bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison between HIV- and CMV-specific T cell responses in long-term HIV infected donors
Authors: PAPAGNO L , APPAY V , SUTTON J , ROSTRON T , GILLESPIE G M A , OGG G S , KING A , MAKADZANHGE A T , WATERS A , BALOTTA C , VYAKARNAM A , EASTERBROOK P J , ROWLAND-JONES S L 
Published: March 2003

SummaryThe mechanisms underlying non-progression in HIV-1 infection are not well understood; however, this state has been associated previously with strong HIV-1-specific CD8+ T cell responses and the preservation of proliferative CD4+ T cell responses to HIV-1 antigens. Using a combination of interferon-gamma (IFN-γ) ELISpot assays and tetramer staining, the HIV-1-specific CD8+ T cell populations were quantified and characterized in untreated long-term HIV-1-infected non-progressors and individuals with slowly progressive disease, both in relation to CD4+ T cell responses, and in comparison with responses to cytomegalovirus (CMV) antigens. High levels of CD8+ T cell responses specific for HIV-1 or CMV were observed, but neither their frequency nor their phenotype seemed to differ between the two patient groups. Moreover, while CMV-specific CD4+ T cell responses were preserved in these donors, IFN-γ release by HIV-1-specific CD4+ T cells was generally low. These data raise questions with regard to the role played by CD8+ T cells in the establishment and maintenance of long-term non-progression.
Expansion of activated human naïve T-cells precedes effector function
Authors: BRENCHLEY J M , DOUEK D C , AMBROZAK D R , CHATTERJI M , BETTS M R , DAVIS L S , KOUP R A 
Published: March 2003

SummaryNaïve T-cells divide and mature, both functionally and phenotypically, upon stimulation through the T-cell receptor. Although much is known about the overall changes that occur in naïve cells upon TCR stimulation, and the different memory/effector populations that arise following stimulation, the relationship between cell division and functional and phenotypical changes that occur after activation is poorly understood. Here, we examine the early stages of human naïve and antigen-experienced T-cell activation, and the relationship between cell division and acquisition of effector function during the transition from resting antigen-experienced or naïve T-cells into effector cells. Stimulated naïve T-cells proliferate prior to acquisition of effector function, as measured by cytokine production and expression of effector-associated cell surface molecules. Additionally, we show that interlukin-7 (IL-7) can drive proliferation of naïve T-cells without TCR:MHC peptide interactions. IL-7 alone does not, however, drive the proliferation of antigen-experienced T-cells. Memory T-cells will divide in response to exogenous IL-7 but only in the presence of naïve T-cells and IL-2. This study contributes to the current understanding of the mechanistic differences between naïve and memory T-cell responses by defining the functional and phenotypic changes that occur to T-cells after stimulation.
Differential CD86 and CD40 co-stimulatory molecules and cytokine expression pattern induced byTrypanosoma cruziin APCs from resistant or susceptible mice
Authors: PLANELLES L , THOMAS M C , MARAÑÓN C , MORELL M , LÓPEZ M C 
Published: March 2003

SUMMARYDifferential aspects of the host immune response generated by Trypanosoma cruzi infection were examined in two different mouse strains, BALB/c (haplotype H2-Kd) which does not overcome the acute phase of the infection and C57BL/6 (haplotype H2-Kb) which survives to the acute phase. After infection an increase in CD3+ T cells was observed in both mouse strains in the peritoneal cavity. However, while the CD3+ T cells from the BALB/c mice showed an increase in the IL-4 cytokine expression level, the same type of cells from the C57BL/6 mice showed an increase in IFN-γ expression. In addition, only the macrophages from the C57BL/6 mice were activated secreting IL-12 and TNF-α and producing, moreover, high levels of nitrites. It was observed that also after parasite infection the expression of macrophage and dendritic cells CD40 and CD86 co-stimulation molecules from the spleen were diminished in BALB/c but not in C57BL/6 mice. In correlation with this observation the macrophages from the spleen of infected BALB/c mice secreted lower concentrations of nitrites than the C57BL/6 mouse cells. Also, the spleen dendritic cells from infected BALB/c mice had a small potential to present alloantigens in contrast to that observed in the infected C57BL/6 mouse cells.
TH1/TH2 cytokine profile, metalloprotease-9 activity and hormonal status in pregnant rheumatoid arthritis and systemic lupus erythematosus patients
Authors: MUñOZ-VALLE J F , VáZQUEZ-DEL MERCADO M , GARCíA-IGLESIAS T , OROZCO-BAROCIO G , BERNARD-MEDINA G , MARTíNEZ-BONILLA G , BASTIDAS-RAMíREZ B E , D. NAVARRO A , BUENO M , MARTíNEZ-LóPEZ E , BEST-AGUILERA C R , KAMACHI M , ARMENDáRIZ-BORUNDA J 
Published: March 2003

SUMMARYDuring the course of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), several immune and neuroendocrine changes associated with pregnancy may exert positive (amelioration) or negative (exacerbation) effects on the clinical outcome. In order to shed light on the mechanisms underlying these responses, we performed a prospective longitudinal study in RA and SLE pregnant women, including healthy pregnant women as a control group. Cytokine messenger RNA (mRNA) expression assessed by quantitative competitive polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMC), cytokine levels and lymphocyte proliferation responses (LPR) following phytohaemagglutinin (PHA) stimulation of PBMC, plasma metalloprotease-9 activity (MMP-9) and hormonal status during pregnancy were determined. TNFa was the most abundant cytokine mRNA expressed in PBMC in all groups studied (healthy pregnant women, RA and SLE pregnant patients). However, a general TH2 response reflected by high IL-10 levels was found in RA, as well as SLE, patients. A significant change in IFN-γ was observed in RA patients but only during the first trimester of pregnancy. This compared with a major TH1 response in healthy pregnant women. Interestingly, our study showed a homogeneous hormonal pattern in RA and SLE patients. Although decreased cortisol levels were observed in all patients studied, this is possibly related to the remission of disease activity status brought about by steroid treatment before and during pregnancy. In summary, we suggest that complex immune and hormonal networks are involved in pregnancy and that rheumatic diseases are very dynamic immune processes that cannot be described with a clear-cut cytokine profile. Furthermore, the observations in this study may reflect treatment-related immune effects more than those associated with disease.
Th1 and Th1-inducing cytokines inSalmonellainfection
Authors: MIZUNO Y , TAKADA H , NOMURA A , JIN C-H , HATTORI H , IHARA K , AOKI T , EGUCHI K , HARA T 
Published: March 2003

SUMMARYThl and Thl-inducing cytokines and T cell responses were investigated in human salmonellosis. Serum IFN-γ, IL-12 and IL-18 levels were increased significantly in patients with salmonellosis. The increase in serum IL-15 and IL-18 levels was more significant and prolonged in patients with the systemic form of salmonellosis than in those with the gastroenteric form. The serum IFN-γ level was correlated significantly with IL-12 and IL18 levels, and the IL-15 level was correlated significantly with IL-18. Upon stimulation with Salmonella in vitro, mononuclear cells from salmonellosis patients produced significantly higher amounts of IFN-γ and IL-12 compared with those from healthy controls. Anti-IL-12 moAb or anti-IL18 MoAb significantly inhibited Salmonella-induced IFN-γ production in vitro. γδ T cells expressed significantly higher levels of IFN-γ mRNA in salmonellosis patients than in healthy controls. The results suggest that Th1-inducing cytokines appear to be involved in the in vivo response against Salmonella infection, promoting IFN-γ production by αβ and γδ T cells which plays a protective role against Salmonella.
Autoimmune diseases in vitiligo: do anti-nuclear antibodies decrease thyroid volume?
Authors: ZETTINIG G , TANEW A , FISCHER G , MAYR W , DUDCZAK R , WEISSEL M 
Published: March 2003

SUMMARYAn increased prevalence of autoimmune thyroiditis (AT) in vitiligo patients is well known. The aim of this study was firstly, to evaluate the clinical course of patients with both vitiligo and AT and secondly, to identify additional autoimmune disorders affecting the thyroid gland in a large cohort of vitiligo patients. We analysed a study group of 106 vitiligo patients and 38 controls. A detailed thyroid examination including sonography was performed in all study participants. In addition, the study participants were HLA typed and screened for various autoimmune disorders.AT was significantly more frequent in vitiligo patients than in controls (21%versus 3%; P &lt;  0·01). In 12 of the 22 patients with AT, vitiligo was the initial disease preceding AT by 4–35 years. In the other 10 patients with AT, both vitiligo and AT were diagnosed within one year. There were two individuals with diabetes mellitus type 1 and a single patient with Addison's disease. Anti-nuclear antibody (ANA), anti-smooth muscle cell antibody, and parietal cell antibody levels occurred with a similar frequency in patients and controls. In all vitiligo patients with both elevated ANA levels and AT (n = 6), the atrophic but not the goitrous variant was diagnosed. These vitiligo patients with both AT and elevated ANA levels had a significantly smaller thyroid volume compared to the vitiligo patients with AT whose ANA levels were normal (6·7 ± 4·5 ml versus 13·4 ± 9·1 ml, respectively; P &lt;  0·05). The same was found in the entire study group: Thyroid volume of all vitiligo patients (with or without concomitant AT) was significantly smaller in the presence of ANA (6·9 ± 5·3 versus 10·5 ± 5·9 ml, espectively; P &lt;  0·05). However, this phenomenon was not observed in the control group. There was a trend for a decreased frequency of HLA-DR3 (6·7%versus 23%) in our study group, but after correction for the number of comparisons, no HLA-allele was statistically significant associated neither with vitiligo nor with multiple autoimmune diseases in our patient sample. Our findings suggest that AT is the most frequent autoimmune disease associated with vitiligo. In our patients, AT presented simultaneously or after the onset of vitiligo but not before. Elevated ANA levels were associated with the atrophic variant of AT and may affect the volume of the thyroid gland, and there was no statistically significant association with the HLA system.
Echocardiographic evidence for a direct effect of GH/IGF‐I hypersecretion on cardiac mass and function in young acromegalics
Authors: Minniti G. , Jaffrain‐Rea M. L. , Moroni C. , Baldelli R. , Ferretti E. , Cassone R. , Gulino A. , Tamburrano G. 
Published: March 2003

OBJECTIVEThe interpretation of echocardiographic abnormalities in acromegalic patients is complicated by non‐specific age‐related diseases, many of which are commoner in acromegaly. We have therefore investigated the cause‐effect relationship between GH/IGF‐I hypersecretion and precocious cardiovascular abnormalities in a series of young acromegalic patients.DESIGNAn open prospective study.PATIENTS20 acromegalic patients aged under 30 years, with normal blood pressure and glucose tolerance, and 20 age‐matched control subjects.MEASUREMENTSCardiac morphological parameters and indices of systolic and diastolic function at rest were studied by Doppler echocardiography.RESULTSLeft ventricular mass (LVM) and LVM index (LVMi) were higher in acromegalics than in control subjects (215.0 ± 15.4 g vs 140.8 ± 8.5 g, P = 0.0002 and 109.8 ± 5.9 g/m2vs 82.13.7 g/m2, P = 0.0008, respectively), reaching values of left ventricular hypertrophy in 4 patients (20%). Both ejection fraction and fractional shortening were normal (66.4 ± 2.1% vs 62.2 ± 1.9% and 37.5 ± 1.5% vs 35.8 ± 1.3%, respectively), indicating normal left ventricular systolic function. Abnormalities of left and right diastolic ventricular filling were found, which consisted of an increased isovolumic relaxation time (99.2 ± 2.7 ms vs 89.0 ± 2.7 ms, P = 0.01) and impaired mitral and tricuspidal flow velocity curves.CONCLUSIONSAn increase in cardiac mass and subclinical biventricular diastolic dysfunction were observed in young acromegalic patients. These findings argue for a direct cause‐effect relationship between GH/IGF‐I hypersecretion and myocardial abnormalities, and indicate that careful cardiological evaluation is mandatory in all acromegalics, whatever their age.
Peripheral catecholamine alterations in adolescents with polycystic ovary syndrome
Authors: Garcia‐Rudaz Cecilia , Armando Ines , Levin Gloria , Escobar María Eugenia , Barontini Marta 
Published: March 2003

OBJECTIVEPolycystic ovary syndrome (PCO) is one of the most common endocrine disorders affecting women. Several lines of evidence have suggested the involvement of the sympathetic nervous system (SNS) in this condition. The present work was designed to assess neurochemically SNS activity in patients during the early stages of PCO.DESIGN AND PATIENTSFourteen patients with PCO (aged 14 to 21 years) were studied on a random day and 9 normal regularly cycling adolescents (aged 14 to 20 years) were studied during the early follicular phase (days 2 to 5).MEASUREMENTSHormonal profile was determined in basal conditions. LH and FSH were also measured after iv administration of 100 μg GnRH. Plasma concentrations of dihydroxyphenylalanine (Dopa), noradrenaline (NA), adrenaline (A), total dopamine (DA) and dihydroxyphenylglycol (DHPG) were determined in basal conditions and in response to GnRH by HPLC with electrochemical detection or a radioenzymatic method. Basal urinary Dopa, catecholamines and catechol metabolites (DHPG, vanillylmandelic acid (VMA), 3‐methoxy‐4‐hydroxyphenylglycol (MHPG), homovanillic acid (HVA), metanephrine (MN) and normetanephrine (NMN)) were determined by HPLC with electrochemical detection.RESULTSBasal plasma LH, testosterone, androstenedione, oestrone and LH/FSH ratio were higher (P < 0.01) and serum sex hormone‐binding globulin (SHBG) were lower (P < 0.01) in PCO patients than in control subjects. Basal and GnRH‐stimulated plasma free Dopa, A, NA and total DA were similar in patients and controls. Plasma DHPG was lower (P < 0.01) in PCO patients (4.20 ± 0.30 nmol/l) than in controls (8.0 ± 1.0 nmol/l) throughout the study. Urinary A, NA, DA, Dopa, MN, MHPG, HVA, and VMA were similar in patients and controls. Urinary DHPG was lower (P < 0.01) in PCO patients (0.50 ± 0.02 μmol/d) than in controls (0.73 ±0.09 μmol/d). On the other hand PCO patients had a higher urinary excretion of NMN than controls (PCO: 1.20 ± 0.10; C: 0.78 ± 0.10 μmol/d, P < 0.05).CONCLUSIONSOur results show the same endocrinological features in adolescent PCO patients as those reported in adults. The results also demonstrate a peripheral catecholaminergic alteration which suggests an alteration in noradrenaline deamination and/or uptake in adolescent patients. This study however does not permit us to conclude that PCO is primarily caused by this sympathetic alteration.
The outcome of surgery for acromegaly: the need for a specialist pituitary surgeon for all types of growth hormone (GH) secreting adenoma
Authors: Lissett  , Peacey  , Laing  , Tetlow  , Davis  , Shalet  
Published: March 2003

OBJECTIVEAcromegaly is associated with reduced life expectancy, while therapeutic ‘cure’ (defined by achievement of GH levels <5 mU/l) is associated with normalization of life expectancy. Surgery remains the treatment of choice but in those in whom operative ‘cure’ is not achieved, radiotherapy and/or medical treatment are valuable treatment modalities. The chance of subsequent ‘cure’ with radiotherapy or somatostatin analogue therapy is increased if the post‐operative GH level is reduced below 30 mU/l. Using strict criteria for cure and a single dedicated pituitary surgeon, two large European studies reported ‘cure’ rates of 42% and 56%. In the Manchester region, surgery for these patients has been performed by a number of neurosurgeons, with no specific designated pituitary surgeon dominating the picture. We wished to examine the impact of this surgical strategy on cure rates and the incidence of a post‐operative GH level below 30 mU/l.DESIGNWe reviewed the GH results between 1974 and 1997 for every acromegalic who had been referred to the endocrine departments of the two Manchester hospitals responsible for the majority of pituitary disease referrals in Manchester and who had been subsequently referred for pituitary surgery.PATIENTS AND MEASUREMENTSSeventy‐three (33 male) patients had had GH status assessed before and after surgery by an OGTT or GH profile. The patients were aged between 19 and 70 (mean 43) years at surgery. Seventy‐one underwent transsphenoidal and 2 transfrontal surgery. Nine surgeons performed operations.RESULTSEighteen (24.7%) had microadenomas and 51 (69.9%) macroadenomas. In 4 patients (5.5%) insufficient data were available to size the adenoma. 17.8% of patients were cured by surgery, 38.8% with microadenomas and 11.8% with macroadenomas. In addition, of 52 patients whose GH levels were >30 mU/l before surgery, only 27 (51.9%) had GH levels below 30 mU/l post‐operatively (81.8% of microadenomas, 43.2% of macroadenomas).CONCLUSIONIn comparison with other series, the cure rate in this study is significantly lower. The success in reducing GH levels below 30 mU/l post‐operatively is difficult to compare with previously published studies, as few groups have analysed their data in this manner. Nonetheless, of our acromegalic patients with a pretreatment GH level in excess of 30 mU/l, nearly 50% have similar GH status postoperatively, thereby rendering them less amenable to cure by alternative therapeutic modalities. This highlights the importance of a specialist pituitary surgeon, not only for GH secreting microadenomas but also for GH secreting macroadenomas. If these patients are not ‘cured’, the cost of continuing therapy becomes a significant burden on health‐care costs. In addition, if the postoperative GH levels remain above 30 mU/l the chances of achieving adequate control of GH levels are greatly reduced, thereby increasing mortality rates as well as morbidity in these patients.
Decreased regional blood flow in patients with acromegaly
Authors: Chanson Philippe , Megnien Jean‐Louis , Del Pino Murielle , Coirault Catherine , Merli Isabelle , Houdouin Laurence , Harris Alan G. , Levenson Jaime , Lecarpentier Yves , Simon Alain , Chemla Denis 
Published: March 2003

BACKGROUND AND AIMSOne‐third of acromegalic patients have hypertension. Acromegaly is also associated with intrinsic cardiac abnormalities known collectively as a hyperkinetic heart syndrome, which is characterized by an increased cardiac index and decreased systemic vascular resistance. As a result, blood flow should be increased in the regional vascular beds of acromegalic patients. The aim of the study was to measure, using direct methods, blood flow and vascular resistance at the level of the brachial artery in acromegalic patients with a confirmed hyperkinetic heart syndrome.PATIENTS AND CONTROLSTwelve patients with active acromegaly (five females, seven males; mean (± SD) age, 43 ± 10 years) were studied. Twelve age‐and sex‐matched normal subjects served as controls.METHODSRight heart catheterization was used to measure the cardiac index and stroke volume and to calculate systemic vascular resistance in the acromegalic patients. Brachial haemodynamics were evaluated with a two‐dimensional pulsed Doppler system (double transducer probe and range‐gated time system of reception). The mean diameter of the brachial artery and mean blood velocity were measured and used to calculate mean blood flow. Vascular resistance was calculated in the brachial artery as the mean arterial pressure/blood flow ratio.RESUTLSAge, body weight, height, body surface area and heart rate were similar in the acromegalic patients and controls, while mean arterial pressure was higher in patients. The cardiac index and stroke volume were increased in the acromegalic patients, at 4.08 ± 0.47 (mean ± SD) l/min/m2 body surface area and 116.7 ± 19.4 ml, respectively, while systemic vascular resistance was low (12.5 ± 2.1 U). Brachial artery diameter was similar in the patients and controls. Brachial artery mean blood velocity (P < 0.01) and mean blood flow (P < 0.05) were lower in the patients than in the controls (3.35 ± 1.26 vs. 5.12 ± 1.74 cm/s, and 16.4 ± 9.4 vs. 25.6 ± 11.6 ml/min/m2, respectively). The higher mean arterial pressure and lower mean blood flow resulted in higher forearm vascular resistance in the patients than in the controls (132 ± 61 vs. 83.8 ± 47 mmHg/ml/s/m2, respectively, P < 0.01).CONCLUSIONWhile cardiac output is increased and systemic vascular resistance is decreased in active acromegaly, direct measurement of brachial artery haemodynamics showed lower regional blood flow and increased local resistance relative to healthy controls. These results suggest a heterogeneous distribution of cardiac output in acromegaly.
Disturbances of menstruation in hypothyroidism
Authors: Krassas G. E. , Pontikides N. , Kaltsas Th. , Papadopoulou Ph. , Paunkovic J. , Paunkovic N. , H. Duntas L. 
Published: March 2003

OBJECTIVESMost thyroid textbooks describe hypo‐thyroidism resulting in changes in the length of the menstrual cycle and in the amount of bleeding. Our experience at a busy thyroid clinic had given a picture which differs from that presented in the literature. The aim of this study was to determine the frequency and type of menstrual irregularities in premenopausal hypothyroid patients.DESIGN AND PATIENTSWe investigated the menstrual history, starting 6 months before the discovery of the disease, in 171 female premenopausal hypothy‐roid patients and 214 normal controls, with similar age and body mass index (BMI).MEASUREMENTSTSH, TT4, TT3 and thyroid anti‐bodies were measured by radioimmunoassay, while BMI was calculated from the ratio of body weight in kg to height in m2.RESULTSOf the 171 hypothyroid patients, 131 (76.6%) had regular cycles and 40 (23.4%) irregular periods. Oligomenorrhoea and menorrhagia were the most common features in the latter group. No difference in BMI was found between the patients with or without menstrual abnormalities, or between patients and controls. TSH, TT4 and TT3 levels did not differ between patients with normal and abnormal menstruation. Forty‐six (26.9%) out of 171 patients had subclinical hypothyroidism (group A), 42 (24.6%) mild hypothyroidism (group B) and 83 (48.5%) severe hypothyroidism (group C). Thirty‐seven from group A (80.4%), 32 from group B (76.2%) and 62 from group C (74.7%) had normal periods. These differences were not statistically significant. Eighty‐eight (88.9%) out of 99 patients in whom thyroid antibodies were measured had positive titres. Nineteen (21.6%) of the patients with positive thyroid antibodies had menstrual irregularities. This percentage did not differ from that found in the whole group of patients (23.4%). Out of 214 normal controls, 196 (91.6%) had normal menstruation and 19 (8.4%) irregular cycles. The latter group included mainly women with oligomenorrhoea.CONCLUSIONSThese data demonstrate that hypo‐thyroidism in women is less frequently associated with menstrual disturbance than was previously described. Also, menstrual irregularities tend to be more frequent in sever hypothyroidism in com‐parison with mild cases, although this finding was not statistically significant. Oligomenorrhoea and menorrhagia are the most common menstrual disturbances.