bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphocyte and mast cell counts are increased in the nasal mucosa in symptomatic natural colds
Authors: ALHO O-P , KARTTUNEN T J , KARTTUNEN R , TUOKKO H , KOSKELA M , UHARI M 
Published: March 2003

SUMMARY
Knowledge of the virus-induced immune response is important in understanding the pathophysiology of respiratory virus infections. Data on the cellular immune response is still limited and based mainly on experimental studies. Natural colds may differ in their pathophysiology from experimentally induced ones. To evaluate the inflammatory cell responses in the upper respiratory tract during natural colds we counted the number of lymphocytes, mast cells and macrophages in the nasal mucosa. Nasal biopsies were taken from 22 adult volunteers during the acute (2–4 days of symptoms) and convalescent phases (day 21) of the cold, and the numbers of cells were counted with immunohistochemical methods. Viral aetiology was identified in 14 (64%) subjects by using viral isolation, antigen detection and rhino-polymerase chain reaction assays. The number of T lymphocytes was increased in the nasal epithelium and that of T and B lymphocytes and mast cells in the subepithelial layer in the acute phase compared to the convalescent phase. Intraepithelial T lymphocyte counts were significantly higher in the subjects who had a proven viral infection or a finding of pathogenic bacteria in the nasopharynx compared to the subjects without such findings (P = 0·005 and P = 0·04, respectively). Contrary to the earlier experimental studies, we found that viruses cause accumulation of T and B lymphocytes and mast cells during the first days of a symptomatic naturally acquired respiratory infection.
γ/δT cell subsets in patients with activeMycobacterium tuberculosisinfection and tuberculin anergy
Authors: SZEREDAY L , BALIKO Z , SZEKERES-BARTHO J 
Published: March 2003

SUMMARYEarlier data suggest that γ/δ T cells may play an important role in the immune response to Mycobacterium tuberculosis. The aim of this study was to determine the percentage of different γ/δ subsets in peripheral blood of active tuberculosis patients with a positive or negative tuberculin reaction. Thirty-eight patients infected with M. tuberculosis and 22 healthy controls were included in the study. Venous blood was taken before starting antimycobacterial treatment. Lymphocytes were reacted with monoclonal antibodies specific for different γ/δ V chains (Vδ1, Vδ2, Vγ9 and Vγ4). The results were analysed in the context of tuberculin reactivity and X-ray findings. Our results revealed a selective loss of Vγ9/Vδ2 T cells in the peripheral blood of tuberculin-negative patients with active tuberculosis compared to healthy controls, while the ratio of Vγ9/Vδ2 T cells in the peripheral blood of patients with a positive skin test did not differ from that of healthy controls. These findings demonstrate a relationship between the loss of the major M. tuberculosis-reactive subset of γδ T cells and the absence of tuberculin reactivity. The data are consistent with the hypothesis that γδ T cells play a role in the protective immune response to M. tuberculosis infection.
Interleukin 10 induced augmentation of delayed-type hypersensitivity (DTH) enhances Mycobacterium bovis bacillus Calmette-Guérin (BCG) mediated antitumour activity
Authors: NADLER R , LUO Y , ZHAO W , RITCHEY J K , AUSTIN J C , COHEN M B , O'DONNELL M A , RATLIFF T L 
Published: March 2003

SUMMARY
Intravesical BCG therapy is effective in the treatment of superficial bladder cancer. Both clinical and experimental results suggest a role for cytokines and delayed-type hypersensitivity (DTH) in BCG-induced antitumour immunity. We characterized the modulatory effects of BCG on bladder cytokine expression and determined the relationship between DTH and BCG antitumour activity. The bladders of mice were instilled with BCG through a catheter. Bladder tissue RNA and urine were collected for evaluation of cytokine expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and/or ELISA. IFN-γ and TNF-α, the two major cytokines associated with DTH, were efficiently induced by BCG. IL10, an important down-regulator of DTH, was also induced by BCG. Constitutive levels of IL4 and IL5 were observed, but neither IL4 nor IL5 were modulated by BCG. Similar results were observed in the kinetic analysis of urinary cytokines in patients after intravesical BCG therapy. Production of Th1 (T helper type 1) cytokines (IFN-γ, IL2 and IL12) preceded that of the Th2 (T helper type 2) cytokine IL10. A tendency toward higher ratios of IFN-γ versus IL10 for BCG responders also was observed. In animal studies the absence of IL10 abrogated either by antibody inhibition or the use of genetically modified, IL10 deficient (IL10–/–) mice resulted in enhanced DTH responses. Under conditions of enhanced DTH, a significant enhancement in antitumour activity was observed. These data demonstrate that DTH and its associated mononuclear infiltration and cytokine production are important to the antitumour activity of intravesical BCG therapy, and suggest that effects to diminish IL10 production may have therapeutic value.
Role of thyroid‐stimulating blocking antibody in patients who developed hypothyroidism within one year after 131I treatment for Graves' disease
Authors: Yoshida Katsumi , Aizawa Yoshihiko , Kaise Nobuko , Fukazawa Hiroshi , Kiso Yoshinori , Sayama Noriyo , Hori Hironobu , Nakazato Naoki , Tani Jun‐ichi , Abe Keishi 
Published: March 2003

OBJECTIVEWe recently reported that thyroid‐stimulating blocking antibody (TSBAb) may not contribute to the development of hypothyroidism more than six years after 131I treatment. In the present study, we attempted to determine whether hypothyroidism that develops within a shorter period of time following 131I therapy is associated with TSBAb.DESIGNRetrospective study.PATIENTSSera were obtained from 8 patients who developed hypothyroidism within 6 months after 131I therapy (Group 1), 8 patients who became euthyroid one year after 131I therapy (Group 2), and 7 patients who developed transient hypothyroidism (Group 3).MEASUREMENTSThyroid stimulating antibody (TSAb) activity was measured as the amount of cyclic adenosine monophosphate (cAMP) produced by cultured FRTL‐5 cells, and TSBAb activity as the inhibition of cAMP produced in response to 100 mU/l bovine TSH.RESULTSAt about 3 months after 131I treatment, TSAb activity increased significantly in Groups 2 and 3, but did not change in Group 1. In contrast, TSBAb activity in Group 1 increased significantly and was positive in 6 patients at that time. At 12–18 months after 131I treatment, TSBAb activity tended to decrease and remained positive in 3 patients but became negative in 3 patients. It did not change in the patients in Groups 2 and 3. The patients in Group 1 were treated with levothyroxine, 75–125 μg/day. Levothyroxine was discontinued in the 3 patients whose TSBAb activity disappeared. Two of them remained euthyroid, and 1 became hypothyroid.CONCLUSIONResults indicate that the hypothyroidism that develops within a short time after 131I treatment may be caused by TSBAb activity. Thyroid function may be recovered when TSBAb activity disappears.
Gonadal status is an important determinant of bone density in acromegaly
Authors: Lesse  , Fraser  , Farquharson  , Hipkin  , Vora  
Published: March 2003

OBJECTIVETo measure bone mineral density (BMD) in patients with acromegaly and to look for clinical features which may explain previously reported discrepant results.DESIGNProspective case controlled observational study.PATIENTS18 patients with acromegaly (seven women, 11 men; mean age 53.2±3.5 years). Eight patients had active disease and 10 had controlled acromegaly. Growth hormone and insulin‐like growth factor‐1 (IGF‐1) concentrations were measured to assess disease activity.MEASUREMENTSBMD was measured at four sites on the lumbar spine, three at the femoral neck and at Ward's triangle using a Hologic dexa scanner. Results were compared to a locally determined control population (n=1800). In eight patients with active acromegaly, urinary free pyridinoline and deoxypyridinoline, and serum osteocalcin, propeptide of type 1 procollagen, vitamin D, 1000 h parathyroid hormone, bone specific alkaline phosphatase, calcium and phosphate concentrations were measured before and after 6 months treatment with octreotide.RESULTSThe mean BMD for all acromegalic patients was not significantly different from the control population except at the femoral neck where it was increased (P=0.05). At all sites, the BMD of patients who had been hypogonadal (n=12/18) was significantly lower (P<0.05–0.01) than that of patients who had been eugonadal (n=6/18). BMD for hypogonadal patients was lower than the control population at Ward's triangle (P=0.03). Eugonadal acromegalic patients had BMD greater than non‐ acromegalic controls at all sites. Patients with controlled acromegaly had a higher BMD than non‐acromegalic controls, but there were no differences in BMD between patients with active and controlled acromegaly. Serum IGF‐1 concentrations decreased from 64.5±5.1 nmol/l to 37.5±6.9 nmol/l (P=0.02) after 6 months treatment with octreotide, but there was no change in any of the biochemical markers of bone turnover.CONCLUSIONSEugonadal acromegalic patients have increased lumbar spine and femoral neck BMD compared to hypogonodal acromegalic patients and the general population, but it is reduced if patients have been hypogonadal.
Lean body mass as a determinant of thyroid size
Authors: Wesche Maria F. T. , Wiersinga Wilmar M. , Smits Nico J. 
Published: March 2003

OBJECTIVEMales have a larger thyroid gland than females, and this has been related to the difference in body weight. In view of the different body composition of men and women, we hypothesized that lean body mass is a better determinant of thyroid volume than body weight.DESIGNA cross‐sectional study in an area not deficient in iodine.SUBJECTS44 non‐obese healthy adults (group I, 21 men, 23 women with equal distribution of sexes in age groups between 21 and 70 years) and 20 adults with marked obesity (group II, 8 men, 12 women, BMI > 30 kg/m2) were studied. None used medication and all had normal thyroid function tests.MEASUREMENTSThyroid volume was measured by ultrasonography, and lean body mass with a body impedance analyser.RESULTSThe thyroid volume in men was larger than in women in both groups; it was also larger in the obese than in the non‐obese subjects. In the non‐obese subjects, thyroid volume was related both to body weight (r = 0.42, P < 0.005) and to lean body mass (r = 0.55, P = 0.0001). In the obese subjects, thyroid volume was no longer related to body weight (r = 0.23, NS) but was still correlated with lean body mass (r = 0.54, P = 0.01). Taking both groups together, the correlation between thyroid volume and lean body mass (r = 0.64, P < 0.001) was stronger than between thyroid volume and body weight (r = 0.50, P < 0.001). Thyroid volume was also related to body length (group I, r = 0.42, P < 0.005; group II, r = 0.54, P = 0.01), but to body‐surface area only in the non‐obese subjects (group I, r = 0.45, P < 0.01; group II, r = 0.38, NS). The larger thyroid size in the obese was associated with slightly but significantly higher TSH and lower free T4 serum concen_trations as compared to the non‐obese subjects.CONCLUSIONSIn healthy adults, lean body mass rather than body weight explains the differences in thyroid volume between males and females and between obese and non‐obese subjects. Lean body mass appears to be a major determinant of thyroid size.
The low dose ACTH test in chronic fatigue syndrome and in health
Authors: Scott Lucinda V. , Medbak Sami , Dinan Timothy G. 
Published: March 2003

OBJECTIVEA number of dynamic tests of the hypothalamic–pituitary–adrenal axis provide evidence for a mild cen_tral adrenal insufficiency in chronic fatigue syndrome (CFS). The 1 μg adrenocorticotropin (ACTH) test has been proposed to be more sensitive than the standard 250 μg ACTH test in the detection of subtle pituitary–adrenal hypofunctioning. We aimed to establish whether the 1 μg ACTH test would support such a dysregulation in CFS, and also, given the relative novelty of this test in clinical practice and the uncertainty with regard to appropriate cut‐off values for normality, to compare our healthy volunteer data with those of previous studies.PATIENTS AND DESIGNTwenty subjects with CFS, diagnosed according to Cen_tres for Disease Control and Prevention criteria, were compared with 20 healthy volunteer subjects. All participants underwent a 1 μg ACTH test beginning at 1400 h. Plasma samples for cortisol estimation were drawn at 0, +30 and +40 min.RESULTSBaseline cortisol values did not differ between CFS patients and healthy subjects. The δ cortisol (maximum increment from baseline) value was significantly lower in the CFS than the volunteer group (P < 0.05). Comparison of the + 30 min cortisol values revealed no significant differences. Using an incremental cortisol of > 250 nmol/l as an arbitrary cut‐off point, two (10%) of the healthy subjects and nine (45%) of the CFS subjects failed the test on this basis (χ2 = 4.3, df = 38, P < 0.05).CONCLUSIONSThis study provides further evidence for a subtle pituitary–adrenal insuffiency in subjects with chronic fatigue syndrome compared to healthy volunteers. Disparities between our healthy volunteer data and those of other groups using the 1 μg ACTH test suggest that the test may not be as reliable as previously indicated.
Elevated serum granulocyte colony‐stimulating factor levels in patients with Graves' disease
Authors: Iitaka Makoto , Noh Jaeduk Yoshimura , Kitahama Shinji , Fukasawa Nobuhiko , Miura Shiro , Kawakami Yoshito , Kawasaki Satomi , Yamanaka Kayo , Ishii Jun , Katayama Shigehiro , Ito Kunihiko 
Published: March 2003

OBJECTIVEAgranulocytosis is a serious side effect of anti‐thyroid drugs (ATD). Granulocyte colony‐stimulating factor (G‐CSF) is one of the cytokines that increase granulocyte number. The aim of this study was to examine the sequential variation of serum G‐CSF levels in patients with Graves' disease before and after ATD therapy.PATIENTSSixty‐three patients with Graves' disease were studied before, during and after treatment with methimazole (MMI). Serum samples from 71 healthy subjects were used as controls.DESIGN AND MEASUREMENTSSerum levels of G‐CSF were measured by a novel chemiluminescent enzyme immunoassay, which was sensitive enough to determine G‐CSF levels in healthy subjects. Blood granulocyte counts, serum, thyroid hormone and TSH levels, and titres of thyroid autoantibodies were also measured.RESULTSSerum G‐CSF levels in Graves' patients before and 2 weeks after MMI were significantly higher than in healthy subjects. There was a significant correlation between serum G‐CSF levels and granulocyte counts in untreated patients with Graves' disease. Untreated patients with granulocyte counts less than 2 × 109/l had significantly lower serum G‐CSF levels as compared with other untreated patients. Serum G‐CSF levels gradually decreased thereafter. No correlation was observed between serum G‐CSF levels and serum thyroid hormone levels or titres of thyroid autoantibodies. After ATD treatment, no correlation was found between serum G‐CSF levels and granulocytes counts. There was no significant correlation between the change of serum G‐CSF levels and that of granulocyte counts before and after MMI treatment. Graves' patients with mild agranulocytosis had normal or elevated serum G‐CSF levels.CONCLUSIONSSignificantly elevated serum G‐CSF levels were observed in patients with Graves' hyperthyroidism. During ATD therapy, deficiency of G‐CSF was not identified as a cause of agranulocytosis in this study.
Determinants of serum insulin‐like growth factor I in growth hormone deficient adults as compared to healthy subjects
Authors: Jørgensen Jens O. L. , Vahl Nina , Hansen Tony B. , Skjærbæk Christian , Fisker Sanne , Ørskov Hans , Hagen Claus , Christiansen Jens. S. 
Published: March 2003

OBJECTIVEGrowth hormone status is an important determinant of serum IGF‐I but it is well known that hypopituitary adults with pronounced GH‐deficiency (GHDA) may exhibit normal IGF‐I levels. To elucidate possible causes of this apparent paradox we compared the significance of putative IGF‐I predictors in GHDA and normal subjects.DESIGNA cross‐sectional study.SUBJECTSTwenty‐seven GHDA (9 females, 18 males, mean ± SE age 44 ± 1 years) and 27 healthy control subjects (9 females, 18 males, mean ± SE age 43 ± 2 years).RESULTSSerum IGF‐I and IGFBP‐3 were significantly lower in GHDAs, but a considerable overlap existed (IGF‐I (μg/l) 87 ± 12 (GHDA) vs 177 ± 10 (Control) (P < 0.001)). In both Controls and GHDA, IGF‐I was higher in males than females (Control: 196 ± 12 vs 138 ± (P = 0.004); GHDA: 97 ± 16 vs 56 ± 11 (P = 0.05)). In GHDA, males on testosterone substitution had the highest IGF‐I concentrations. The molar IGF‐I:IGFBP‐3 ratio was significantly lower in GHDAs (0.18 ± 0.01 vs 0.23 ± 0.02 (P = 0.002)). IGFBP‐1 (μg/l) was significantly elevated in GHDAs (6.28 ± 1.11 vs 3.07 ± 0.32 (P < 0.001)) despite comparable fasting insulin levels. Percentage total body fat (TBF, DEXA, waist/hip ratio, and intra‐abdominal fat (CT) were all elevated in GHDAs. IGF‐I correlated positively with lean body mass (DEXA) and negatively with TBF and IGFBP‐1 in both groups. IGF‐I correlated negatively with age in CON but not in GHDAs, whereas IGF‐I correlated positively with IGFBP‐3 only in GHDAs. Multiple regression analysis revealed that age and IGFBP‐1 were the only significant predictors of IGF‐I in CON, whereas IGFBP‐3 and, to a lesser extent TBF, were the only independent predictors of IGF‐I in GHDAs. Neither peak stimulated GH, nor physical fitness contributed in any equations in the two groups.CONCLUSIONS1) IGF‐I levels are regulated by several variables in addition to GH status 2) age per se is an independent negative determinant in healthy subjects but not in GHDA 3) It is probable that some cases of paradoxically high IGF‐I levels in GHDA are secondary to inappropriately elevated IGFBP‐3 levels. 4) in mid‐adulthood males have higher IGF‐I levels than females and it is likely that testosterone directly stimulates IGF‐I. The influence of gender and sex steroids must therefore be accounted for when comparing IGF‐I levels between hypopituitary and healthy subjects.
Effect of corticotrophin‐releasing hormone on arginine vasopressin and atrial natriuretic factor in patients with Cushing's disease
Authors: Colao Annamaria , Pivonello Rosario , Ferone Diego , Faggiano Antongiulio , Facciolli Giuseppina , Di Somma Carolina , Boudouresque Françoise , Oliver Charles , Lombardi Gaetano 
Published: March 2003

OBJECTIVETo evaluate the effect of CRH administration on plasma AVP and ANF concentration in patients with Cushing's disease and healthy subjects.SUBJECTSFifteen patients with Cushing's disease and 15 sex‐ and age‐matched healthy subjects entered the study.STUDY DESIGNAll subjects were randomly given i.v. 100 μg hCRH and placebo (NaCl 0.9%) on two non consecutive days. Blood samples for plasma AVP and ANF assay were taken before and every 15 min for 2 hr after CRH or placebo. Five out of the 15 patients with Cushing's disease underwent a repeat CRH test after surgical cure of the disease.RESULTSAt baseline evaluation, plasma ANF concentrations were significantly higher in patients with Cushing's disease compared to healthy subjects (15.0 ± 0.8 vs 10.8 ± 0.6 pmol/l, P < 0.001) whereas plasma AVP concentrations were similar between the two groups of subjects (8.0 ± 0.4 vs 6.8 ± 0.6 pmol/l). CRH administration induced a significant increase in plasma ANF concentrations both in patients with Cushing's disease (24.0 ± 1.6 pmol/l, P < 0.05) and healthy subjects (29.4 ± 1.5 pmol/l, P < 0.05). Conversely, a significant increase in plasma AVP concentrations was found only in patients with Cushing's disease (14.7 ± 1.4 vs 8.0 ± 0.4 pmol/l, P < 0.05). In addition, patients with Cushing's disease had an increase in ANF levels after CRH significantly lower than that observed in healthy subjects (peak/basal ratio: 1.7 ± 0.1 vs 3.1 ± 0.4, P < 0.01). In 5 patients re‐tested after disease cure, CRH administration significantly increased plasma ANF levels (26.8 ± 1.1 vs 10.7 ± 0.4 pmol/l, P < 0.05) but it did not modify plasma AVP levels (8.4 ± 0.4 vs 7.3 ± 0.5 pmol/l). ANF response to CRH in patients cured from Cushing's disease was similar to that recorded in healthy subjects (peak/basal ratio: 2.6 ± 0.2 vs 3.1 ± 0.4).CONCLUSIONCRH stimulates ANF secretion both in patients with Cushing's disease and healthy subjects. Plasma ANF response to CRH is blunted in patients with Cushing's disease compared to patients cured from Cushing's disease and healthy subjects, probably because of hypercortisolism. By contrast, CRH stimulates AVP secretion only in patients with Cushing's disease, but not in patients cured from Cushing's disease and healthy subjects. This phenomenon could be related to the activity of the disease.
Effect of isoprenaline on plasma leptin and lipolysis in humans
Authors: Pinkney Jonathan H. , Coppack Simon W. , Mohamed‐Ali Vidya 
Published: March 2003

OBJECTIVEThe sympathetic nervous system may play a central role in the regulation of both lipolysis and leptin production. Therefore, we investigated the effect of intravenous infusions of the β‐adrenergic agonist isoprenaline on plasma concentrations of leptin and nonesterified fatty acids.DESIGN AND PATIENTSEight lean, healthy human volunteers, (4M:4F; median (interquartile range) age 36.5 (30.8‐40.0) years; BMI 22.9 (20.1‐29.2)kg.m−2; % body fat 24.5 (17.9–26.3)), were studied following an overnight fast. Intravenous infusion of isoprenaline was carried out for 3 h, followed by a 1 hour recovery phase. The isoprenaline infusion rates (0.5–3.5 μg.min−1) were titrated individually for each subject in order to achieve similar biological sympathetic responses based on heart rate (target heart rates were > 100 min−1 but < twice resting heart rate).MEASUREMENTSPlasma leptin was determined using an in‐house radioimmunoassay, nonesterified fatty acids estimated with an enzymatic colourimetric assay and insulin concentrations were assayed using a specific, two‐site immunoenzymometric assay.RESULTSFasting preinfusion plasma leptin concentrations (6.3 (3.0–12.8)μg/l) correlated with percentage body fat measured by bioimpedance (r = 0.95; P < 0.001). Plasma leptin concentrations were rapidly suppressed by isoprenaline, with maximal suppression (20.5 (15.0–25.0)% of preinfusion levels (Wilcoxon rank sum test; P < 0.05)), observed after 2 h. In the recovery period, plasma leptin concentrations rapidly returned to preinfusion levels (postinfusion vs maximally suppressed leptin concentrations P < 0.05; vs preinfusion leptin concentrations P = NS). Plasma nonesterified fatty acids and insulin concentrations showed opposite changes to those observed with leptin.CONCLUSIONPlasma leptin concentrations are rapidly and reversibly suppressed by the infusion of isoprenaline in humans in vivo.