bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential cytokine expression of human retinal pigment epithelial cells in response to stimulation by C5a
Authors: FUKUOKA Y , STRAINIC M , MEDOF M E 
Published: March 2003

SUMMARYHuman retinal pigment epithelial (RPE) cells form part of the blood–retina barrier where they potentially can regulate leucocyte function. RPE cells are known to secrete several cytokines in response to stimulation by other cytokines. Anaphylatoxin C5a, a potent inflammatory mediator produced during complement activation, binds to G-protein coupled C5a receptors (C5aR) on monocytes/macrophages and releases various cytokines from the cells. We previously reported that the human RPE cell line ARPE-19 possesses C5aR and expresses IL-8 mRNA in response to C5a stimulation. In this study, we used a primary human RPE cell line (RPE43) and found that C5a induces increased expression of IL-1β, IL-6, MCP-1 and GM-CSF mRNAs as well as IL-8 mRNA. ARPE-19 cells showed similar increases in the same cytokines. Interestingly, the kinetics of expression of the various cytokines differed. These results provide further evidence that C5a stimulation of RPE cells may play a role in regulating leucocyte function during ocular inflammation in which there is complement activation.
Erythrocyte insulin‐like growth factor‐I binding in younger and older males
Authors: Moromisato David Y. , Roberts Jr Charles , Brasel Jo Anne , Mohan Subburaman , Cowles Elizabeth , King Stephen M. , Cooper Dan M. 
Published: March 2003

OBJECTIVEInsulin‐like growth factor‐I (IGF‐I) levels are lower in older compared with younger subjects. We tested the hypothesis that the reduction in circulating IGF‐I would be accompanied by upregulation in tissue IGF‐I binding in at least some tissues. We tested erythrocyte IGF‐I binding since blood is an accessible tissue in humans, and there is growing evidence to suggest that erythrocyte IGF‐I binding is influenced by circulating IGF‐I.DESIGN AND PATIENTSWe compared 9 healthy older males (61–68 years old) with 9 healthy younger males (15–19 years old).MEASUREMENTSStandard techniques were used to assay circulating IGF‐I and IGF binding proteins 1–5 (IGFBPs 1–5). Erythrocyte IGF‐I binding was first measured by studies in which native [125I]‐IGF‐I was displaced with unlabelled native IGF‐I. In order to determine a possible role for IGF binding proteins (IGFBP), native [125I]‐IGF‐I was displaced with des‐(1‐3)IGF‐I, which binds with IGF receptors but not IGFBPs.RESULTSAs expected, circulating IGF‐I was significantly lower in the older compared with the younger subjects. In addition, IGFBP‐3 and 5 were significantly lower, and IGFBP‐4 higher, in older compared with younger subjects. When native [125I]‐IGF‐I was displaced with unlabelled native IGF‐I, the number of IGF‐I binding sites per erythrocyte was higher in the older subjects (43 ± 5 vs. 18 ± 2, older vs. younger, respectively; P < 0.05). In contrast, when native [125I]‐IGF‐I was displaced with des‐(1‐3), IGF‐I binding capacity was not different between the two age groups.CONCLUSIONSErythrocyte IGF binding was increased in older compared with younger subjects. Surprisingly, the mechanism of the increase may not be a simple up regulation of IGF‐I receptors in response to reduced circulating IGF‐I, but possibly by an increase in the levels of as yet unidentified erythrocyte membrane‐associated IGF binding proteins.
Normalization of serum thyrotrophin by means of radioiodine treatment in subclinical hyperthyroidism: effect on bone loss in postmenopausal women
Authors: Faber  , Jensen  , Petersen  , Nygaard  , Hegedüs  , Siersbæk‐Nielsen  
Published: March 2003

BACKGROUNDPatients with subclinical hyperthyroidism (reduced serum TSH and normal free T4 and T3 concentrations) have slightly increased bone turnover and might have reduced bone mass, especially among postmenopausal women (due to concomitantly reduced oestrogen production), as also seen during suppressive L‐T4 treatment.OBJECTIVEWe have evaluated whether normalization of serum TSH using radioiodine treatment (RAI) in postmenopausal women with a nodular goitre and subclinical hyperthyroidism, protects against bone loss?DESIGNProspective, non‐randomized study, out‐patients, 2 years follow‐up.PATIENTSPostmenopausal women with a nodular goitre, biochemically subclinical hyperthyroidism (TSH < 0.2 mU/l, and signs of a growing goitre or compression symptoms. Sixteen were treated with RAI (median dose 555 MBq) (+RAI), whereas 12 were followed without treatment (−RAI).MEASUREMENTSSerum TSH (third generation technology), free T4 and T3 indices, and bone mass (BMD) as measured by Dual Photon Absorptiometry (4 in each group) (only spine) or Dual X‐ray Absorptiometry (DEXA) (both spine and hip), were measured yearly for up to 2 years.RESULTSThe two groups did not differ regarding age, thyroid hormone parameters, and absolute levels of BMD at spine and hip. RAI resulted in normalization of TSH in all 16 women, and FT4I as well as FT3I decreased to 78% after one year (P < 0.01). These parameters did not change in the untreated group, thus serum TSH remained reduced.BMD at the spine tended to increase (n.s.) after RAI to (median) 101.9% after one year, and 101.5% after 2 years. In contrast the −RAI group experienced a continued fall in BMD to 97.3% after one year, and 95.5% after 2 years, both reduced as compared to the +RAI group (P < 0.02). BMD of the hip also increased after RAI, to 102.3% after one year, and 101.7% after 2 years. In contrast BMD in the −RAI group decreased to 94.8% after one year, and 98.0% after 2 years, both lower than in the +RAI group (P < 0.01).CONCLUSIONSSubclinical hyperthyroidism due to a nodular goitre in postmenopausal women resulted in a continued loss of bone mass of about 2% per year. Radioiodine treatment resulting in normalization of serum TSH prevented this continued bone loss for at least 2 years. Our study supports earlier intervention in such patients.
Effect of long‐term treatment with GH on bone metabolism, bone mineral density and bone elasticity in GH‐deficient adults
Authors: Kann P. , Piepkorn B. , Schehler B. , Andreas J. , Lotz J. , Prellwitz W. , Beyer J. 
Published: March 2003

OBJECTIVEAdults with GH deficiency (GHD) commonly have subnormal bone mineral density (BMD), and have been reported to have an increased risk of fractures. It has been suggested that GH replacement therapy may have beneficial effects on bone in such patients. The aim of this study was to investigate the effects of long‐term GH replacement therapy on bone metabolism, BMD and bone elasticity in adults with GHD.DESIGNAt the start of the study, 20 adults with GHD were randomized to receive either GH, 0.25 IU/kg/week (the ‘GH group’) or placebo (the ‘placebo group’). After 6 months, patients in the placebo group were switched to GH therapy, and all patients received GH for a further 42 months.PATIENTSOf the 20 patients included in the study, 11 were male and nine were female. Mean age at the start of the study was 42.5 ± 10.1 years. All patients had been GH‐deficient for at least 2 years before the start of the study.MEASUREMENTSRates of bone resorption and formation were assessed by measuring serum levels of type I collagen carboxyterminal cross‐linked telopeptide (ICTP) and carboxyterminal propeptide of type I procollagen (PICP), respectively. BMD was measured at the lumbar spine by dual‐photon absorptiometry (DPA) and at the non‐dominant forearm by single‐photon absorptiometry (SPA). Bone elasticity was assessed by measuring apparent phalangeal ultrasound transmission velocity (APU).RESULTSThe main results in the GH group were as follows. The rate of bone resorption increased significantly during the first 6 months of treatment and remained significantly elevated above its baseline level thereafter. The rate of bone formation also rose during the first 6 months of treatment and remained elevated thereafter, but was significantly higher than at baseline only after 24 months of treatment. At both sites measured, BMD was subnormal at baseline, decreased during the first 6 months of treatment, and increased progressively for the rest of the study, eventually rising well above its baseline level. Bone elasticity decreased during the first 6 months of treatment, but had returned to its baseline level after 24 months.CONCLUSIONSOur results support previous findings that BMD is subnormal in adults with GHD, that GH replacement therapy can stimulate bone turnover in such adults and that, in the long term, such stimulation results in a significant increase in BMD. In addition they show, for the first time, that BMD may continue to rise even after GH replacement therapy has been administered for 4 years, and indicate that bone elasticity is not adversely affected by long‐term GH therapy.
Effects of four years' treatment with biosynthetic human growth hormone (GH) on glucose homeostasis, insulin secretion and lipid metabolism in GH‐deficient adults
Authors: Al‐Shoumer Kamal A. S. , Gray Robert , Anyaoku Victor , Hughes Carol , Beshyah Salem , Richmond William , Johnston Desmond G. 
Published: March 2003

OBJECTIVETo study the effects of long‐term growth hormone (GH) treatment on lipid metabolism and carbohydrate tolerance in GH‐deficient adults.DESIGNOpen trial of GH treatment for 4 years. GH dose was (median, range) 0.025 (0.010–0.050) IU/kg daily.PATIENTSThirteen GH‐deficient hypopituitary adults (seven men, six women), aged (median, range) 47 (24–65) years were followed for 4 years.MEASUREMENTSFasting lipids, lipoproteins, apolipoproteins, glucose and insulin concen_trations were measured at yearly intervals during GH therapy. A 75‐g oral glucose tolerance test (OGTT) was also performed yearly, during which circulating glucose and insulin were measured at 30‐minute intervals for 3 h.RESULTSFasting total and low density lipoprotein (LDL) cholesterol concen_trations decreased on GH therapy, but no change was observed in fasting triglyceride or high density lipoprotein (HDL) concen_trations. Compared to pretreatment values, total and LDL cholesterol levels were significantly lower at 1 year (mean ± SEM) (6.39 ± 0.46 vs. 5.71 ± 0.38 mmol/l, P < 0.05; 4.46 ± 0.36 vs. 3.24 ± 0.20 mmol/l, P < 0.01, respectively) and the reductions were maintained for the 4 years. Apolipoproteins A‐1 and B did not differ significantly from the pretreatment levels. Fasting plasma glucose increased significantly at the first year (4.9 ± 0.1 vs. 5.3 ± 0.1 mmol/l, P < 0.05) but it returned to the pretreatment value in the following years. Fasting plasma insulin increased significantly at 1 year (4.3 (1.0–13.6) vs. 11.9 (1.2–26.9) mU/l, P < 0.05) and showed a progressive downward trend but remained significantly raised throughout the subsequent years. The 3‐h area under the glucose curve (AUC) during the OGTT tended to be increased at the first year (P = 0.07) and it returned to the pretreatment level in the following years. The AUC of plasma insulin was significantly raised at 1 year (P = 0.024) and it returned to the pretreatment level in the following years.CONCLUSIONSFour years of GH therapy in GH‐deficient adults resulted in a sustained improvement in total and LDL cholesterol concen_trations. Mild fasting hyperinsulinaemia persisted, although an initial deterioration in glucose tolerance, associated with post‐glucose hyperinsulinaemia, was not sustained.
Serum concentrations of insulin, insulin‐like growth factor(IGF)‐I, IGF binding protein (IGFBP)‐1 and ‐3 and growth hormone binding protein in obese children: fasting IGFBP‐1 is suppressed in normoinsulinaemic obese children
Authors: Saitoh Hisako , Kamoda Tomohiro , Nakahara Satoko , Hirano Takeki , Nakamura Norimasa 
Published: March 2003

OBJECTIVESimple obesity is characterized by normal or accelerated growth in the presence of reduced serum levels of GH, whereas its detailed mechanism remains unknown. We, therefore, evaluated interrelationships among serum levels of insulin, IFG‐I, IGF binding protein (IGFBP)‐1 and ‐3 and growth hormone binding protein (GHBP) in prepubertal obese children.SUBJECTSPrepubertal 20 obese children and 20 age‐matched control children were included in the study.RESULTSSerum levels of insulin, IGF‐I and IGFBP‐3 in obese children did not differ from those in controls. The serum level of IGFBP‐1 was significantly lower in obese children (22.1 ± 18.4 μg/l, P<0.001) than in control children (76.0 ± 62.9 μg/l). No relationship was found between the serum levels of insulin and IGF‐I, IGFBP‐1, or IGFBP‐3 in obese subjects. The serum level of GHBP in obese children was significantly elevated as compared with that in controls and was positively correlated with body mass index (BMI). No relationship was found between the serum levels of GHBP and IGF‐I in obese subjects.CONCLUSIONSThe present study showed for the first time that the fasting IGFBP‐1 level was suppressed in prepubertal obese children with fasting normoinsulinaemia. We speculate that the hyperinsulinaemia which cannot be detected in the fasting state may have suppressed hepatic production of IGFBP‐1. Alternatively, the reduced IGFBP‐1 is likely to be a compensatory response to impaired insulin sensitivity. Thus, the IGFBP‐1 level may be a useful predictor for the early identification in the development of insulin resistance in prepubertal obese children.
Usefulness of surface phenotype study of intrathyroidal lymphocytes obtained by fine needle aspiration cytology in autoimmune thyroid disease and malignant lymphoma of the thyroid
Authors: Fujikawa Megumi , Okamura Ken , Sato Kaori , Mizokami Tetsuya , Tanabe Shoko , Ikenoue Hiroshi , Okamura Seiichi , Ohta Masayuki , Fujishima Masatoshi 
Published: March 2003

OBJECTIVESThe surface phenotypes of intrathyroidal lymphocytes have been studied in various thyroid diseases. In most of the previous reports, intrathyroidal lymphocytes were obtained by surgical operation. We evaluated the usefulness of surface phenotype study of intrathyroidal lymphocytes obtained by fine needle aspiration in the diagnosis of Graves' disease, chronic thyroiditis, and malignant lymphoma of the thyroid.PATIENTS AND DESIGNEighty‐seven untreated patients including 24 with Graves' disease, 59 with chronic thyroiditis, and 4 with malignant lymphoma of the thyroid, and 2 treated patients with malignant lymphoma of the thyroid were studied. Surface phenotypes of the peripheral lymphocytes and the intrathyroidal lymphocytes obtained by fine needle aspiration were analyzed using a FACScan and the monoclonal antibodies: anti‐Leu5b/CD2, Leu4/CD3, Leu3a/CD4, Leu2a/CD8, and Leu12/CD19. Percentages of cells positive for each monoclonal antibody were calculated. In one case with malignant lymphoma, monoclonal antibodies to surface‐immunoglobulin markers were also studied.RESULTSIn peripheral lymphocytes, the percentage of positive cells in each phenotype was almost normal in each disease. In intrathyroidal lymphocytes, the percentage of CD19 positive cells was increased, and the percentage of CD2 and CD3 positive cells was reduced compared to those of peripheral lymphocytes in each disease. The percentage of intrathyroidal CD19 positive cells was remarkably high in malignant lymphoma, constituting more than 70% of cells. In Graves' disease, a relative decrease in the percentage of intrathyroidal CD4 positive cells and an increase in CD8 positive cells compared to peripheral lymphocytes were observed. In 2 treated patients with malignant lymphoma of the thyroid, the intrathyroidal CD19 positive cells almost disappeared in a patient shortly after successful treatment, and reappeared to constitute 76% of cells in a patient in relapse. In one case with malignant lymphoma in which monoclonal antibodies to surface‐immunoglobulin markers were studied, the clonality of the affected cells could be demonstrated; more than 70% of the cells were positive for κ light‐chain and μ and δ heavy‐chain. This finding was proved by subsequent immunohistochemical study based on open biopsy.CONCLUSIONSSurface phenotype study of intrathyroid lymphocytes obtained by fine needle aspiration has limited utility in the evaluation or diagnosis of Graves' disease and chronic thyroiditis. However, this simple rapid method is very helpful in the diagnosis and follow up of malignant lymphoma of the thyroid.
Determination of a common genetic variant of luteinizing hormone using DNA hybridization and immunoassays
Authors: Nilsson Christel , Jiang Min , Pettersson Kim , Iitiä Antti , Mäkelä Minna , Simonsen Henrik , Easteal Simon , Herrera René J. , Huhtaniemi Ilpo 
Published: March 2003

OBJECTIVEAn immunologically anomalous form of LH, due to two point mutations in codons 8 and 15 of the LHβ gene, has previously been described. LH status, i.e. the discrimination between wild‐type (WT) and variant (V) LH, is usually determined by immunoassays, which can be unreliable at low serum concentrations of LH. A DNA hybridization assay was therefore developed to score the LH genotype in all subjects, independent of their serum LH concentrations. To evaluate the performance of the hybridization method, and to expand our observations of the worldwide occurrence of the V‐LH, we determined its frequency in additional populations. To confirm the connection between the anomalous immunoreactivity and the V‐LHβ gene, we also sequenced the LHβ subunit gene of a homozygous person.DESIGNAccording to the ratio of two immunoassays, one detecting only WT‐LH and the other detecting equally WT and V‐LH, individuals can be classified as homozygotes for the V‐LHβ allele, heterozygotes or WT. DNA samples from persons with known LH status, according to the immunoassays, were used for the development and evaluation of a new allele‐specific DNA hybridization assay. This assay, and PCR and restriction fragment length polymorphism analysis, were used to determine the frequency of the V‐LHβ allele in DNA samples obtained from eight populations.PATIENTSAmbulatory adult men and women, apparently healthy and with no endocrine disorders.RESULTSThe LH genotyping by immunoassays and by the new hybridization method gave identical results with all samples analysed (n = 25). The V‐LHβ subunit was observed to always have the two point mutations, and to be identical with the ones previously reported. The V‐LHβ carrier frequency in the DNA samples collected from various populations varied between 0 and 53.5%.CONCLUSIONSThe immunoassay technique and the hybridization assay can be used as alternatives to determine the LH status. A great variation in carrier frequency of the V‐LHβ allele is observed in different populations.
Increased incidence of neoplasia in patients with pituitary adenomas
Authors: Popovic V. , Damjanovic S. , Micic D. , Nesovic M. , Djurovic M. , Petakov M. , Obradovic S. , Zoric S. , Simic M. , Penezic Z. , Marinkovic J. , The Pituitary Study Group  
Published: March 2003

OBJECTIVEThe goal of our study was to determine the rate of neoplasms in patients with other pituitary adenomas (non‐functioning and prolactinomas) in comparison with acromegaly which is known to favour the development of neoplasia.DESIGN AND PATIENTSWe reviewed clinical records for 220 patients with acromegaly, 151 patients with non‐functioning pituitary adenoma (NF) and 98 patients with prolactinomas. Incidence rates of cancer for patients with pituitary tumours were calculated per person‐years of follow‐up study. These rates were then compared with sex and age adjusted incidence rates reported by National Tumour Registry. An internal control group of 163 subjects with a non‐neoplastic condition, i.e. Graves' disease followed chronically in the same clinic was also studied. The ratios observed to expected were expressed as standardized incidence rates (SIR). The only significant difference between the acromegalic and other pituitary tumours patients was in hypopituitarism, present in 18.2% (acromegaly) 47% (NF) and 18.6% (prolactinomas).RESULTSTwenty‐three malignant tumours were registered in 19 acromegalics (1 Hodgkin disease, 1 myelogenous leukaemia, 1 lymphocytic leukaemia , 3 papillary thyroid carcinomas, 1 ovarian carcinoma, 2 colorectal carcinoma, 1 renal cell carcinoma, 4 cervical carcinoma, 2 skin cancers, 2 pancreatic carcinoma, 4 breast carcinoma, 1 bladder carcinoma). Three acromegalics harboured two malignancies. Patients with acromegaly had a 3.39‐fold increased rate of malignant tumours compared with the general population and a 3.21‐fold increased rate compared with our internal control group. Eleven malignant tumours were found in patients with NF‐pituitary adenomas and 2 in prolactinoma patients (1 lymphoma, 1 multiple myeloma, 1 colonic cancer, 1 renal cell cancer, 1 stomach cancer, 2 lung cancers, 1 cervix carcinoma, 1 breast cancer, 1 testicular carcinoma and 3 melanoma). Patients with NF pituitary adenomas had a 3.91‐fold increased rate of malignant tumours compared with the general population and 4.07‐fold increase compared with the internal control group. Patients harbouring prolactinomas did not have an increased incidence rate of malignancy compared with the general population or our internal controls. Female patients with acromegaly and male patients with NF‐pituitary adenoma had higher incidences of neoplasia.CONCLUSIONWe have demonstrated that the overall incidence of malignant tumours in patients with non‐functioning pituitary adenomas and acromegaly is significantly higher than expected for general population and for our internal control group.
The effect of body composition on hexarelin‐induced growth hormone release in normal elderly subjects
Authors: Rahim  , O'Neill  , Shalet  
Published: March 2003

OBJECTIVEGrowth hormone (GH) release is influenced by several factors including age, gender, physical exercise, nutritional status, sex steroids and body composition. The relationship with body composition is complex. Obesity is accompanied by suppression of spontaneous and stimulated GH release. As increasing body fat reduces stimulated GH secretion following a standard provocative test, the potential clinical uses of GH‐releasing peptides (GHRPs), therapeutically or diagnostically, may be dependent on the relationship between body fat and GHRP‐stimulated GH release. We have therefore assessed the effect of body composition and gender on the GH releasing capacity of hexarelin.DESIGNA single bolus of subcutaneous hexarelin at a dose of 1.5 μg per kg of body weight was administered at time 0. Blood samples were taken at − 10, 0, 10, 20, 30, 40, 50, 60, 90, 120, 170 and 180 min.SUBJECTSTwenty‐one (eight male) healthy elderly subjects with a median (range) age of 68 (60–81) years and BMI of 26 (19–30) kg/m2 were studied.METHODSDual‐energy X‐ray absorptiometry (DEXA) was used to assess body composition.RESULTSPeak GH response correlated negatively with fat mass, BMI, percentage body fat, and weight [r = − 0.72, P = 0.0001; r = − 0.56, P = 0.009; r = − 0.63, P = 0.002 and r = − 0.48, P = 0.029, respectively,]. AUC GH correlated negatively with fat mass, BMI and percentage fat mass [r = − 0.58, P = 0.006; r = − 0.51, P = 0.019 and r = − 0.66, P = 0.001 respectively]. Using multiple linear regression, fat mass was the most useful predictor for both peak GH response [R2 = 0.61, P < 0.0001] and AUC GH [R2 = 0.38, P = 0.003]. Gender was not a significant variable.CONCLUSIONSIncreasing total fat mass results in a blunted GH response following subcutaneous hexarelin. Total fat mass appears to be a useful predictor of peak GH response even in normal individuals as none of the subjects in the present study was morbidly obese. This indicates that there is a continuum of effect of fat mass on hexarelin‐stimulated GH release. Any impact of gender on the GH response to hexarelin is almost certainly indirect and mediated via differences in body composition.This observation will have an impact on the potential diagnostic and therapeutic uses of hexarelin and related GH secretagogues.