bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dendritic cells infected with adenovirus expressing the thyrotrophin receptor induce Graves’ hyperthyroidism in BALB/c mice
Authors: KITA-FURUYAMA M , NAGAYAMA Y , PICHURIN P , MCLACHLAN S M , RAPOPORT B , EGUCHI K 
Published: March 2003

SUMMARYDendritic cells (DCs) are the most potent antigen-presenting cells and a prerequisite for the initiation of primary immune response. This study was performed to investigate the contribution of DCs to the initiation of Graves’ hyperthyroidism, an organ-specific autoimmune disease in which the thyrotrophin receptor (TSHR) is the major autoantigen. DCs were prepared from bone marrow precursor cells of BALB/c mice by culturing with granulocyte macrophage-colony stimulating factor and interleukin−4. Subcutaneous injections of DCs infected with recombinant adenovirus expressing the TSHR (but not β-galactosidase) in syngeneic female mice induced Graves’-like hyperthyroidism (8 and 35% of mice after two and three injections, respectively) characterized by stimulating TSHR antibodies, elevated serum thyroxine levels and diffuse hyperplasitc goiter. TSHR antibodies determined by ELISA were of both IgG1 (Th2-type) and IgG2a (Th1-type) subclasses, and splenocytes from immunized mice secreted interferon-γ (a Th1 cytokine), not interleukin-4 (a Th2 cytokine), in response to TSHR antigen. Surprisingly, IFN-γ secretion, and induction of antibodies and disease were almost completely suppressed by co-administration of alum/pertussis toxin, a Th2-dominant adjuvant, whereas polyriboinosinic polyribocytidylic acid, a Th1-inducer, enhanced splenocyte secretion of IFN-γ without changing disease incidence. These observations demonstrate that DCs efficiently present the TSHR to naive T cells to induce TSHR antibodies and Graves’-like hyperthyroidism in mice. In addition, our results challenge the previous concept of Th2 dominance in Graves’ hyperthyroidism and provide support for the role of Th1 immune response in disease pathogenesis.
Circulating endothelial cells in Kawasaki disease
Authors: NAKATANI K , TAKESHITA S , TSUJIMOTO H , KAWAMURA Y , TOKUTOMI T , SEKINE I 
Published: March 2003

summary
Recent reports have demonstrated that circulating endothelial cells (CECs) are observed in several diseases with vascular injury. Because Kawasaki disease (KD) is one type of systemic vasculitis, we hypothesized that an increased number of CECs may be associated with the appearance of complicated coronary artery lesions (CAL). In the present study we investigated the enumeration and origin of CECs in 20 patients with KD, using an immunohistochemical method with monoclonal antibodies: clone P1H12 against ECs and clone AC133 against endothelial progenitor cells (EPCs), which were derived from the bone marrow. The mean number of CECs increased significantly (P &lt; 0·05) from the acute through the subacute phases of KD compared with both the convalescent phase of KD and healthy children. The mean number of CECs was significantly (P &lt; 0·05) higher in six KD patients with CAL than in 14 KD patients without CAL. The population of EPCs in the total CECs in KD was 4·4 ± 1·2% (range 0–18%). The number of EPCs during the subacute phase was also significantly higher (P &lt; 0·05) in KD patients with CAL than in those without CAL. Our findings indicate that the number of CECs increase in KD vasculitis and suggest that the increased numbers of CECs and EPCs may reflect the EC damage of this disease.
Oxygen free radicals and systemic autoimmunity
Authors: AHSAN H , ALI A , ALI R 
Published: March 2003

SummaryReactive oxygen species generated during various metabolic and biochemical reactions have multifarious effects that include oxidative damage to DNA leading to various human degenerative and autoimmune diseases. The highly reactive hydroxy radical (·OH) can interact with chromatin and result in a wide range of sugar and base-derived products, DNA–protein cross-links and strand breaks. Studies from our laboratory have demonstrated that after modification the DNA becomes highly immunogenic and the induced antibodies exhibit variable antigen-binding characteristics. Systemic lupus erythematosus, a prototype autoimmune disease, is characterized by the presence of autoantibodies to multiple nuclear antigens. The detection of 8-hydroxyguanosine in the immune complex derived DNA of systemic lupus erythematosus patients reinforces the evidence that reactive oxygen species may be involved in its pathogenesis. Increased apoptosis and decreased clearance of apoptotic cells as observed in systemic lupus erythematosus (SLE) might well be a contributory factor in systemic autoimmunity. Clinically, titres of autoantibodies are closely related to the degree of renal inflammation. Anti-DNA antibodies may combine with circulating antigen and contribute to the deposition of immune complexes in renal glomeruli.
Combination therapy with GH and cyproterone acetate does not improve final height in boys with non‐GH‐deficient short stature
Authors: Kawai Masahiko , Momoi Toru , Yorifuji Tohru , Muroi Junko , Yamanaka Chutaro , Sasaki Hiroshi , Furusho Kenshi 
Published: March 2003

BACKGROUND AND OBJECTIVERecently, we reported that GH therapy without gonadal suppression (GS) decreased the final height of boys with non‐GH‐ deficient short stature by decreasing the height standard deviation score (SDS) for bone age (BA) during puberty. Combination therapy with GH and GS has been reported to suppress bone maturation and improve final height in some cases. We evaluated the effects of combination therapy with GH and GS using cyproterone acetate on the final height of boys with non‐GH‐deficient short stature.PATIENTSFifty nine boys with non‐GH deficient short stature were observed retrospectively until they reached their final height. The boys were divided into 3 groups: Group A consisted of 26 boys who were not treated with GH, group B consisted of 13 boys who were treated with GH alone, and group C consisted of 20 boys who were treated with combination therapy with GH and GS using cyproterone acetate. At the start of observation, the height SDS for BA and projected height were matched among these three groups.RESULTSThe mean ± SDS of the final height for groups A, B, and C were 162.7 ± 5.3 cm, 155.4 ± 4.9 cm, and 161.9 ± 3.2 cm, respectively. GH therapy did not affect the height SDS for BA during the prepubertal period. GH therapy without GS decreased the height SDS for BA during puberty in group B. Combination therapy with GH and cyproterone acetate increased the height SDS for BA between 12 and 14 years BA in group C. However, after GS therapy was discontinued at 14 years BA, the height SDS for BA gradually decreased and eventually reached the same value as that in group A.CONCLUSIONSGH therapy during the prepubertal period did not improve the final height of boys with non‐GH‐deficient short stature. GH therapy without GS decreased pubertal height gain, resulting in reduced final height. Combination therapy with GH and GS using cyproterone acetate decelerated the bone maturation during puberty which might be accelerated by GH therapy, but did not improve the final height which might have been attained without treatment.
Aromatase in the human central nervous system
Authors: Sasano Hironobu , Takahashi Kazuhiro , Satoh Fumitoshi , Nagura Hiroshi , Harada Nubuhiro 
Published: March 2003

OBJECTIVEOestrogen produced locally by aromatase is thought to participate in numerous biological functions in the adult central nervous system (CNS). However, little is known about aromatase expression in the human CNS.DESIGNWe examined aromatase expression in human brain regions, (4 men, 2 women) obtained from autopsy, by reverse transcriptase (RT)‐polymerase chain reaction (PCR) and also studied alternative use of multiple exons 1 of its gene, which is involved in tissue specific expression of aromatase in human.RESULTSThe amount of aromatase mRNA determine by RT‐PCR assay in 6 cases tended to be highest in pons, thalamus, hypothalamus and hippocampus. Analysis of multiple exons 1 revealed that 1f, considered specific for brain, as well as 1b (fibrolast type) and 1d (gonadal type), were expressed. 1d and 1f tended to be utilized in hypothalamus, thalamus and amygdala. The amount of overall mRNA expression was also higher in hypothalamus, thalamus and amygdala than in other regions of the brain. There were no differences of utilization of exons 1 and mRNA expression of aromatase between female and male brain.CONCLUSIONSThese results demonstrate that aromatase is expressed widely in various regions of human brain tissues in both men and women.
A randomized trial of short‐term treatment of Graves' disease with high‐dose carbimazole plus thyroxine versus low‐dose carbimazole
Authors: Grebe Stefan K. G. , Feek Colin M. , Ford Henry C. , Fagerström Jocelyn N. , Cordwell Diane P. , Delahunt John W. , Toomath Robyn J. 
Published: March 2003

OBJECTIVEThe optimal treatment regimen with thionamide drugs remains a matter for debate. We have investigated whether high doses of carbimazole, when compared with low doses, reduce relapse rates of Graves' disease.DESIGNIn an open label, randomized, prospective trial of treatment of Graves' disease we compared high doses of carbimazole (6 months of 100 mg carbimazole per day plus thyroxine) to low‐dose carbimazole treatment (starting at 25 mg and titrating the carbimazole dose with the aim to maintain serum thyroid function test results within the normal reference range).PATIENTSThirty‐seven patients with a first episode of Graves' disease were enrolled.MEASUREMENTSDuring the 6 months of treatment we evaluated the rate of normalization of serum thyroid function tests, changes in serum thyroid auto‐antibody levels and the rate of side‐effects during treatment. After completion of the 6‐month treatment course patients were observed for 2 years for evidence of relapse of Graves' disease.RESULTSThere were no differences between the two groups either in the rate of normalization of serum thyroid function tests or in serum thyroid auto‐antibody levels during treatment. Of the 17 patients randomized to high‐dose treatment seven suffered treatment side‐effects, compared to only one of the 20 patients receiving low‐dose treatment (P < 0.006). There was no significant difference in 2‐year post‐treatment remission rates on an intention‐to‐treat basis between the two treatment groups (18.7% vs. 5.9%, P = NS). However, for those patients who completed 6 months of treatment (high‐dose group = 9, low‐dose group = 16), multivariate survival analysis demonstrated a significantly longer median relapse‐free interval (P < 0.04) in the high‐dose group (27 weeks; 25th percentile: 9.6 weeks, 75th percentile: 75 weeks) versus the low‐dose group (6 weeks; 25th percentile: 4.8 weeks, 75th percentile: 13.1 weeks).CONCLUSIONSHigh‐dose carbimazole treatment delays, but does not prevent, relapse from Graves' disease in those patients able to tolerate the treatment. However, it leads to more frequent side‐effects than conventional dose treatment.
Lipoprotein lipase mass and activity in post‐heparin plasma from subjects with intra‐abdominal visceral fat accumulation
Authors: Kobayashi Junji , Tashiro Jun , Murano Shunichi , Morisaki Nobuhiro , Saito Yasushi 
Published: March 2003

OBJECTIVESThe purpose of this study was to investigate the possibility of impaired lipolysis of triglyceride‐rich lipoproteins in patients with abdominal visceral fat accumulation by assessing two major lipolytic enzymes in the plasma, lipoprotein lipase (LPL) and hepatic lipase (HL).DESIGN AND PATIENTSA total of 31 patients [20 men, 11 women, age 50 ± 7 years old, body mass index (BMI) 26 ± 2 kg/m2 (mean ± sd)] were analyzed. Visceral fat and subcutaneous fat areas were evaluated using a computerized tomographic (CT) method at the level of the umbilicus. Total lipolytic activity in the postheparin plasma (PHP) was measured using Triton X‐100‐emulsified triolein and LPL activity was calculated as the activity in whole plasma inhibited by the 5D2 monoclonal antibody for LPL. LPL enzyme mass was determined by a sandwich enzyme immunoassay.RESULTSThe visceral fat area was found to be negatively correlated with LPL mass (V vs LPL mass, r = − 0.37, P = 0.04) in PHP and had a tendency toward negative correlation with the LPL activity in the PHP (V vs LPL activity, r = − 0.29, P = 0.12). Subcutaneous fat area, on the other hand, did not show any correlation with LPL activity (r = 0.13, P = 0.49) or mass (r = 0.22, P = 0.25) in the PHP. The visceral fat area was found to be positively correlated with fasting serum insulin levels (r = 0.67, P < 0.01). Body mass index (BMI) was not correlated with LPL mass or activity in the PHP. Multi‐regressional analysis showed that abdominal visceral fat could be correlated with LPL mass in the PHP, independently of fasting serum insulin. The HL activity from PHP of the patients did not show significant correlation with visceral fat area, subcutaneous fat area or body mass index.CONCLUSIONSFat distribution affects LPL mass and activity, either directly or via another metabolic abnormality such as insulin resistance, leading to impaired hydrolysis of triglycerides in chylomicrons and very low density lipoproteins (VLDL) in these subjects.
Fibromyalgia — a syndrome associated with decreased nocturnal melatonin secretion
Authors: Wikner Johan , Hirsch Ulf , Wetterberg Lennart , Röjdmark Sven 
Published: March 2003

OBJECTIVEMost patients with fibromyalgic syndrome (FMS) complain of sleep disturbances, fatigue, and pain. These symptoms might be a consequence of changed melatonin (MT) secretion, since MT is known to have sleep promoting properties. Moreover, serum concentrations of two MT precursors (tryptophan and serotonin) — affecting both sleep and pain perception — appear to be low in patients with FMS. Therefore, the objective of this investigation was to study whether serum MT (s‐MT) level is also low in these patients.DESIGNEight patients with FMS and 8 healthy sex‐, BMI‐, and age‐matched controls were included in the study. s‐MT concentrations were determined every second hour between 1800 and 0800 h. Urine was collected between 2200 and 0700 h for determination of urinary MT excretion. To evaluate total MT secretion between 1800 and 0800 h and MT secretion during the hours of darkness (between 23 and 07 h) individual MT areas under the curve (AUC) were calculated and expressed as group means.RESULTSThe FMS patients had a 31% lower MT secretion than healthy subjects during the hours of darkness (MT AUC 2300–0700 h (mean ± SEM): 1.70 ± 0.17 vs 2.48 ± 0.38 nmol/l; P < 0.05). Also the s‐MT peak value was significantly lower in the patient group: 0.28 ± 0.03 vs 0.44 ± 0.06 nmol/l; P < 0.05).CONCLUSIONPatients with fibromyalgic syndrome have a lower melatonin secretion during the hours of darkness than healthy subjects. This may contribute to impaired sleep at night, fatigue during the day, and changed pain perception.
Reproducibility of the low dose dexamethasone suppression test: comparison between direct plasma and salivary cortisol assays
Authors: Reynolds  , Bendall  , Whorwood  , Wood  , Walker  , Phillips  
Published: March 2003

BACKGROUNDThe low dose dexamethasone suppression test (DST) has been used to detect subtle variations in the feedback suppression of the hypothalamic–pituitary–adrenal axis, which may contribute to the pathogenesis of several diseases including depression, the metabolic syndrome and coronary artery disease. Little is known about the reproducibility of this test, or whether the test can be combined with analysis of salivary cortisol which would offer a significant advantage over plasma in population studies.SUBJECTS AND DESIGNA low dose DST was carried out in 29 healthy subjects (14 men, 15 women), aged 24–54 (mean 35.1) years, on two separate occasions 1–10 weeks apart. Following the administration of 0.25 mg dexamethasone (DXM) at 2200 h, plasma and saliva were sampled at 0830 h the next day. Cortisol was measured by radioimmunoassay in plasma and time‐resolved immunofluorescent assay (‘DELFIA’) in saliva. Bland–Altman plots were produced for post‐DXM plasma and salivary cortisol measures and used to derive a coefficient of repeatability for each measure, which describes the range of cortisol measurements within which 95% of repeated measurements will fall.RESULTSThe baseline, pre‐DXM cortisol concentrations were far more variable for saliva (mean 16.5, range 4.4–34 nmol/l) than for plasma (mean 407.5; range 232–958 nmol/l). Following DXM both measurements showed an approximately 30% suppression from baseline but the variability of salivary cortisol was much greater. From the Bland–Altman plots the 95% range for the differences about their mean was calculated and used as an indication of repeatability. For plasma 95% of differences were within 0.78 log units, indicating that a repeated measurement was approximately half as small or twice as large as the first. For saliva 95% of differences were within 1.64, indicating that a repeated measurement was approximately five times as small or five times as large as the first.CONCLUSIONSAssessment of dexamethasone suppression by salivary cortisol measurement is far less repeatable than the use of plasma cortisol. In the context of field studies of dexamethasone suppression, salivary cortisol measurements may only be appropriate for large numbers of subjects.
Is opioidergic activity responsible for the circadian variation observed in the gonadotrophin responsiveness of early follicular phase women?
Authors: Rossmanith Winfried G. , Grasshof Claudia 
Published: March 2003

OBJECTIVESIn women, the gonadotrophin response to gonadotrophin‐releasing hormone (GnRH) displays a circadian rhythm during the early follicular phase (EFP), with GnRH‐stimulated luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) release found to be markedly decreased at night. Since the opioidergic inhibition of gonadotrophin secretion is selectively enhanced at night, we reasoned that the circadian changes in the gonadotrophin responsiveness to GnRH might be related to a nocturnal increase of opioidergic activity.STUDY DESIGNEleven women with normal menstrual cycles were studied in the EFP on four different occasions in random order. Studies were conducted either during the day (0900–1300 h) or at night (2100–0100 h). During these times, GnRH (25 μg i.v.) was administered in conjunction with either saline (as control) or naloxone (4 mg i.v.).MEASUREMENTSFrequent blood samples were obtained before and after GnRH stimulation for determination of basal sex steroid and gonadotrophin concentrations by immunoradiometric assays.RESULTSWhile oestradiol levels were comparable (P  > 0.3) at all times, progesterone concentrations were significantly (P < 0.01) higher during day than during night hours, with no difference between control and naloxone conditions. Gonadotropin responses to GnRH stimulation were not significantly different between day and night times, nor did they vary between control and naloxone conditions.CONCLUSIONSOpioidergic blockade imposed by naloxone did not noticeably change GnRH‐stimulated gonadotrophin release at any of the study times. We therefore infer that mechanisms other than a nocturnal increase of opioidergic inhibition may account for eventual circadian changes in the gonadotrophin responsiveness of early follicular phase women.
The use of β‐subunits of gonadotrophin hormones in the follow‐up of clinically non‐functioning pituitary tumours
Authors: Greenman Yona , Tordjman Karen , Sömjen Dalia , Reider‐Groswasser Irith , Kohen Fortune , Ouaknine George , Stern Naftali 
Published: March 2003

OBJECTIVEClinically nonfunctioning pituitary adenomas (NFA) are mostly of gonadotroph origin. However, increased levels of circulating hormones or subunits in patients with NFA usually do not cause clinical symptoms, nor are they used as biological tumour markers. In this study we assessed the value of measuring β subunits of gonadotrophin hormones in the post‐operative follow‐up of patients bearing these tumours.DESIGNPatients harbouring NFA were studied before and three months after transphenoidal pituitary surgery. β‐LH and β‐FSH levels were measured before and following TRH administration on the two occasions. Hormone levels were analyzed in relation to imaging studies performed before and after surgery.PATIENTSTwenty four patients operated at the Tel Aviv‐Sourasky Medical Centre for NFA.RESULTSPathological β‐FSH and β‐LH levels were detected in 79% and 60% of patients respectively. β‐LH levels decreased after surgery but there were no significant changes in β‐FSH levels. There was a tendency for tumours with high basal β‐LH levels to be larger and to have a poor surgical outcome. Normalization of β‐LH levels post‐operatively was usually associated with a decrease in tumour mass or complete removal of the tumour. Persistent pathological responses of β‐LH to TRH after surgery were common in patients with residual tumours on imaging. Nevertheless there were exceptions to this pattern, rendering post‐operative β‐LH levels insufficiently reliable as a marker for the presence of residual tumour.CONCLUSIONAlthough there appears to be a relationship between β‐LH levels, tumour size and surgical outcome, this association is presently insufficient to allow the routine use of either basal or TRH induced β‐LH responses in the post‐surgical follow‐up of clinically nonfunctioning pituitary adenomas.
Leptin and the pituitary–thyroid axis: a comparative study in lean, obese, hypothyroid and hyperthyroid subjects
Authors: Pinkney Jonathan H. , Goodrick Steven J. , Katz Jonathan , Johnson Andrew B. , Lightman Stafford L. , Coppack Simon W. , Mohamed‐Ali Vidya 
Published: March 2003

OBJECTIVETo study interactions between leptin and the pituitary–thyroid axis, both in euthyroid and dysthyroid states.SUBJECTS AND MEASUREMENTSWe investigated the relationships of plasma leptin to levels of free thyroid hormones and TSH in 18 patients with newly diagnosed hyperthyroidism, 22 with newly diagnosed primary hypothyroidism, and 32 lean (body mass index [BMI] < 30) and 37 obese (BMI > 30 kg/m2) euthyroid subjects. Hypothyroid patients were restudied during thyroxine replacement treatment.RESULTSMedian [interquartile range] plasma leptin concentrations were highest in obese euthyroid subjects (31.5 [19.0–48.0] and in untreated hypothyroid patients (19.2 [11.5–31.5]), and lowest levels in untreated hyperthyroid patients (8.9 [5.5–11.1]) and lean euthyroid control subjects (6.6 [3.9–14.4] μg/l (Kruskall–Wallis one‐way analysis of variance; P < 0.0001). In euthyroid subjects, plasma leptin levels were higher in obese than in lean subjects (P < 0.00001). In obese subjects plasma levels of TSH correlated with percentage body fat (r = 0.67; P < 0.001) and plasma leptin (r = 0.61; P < 0.001). In untreated hyperthyroid subjects plasma leptin was unrelated to free T3, and in untreated hypothyroidism plasma leptin was unrelated to either free T3 or TSH concentrations (all P = NS). In untreated hyperthyroid, but not hypothyroid, patients plasma leptin concentrations correlated with BMI (r = 0.57; P = 0.02). Treatment of hypothyroidism with thyroxine resulted in a significant reduction in plasma leptin concentrations from 20.8 (11.8 to 31.6) to 12.9 (4.6–21.2) μg/l (P = 0.005), but BMI did not change significantly in the hypothyroid subjects being studied prospectively.CONCLUSIONS(i) In euthyroid subjects, plasma leptin and TSH levels correlate, and both are positively correlated with adiposity. (ii) Plasma leptin was significantly elevated in hypothyroid subjects, to levels similar to those seen in obese euthyroid subjects. (iii) Treatment of hypothyroidism resulted in a reduction in the raised plasma leptin levels. The data are consistent with the hypothesis that leptin and the pituitary–thyroid axis interact in the euthyroid state, and that hypothyroidism reversibly increases leptin concentrations.