bluuebunny/crossref_metadata_2025_split huggingface dataset:
In‐vitro response of erythroid progenitors from children with thalassaemia major to human growth hormone and insulin‐like growth factor I
Authors: Merchav Shoshana , Graif Zvi , Skottner Anna 
Published: March 2008

SummaryOBJECTIVE Most short‐statured children with β‐thalassaemia major have markedly reduced levels of circulating insulin‐like growth factor I (IGF‐I). Both human growth hormone (hGH) and IGF‐I enhance the in‐vitro growth of erythroid progenitors, with hGH exerting its effects via paracrine production of IGF‐I. The aim of this study was to characterize further the hGH‐IGF‐l axis abnormalities in thalassaemia major by evaluating the erythroid potentiating effects of both peptides in cultures of thalassaemic and control erythroid progenitors.DESIGN Ten short‐statured thalassaemic children and nine age‐matched healthy donors were evaluated for the in‐vitro response of their peripheral blood erythroid progenitors to stimulation with hGH and IGF‐I.MEASUREMENTS The frequency of erythroid progenitors in serum‐free cultures of thalassaemic and control peripheral blood mononuclear cells was enumerated following 14 days of incubation in the presence of hGH or IGF‐I.RESULTS Biosynthetic hGH induced a similar dose‐dependent magnitude of colony enhancement in cultures of erythroid progenitors from thalassaemic children, as compared to controls. Significant enhancement of colony growth was detected at 42 μ/I hGH, with a maximal effect detected at 83 μ/I of this hormone (173 ± 8 vs 153 ± 9% of baseline erythroid progenitors in patients versus controls, respectively). Enhancement of both thalassaemic and control erythroid precursors by hGH was completely abrogated by monoclonal antibodies (αIR‐3) directed against the IGF‐I membrane receptor, thereby confirming the normal capacity of thalassaemic accessory cells to produce IGF‐I in response to hGH. Biosynthetic IGF‐I also enhanced the growth of thalassaemic and control erythroid precursors to 172±17 and 159±10% of baseline at 100 and 10 U/I, respectively.CONCLUSIONS Our detection of a normal capacity of thalassaemic peripheral blood target cells to response to hGH and IGF‐I suggests that these patients do not suffer from a specific defect in receptor and/or post‐receptor mechanism(s) involving the response of these cells to both peptides. The normal responsiveness of thalassaemic target cells to hGH and IGF‐I suggests that both peptides may be useful in the treatment of growth retardation in thalassaemia.
A case of antibody formation against octreotide visualized with 111In‐octreotide scintigraphy
Authors: Kwekkeboom D. J. , Assies J. , Holland L. J. , Reubi J. C. , Lamberts S. W. J. , Krenning E. P. 
Published: March 2008

SummaryA case of antibody formation in a patient with carcinoid syndrome is described. The patient was treated with octreotide in dosages up to 1 5 mg/day. Serum samples were analysed for the presence of octreotide antibodies before and after 20 months of octreotide treatment. In‐vivo 111ln‐octreotide scintigraphy was performed before and during therapy, and after antibodies had developed.Before treatment, no serum antibodies against octreotide were detected. After 20 months of treatment, they were detectable up to a 1:115 serum dilution. The serum binding of 125I‐Tyr3‐octreotide was blocked by adding excess unlabelled Tyr3‐octreotide, indicating the presence of specific octreotide antibodies. Before treatment, a normal distribution of radioactivity in the spleen and kidneys, irregular uptake in the liver due to metastases, and a hot spot in the lower abdomen were found during 111ln‐octreotide scintigraphy. After antibodies had developed, increased radioactivity over the heart and high background radioactivity in the abdomen with only faint visualization of the spleen, liver, and kidneys were found, indicating a prolonged presence of 111ln‐octreotide in the blood resulting from its being bound to antibodies. Increased radioactivity was also seen at the injection sites of the drug in the upper legs. In‐vitro incubation of biopsy tissue from this site with 125l‐Tyr3‐octreotide revealed diffuse guanosine triphosphate (GTP) independent specific binding, indicating non‐G‐protein linked binding of labelled octreotide.This report describes the characteristic abnormalities during in‐vivo 111ln‐octreotide scintigraphy in a patient with octreotide antibodies. These consisted of high back ground radioactivity due to prolonged circulation of antibody coupled 111ln‐octreotide together with visualization of the injection sites, which most probably results from local accumulation of antibodies.
Reversibility of hypogonadotrophic hypogonadism associated with genetic haemochromatosis
Authors: Cundy Tim , Butler Joan , Bomford Adrian , Williams Roger 
Published: March 2008

SummaryOBJECTIVE Recent reports have suggested that hypogonadotrophic hypogonadism in men with genetic haemochromatosis can be reversed by aggressive venesection therapy. We have studied prospectively men with this complication of haemochromatosis in order to document the frequency and completeness of recovery from hypogonadism.PATIENTS AND DESIGN Six men with symptomatic hypogonadotrophic hypogonadism and genetic haemochromatosis were studied before beginning venesection therapy and again after depletion of body iron stores.MEASUREMENT Symptoms of hypogonadism, serum gonadotrophins and serum total and free testosterone concentrations.RESULTS Five men aged 47–66 showed no symptomatic improvement and no change in serum gonadotrophin or testosterone concentrations. The symptoms of one man, aged 33, resolved completely after venesection and this was accompanied by increases in serum LH and FSH. Serum total and free testosterone concentrations increased fourfold, but remained subnormal.CONCLUSION Only one partial recovery from hypogonadotrophic hypogonadism was seen and this was in the youngest subject. In reviewing the other documented cases of reversal it would appear that the age at diagnosis is critical and there are no proven cases of reversal of hypogonadotrophic hypogonadism in men over the age of 40 at the start of venesection therapy.
Expression of thyrotrophin receptor gene in thyroid carcinoma is associated with a good prognosis
Authors: Shi Yufei , Zou Minjing , Farid Nadir R. 
Published: March 2008

SummaryOBJECTIVE The clinical course of thyroid carcinoma is very variable. It is well known that thyroid carcinomas of similar histology can behave differently in terms of local invasion and distant metastases: there is no reliable way to predict the disease course with confidence. In the present study we compared the TSH receptor and c‐myc mRNA levels in different stages of thyroid carcinomas to identify whether they are useful markers for thyroid tumour biological behaviour and prognosis.DESIGN Thyroid tumour specimens were used as the source of RNA. The TSH receptor and c‐myc mRNA levels were detected by Northern blot analysis and quantitated by laser densitometry.PATIENTS Thyroid tissues were obtained from five patients with multinodular goitres, 22 with differentiated and three with anaplastic carcinomas.MEASUREMENTS Total cellular RNA was extracted from thyroid tissue specimens and blotted onto nylon membranes. Northern blot analysis was used to detect TSH receptor and c‐myc mRNA. The mRNA levels were then quantitated by laser densitometry and compared with each disease stage.RESULTS TSH receptor mRNA levels were significantly lower in carcinomas as compared to benign tumours. With advancing disease stage, the neoplastic tissues generally showed a progressive decline in TSH receptor mRNA levels. Interestingly, in two specimens from patients with distant metastases, TSH receptor mRNA levels were not significantly reduced and were comparable to those in benign tumours. Both patients are still alive, one of them 18 years after operation, indicating that tumour histology is dissociated from its biological behaviour, c‐myc mRNA levels were increased but not significantly so in stage 1–3 carcinomas. However, in stage 4 carcinomas c‐myc expression was significantly increased. Thus c‐myc overex‐pression is associated with poor prognosis. Although there is a negative correlation between TSH receptor and c‐myc mRNA levels, the correlation was not significant. CONCLUSIONS These results indicate that decreased TSH receptor and increased c‐myc gene expression levels are associated with thyroid cell de‐differentiation. They are useful markers for thyroid tumour de‐differentiation and disease prognosis.
The effect of treatment with levothyroxine or iodine on thyroid size and thyroid growth stimulating immunoglobulins in endemic goitre patients
Authors: Wilders‐Truschnig M. M. , Warnkroß H. , Leb G. , Langstegert W. , Eber O. , Tiran A. , Dobnig H. , Passath A. , Lanzer G. , Drexhage H. A. 
Published: March 2008

SummaryOBJECTIVE We assessed the effect of levothyroxine or iodine on thyroid size and on thyroid growth stimulating immunoglobulins in endemic goitre patients.DESIGN Levothyroxine or iodine was given orally in an open randomized prospective study (100 and 200 μ g respectively).PATIENTS Thirty‐seven euthyroid patients with diffuse iodine deficiency goitres and thyroid growth stimulating immunoglobulins were studied.MEASUREMENTS Thyroid size, thyroid growth stimulating immunoglobulins (mitosis arrest assay), basal TSH, free T3, free T4, thyroid anti‐microsomal antibodies, anti‐thyroglobulin antibodies, anti‐TSH receptor antibodies and urinary iodine excretion were measured.RESULTS Thyroid size decreased significantly in both groups, in the levothyroxine group more than in the iodine treated group. Thyroid growth stimulating immunoglobulins levels also decreased significantly in both groups. Between groups there was no statistically significant difference. A statistically significant correlation between thyroid growth stimulating immunoglobulins reduction profiles and goitre size reduction could not be established. TSH levels became suppressed in the levothyroxine group while the T4 values rose; in the iodine treated group TSH levels stayed constant as did T4. None of the patients developed thyroid microsomal or thyroglobulin auto‐antibodies and/or hyperthyroidism during the treatment.CONCLUSIONS Levothyroxine as well as iodine was effective in reducing thyroid size as well as thyroid growth stimulating immunoglobulins levels in endemic goitre patients. Since in both groups TSH levels were not related to thyroid size reduction, other factors than TSH suppression must be responsible for the observed thyroid size reduction. Iodine itself by virtue of its antiproliferative action on thyrocytes may have had a direct action on the goitre reduction during iodine treatment; however, the levothyroxine dose, containing less iodine, had a similar effect. A complicated picture hence emerges with regard to factors involved in the shrinkage of iodine deficiency goitre during thyroxine or iodine therapy. These findings indicate that TSH and thyroid growth promoting immunoglobulins are not the only influences on the size of endemic goitres, although it cannot be excluded that these two factors contribute to influence the pathogenetic process.
Metabolic clearance rate of biosynthetic growth hormone after endogenous growth hormone suppression with a somatostatin analogue in chronic renal failure patients and control subjects
Authors: Garcia‐Mayor Ricardo V. G. , Perez Angel J. , Gandara Argimiro , Andrade Amalia , Mallo Federico , Casanueva Felipe F. 
Published: March 2008

SummaryOBJECTIVE Several disturbances in the regulation of growth hormone secretion have been reported in chronic renal failure. The general assumption is that an altered hormonal clearance is at the basis of such GH alterations. Nevertheless, details of GH elimination kinetics in uraemia are not available. To clarify the role played by the kidney in its catabolism, GH elimination kinetics were studied in uraemic and control subjects after suppression of endogenous secretion of GH.DESIGN In all subjects an analogue of somatostatin (octreotide 100 μ g i.v.) was administered as a bolus before GH (– 60 minutes). Sixty minutes later (0 min) biosynthetic GH (0 5 IU = 200 μ g) was administered intravenously as a bolus.PATIENTS Six chronic renal failure patients before dialysis and six matched normal volunteers.MEASUREMENTS Plasma GH levels were measured by an immunoradiometric assay.RESULTS In both groups, the GH elimination curve fitted a bi‐exponential model. The calculated plasma volume and GH concentration at 0 minutes were similar in both groups, while uraemic patients presented a reduced distribution volume. In all parameters measuring GH elimination, chronic renal failure patients showed an impaired clearance. In fact, the area under the curve (mU/l/150 min) was 912.8 ± 170.6 for controls and 3524.8 ± 642.8 for chronic renal failure patients (P < 0.005). The GH half‐life was 13.8 ± 1.6 and 26.4 ± 2.9 minutes for control and uraemic subjects respectively (P<0.05), and the metabolic clearance rate MCR (ml/min/m2) was 265.3 ± 50.6 for controls and 79.9 ± 16.4 for uraemic patients (P< 0.05). The GH mean residence time (minutes) (MRT) calculated was 12.0 ± 0.5 for controls and 31.8 ± 4.6 for chronic renal failure patients (P<0.05).CONCLUSIONS Contrary to previous estimates, GH elimination kinetics follows a bi‐exponential model and in normal subjects the GH half‐life of the second phase is 13.8 ± 1.6 minutes. Uraemic patients have impaired clearance of GH, suggesting that the kidney plays a role in GH disposal. However, the degree of impairment does not fully explain the alterations in GH secretion previously described in chronic renal failure.
Hyperactivity of the hypothalamo‐pituitary‐adrenal axis in obesity: a study of ACTH, AVP, β‐lipotrophin and Cortisol responses to insulin‐induced hypoglycaemia
Authors: Weaver J. U. , Kopelman P. G. , McLoughlin L. , Forslingt M. L. , Grossman A. 
Published: March 2008

SummaryOBJECTIVE The purpose of this study was to determine whether alterations in the hypothalamo‐pituitary‐adrenal axis and arginine vasopressin secretion, which have been associated with animal obesity, also occur in man.DESIGN Cross‐sectional analysis of extremely obese women and normal weight controls.PATIENTS Thirty‐three obese premenopausal, non‐diabetic women (mean age 31 years, mean body mass index (BMI) 41), and 15 normal weight controls (mean age 24 years, mean BMI 22).MEASUREMENTS AND RESULTS Arginine vasopressin (AVP), ACTH, β‐lipotrophin and Cortisol responses to insulin‐induced hypoglycaemia (0 2 units Actrapid/kg body weight for obese; 0.15 unit/kg for controls) were measured. The obese women were further characterized by anthropometric measurements (weight, body mass index, fat distribution) and indices of insulin secretion/ resistance: fasting insulin, insulin secretion during 75‐g oral glucose tolerance test area under curve, insulin‐stimulated gucose disposal and an index of insulin resistance. No significant differences were found in the basal levels of ACTH, AVP, β‐lipotrophin or Cortisol. An augmented peak β‐LPH (n = 16, P<0 02, the difference of the mean 3 65,95% confidence interval 1 33–10) and ACTH (n=16, P= 0 05, the difference of the mean 2 12, 95% CI 1–0–4 5) response were found in obese as compared with normal weight controls. Both ACTH and AVP areas under the curve were similar in both groups studied. There was additionally a direct positive association between the integrated ACTH response (area under the curve) and the weight of the obese subjects (P<0 05, r2= 0 265). The Cortisol response was negatively correlated with insulin‐stimulated glucose disposal (P<001, r2= 0 23), but not with other indices of insulin secretion/resistance (fasting insulin, oral glucose tolerance test area under the curve, index of insulin resistance) or fat distribution.Comparable responses to hypoglycaemia were seen for AVP and Cortisol. There was no correlation between the ACTH, AVP or Cortisol responses.CONCLUSION Obesity is associated with increased activity of the hypothalamo‐pituitary‐adrenal axis as supported by augmented ACTH and β‐lipotrophin secretion in response to insulin‐induced hypoglycaemia and the positive association between the ACTH response and the body weight of obese women studied.
Pharmacokinetic properties of the tocolytic agent [Mpa1d‐Tyr(Et)2, Thr4, Orn8]‐oxytocin (antocin) in healthy volunteers
Authors: Lundin S. , Broeders A. , Melin P. 
Published: March 2008

SummaryOBJECTIVE The aim of this study was to study the pharmacokinetics of antocin, the tocolytic oxytocin antagonist [Mpa1d‐Tyr2(Et), Thr4, Orn8]‐oxytocin.DESIGN Antocin was injected intravenously as a bolus dose (5 μmol). Blood samples were taken at intervals for 240 minutes. In addition, the binding of 125I‐Tyr10‐antocin to blood constituents was determined and compared with 125I‐AVP and 125I‐[Mpa‐1d‐Arg8]‐vasopressin (desmopressin).SUBJECTS Eight healthy, non‐smoking adults, three male and five female.MEASUREMENTS Antocin was measured using a specific radioimmunoassay after prior extraction of the plasma. Plasma binding was estimated using polyethyleneglycol precipitation.RESULTS The rate of plasma disappearance of antocin was best fitted by a biexponential curve. The clearance of antocin was 23.5 ± 7–6 I/h, the volume of distribution was 13.1 ± 3.8 I and the biological half‐life was 39.0 ± 4.1 minutes, A greater proportion of 125l‐Tyr,10‐antocin bound to plasma proteins (33.5%) and red blood cells (13%) than did 125I‐AVP, 125l‐desmopressin and unlabelled desmopressin.CONCLUSIONS The half‐life was longer and the clearance of antocin was less than that found in a previous study when a non‐specific antiserum was used. This is most likely because of the extended blood sampling time period which revealed the biphasic decay pattern. The higher plasma clearance of antocin compared to oxytocin and desmopressin may be explained by its increased binding to blood constituents rather than by differences in enzymatic degradation of the molecules.
Pituitary adenomas with high and low basal inositol phospholipid turnover; the stimulatory effect of kinins and an association with interleukin‐6 secretion
Authors: Jones T. H. , Kennedy R. L. , Justice S. K. , Price A. 
Published: March 2008

SummaryOBJECTIVE We examined basal inositol phospholipid turnover and the response to the kinin, kallidin, in human pituitary adenomas and determined whether or not there was an association between these parameters and interleukin (IL‐6) secretion status by the tumours.DESIGN Pituitary adenoma tissue was dispersed and cells were cultured in monolayer for 96 hours. The medium was then removed and assayed for IL‐6 and anterior pituitary hormones. The cells were labelled with 3H‐myoinositol for 24 hours and then incubated under basal conditions with kallidin and, in some cases, with TRH and GnRH for 60 minutes. Total inositol phosphate accumulation and pituitary hormone secretion were assessed.PATIENTS Tissue was collected from 29 consecutive patients being treated surgically for pituitary adenomas.MEASUREMENTS Total 3H‐inositol phosphates, growth hormone, prolactin, LH, FSH, TSH and immunoreactive IL‐6.RESULTS Two groups of pituitary adenomas were identified, one with high and one with low basal inositol phospholipid turnover. Kallidin stimulated inositol phosphate accumulation in seven of the 29 adenomas studied. The kallidin‐responsive adenomas were associated with high basal phosphoinositide turnover. All seven kallidin‐responsive adenomas secreted IL‐6. The adenomas studied with high basal inositol phosphate production were also responsive to TRH and in two tumours to GnRH. Kallidin stimulated GH release in one GH‐secreting adenoma but had no effect on hormone secretion from any other tumour.CONCLUSION Two groups of pituitary adenomas have been identified with high and low basal inositol phosphoinositide turnover. Phosphoinositide metabolism is readily stimulated by kallidin and TRH in adenomas with high but not low turnover. Kinin‐responsive adenomas secreted IL‐6 but IL‐6 secretor status does not preclude that they will respond to kallidin.
Discrimination between β‐endorphin and β‐lipotrophin in human plasma using two‐site immunoradiometric assays
Authors: Gibson S. , Crosby S. R. , White A. 
Published: March 2008

SummaryOBJECTIVE We wished to discriminate between the opioid peptide β‐endorphin (β‐EP) and its non‐opioid precursor β‐lipotrophin (β‐LPH) in normal subjects and patients with ACTH‐related disorders.DESIGN We produced monoclonal antibodies to β‐EP and β‐LPH for the development of two‐site immunoradiometric assays (IRMAs) which specifically quantitate β‐EP and β‐LPH.PATIENTS Samples were obtained from patients with a range of ACTH‐related disorders and compared with 18 normal subjects. Peptide levels were also compared in six patients with Cushing's syndrome undergoing bilateral inferior petrosal sinus sampling with corticotrophin releasing hormone administration.MEASUREMENTS In the β‐EP IRMA, antibody 6B2, specific for β‐EP 18–27, is radiolabeled and antibody 2E10, recognizing β‐EP 1–5, is coupled to Sephacryl S‐300 as solid phase. The IRMA is specific for β‐EP (β‐LPH cross‐reacts <0.02%), has a detection limit of 14 ± 0 7 pmol/l (n = 7) and has a within‐assay coefficient of variation of <10% between 4.9 and 1200 pmol/l. In the β‐LPH IRMA, antibody 6B2, which recognizes an epitope common to β‐LPH and β‐EP, is radiolabeled and paired with solid‐phase antibody 5C11 which recognizes β‐LPH 39–56. The binding site of this antibody ensures that β‐EP cannot be measured in the β‐LPH assay. The detection limit is 0.8 ± 0.1 pmol/l (n= 9) and the within‐assay coefficient of variation is <10% at concentrations 1.7–870 pmol/l.RESULTS In normal subjects, β‐EP and β‐LPH levels were < 1.4–1.7 pmol/l (< 5–6 ng/l) and 2.5–6.7 pmol/l (29–77 ng/l) at 0930 h and < 1.4–1.7 pmol/l (<5–6 ng/l) and 1.9–4.5 pmol/l (22–49 ng/l) at 1600 h, respectively. In patients with ACTH‐related pathologies concentrations of β‐EP and β‐LPH paralleled those of ACTH. The ratio of β‐LPH: β‐EP in plasma varied between 3.2:1 and 38:1 in these patients demonstrating that β‐LPH is the major circulating peptide derived from the C‐terminal of pro‐opiomelanocortin in man. However, in two patients undergoing bilateral inferior petrosal sampling with corticotophin releasing hormone for diagnosis of Cushing's disease β‐EP concentrations increased rapidly during the first 5 minutes of the test, resulting in a sharp decrease in the β‐LPH: β‐EP ratio. These results suggest that β‐EP is preferentially released in response to acute corticotrophin releasing hormone stimulation.CONCLUSIONS It is concluded that two‐site IRMAs for β‐EP and β‐LPH provide an easy approach to study the dynamic changes in processing of β‐LPH to β‐EP.
The determination of delta‐5‐androstenediol and its sulphate in serum and urine by gas chromatography‐mass spectrometry
Authors: Dikkeschei L. D. , Wolthers B. G. , Willemse P. H. B. , van der Pol H. , der Ruyter‐Buitenhuis A. W. , Nagel G. T. 
Published: March 2008

SummaryOBJECTIVES We developed an assay for delta‐5‐andro‐stenediol (adiol) and delta‐5‐androstenediol‐3‐sulphate (adiol‐3S) in serum and adiol and total adiol sulphate (adiol‐S) in urine.DESIGN An analytical procedure using HPLC and gas chromatography‐mass spectrometry was devised and tested for its reliability.MEASUREMENTS After addition of deuterated androstenediol as internal standard, serum and urine samples were extracted. Steroid sulphates were hydrolysed. The extracts and hydrolysates were purified on HPLC, adiol was derivatized using heptafluorobutyric anhydride and finally quantified by gas chromatography‐mass spectrometry.RESULTS The assay is accurate and reproducible. The coefficient of variation (CV) for the determination of adiol in serum samples is 4% (intra‐assay) and 9% (interassay) and for urine samples 3 and 8% respectively. The intra‐assay CV for the adiol‐3S analyses is 5% for serum and 2% for urine samples while the interassay CV values for adiol‐3S are 10% for serum and 7% for urine samples. The recovery of adiol and adiol‐3S from serum and urine samples is 97%.CONCLUSIONS The developed assay meets the analytical demands needed for clinical applications.