradiol (1.04 and 1.06, respectively), the y‐intercepts were −0.21 and −0.16 and the correlation coefficients 0.98 and 0.88, respectively. When the data obtained by both techniques in fourteen menstrual cycles were compared, the results were practically identical.

In ten repeated studies conducted by four investigators it was shown that two workers can complete the assay of both progesterone and oestradiol in twentyfive plasma samples in duplicates within 5 h. The same time is required for the assay of either progesterone or oestradiol in twenty‐five duplicates by one worker.
SERUM TRIIODOTHYRONINE CONCENTRATION IN THE DIAGNOSIS OF HYPERTHYROIDISM
Authors: MARSDEN P. , McKERRON C. G.
Published: March 2008

The serum triiodothyronine concentration is superior to the serum thyroxine concentration, the resin uptake test and the free thyroxine index in the diagnosis of hyperthyroidism.

Over a 14 month period fifty‐five patients attending an endocrine clinic with suspected thyrotoxicosis of all degrees of severity had blood taken on initial attendance and the serum was stored for routine thyroid function tests and triiodothyronine estimation. The patients were followed up and forty‐six proved to be toxic and seven to be euthyroid; two could not be classified. Analysis of the initial serum showed that the serum triiodothyronine concentration was superior to the serum thyroxine concentration, the resin uptake test and the free thyroxine index in predicting the clinical outcome.
INDICES OF GONADAL FUNCTION IN THE HUMAN MALE
Authors: PURVIS K. , BRENNER P. F. , LANDGREN B.‐M. , CEKAN Z. , DICZFALUSY E.
Published: March 2008

A radioimmunoassay technique for the simultaneous measurement of eight unconjugated steroids (progesterone, pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotesterone, oestrone and oestradiol) in the peripheral plasma of human males is described. Determinations of these steroids and of immunoreactive FSH and LH were carried out on the plasma of twentyone normal individuals and the levels were compared to those of eleven and ten males exhibiting oligospermia and azoospermia, respectively.

Mean values and tolerance limits for each hormone, based on a lognormal distribution of individual values, are presented for all groups.

Oligospermia was associated with a significant reduction in plasma dihydrotestosterone and testosterone levels. Azoospermic subjects also exhibited decreased dihydrotestosterone levels but a normal range of testosterone concentrations. Mean peripheral plasma levels of FSH were significantly elevated in both pathological groups and this was paralleled in the azoospermic men by increased concentrations of plasma LH.
INDICES OF GONADAL FUNCTION IN THE HUMAN MALE
Authors: PURVIS K. , LANDGREN B.‐M. , CEKAN Z. , DICZFALUSY E.
Published: March 2008

A radioimmunoassay method developed previously for the measurement of unconjugated pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone and oestradiol in peripheral plasma was applied to the assay of these steroids in seminal plasma of normal, oligospermic and azoospermic males. It was not possible to use the plasma assay method for the determination of progesterone and oestrone in seminal plasma, because some of the reliability criteria were not fulfilled.

A detailed analysis of these steroids in the peripheral plasma of the same subjects has been described previously. The levels of all steroids in seminal plasma were significantly lower than the corresponding blood levels. The ratios of blood plasma/seminal plasma levels of the various steroids varied from 37 (testosterone) to 1.7 (dihydrotestosterone). There was a positive correlation between the testosterone and dihydrotestosterone levels of the seminal plasma of normal and azoospermic subjects. The concentrations of dihydrotestosterone, pregnenolone and oestradiol were significantly lower in azoospermic subjects than in normals. The only pathological finding in the seminal plasma of oligospermic subjects was a diminished level of dihydrotestosterone.

Enzymic hydrolysis of a seminal plasma pool resulted in a 3‐ to 8‐fold increase in the concentration of pregnenolone, dehydroepiandrosterone, testosterone, dihydrotestosterone and oestradiol, indicating that human seminal plasma contains large amounts of steroid conjugates.

It is suggested that the analysis of steroids in the seminal plasma in combination with determinations in peripheral plasma may be a valuable aid to the assessment of testicular function.
COMPARISON OF THE EFFECT OF APOMORPHINE AND l‐DOPA ON SERUM GROWTH HORMONE LEVELS IN NORMAL MEN
Authors: LAL SAMARTHJI , MARTIN JOSEPH B. , DE LA VEGA CHARLES E. , FRIESEN HENRY G.
Published: March 2008

Apomorphine hydrochloride (0.75 mg s.c.) has been compared with l‐dopa (500 mg p.o.) in their effects on growth hormone secretion in a double blind cross‐over study involving nine healthy men. Apomorphine increased serum GH levels above 10 ng/ml in all nine subjects 30–60 min after injection. In contrast, only six of these subjects showed a similar elevation with l‐dopa and in only three had the level increased above 6 ng/ml by 60 min. One subject failed to respond to l‐dopa and in two others the peak was less than 6 ng/ml. GH levels were significantly higher at 30, 45 and 60 min following apomorphine than following l‐dopa. Apomorphine‐induced GH release was not related to changes in serum cortisol or blood sugar. Benztropine mesylate (1 mg i.m.) had no effect on apomorphine‐induced GH release. These results suggest: (a) apomorphine may have advantages over l‐dopa as a provocative agent to assess GH secretory capacity; (b) a dopaminergic mechanism subserves GH secretion; (c) cholinergic mechanisms do not antagonize dopaminergic‐related GH release.