bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential killing of pre-B acute lymphoblastic leukaemia cells by activated NK cells and the NK-92 ci cell line
Authors: REID G S D , BHARYA S , KLINGEMANN H-G , SCHULTZ K R 
Published: March 2003

SUMMARYThe use of NK cells in adoptive therapy for malignant disease is an area of great potential. Currently the only NK cell line in clinical trials is NK-92, an activated NK cell line with a broad range of cytotoxicity against malignant cells. The activity of NK-92 against pre-B acute lymphoblastic leukaemias, however, is highly variable. In this study we compare the cytotoxic mechanisms and signalling pathways utilized by NK-92 ci and IL-2 activated NK cells to mediate killing of pre-B acute lymphoblastic leukaemia cell lines. Deficiencies in TNF family mediated apoptosis, phosphoinositide-3 kinase dependent and phosphoinositide-3 kinase independent killing limit the efficiency of NK-92 ci against pre-B acute lymphoblastic leukaemia cells. Importantly, treatment of the poorly killed leukaemia cells with TNF-α augmented both phosphoinositide-dependent and -independent cytolysis.
Loss of cytomegalovirus-specific immunological memory in a patient with thymoma
Authors: HUISSOON A P , DAVIES G , COX R A , SLOPER C M L , THOMSON B J , ROBINS R A 
Published: March 2003

SUMMARY
Cytomegalovirus (CMV) retinitis is a re-activation infection associated with severely impaired T cell-mediated immunity. We describe a patient with long-standing Crohn's disease and thymoma who developed severe CMV retinitis. While thymoma can be associated with impaired humoral immunity and a quantitative CD4+ T helper cell deficiency, these were not evident in our patient. However, more detailed investigation of anti-CMV responses showed absence of specific T cell responses to CMV antigen. Normal CMV seropositive controls have detectable proliferation and interferon-γ production by T cells in response to stimulation with CMV antigen, but this was absent in this patient both during the acute infection and in convalescence. Other measures of T cell function were normal. Since CMV retinitis is due to reactivation of latent CMV infection, it appears that selective loss of CMV-specific immunity had occurred, perhaps secondary to a thymoma. The causes of thymoma-associated immune impairment are not understood, but this case demonstrates that selective defects can occur in the absence of global T cell impairment. Opportunistic infections should therefore be suspected in patients with thymoma even in the absence of quantitative immune deficiencies.
Long-term serological evaluation of patients with cystic echinococcosis treated with benzimidazole carbamates
Authors: RIGANÒ R , IOPPOLO S , ORTONA E , MARGUTTI P , PROFUMO E , ALI M D , VICO B D I , TEGGI A , SIRACUSANO A 
Published: March 2003

SUMMARY
Seeking better immunological markers indicating the long-term outcome of cystic echinococcosis (CE) after chemotherapy we studied 23 patients receiving albendazole, clinically followed for 8 years, and grouped ultrasonographically according to therapeutic outcome. Antibody responses against a partially purified fraction of hydatid fluid (HFF) and antigen B (AgB) were evaluated by indirect haemagglutination (IHA), ELISA and immunoblotting (IB). Although IHA titres varied over the course of treatment, differences in mean antibody titres to HFF between groups were significant only at 4 years (P = 0·031). IgG isotype expression remained unchanged during follow-up whereas IgE expression decreased in patients with cured or stable disease. AgB disclosed higher IgG4 expression (P &lt; 10–4; P = 0·025) and lower IgG1 expression than HFF (P &lt; 10–4; P = 0·022). IHA antibody titres were higher in patients with progressive than in those with cured or stable disease, even in those with the same cyst type. ELISA isotype profiles differed between groups, particularly for type CE 3, 4 and 5 cysts: higher serum IgG1 and IgG3, lower IgG4 and IgE in patients with cured or stable disease. Although combined serological testing provides scarce information on the long-term outcome of CE after chemotherapy it may be useful for reviewing in a retrospective study the outcome of a cyst and for assessing the host-parasite relationship.
The Th2-response in mercuric chloride-induced autoimmunity requires continuing costimulation via CD28
Authors: MACPHEE I A M , TURNER D R , YAGITA H , OLIVEIRA D B G 
Published: March 2003

SUMMARYMercuric chloride (HgCl2)-induced autoimmunity in Brown Norway (BN) rats is a highly polarized polyclonal Th2-driven autoimmune response with increased IgE production, lymphoproliferation, vasculitis and proteinuria. The increase in serum IgE concentration is clearly measurable by day 4 after the first HgCl2 injection and peaks between days 15 and 20. Treatment with CD80 and CD86 antibodies prior to administration of HgCl2 completely suppresses the autoimmune process. To determine whether interruption of CD28 signalling after initial stimulation of the Th2-response would be suppressive, antibody treatment was delayed. BN rats were given 5 doses of HgCl2 subcutaneously on alternate days. CD80 and CD86 antibodies, or an isotype control, were given daily for 3 days and then on alternate days until day 12 commencing either on the day of the first HgCl2 injection (day 0) or on days 4 or 8. Treatment from day 0 reduced serum IgE concentrations to below baseline (median 9·34μg/ml on day 0 versus 4·6μg/ml, on day 5, P = 0·03) suggesting that ongoing costimulation via CD28 is required to maintain basal serum IgE production. Delaying treatment until day 4 or day 8 after the first HgCl2 injection resulted in significant inhibition of IgE secretion, lymphoproliferation, and vasculitis, although less markedly than when treatment was commenced on day 0.These data indicate that CD28-mediated costimulation is not only required for the initiation of the Th2-response but is required for maintenance of a maximal response, making this an attractive therapeutic target for antibody-mediated autoimmune diseases.
Changes in thymus volume in adult HIV-infected patients under HAART: correlation with the T-cell repopulation
Authors: RUBIO A , MARTÍNEZ-MOYA M , LEAL M , FRANCO J M , RUIZ-MATEOS E , MERCHANTE E , SÁNCHEZ-QUIJANO A , LISSEN E 
Published: March 2003

Summary
An important thymus role has been suggested in T-cell repopulation after HAART in adult HIV-1 infected patients. Thymus volume increase after treatment has been described in HIV-1 infected children but not in adult patients. The objective of this work was to evaluate the effect of HAART on the thymic volume of adult HIV-1 infected patients and its relation with the T-cell repopulation. Twenty-one adult patients following 24 weeks under HAART were included in the study. All patients underwent a thoracic computed tomography (CT) evaluation for the measurement of thymic volumes at weeks 0, 12 and 24.
Baseline thymus volume showed a significant correlation with the patient's age. Thymic volume significantly increased after 24 weeks of HAART. Besides, a significant correlation between changes in the thymus volume and changes in both total and naïve CD4+ cell counts was found. Only patients with increases ≥100 CD4+ cell counts after treatment significantly increased the thymic volume.
These data show the first evidence of an early change in thymic volume of adult HIV-1 infected patients under HAART. This increase was related to the rise of both total and naïve CD4+ cell counts suggesting a functional role of thymic volume increase.
Elevated levels of soluble CD163 in sera and fluids from rheumatoid arthritis patients and inhibition of the shedding of CD163 by TIMP-3
Authors: MATSUSHITA N , KASHIWAGI M , WAIT R , NAGAYOSHI R , NAKAMURA M , MATSUDA T , HOGGER P , GUYRE P M , NAGASE H , MATSUYAMA T 
Published: March 2003

SummaryThe aim of the present study was to evaluate levels of soluble CD 163 in sera and fluids from rheumatoid arthritis (RA) patients and elucidate the mechanism that regulates the shedding of CD163. Levels of soluble CD163 in sera and fluids from RA patients were examined by a sandwich enzyme immunoassay and Western blotting. To determine the effects of tissue inhibitors of metalloproteinase (TIMPs) on the shedding of CD163 from monocytes/macrophages, levels of soluble CD163 in cultures of monocytes/macrophages and the expression of CD163 on monocytes/macrophages in the presence or absence of TIMPs were examined by a sandwich enzyme immunoassay and flow cytometry, respectively. The clinical marker that was most associated with serum levels of soluble CD163 was levels of CRP. TIMP-3, but not TIMP-1 or TIMP-2, inhibited the shedding of CD163 from monocytes/macrophages. It was shown that serum levels of soluble CD163 are a sensitive and reliable marker to monitor activated macrophages in synovitis from RA patients and the results imply that the responsible proteinase for the shedding of CD163 is not a member of the matrix metalloproteinases, but is likely to be a member of ADAMs.
A potassium ion channel is involved in cytokine production by activated human macrophages
Authors: QIU M R , CAMPBELL T J , BREIT S N 
Published: March 2003

SummaryMacrophages play an important role in immune and inflammatory responses, largely through secretion of bioactive molecule such as cytokines. While calcium is known to be an important regulator of this process, less is known about the role of other ions and the ion channels that regulate them. We have previously implicated an outwardly rectifying potassium channel (Kor) in this process and for this reason we have investigated the role of potassium (K+) and K+ channels in the regulation of tumour necrosis factor-α (TNF-α)and interleukin (IL)-8 production by activated human culture-derived macrophages. The effect of blockade of Kor is to inhibit phorbol myristate acetate (PMA)-induced cytokine production by translational or post-translational mechanisms, an effect that is duplicated by increasing extracellular K+. By contrast, the effects of K+ on LPS-stimulated cells are far more complex and are probably mediated through the change of osmolality and occur largely at the mRNA level. This data directly implicates K+, and its regulation through Kor, in early events following PMA stimulation of these cells.
Transient elevation of interleukin-16 levels at the initial stage of meningitis in children
Authors: SUZUKI T , ISHIGURO A , SHIMBO T 
Published: March 2003

SummaryIL-16 is an immunomodulatory cytokine that is characterized by chemotactic activity and stimulation of proinflammatory cytokine expression in monocytic cells. We studied IL-16 using ELISA in children with meningitis. When meningeal symptoms existed, IL-16 levels were high in the cerebrospinal fluid (CSF) of both bacterial (939 ± 877 ng/l, n = 20) and aseptic (341 ± 371 ng/l, n = 23) meningitis. The values in the CSF were significantly higher than those in non-meningitis controls (29 ± 8 ng/l, n = 22, P &lt; 0·0001). After meningeal symptoms disappeared, IL-16 levels in bacterial (191 ± 149 ng/l, n = 10, P = 0·0042) and aseptic (159 ± 188 ng/l, n = 13, P = 0·0118) meningitis were lower than those during the symptomatic stage. IL-16 levels were the highest before day 5 of the illness and then gradually fell. Significant correlations were found between IL-16 levels and both G-CSF levels (r = 0·783, n = 11, p = 0·0029) and IL-6 levels (r = 0·818, n = 12, P = 0·0005) in the CSF of bacterial and aseptic meningitis. IL-16 levels in all CSF samples from non-meningitis controls were lower than those in serum. In contrast, IL-16 levels in the CSF in six of 16 samples from bacterial meningitis and two of 18 samples from aseptic meningitis were higher than those in serum. Serum levels of IL-16 did not fluctuate throughout the course of meningitis. These data indicate that IL-16 levels rise transiently in CSF at the initial stage of meningitis. We speculate that IL-16 may promote inflammatory responses during meningitis in concert with other proinflammatory cytokines.
Elevated serum prolactin concentrations in phenylketonuric patients on a ‘loose diet’
Authors: Schulpis  , Papakonstantinou  , Michelakakis  , Theodoridis  , Papandreou  , Constantopoulos  
Published: March 2003

OBJECTIVEHigh levels of phenylalanine (Phe) have been shown to reduce dopamine (DA) and noradrenaline (NA) production. We have therefore evaluated whether increased serum Phe concentrations lead to increased prolactin (PRL) secretion in phenylketonuria.PATIENTSForty‐two patients with classical phenylketonuria were divided into two groups. Group A (n = 19) adhered very strictly to their special diet (Phe = 0.09 ± 0.039 mmol/l) and Group B (n = 23) were on a ‘loose diet’ (Phe = 0.77 ± 0.45 mmol/l). Thirty healthy children of comparable age served as controls.MEASUREMENTSPRL was measured by RIA, and Phe and tyrosine (Tyr) with an amino‐acid autoanalyser. Adrenaline (A), noradrenaline (NA), and dopamine (DA) were measured by HPLC.RESULTSSerum PRL in group B patients (1595 ± 57 mU/l) was significantly raised compared to Group A patients (243 ± 57 mU/l) and controls (201 ± 55 mU/l) (P < 0.001). Serum DA, A and NA in group B were lower than in group A patients and controls. Serum Phe in group B patients was significantly correlated to serum PRL (r = 0.59) and DA (r = − 0.41). Irregular menses were observed in 1/10 women from group A but in 10/13 in group B.CONCLUSIONHigh serum phenylalanine concentrations in phenylketonuric patients not strictly adhering to their diets are correlated with high serum PRL and low serum dopamine concentrations, and a high prevalence of menstrual irregularities.
Overnight urinary free cortisol determination: A screening test for the diagnosis of Cushing's syndrome
Authors: Corcuff Jean‐Benoît , Tabarin Antoine , Rashedi Michel , Duclos Martine , Roger Patrick , Ducassou Dominique 
Published: March 2003

OBJECTIVEThe collection of urine over 24 h to measure free cortisol (UFC) is used to diagnose Cushing's syndrome. However, a complete collection of urine is not easy to achieve and the sampling is frequently inaccurate, so a 24 h collection for the determination of UFC excretion is used as a confirmatory rather than a screening test for Cushing's syndrome. Our objective was to evaluate a more convenient urine collection for screening patients suspected of Cushing's syndrome.DESIGNWe have studied the possibility of using night‐time (from 2000 h to 0800 h) UFC excretion as a screening test for Cushing's syndrome (‘overnight UFC’).PATIENTSThirty patients with proven Cushing's syndrome were studied before treatment (21 cases of Cushing's disease, two cases of ectopic ACTH secretion, seven of adrenal adenoma). The results were compared to those from 150 control obese subjects.MEASUREMENTSOvernight UFC, and creatininuria (UC), were evaluated at least once in the patients and in all subjects. The 24 h‐UFC and UC were determined at least once in the patients and in 56 control subjects.RESULTSThe overnight UFC/UC ratio clearly separated all but one patient of the two groups: 194 ± 386 vs 5.7 ± 3.4 nmol/μmol (P < 0.0005) (ranges 16.2–2024 vs 0.6–17.4, Cushing's syndrome vs controls, respectively). The only patient with Cushing's syndrome who had an overnight UFC/UC ratio that overlapped with that of controls suffered from renal failure. The 24 h UFC/UC ratio of the patients differed from the ratio of controls: 184 ± 365 vs 8.4 ± 4.1 nmol/μmol (P < 0.0005) (ranges 14–1639 vs 1.5–21.2, respectively). Four patients with Cushing's syndrome had 24 h UFC/UC ratios lower than the upper control ratio.CONCLUSIONThe overnight urinary sampling is a simple procedure compared to the 24 h urine collection performed in out‐patients. For a sensitivity set at 100%, the specificities were 97% for the overnight UFC/UC ratio and 87% for the 24 h‐UFC/UC ratio. This therefore appears to provide a good screening method for Cushing's syndrome.
Serum collagen crosslinks as markers of bone turn‐over during GH replacement therapy in growth hormone deficient adults
Authors: Rodríguez‐Arnao  , James  , Jabbar  , Trainer  , Perrett  , Besser  , Ross  
Published: March 2003

OBJECTIVESBone metabolism is an important target for GH replacement therapy. However, in adults, treatment periods exceeding 12 months are required for a positive effect of GH on bone mineral density. Thus, to detect an early effect of GH on bone, markers of bone turn‐over are important. Pyridinoline (PYR) and deoxypyridinoline (DPYR) are well‐defined sensitive markers of bone resorption, but to date only urinary assays have been available. We report the use of a novel assay to measure changes in serum PYR and DPYR in GH deficient (GHD) adults during GH replacement therapy.STUDY DESIGNThe study consisted of a 6‐month randomized, double‐blind, placebo‐controlled study of the administration of GH (Genotropin®) (0.25 IU/Kg/week (0.125 IU/kg/week for the first four weeks)) followed by a 6‐month open phase of GH therapy.PATIENTSThirty‐five GHD adults (17 women; mean age 39.8 years; range 21.1–59.9) on conventional hormone replacement therapy as required, were studied.MEASUREMENTSBone formation was analysed using serum bone alkaline phosphatase (BAP) and serum osteocalcin (OC). Bone resorption was analysed using serum pyridinoline (PYR) and serum deoxypyridinoline (DPYR). Bone mineral density (BMD) was determined by dual energy X‐ray absorptiometry (DEXA).RESULTSAfter 6 months placebo treatment there were no significant changes in any of the bone markers analysed, nor in BMD. In the active arm of the study there was a significant increase in serum OC, BAP, PYR and DPYR (P = 0.03, P = 0.004, P = 0.003 and P = 0.01, respectively), remaining significantly elevated over their baseline levels for the subsequent 6 months of treatment (P = 0.04, P = 0.009, P = 0.003 and P = 0.04, respectively). No changes were observed in BMD in any of the groups after 6 months GH treatment. In the active arm of the study, after 12 months GH treatment there was a significant increase in BMD at both the lumbar spine and femoral neck (P = 0.01 for both sites).CONCLUSIONSIn summary, the present study confirms that administration of GH treatment to GHD adult patients significantly activates bone remodelling, with the effect of GH both in bone formation and bone resorption markers being maximal after 6 months of treatment. The serum assay for PYR and DPYR has a number of practical and theoretical advantages over the urine assay and gave similar results to those previously reported for the urine assay.
Can intra‐operative GH measurement in acromegalic subjects predict completeness of surgery?
Authors: Van Den Berg Gerrit , Van Dulken Hans , Frölich Marijke , Meinders A. Edo , Roelfsema Ferdinand 
Published: March 2003

OBJECTIVEResults of trans‐sphenoidal pituitary surgery, in terms of long‐term cure, vary considerably between centres. Additional techniques, which can assist the neurosurgeon in deciding whether surgery is complete or not, might therefore be important. One such potential tool is the intra‐operative measurement of GH and calculating the plasma half‐life from the plasma samples obtained after the presumed complete resection of the adenoma.METHODSGH half‐life was calculated from 5–10 min plasma samples after adenomectomy in 20 patients. GH was measured with a sensitive and rapid IFMA, and the results could be reported within 30 min, but were not used in this study for per‐operative decisions. Cure was defined by a glucose suppressed plasma GH concentration below 1 mU/l (0.38 μg/l) during follow‐up studies and a normal plasma IGFI concentration.RESULTSIn 13 cured patients the plasma half‐life was 22.2 ± 1.9 min (range 14–40.6). In three non‐cured patients the plasma half‐life could not be calculated, and in four other patients the plasma half‐life was 35.8 ± 5.9 min (range 25.8–51 min). By applying 25 min as the upper normal limit for the GH plasma half‐life, the sensitivity was 77%, specificity 100%, and positive predictive value 100%.CONCLUSIONPer‐operative plasma GH monitoring is a potentially useful tool for determining the completeness of trans‐sphenoidal surgery in acromegaly.
Functional evidence for two types of parathyroid adenoma
Authors: D'Amour P. , Weisnagel J. , Brossard J. H. , Ste‐Marie L. G. , Rousseau L. , Lepage R. 
Published: March 2003

OBJECTIVEThe carboxyterminal parathyroid hormone (C‐PTH)/intact (I‐) PTH ratio is influenced by serum calcium concentrations in man, increasing to a maximum value in hypercalcaemia and decreasing to a minimum value in hypocalcaemia. We decided to use this ratio to screen for parathyroid tumour with a normal sensitivity to calcium, symptomatic mainly through a mass effect.DESIGN AND SUBJECTSNineteen patients with hypercalcaemia and elevated or inappropriate PTH, were studied in the basal state and during CaCl2 and Na2EDTA infusion and compared with 26 normal individuals. They all had one parathyroid adenoma removed surgically, and two remained hypercalcaemic.RESULTSIn the basal state, the patients were hypercalcaemic (ionized calcium 1.44 ± 0.12 vs. 1.23 ± 0.03 mmol/l, P < 0.001) and had elevated PTH levels (I‐PTH: 10.8 ± 8.0 vs. 2.3 ± 0.6 pmol/l, P < 0.001; C‐PTH: 31.6 ± 38.9 vs. 5.25 ± 1.11 pmol/l, P < 0.001) when compared with normals. Their mean C‐PTH/I‐PTH ratio was similar to normals (2.7 ± 1.3 vs. 2.4 ± 0.6, NS) but, when individual values were considered, three patients had elevated values at 4.9, 5.3 and 5.8 (normal = 1.2–3.6). The regression line between basal C‐ and I‐PTH revealed a significantly higher slope in these patients (P  < 0.0001). The 16 patients with a normal basal C‐PTH/I‐PTH ratio had, as a group, an increased set point of I‐ or C‐PTH stimulation by calcium and increased values of stimulated and non‐suppressible I‐ and C‐PTH, but these abnormalities were not all present in the smaller tumours (≤200 mg). Only three tumours in that group were larger than 1000 mg. Serum calcium concentration was related to the increased set point and non‐suppressible fraction of I‐PTH in these patients (r2 = 0.797). The three patients with a high basal C‐PTH/I‐PTH ratio had large tumours (2346, 4364 and 17 300 mg) and were more difficult to study, requiring a larger decrease in calcium concentration to achieve maximal stimulation. In the basal state, they were already expressing a non‐suppressible level of I‐ or C‐PTH and already had a maximal C‐PTH/I‐PTH ratio. Our data further suggest a normal set point of I‐ and C‐PTH stimulation in the two patients who achieved sufficient hypocalcaemia and a normal set point of C‐PTH/I‐PTH ratio modulation in these three patients. Their hypercalcaemia was essentially related to the non‐suppressible fraction of PTH. Furthermore, larger tumours were less active than smaller ones and produced less stimulated I‐PTH/100 mg of tissue.CONCLUSIONSThese data indicate two types of parathyroid tumours when calcium sensitivity is considered: (1) a majority of small tumours with abnormal sensitivity to calcium, symptomatic through an abnormal set point and an increased non‐suppressible fraction and (2) a smaller number of larger tumours, with normal sensitivity to calcium and an increased non‐suppressible fraction, of PTH.