摘要:

SummaryIn order to directly evaluate the role of parathyroid hormone (PTH) and Its Interaction with oestrogens for postmenopausal bone loss, studies were performed where synthetic human (1–38) PTH was Infused s.c. over 24 h in 15 healthy females. Measurements were made of serum electrolytes, PTH and biochemical Indices of bone turnover: serum osteocalcin and alkallne phosphatase and fasting urinary hydroxyproline and calcium.During the Infusion of PTH there were significant Increases of serum calcium (15%), fasting urinary calcium (55%) and hydroxyproline (80%) but a reduction of the serum osteocalcin concentrations (15%). There were significant relations between the calcaemic response and the Increases of urinary calcium and hydroxyproline and the two latter were also closely related. There was, however, no correlation between the responses to PTH for the formative vs the resorptive indices.Postmenopausal women displayed greater increases of serum calcium and fasting urinary hydroxyproline indicating greater skeletal sensitivity to exogenous PTH. Follow ing treatment with oestrogens the indices of skeletal responsiveness were reversed towards the premenopausal values.The findings demonstrate that during short‐term infusion of PTH there Is a dissociation between bone resorptlon and formation and, furthermore, that the menopause is associated with an enhanced skeletal sensitivity for

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00302.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryTo determine the effect of androgen Insensitivity on cognitive abilities, subjects with the syndrome of complete androgen Insensitivity (Al) were compared to control males and females from the same kindred on the Spanish version of the Wechsler Adult Intelligence Scale (WAIS). All subjects had similar sociocultural backgrounds and only right‐handed subjects were used In the primary analysis. This design was chosen to diminish the effect of critical variables on test performance, thereby highlighting the effect of androgen unresponslveness on cognition.The results indicated that control males and females were superior to androgen Insensitive subjects on the Perceptual Organization factor, which Included five visuospatlal subtests. Separate analysis of these subtests revealed that males performed significantly better than females on Block Design, Picture Completion, and Object Assembly, and better than androgen Insensitive subjects on all five subtests. Females were superior to androgen Insensitive subjects on four subtests (Block Design, Picture Completion, Digit Symbol, and Picture Arrangement). Despite the small sample size, when female siblings were compared to their Al sisters, they were also superior on these four visuospatlal subtests.The difference between the Verbal Comprehension and Perceptual Organization factors was greatest In androgen‐insensitive subjects, while control males demonstrated the least difference.Females and Al subjects did not differ from one another on the Freedom from Distractlblllty factor nor on the subtests comprising it, but their performances were poorer than control males.None of the groups differed significantly on Full Scale IQ, Verbal IQ, the Verbal Comprehension factor, or any subtests Included In this category.These data Indicate that Al subjects differ from normal males and normal females on subtests relating to visuospatial ability, and suggest that androgens play a role In the development of spatial ability In hum

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00303.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryThe present study was conducted to evaluate effects of autoantlbodles In patients with Graves’ disease on Induction of c‐fos and c‐myc mRNA expression In rat thyroid cell line (FRTL5). IgG fractions were Isolated from 11 patients with Graves’ disease, and six healthy subjects, with protein A‐Sepharose. FRTL5 cells which had been grown to subconfluency and deprived of TSH for a week were exposed to the IgG for an hour. Expression of c‐fos and c‐myc mRNAs was examined by the Northern blot method using nick‐translated v‐fos and c‐myc probes. C‐fos and c‐myc transcripts were Induced by IgGs from two patients with Graves’ disease, which displayed much higher activities In assays for TSH binding Inhibitor Immuno‐globullns, thyroid stimulating antibodies and thyroid growth‐stimulating Immunoglobullns, assessed by measuring Inhibition of125I‐TSH binding to the TSH‐receptor, cAMP production and3H‐thymldine Incorporation In FRTL5 cells, respectively, compared with those In the remaining patients. The Induction of c‐fos and c‐myc mRNAs by IgG from a patient with Graves’ disease was suppressed by prelncubatlon with IgGs from two patients with primary myxoedema who were known to have a blocking type TSH‐receptor antibody. These data suggest that the binding of the antibodies to the TSH–receptor followed by cAMP production Is related to the induction of c‐fos and c‐myc mRNAs and, thus, to the growth of FRTL5 cells. To our knowledge, this Is the first report demonstrating that aut

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00304.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryThis study has considered the effects of primary affective disorders and lithium therapy on a number of factors thought to be Important In the development of autoimmune thyroid disease. These factors were examined In (a) controls with no history of any such disorders; (b) patients with primary affective disorders treated with drugs other than lithium and (c) patients with primary affective disorders treated with lithium alone.Eight of 40 patients who were receiving lithium therapy were found to be positive for thyroid microsomal and/or thyroglobulin antibodies, compared to only 3/40 patients who were receiving some other form of treatment for their depression. Peripheral blood mononuclear ceils from patients receiving lithium were found to have significantly reduced numbers of suppressor/cytotoxlc T cells (p>0.05). In addition, suppressor T cells from these patients showed a significantly reduced response to stimulation with concanavalin A (p>0.01). These effects were greatest In patients found to be antibody positive. Increased B cell activity, as measured by Increased IgG and IgM release following mltogen stimulation, was seen in patients receiving lithium and in those patients receiving other forms of treatment for their depression. This would suggest that the Increase Is a feature of primary affective disorders and is not due specifically to lithium treatment. It would appear from this study that lithium therapy induces antibody formation In susceptible Individuals and this may ultimately lead to the development of thyroid disease.

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00305.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryFifteen patients with primary aldosteronism were classified as anglotensin II‐unresponsive aldosterone‐producing adenoma (All‐U APA, n = 9), or anglotensin II‐responsive aldosterone‐producing adenoma (All‐R APA,n= 6), based on the responsiveness of aldosterone to upright posture and to anglotensin II infusion. Lack of aldosterone response to anglotensin II Infusion immediately post‐operatively In the All‐R APA subtype was consistent with previous responsiveness residing solely within the adenoma. Cortisol levels In five of the six patients with All‐R APA failed to suppress normally with dexamethasone consistent with some autonomous production of cortisol by the adenoma. In contrast, cortisol levels suppressed normally during dexamethasone administration In all patients with All‐U APA. This biochemical distinction can be added to the previously described overproduction of 18‐oxo cortisol in All‐U APA but not in All‐R APA. Histological examination of adenoma sections revealed predominantly (±‐50%) zone fascicuiata type cells in All‐U APA. In contrast, All‐R APA contained less than 20% zona fasciculata type. Thus, biochemical differences between All‐U APA and All‐R APA subtypes of primary aldosteronism may be due to underlying differences In cellular composition o

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00306.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryA comparison was made between the pulsatile pattern of growth hormone secretion In 14 growth hormone deficient adults (serum growth hormone less than 7 mU/l following insulin‐stimulated hypoglycaemia) and 14 age and sex matched controls. The 24‐h secretory profile was generated by 2‐hourly sampling from 0800 to 2200 h, and 30‐min sampling from 2200 to 0600 h. Plasma GH in each sample was measured using a double antibody radloimmunoassay. The profiles were analysed using a computer program (Pulsar). Sleep‐electroencephalography was recorded In all subjects. The total amount of GH secreted In a 24‐h period (area under the curve over baseline) was significantly less In the growth hormone deficient group (P>0·002). The pulse frequency, amplitude, height and percentage GH secreted in peaks were also significantly less in the growth hormone deficient group (P>0± 002 respectively). We conclude that adults deficient In GH, as defined by conventional pharmacological stimuli, are in addition physiologically deficient of pulsatile

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00307.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryIn order to study the mechanism of GH secretion from somatotroph adenoma cells, we have compared the effect of 12–O‐tetradecanoyl phorboi‐13‐acetate (TPA) with that of growth hormone releasing factor (GRF) on GH secretion from human somatotroph adenoma cells cultured in monolayer. Pituitary adenoma cells were obtained from 13 patients with acromegaly undergoing surgery. On the 7th day of culture, the cells were exposed for 2 h to secretagogues. All 13 adenoma cell cultures (100%) responded to TPA (1·6–16·0 nmol/I) with a two‐ to six‐fold increase in GH release (240·37% Increase of control: mean±SE). The response was detectable within 10 min, and was maximal at 2 h. Phosphollpase C (7·7 mmol/I) also stimulated a two‐to ten‐fold Increase In GH release in all four adenomas examined (100%). GH release was stimulated by GRF (2·0 nmol/I) in eight out of 12 adenoma cells (67%), but the magnitude of the responses to GRF (60·18% Increase of control: mean ± SE) were much smaller than that of TPA. Five out of 13 adenomas secreted detectable amount of PRL Into the medium and these five adenomas (100%) responded to TPA (16·0 nmol/I) with a two‐ to six‐fold Increase. These observations indicate that the activation of protein kinase C is the consistent stimulator in GH and PRL secretion In human somatotroph adenoma cells. However, It is not determin

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00308.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryThere Is disagreement over the HLA‐DR associations of Hashimoto's (goitrous) thyroiditis. We have studied 86 English Caucasian patients with this condition whose DR types were determined by restriction fragment polymorphism analysis. HLA‐DR3 was significantly more frequent In these patients than in 100 controls (χ2= 7·09;P>0·01). The relative risk was 2·23 and aetiological fraction 0·29. HLA‐DPB and DOB alleles were analysed in a proportion of these subjects by enzymatic DNA amplification and oligonucleotide probing. The only significant finding was an excess of HLA‐DQw2 (In linkage disequllibrium with DR3) In the Hashimoto group (χ2=7·43,P>0·007). These results do not support a difference between goitrous and atrophic thyroiditis based on respective associations with HLA‐DR5 and DR3, but confirm a recent study in which HLA‐DR3 was associated with Hashimoto's thyroiditis. However, It Is possible that genes telomeric to DR3 may be Involved in determining which type of thyroiditis a patient with autoimmune hypo

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00309.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryPTH and calcitonln are the two major hormones controlling calcium metabolism. Recently two new substances related to these hormones have been Isolated: calcitonln gene related peptide (CGRP) and PTH‐related protein (PTHrP). CGRP Is a potent vasodilator and stimulant of intestinal secretion while PTHrP Is probably the agent responsible for humoral hypercalcaemla of malignancy. We report here a patient with a prostatlc tumour presenting with vasodilatlon, diarrhoea and hypercalcaemia. Our investigations revealed that the primary prostatic and liver secondary tumour contained CGRP, calcitonln and PTHrP. Most of the immunoreactive CGRP in the tumour and plasma co‐eluted with the biologically active form of CGRP. The circulating levels of CGRP correlated with the presence of the diarrhoea. PTHrP concentration In the tumours was one of the highest reported for any tumour although previous studies may have utilized less than optimal extraction procedures. The somatostatin analogue, octreotide (SMS 201–995), did not reduce the plasma CGRP or the diarrhoea, a finding similar to that seen in patients with medullary thyroid carcinoma and high plasma CGRP. The hypercalcaemla was also unaffected by octreotide administration. This is the first report of a prostatic tumour associated with over‐production of calcltonin, PTHrP and CGRP. The major life‐threatening effects of this unusual case of prostatic carcinoma were diarrhoea and hypercalcaemia. Both these effects could be tentatively ascribed to newly discovered substances, CGRP and PTHrP. With the greater availability of assays to measure CGRP and PTHrP in plasma, a detailed examination of the incidence of over‐production of these substances In various cancers will

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00310.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SummaryTwo patients developed specific IgG antibodies against octreotide after 2–3 years’ treatment for acromegaly with this long acting somatostatln analogue. The presence of these antibodies reduced the plasma disappearance rate of total extractable octreotide by 60 and 80% respectively. When compared to that of non‐Immune acromegalic patients, the plasma half‐life of octreotide in these two patients was 300 and 450 vs 110 min in those with no detectable octreotide antibodies. The sole observed con‐sequence of the immunization was a marked prolongation of the Interval of maximum GH Inhibition from a mean of 5 to 8 and 10 h in the two patients described after octreotide

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00311.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY