摘要:

SUMMARYWe have studied a family with an autosomai dominant Inheritance of primary localized cutaneous amyloidosis (PLCA) and familial medullary thyroid carcinoma (MTC). Ten family members were screened for multiple endocrine neoplasia (MEN) 2; five were found to have MTC and two had C‐cell hyperplasia. None had evidence of phaeochromocytoma or parathyroid abnormalities. Five of these seven patients presented characteristic inter‐scapular hyperpigmented lesions, showing dermal amylold deposits In two of the four patients In which a biopsy was performed. The data are analysed In the light of two recent reports of MEN 2A associated with Identical lesions. We conclude that PLCA should be sought in MTC patients, even If no other endocrinopathies are present. This may be Informative of the familial character of MTC in Index cases and also of the tumour gene status in family members who are being scre

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00322.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYA depressed chemotactic responsiveness of monocytes and a depressed cluster capability of dendritic cells have been found in diseases such as chronic purulent Infections of the respiratory tract and In various types of malignancies. These Impairments in monocyte and dendritic cell function could be ascribed to the action of a low molecular weight factor (LMWF;>25 kDa) circulating In the serum of the patients. The factor, which seems to be a non‐specific Immunoregulatory factor, shares a structural homology with p15E, the capsular protein of murine and feline leukaemogenlc retroviruses. In order to study the chemotactic responsiveness of monocytes and the cluster capability of dendrltic cells of Graves’ patients, monocytes were Isolated from the peripheral blood and dendritlc cells were prepared from these peripheral blood monocytes by exposure to metrizamide. Monocytes were studied for their chemotactic responsiveness measuring their capability to polarize (morphological changes determined by light microscopy) after stimulation with the chemoattractant fMLP. Dendritic cells were studied for their capability to form clusters with allogenelc lymphocytes. A defective fMLP‐Induced monocyte polarization was found (16vs37% In healthy controls), whereas the dendrltic cells showed a defective clustering (60 clusters vs 151 clusters in healthy controls). The effect of fractions of>25kDa prepared from the serum of Graves’ patients on healthy donor monocytes and dendritic cells was studied to test the presence of p15E‐like factors. The serum fractions had a significant inhibitory effect on monocyte polarization and dendrltlc cell clustering. A mixture of two monoclonal antibodies directed against p15E was able to neutralize these suppressive effects. The relationship of this p15E‐like factor occurring In the serum of Graves’ patients to the recently reported genomic expression of retroviral sequences in thyrocytes/leucocytes of Obese Strain chickens and Graves’ patients (ev 22, HIV gag) needs furthe

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00323.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYThe availability of a new specific anti 5HT–2 compound, ritanserin (RTS), led us to further investigate the role of serotonin in controlling PRL secretion. The drug was administered to normoprolactinaemic subjects and to patients with differing hyperprolactinaemic conditions. While RTS failed to modify PRL levels in normoprolactinaemic subjects and in patients with PRL‐secreting pituitary adenomas, a marked decrease in the hormone was obtained in patients with functional and puerperal hyperprolactinaemia. The lack of effect of RTS in PRL‐secreting pituitary adenomas suggests that the reported suppression of PRL by other antiserotoninergic drugs, such as metergoline, is probably due to their concomitant dopamlnergic ac

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00324.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYobjectiveTo study the reproducibility of 24‐h serum growth hormone (GH) concentration profiles in adults. DESIGN 24‐h serum GH concentrations were constructed by drawing blood samples at 20‐min Intervals. Four study occasions over a period of 1 year were chosen to assess the reproducibilitysubjectsSix healthy adult male volunteers of normal height and weight and aged between 20 and 22 years. MEASURES The resulting GH data arrays were analysed by Fourier transformation. Between and within individual variations were calculated and expressed in terms of coefficients of variation and data plotted to show variations between groups and individualsresultsThe frequency component of GH secretion occurred with a dominant periodicity of between 160 and 240 min. Precise estimates of spectral power (strength of oscillatory activity) and period were obtained for group data, but such estimates cannot be inferred from a single profile. There was no significant difference in 24‐h mean serum GH concentration over the year of study: occasion 1 (February) mean 2·0 mU/l (SD 0·5); occasion 2 (March) mean 3·7 mU/l (SD 2·8); occasion 3 (July) mean 2·7 mU/l (SD 1·4); occasion 4 (February) 2·5 mU/l (SD 1·5) (mean within individual coefficient of variation 35%, range 9–58). The concentrations of factors known to influence GH synthesis and secretion, insulin‐like growth factor I, thyroxine, testosterone and oestradiol, varied little over the year of studyconclusionsThese data demonstrate that group data are reproducible in terms of oscillatory activity and the amount of GH secreted and that 24‐h GH profiles should be used predominantly for analysing group data. The varlabllity between individual profiles limits their value in the investigation of children with growth failure and susp

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00325.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYobjectiveThe aim was to investigate the serum levels of growth hormone releasing hormone and GH in patients with lung carcinomadesignAfter an overnight fast a plasma sample was collected for determination of growth hormone releasing hormone and GHpatientsThe investigation was performed in 28 patients with non small cell lung carcinoma, in 44 patients with small cell lung carcinoma, and 10 patients with non malignant lung disease. A group of 37 normal subjects served as controlmeasurementsGrowth hormone releasing hormone and GH were determined by radloimmunoassayresultsPatients with small cell lung carcinoma showed higher plasma growth hormone releasing hormone levels (49·9±4 ng/l) than control subjects (16·3±2·1 ng/l; p>0·05), patients with non small cell lung carcinoma (23·9± 8·8 ng/l; p>0·05), and patients with non malignant lung disease (12·7±5·5;P>0·05). Basal GH level was lower than 5μg/l In all patients except five patients with small cell lung carcinoma and one patient with non small cell lung carcinoma.conclusionsThe higher plasma growth hormone releasing hormone levels in patients with small cell lung carcinoma compared to normal controls and patients with non small cell lung carcinoma and patients with non malignant lung disease, confirm the frequent neuroendocrine activity of this pa

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00326.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYobjectivesThe aim of this study was to determine whether there are any changes in skeletal muscle strength and size and body composition following growth hormone (GH) withdrawal in GH deficient young adultsdesignA longitudinal, 1‐year, open, uncontrolled study of the changes in skeletal muscle and body composition following GH withdrawal was performed. Endocrine status was reassessed at the end of the study period during an insulin tolerance test. Some measurements were repeated after 2 years off treatmentpatientsTwelve (11 male, one female; age range 14–21) patients who had been diagnosed during childhood as growth hormone deficient took part in the study. Four of the 12 patients were found to have a normal GH response on retesting at the end of the study and their results were analysed as a separate groupmeasurementsQuadriceps and forearm flexor maximum voluntary isometric strength, body fat content and serum IGF‐1 were measured at 3‐monthly intervals over 1 year. Every 6 months muscle size was measured from computerized tomography scans and fibre area from quadriceps needle biopsy samplesresultsFor the growth hormone deficient group the 12 month quadriceps strength, size and fibre areas were 94·0%±8·5 (mean±SD), 94·5%±6·3 and 85·6%±17·7 respectively of control (baseline) values. Forearm flexor strength and size were 101·4%±7·9 and 92·0%±9·2 of control. Body fat percentage had Increased from 19·5%±8·6 to 24·1%±9·5. No change was seen In the non‐growth hormone deficient groupconclusionsAlthough the changes measured were relatively small they suggest a role for GH In the maintenance of muscle integrity and body composition in the young adul

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00327.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYobjectiveThe present study was designed to further assess the mechanism of action of GnRH and GnRH analoguesdesignAND PATIENTS Both the Nal‐Glu GnRH antagonist and the D‐Trp6 GnRH agonist were administered sequentially to nine normal, post‐menopausal women. MEASUREMENTS A baseline study of pulsatile LH, FSH and freeα‐subunit secretion was performed, with sampling every 10 min for 8 h, and then repeated 8 h after a single subcutaneous injection of Nal‐Glu GnRH antagonist (5 mg). Sampling was repeated 21 days after the intramuscular injection of a depot preparation of D‐Trp6 GnRH (3·75 mg) in the same women.resultsThe baseline sampling period showed synchronous pulses of LH and freeα‐subunit. The antagonist Nal‐Glu decreased plasma LH (71%) and freeα‐subunit (43%). However, with the single dose of 5 mg, pulsatile LH and freeα‐subunit release were not completely suppressed and remained temporally correlated. The GnRH agonist had a potent inhibitory action on plasma immunoreactive LH (IRMA) (93%). In contrast, it increased the mean plasma levels of freeα‐subunit from 1·66·0±01 to 5·06·0±02μg/l (205%). The pulsatile secretory patterns of both LH and freeα‐subunit were abolished by the agonist. Immunoreactive FSH levels were decreased by the antagonist (24%) and suppressed by the agonist (93%).conclusionsThe pulsatile study confirms the different mechanism of action of GnRH analogues. Following antagonist administration, low amplitude freeα‐subunit pulses persist and are synchronous with residual LH pulses. In contrast, LH and freeα‐subunit are not maintained under agonist treatment. These data provide evidence for the differential

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00328.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYobjectiveThe aim of our study was to establish the definitive diagnosis In an adult patient with male pseudohermaphroditism in whom testicular feminization syndrome had been suspected at the ago of 8, based on genetic, clinical and pathological studiesdesignHypothalamo–hypophysio–testicular function was assessed invivo. Androgen mechanism of action and testicular gonadotrophin binding were studiedin vitro.patientAt the age of 33 the phenotype was almost completely feminine except for slight clitoral enlargement and posterior labial fusion. Internal genital duct derivatives were masculine except for a short vagina. Both testes were cryptorchidmeasurementsLH and FSH were determined pre‐ and post‐gonadectomy. Progesterone, 17‐OH‐progesterone, androstenedione, dehydroepiandrosterone testosterone (1) and oestradlol were determined basally in peripheral and spermatic blood post‐hCG stimulation, and in peripheral blood after orchidectomy. Dihydrotestosterone (DHT) receptors and 5a‐reductase activity were determined in genital skin fibroblasts. Receptors for LH and FSH were determined in membrane preparations from both testes. RESULTS LH was high (31 IU/l) and FSH (8 IU/ml) normal. T or steroid precursors were detected basally or after hCG stimulation in peripheral blood showing absence of testicular production. Spermatic venous blood steroid concentrations were consistent with slight T production, in accordance with testis histology which showed few Ley‐dig‐like cells among fibroblasts in the interstitial space. DHT specific binding capacity and affinity and 5α‐reductase activity were normal in genital skin fibroblasts. Gonadotrophin binding studies in testicular membranes confirmed the absence of LH specific binding, whereas FSH binding was higher than normal when expressed per mg of protein (27·0vs9·4 ± 0·8 ± mol/mg protein in controls), and lower than normal in both testes since patient's testicular weights were abnormally low.conclusionsThe patient was considered to have an almost complete form of Leydig cell agenesia/hypoplasia in which absence of specific LH binding correlated with total absence of differentiated Leydig cells and Insensitivity of undifferentiated intersti

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00329.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYobjectiveThe aim was to examine the effects of atrial natriuretic factor (ANF) 99–126 and ANF 103–126, an N‐terminal shortened analogue of the peptide, on the plasma renin activity response to captopril, an inhibitor of angiotensin‐converting enzymedesignTwo protocols were performed. In the first protocol, subjects were studied on three occasions. Captopril 25 mg was given and a 60 minute infusion of 5%d‐glucose (placebo), or ANF 99–126 3 or 10 pmol/kg/min, was administered In a single blind randomized manner. The second protocol was divided in two parallel phases comparing ANF 103–126 either 3 or 10 pmol/kg/min to placebosubjectsThirty‐three salt‐replete healthy male volunteers aged 21–39 years were studied in the supine positionmeasurementsPlasma renin activity, plasma ANF 99–126 and ANF 103–126 levels, heart rate and blood pressure were measuredresultsCompared to placebo Infusion, the rise in plasma renin activity after captopril was attenuated by ANF 99–126 infusion (from 755% of baseline to 294% by ANF 99–126 3 pmol/kg/min and from 755 to 202% by 10 pmol/kg/min;P>0·03 andP>0·01 respectively). The comparable findings with ANF 103–126 were 492 to 218% (3 pmol/kg/min) and 645 to 364% (10 pmol/kg/min) (P>0·01 andP>0·01 respectively).conclusionsThe results, taken in conjunction with previous findings, suggest that artrial natriuretic factor inhibits in a non‐selective manner the renin response to all secretagotues so far tested In man. The current results also suggest that the anti‐renin action of atrial natriuretic factor does not depend on the first four N‐te

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00330.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYobjectiveThe aim was to Investigate the sera of pregnant women for the presence of specific proteases for insulin‐like growth factor binding proteins (IGFBPs) and to determine the effect of these on the distribution of IGFs in the circulationdesignThe method used was the chromatographic and electrophoretic analysis of patients’ serumpatientsSera were examined from normal women during pregnancy: first trimester (n=4), second trimester (n= 4) and third trimester (n= 10). Eight women with Type I diabetes in the third trimester were also studied along with sera from ten normal adult volunteers.measurementsCirculating IGF‐I and IGF‐II levels were measured by RIA and their distribution examined by gel filtration. The pattern and stability of the IGFBPs was Investigated by Western Iigand blottingresultsA marked reduction in the serum levels of IGFBP‐2, IGFBP‐3 and IGFBP‐4 on Western Iigand blotting, which was associated with the presence of three Independent, cation‐dependent proteases that were specific for different IGFBPs, was found in late pregnancy. Gel filtration of third trimester serum revealed most of the IGF‐I to be present in a complex larger than 130 kDa, with a similar distribution to that found in serum of non‐pregnant women. The enzymatic modification of the binding proteins made apparent by the decrease in binding protein bands on Western Iigand blotting of preincubated samples had no effect on the distribution of IGF‐I following size ractionationconclusionsThere appear to be at least three Independent enzymes that are Induced or activated during pregnancy to modify IGFBP‐2, IGFBP‐3 and IGFBP‐4 sufficiently to prevent their detection by Iigand blotting. However, this enzymatic processing does not alter the distribution of IGFs, suggesting that the altered binding proteins are still able to carry IGFs but with reduced affinity. Such an alteration in the carrying mechanism of IGFs may have profound effects upon the bioavailability of the IGFs to the maternal tissues and contribute to the altered me

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1991.tb00331.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY