bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of immunity induced by viral antigen or conferred by antibody via different administration routes
Authors: MATSUOKA T , OKAMOTO Y , MATSUZAKI Z , ENDO S , ITO E , TSUTSUMI H , WILLIAMSON R A , SAKURAI H , BURTON D R , SAITO I 
Published: March 2003

SummaryThe characteristics of the immunity induced by viral antigens or conferred by antiviral antibody via different routes of administration were evaluated comparatively. C57BL/6 mice were immunized via intranasal, intradermal or enteric routes with a live recombinant vaccinia virus expressing the respiratory syncytial virus (RSV) F glycoprotein (F·rVV) or RSV, and then challenged intranasally with RSV. Inhibition of RSV replication was observed in the lungs of all the mice; however, only intranasal immunization hindered virus replication in the nose. Lung inflammation, characterized by infiltration of neutrophils and of mononuclear cells was strongest in the intradermally immunized mice, but was observed in all F·rVV immunized mice to various degrees. Intranasal administration of a potently neutralizing human anti-RSV antibody Fab fragment to infected mice inhibited RSV replication in the nose and, when combined with intraperitoneal administration, protected both the lung and the nose in the absence of deleterious lung pathology. These data suggest that intranasal immunization with F·rVV reduces RSV replication in the respiratory tract, but still induces pathological lung inflammation, even though this is milder than that observed following intradermal immunization. Local neutralizing antibody is indispensable for protection in the nose.
CD4+ T regulatory cells from the colonic lamina propria of normal mice inhibit proliferation of enterobacteria-reactive, disease-inducing Th1-cells from scid mice with colitis
Authors: GAD M , BRIMNES J , CLAESSON M H 
Published: March 2003

SUMMARYAdoptive transfer of CD4+ T cells into scid mice leads to a chronic colitis in the recipients. The transferred CD4+ T cells accumulate in the intestinal lamina propria (LP), express an activated Th1 phenotype and proliferate vigously when exposed ex vivo to enteric bacterial antigens. As LP CD4+ T cells from normal BALB/c mice do not respond to enteric bacterial antigens, we have investigated whether colonic LP-derived CD4+ T cells from normal mice suppress the antibacterial response of CD4+ T cells from scid mice with colitis. LP-derived CD4+ T cells cocultured with bone marrow-derived dendritic cells effectively suppress the antibacterial proliferative response of CD4+ T cells from scid mice with colitis. The majority of these LP T-reg cells display a nonactivated phenotype and suppression is independent of antigen exposure, is partly mediated by soluble factor(s) different from IL-10 and TGF-β, and is not prevented by the addition of high doses of IL-2 to the assay culture. Functionally and phenotypically the T-reg cells of the present study differ from previously described subsets of T-reg cells. The presence of T cells with a regulatory potential in the normal colonic mucosa suggests a role for these cells in the maintenance of local immune homeostasis of the gut.
Benzylpenicillin differentially conjugates to IFN-γ, TNF-α, IL-1β, IL-4 and IL-13 but selectively reduces IFN-γactivity
Authors: BROOKS B M , THOMAS A L , COLEMAN J W 
Published: March 2003

SUMMARYIt is known that β-lactam antibiotics can conjugate to lysine and histidine residues on proteins via the carbonyl group of the opened β-lactam ring. However, it is not known which proteins these drugs target and there is little work addressing whether conjugation is preferential for some proteins over others or if conjugation has functional consequences for the protein. We have previously shown that the β-lactam antibiotic benzylpenicillin (BP) conjugates to IFN-γ and reduces its activity. This interaction demonstrates selectivity, as BP does not bind to IL-4. Here, we extend our study to include other Th1 and Th2 cell-associated cytokines and two cytokines associated with inflammatory responses. We demonstrate by Western blotting that BP also conjugates to IL-1β, IL-2, IL-5, IL-13 and TNF-α but not to IL-10. Densitometric analysis of leading cytokine bands on blots revealed that IFN-γ always gave more intense BP-positive bands than any other cytokine analysed. Cytokines pre-incubated with BP at 37°C in a protein-containing, serum-free medium were assayed for their biological activity. By in vitro bioassay, BP inhibited the ability of IFN-γ but not IL-1β or TNF-α to induce CD54 expression on epithelial cells. In addition, BP did not affect IL-4 or IL-13 inhibition of mast cell proliferation. When the pre-incubation temperature was reduced to 4°C, BP did not conjugate to IFN-γ or modulate its activity. BP retained its inhibitory effect on IFN-γ activity when 20% FCS was added to the pre-incubation medium. In conclusion, BP conjugates to some cytokines but not others and this does not appear to be related to primary protein structure. Furthermore, of the cytokines studied, conjugation only to IFN-γ is accompanied by inhibition of activity. This phenomenon is temperature dependent and occurs in the presence of serum. These findings provide further evidence for differential, direct drug–cytokine interactions. Such interactions may have therapeutic implications in terms of targeting cytokines to regulate their activity.
Anti-SSB/La is one of the antineutrophil autoantibodies responsible for neutropenia and functional impairment of polymorphonuclear neutrophils in patients with systemic lupus erythematosus
Authors: HSIEH S-C , YU H-S , LIN W-W , SUN K-H , TSAI C-Y , HUANG D-F , TSAI Y-Y , YU C-L 
Published: March 2003

SummaryDecreased number and impaired functions of polymorphonuclear neutrophils (PMN) due to the presence of anti-PMN autoantibodies in the serum render patients with systemic lupus erythematosus (SLE) susceptible to bacterial infections. However, the cognate antigens and pathological mechanisms of anti-PMN autoantibodies in SLE are rarely reported in the literature. In this study, we found approximately 20% of SLE sera contained anti-PMN autoantibodies detected by human PMN-coated cellular ELISA. A membrane protein with molecular weight of 50 kDa was identified as the cognate antigen of anti-PMN in Western blot after membrane-biotinylation and streptavidin column elution. The 50 kDa molecule was proved to be SSB/La after immunoscreening, molecular cloning and nucleotide sequencing of the gene from the human leucocyte cDNA library. Human anti-SSB/La autoantibodies purified from active SLE sera passing through the recombinant SSB/La conjugated Sepharose 4B affinity column could bind and penetrate into normal human PMN. Functional analysis revealed that the anti-SSB/La autoantibodies exerted a number of potent effects on human PMN, including suppressed phagocytosis, accelerated apoptosis and enhanced IL-8 production. These in vitro results suggest that anti-SSB/La is one of the anti-PMN autoantibodies capable of penetrating into PMN and responsible for neutropenia and functional impairment of PMN in patients with SLE.
The prevalence of hyperprolactinaemia and association with markers of autoimmune thyroid disease in survivors of the Whickham Survey cohort
Authors: Vanderpump  , French  , Appleton  , Tunbridge  , Kendall‐Taylor  
Published: March 2003

OBJECTIVEFew data exist on the prevalence of hyperprolactinaemia in the community. This study was intended to determine the prevalence of hyperprolactinaemia in a sample closely matched to the current British population aged 38 years and over.DESIGN AND PATIENTSThe 1877 survivors at the 20‐year follow‐up of the Whickham Survey were a cross‐sectional sample of the community aged 38 years and over. Serum was frozen and stored at −30°C from 90% of the survivors (751 men, 924 women, median age 58 years (range 38 to 93 years)) who participated in the follow‐up survey.MEASUREMENTSTwo years after the follow‐up survey, serum prolactin concentrations were measured by ELISA/1 step sandwich assay (reference range ≤ 600 mU/l in men and women). A repeat prolactin measurement was made in those subjects who had prolactin levels within the top 2.5% of men and women in this sample.RESULTSAt screening, 0.7% of the men and 2.5% of the women had serum prolactin levels greater than 600 mU/l. For men, 2.5% were above 400 mU/l. The prevalence of hyperprolactinaemia, if defined as greater than 400 mU/l in men and greater than 600 mU/l in women on repeat testing, was 1.4% in the men and 1.2% in the women. The aetiology in men was prolactin‐raising drugs (n = 3), renal failure (n = 1), microprolactinoma (n = 1), and unknown (n = 2), and in women it was prolactin‐raising drugs (n = 7), microprolactinoma (n = 1), and unknown (n = 1). Logarithmic transformation of serum prolactin concentrations produced Gaussian distributions with 95% reference ranges of 60–430 mU/l in men and 40–560 mU/l in women. No significant relationship was found in either sex between hyperprolactinaemia and age or evidence of autoimmune thyroid disease at either survey. In women, there was no association with age, distance beyond the menopause or duration of reproductive years but prolactin levels were slightly higher in those on oestrogen therapy (geometric mean prolactin 226 mU/l compared to 178 mU/l; t‐test on log prolactin t = 3.79; P < 0.0001).CONCLUSIONSThis study has demonstrated that a gender‐related reference range for serum prolactin is necessary. Pituitary pathology is not common and screening with measurement of serum prolactin is not warranted in middle‐aged and elderly subjects. In asymptomatic subjects with modestly elevated serum prolactin levels (< 3 SD above the mean), extensive pituitary imaging and investigation is unwarranted. Autoimmune thyroid disease was not a significant cause of hyperprolactinaemia in this sample.
Adrenal steroid hormones in short children born small for gestational age
Authors: Dahlgren Jovanna , Boguszewski Margaret , Rosberg Sten , Albertsson‐Wikland Kerstin 
Published: March 2003

OBJECTIVEProgramming of the endocrine axis has been postulated to occur during critical phases of fetal development and is affected by intrauterine growth retardation. The aim of this study was to investigate this hypothesis with regard to adrenal steroid hormones. Thus, serum cortisol and dehydroepiandrosterone sulphate (DHEAS) levels were compared in children born small for gestational age (SGA) who remained short and in children born at an appropriate size for gestational age (AGA), of both short and normal stature.DESIGN AND PATIENTSSeven serum samples for cortisol measurements were taken during a 24‐h period from a total of 184 prepubertal individuals. The study group comprised 53 children born SGA who remained short (41 boys, 12 girls; mean chronological age, 8.8 ± 2.5 years). The reference groups of children born AGA were as follows: 75 healthy short children (56 boys, 19 girls; mean chronological age, 10.8 ± 2.6 years) and 56 healthy children of normal height (37 boys, 19 girls; mean chronological age, 11.3 ± 1.8 years). A single serum sample for measurement of DHEAS was taken between 1000 and 1400 h in 110 of the 184 children (33 short SGA, 42 short AGA and 35 AGA of normal height).MEASUREMENTSSerum cortisol and DHEAS were measured by radioimmunoassay.RESULTSNo differences were found between children born SGA and children born AGA in either cortisol levels, calculated as area under the curve (AUC), or the circadian cortisol rhythm, estimated from the calculated nadir, the peak and the amplitude. No difference between the groups was found for serum DHEAS concentrations. Serum cortisol levels, expressed as AUC, and serum DHEAS levels did not correlate with size at birth. However, when adjusted for age at investigation, serum DHEAS, but not serum cortisol, correlated with weight at birth.CONCLUSIONSSerum cortisol levels and rhythms do not correlate with size at birth and are similar in children born small for gestational age who remain short and children born appropriate size for gestational age of both short and normal stature. However, DHEAS levels in young children before adrenarche correlated inversely with weight at birth, indicating a relationship with fetal growth.
The effect of past use of the injectable contraceptive depot medroxyprogesterone acetate on bone mineral density in normal post‐menopausal women
Authors: Orr‐Walker Brandon J. , Evans Margaret C. , Ames Ruth W. , Clearwater Judith M. , Cundy Tim , Reid Ian R. 
Published: March 2003

OBJECTIVEDepot medroxyprogesterone acetate (DMPA), an injectable progestogen, is a widely used contraceptive acting primarily by inhibiting secretion of pituitary gonadotrophins, thus producing oestrogen deficiency. Cross‐sectional and prospective studies in pre‐menopausal women have shown DMPA use to be associated with reduced bone density, but bone density increases following discontinuation of the drug. Because fracture rates are low in pre‐menopausal women, the principal concern arising from the effects of DMPA on bone is that there may be residual osteopenia in former users such that their post‐menopausal fracture risk is increased. The present study addresses this question.DESIGNCross‐sectional study of bone density in post‐menopausal former users of DPMA and controls.SUBJECTSThree hundred and forty‐six normal post‐menopausal women, of whom 34 had previously used DMPA. The median age at which DMPA use began was 41 years and the median duration of use was 3.0 years.MEASUREMENTSBone density was measured in the spine, proximal femur and total body by dual‐energy, X‐ray absorptiometry.RESULTSThere were no significant differences in bone density at any site between the women who had previously used DMPA and the others in the cohort. However, in those who had used DMPA for > 2 years there was a trend towards bone densities being lower in the former users, the differences from non‐users being 1.6% in the lumbar spine (P = 0.6), 3.1% in the femoral neck (P = 0.4) and 0.5% in the total body (P = 0.8). There was no correlation between bone densities and the duration of DMPA use, the age at discontinuation of DMPA, or the time between DMPA discontinuation and the menopause.CONCLUSIONSAny residual effects of depot medroxyprogesterone acetate use on post‐menopausal bone density are small and therefore unlikely to have a substantial impact on fracture risk in the post‐menopausal years.
Sleep deprivation effects on the activity of the hypothalamic–pituitary–adrenal and growth axes: potential clinical implications
Authors: Vgontzas Alexandros N. , Mastorakos George , Bixler Edward O. , Kales Anthony , Gold Philip W. , Chrousos George P. 
Published: March 2003

OBJECTIVESAlthough several studies have shown that sleep deprivation is associated with increased slow wave sleep during the recovery night, the effects of sleep deprivation on cortisol and growth hormone (GH) secretion the next day and recovery night have not been assessed systematically. We hypothesized that increased slow wave sleep postsleep deprivation is associated with decreased cortisol levels and that the enhanced GH secretion is driven by the decreased activity of the HPA axis.DESIGN AND SUBJECTSAfter four consecutive nights in the Sleep Laboratory, 10 healthy young men were totally deprived of sleep during the fifth night, and then allowed to sleep again on nights six and seven. Twenty‐four hour blood sampling was performed serially every 30 minutes on the fourth day, immediately following the previous night of sleep and on the sixth day, immediately after sleep deprivation.MEASUREMENTEight‐hour sleep laboratory recording, including electroencephologram, electro‐oculogram and electromyogram. Plasma cortisol and GH levels using specific immunoassay techniques.RESULTSMean plasma and time‐integrated (AUC) cortisol levels were lower during the postdeprivation nighttime period than on the fourth night (P < 0.05). Pulsatile analysis showed significant reduction of both the 24 h and daytime peak area (P < 0.05) and of the pulse amplitude (P < 0.01), but not of the pulse frequency. Also, the amount of time‐integrated GH was significantly higher for the first 4 h of the postdeprivation night compared to the predeprivation night (P < 0.05). Cross‐correlation analyses between the absolute values of the time‐series of each hormone value and percentage of each sleep stage per half hour revealed that slow wave sleep was negatively correlated with cortisol and positively correlated with GH with slow wave sleep preceding the secretion of these hormones. In contrast, indices of sleep disturbance, i.e. wake and stage 1 sleep, were positively correlated with cortisol and negatively correlated with GH.CONCLUSIONWe conclude that sleep deprivation results in a significant reduction of cortisol secretion the next day and this reduction appears to be, to a large extent, driven by the increase of slow wave sleep during the recovery night. We propose that reduction of CRH and cortisol secretion may be the mechanism through which sleep deprivation relieves depression temporarily. Furthermore, deep sleep has an inhibitory effect on the HPA axis while it enhances the activity of the GH axis. In contrast, sleep disturbance has a stimulatory effect on the HPA axis and a suppressive effect on the GH axis. These results are consistent with the observed hypocortisolism in idiopathic hypersomnia and HPA axis relative activation in chronic insomnia. Finally, our findings support previous hypotheses about the restitution and immunoenhancement role of slow wave (deep) sleep.
The quality of life of adults with growth hormone deficiency: comparison with diabetic patients and control subjects
Authors: Wallymahmed  , Foy  , MacFarlane  
Published: March 2003

OBJECTIVEAdults with GH deficiency (GHD) frequently report a poor quality of life (QOL). Whether this poor QOL is specifically due to hormone deficiency or a non specific effect of a chronic condition is not known. We therefore assessed QOL in adults with hypopituitarism and GHD and compared scores with a group of patients with diabetes mellitus, another life‐long condition with potentially serious complications and a group of healthy controls.PATIENTSWe studied 57 patients with hypopituitarism and GHD (peak stimulated GH response < 9 mU/l) (23 male, mean age 36.4 years, mean stimulated GH response 2.3 mU/l), secondary to a variety of hypothalamic‐pituitary disorders. Fifty had been treated surgically (39 cranial surgery, 11 transsphenoidal) and 37 had received external cranial irradiation involving the hypothalamic region. Fifty‐seven age and sex matched patients with diabetes mellitus (31 insulin treated, 18 on oral hypoglycaemic agents, 8 on diet alone) and 57 matched healthy controls were also studied.DESIGN AND MEASUREMENTSWe assessed and compared health related QOL in the 3 groups using 4 self rating questionnaires: Hospital Anxiety and Depression Scale, Self Esteem Scale, Mental Fatigue Questionnaire and Life Fulfilment Scale. In addition the GHD and diabetic groups also completed the Disease Impact Scale.RESULTSThe GHD group reported significantly more depression (P < 0.05) and mental fatigue (P < 0.05) and significantly less self esteem (P < 0.05) and life fulfilment (P < 0.05) than either the group with diabetes or the controls. Patients with GHD reported significantly higher anxiety scores (P < 0.05) than the controls. Within the GHD group there were no differences in QOL scores between patients with pituitary tumours (n = 24), craniopharyngiomas/hypothalamic tumours (n = 18) or other brain tumours. In addition there were no significant differences according to surgical treatment modality or radiotherapy. However subgroup analysis revealed that the patients who had undergone transsphenoidal surgery (n = 11) differed significantly from the control group in life fulfilment and depression (P < 0.01) only and did not differ from the DM group in any of the questionnaires used. There were no significant differences between the group with diabetes and the control group in any of the measures except depression (P < 0.05).CONCLUSIONSThis study revealed a significant impairment of QOL in adults with GHD, particularly those who had undergone cranial surgery, when compared to matched patients with diabetes and healthy controls.
The insulin resistance syndrome and the binding capacity of cortisol binding globulin (CBG) in men and women
Authors: Fernández‐Real  , Grasa  , Casamitjana  , Ricart  
Published: March 2003

BACKGROUNDBoth insulin resistance and cortisol binding globulin (CBG) capacity have been found to correlate with plasma free fatty acid (FFA) concentration.OBJECTIVETo examine the changes in CBG binding with varying degrees of insulin resistance and plasma FFA levels.SUBJECTS AND METHODSAnthropometric parameters, serum cortisol levels, plasma CBG, CBG binding and insulin sensitivity (using the frequently sampled intravenous glucose tolerance test with minimal model analysis) were measured in a group of 38 healthy subjects (19 men, mean age 36.2 ± 1.9; body mass index (BMI) 28.8 ± 1.2, range 22.2–35.7), and 19 women, age 34.9 ± 1.4; BMI 28.1 ± 0.8, range 19–37.9)].RESULTSPlasma CBG levels did not differ between men and women. In men, CBG binding was associated with several parameters of the insulin resistance syndrome, including area under the curve for glucose during an oral glucose tolerance test (MBG, r = 0.45, P = 0.04), fasting insulin (r = 0.66, P = 0.002), plasma triglycerides (r = 0.75, P < 0.0001), VLDL‐triglycerides (r = 0.59, P = 0.007), fasting FFA (r = 0.72, P = 0.002), uric acid (r = 0.57 (P = 0.01) and insulin sensitivity (SI, r = − 0.58, P = 0.008). Free cortisol (estimated as the ratio of cortisol to CBG) was not associated with waist‐to‐hip ratio (WHR) or parameters of insulin sensitivity. In contrast to men, CBG binding was not associated with MBG, fasting insulin, plasma triglycerides, VLDL‐triglycerides, FFA, uric acid or SI (all P = NS) in women. Serum free cortisol, however, correlated positively with WHR (r = 0.62, P = 0.02) and negatively with SI (r = − 0.68, P = 0.01) in obese women. A multiple linear regression to predict CBG binding was constructed, with plasma CBG concentration and insulin sensitivity as independent variables. In this model, only SI entered the equation at a statistically significant level (P = 0.0012) contributing to 52% of the variance in CBG binding in men. When plasma FFA levels were added to the model, both SI (P = 0.04) and FFA levels (P = 0.039) contributed to 66% of the variance of CBG binding in men. In women, both plasma CBG concentration (P = 0.0005) and insulin sensitivity (P = 0.047) entered the equation at a statistically significant level, contributing to 60% of the variance in CBG binding. When plasma FFA levels were added to the model, only plasma CBG concentration (P = 0.043) was found to significantly contribute to 38% of the variance in CBG binding. The latter finding suggests that FFA levels constituted a confounding variable in the association between SI and CBG binding in women.CONCLUSIONSBoth plasma free fatty acid and insulin sensitivity influence cortisol binding globulin binding capacity in men. Whether cortisol binding globulin binding is a factor implicated in the pathophysiology of insulin resistance or represents an adaptative tool in this situation awaits further studies.