bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oestradiol regulation of antigen presentation by uterine stromal cells: role of transforming growth factor‐β production by epithelial cells in mediating antigen‐presenting cell function
Authors: Wira Charles R. , Rossoll Richard M. 
Published: June 2003

SummaryWe have previously shown that oestradiol treatment of ovariectomized rats for 3 days inhibits antigen presentation by uterine stromal cells at a time when oestradiol increases the numbers of antigen‐presenting cells (APC) in the uterine stroma. In the present study, we found that oestradiol treatment for 1 day is sufficient to inhibit antigen presentation by stromal cells. To define the mechanism(s) of this inhibition, we examined the effect of cytokines and found that exogenous transforming growth factor‐β (TGF‐β) inhibits antigen presentation when stromal cells from saline‐ but not oestradiol‐treated animals are incubated with ovalbumin (OVA)‐specific T cells and OVA. In contrast, antigen presentation by uterine epithelial cells was not affected by TGF‐β. In other studies, the acute inhibitory effect of oestradiol (1 day) on stromal antigen presentation is fully reversed when anti‐TGF‐β antibody is added to the culture media. When given for 3 days, oestradiol inhibition of antigen presentation is partially reversed by anti‐TGF‐β antibody at a time when antibodies to tumour necrosis factor‐α and interleukin‐10 have no effect. To determine whether uterine epithelial cells produce TGF‐β, epithelial cells were grown to confluence on transwell inserts. Our findings indicate that uterine epithelial cells produce biologically active TGF‐β which is preferentially released basolaterally in the direction of underlying stromal cells. When oestradiol is given to ovariectomized rats 1 day before sacrifice, TGF‐β production by epithelial cells increases within 24 hr in culture, relative to saline controls. Taken together, these results suggest that oestradiol inhibition of stromal cell antigen presentation is mediated through the stimulatory effect of oestradiol on TGF‐β production by epithelial cells.
Appearance of the LAT protein at an early stage of B‐cell development and its possible role
Authors: Oya Kazuyuki , Wang Jiyang , Watanabe Yumi , Koga Ritsuko , Watanabe Takeshi 
Published: June 2003

SummaryThe linker protein LAT is expressed mainly in T and natural killer (NK) cells. LAT‐deficient mice have an arrest of intrathymic T‐cell development at the CD4+ CD8+ stage and lack mature T cells in the periphery. However, no gross abnormality in development and function of the B and NK cells has been described. Here we report that LAT is expressed in mouse progenitor B (pro‐B) and precursor B (pre‐B) cells, but not in immature or mature B cells. LAT in pre‐B cells becomes tyrosine phosphorylated upon cross‐linking of the pre‐B‐cell receptor (pre‐BCR) by anti‐µ antibody. Incubation of 1xN/2b (mouse pre‐B‐cell line) cells or bone marrow cells from µMT/µMT mice, which lack B cells after the small pre‐B‐cell stage, with anti‐Igβ antibody resulted in the downregulation of LAT expression. Transgenic mice which expressed LAT protein in B‐lineage cells showed an increased proportion of pro‐ and large pre‐B cells in the bone marrow and a remarkable reduction in the numbers of mature B cells in peripheral lymphoid tissues. Collectively, the present results indicate that LAT is expressed in the cells at the early stages of B‐lineage development, but is absent in immature and mature B cells. LAT may play a crucial role in the negative regulation of B‐cell development at the transition from pre‐B to mature B‐cell stages, and signal(s) via the pre‐BCR may extinguish LAT expression, thus allowing pre‐B‐cell differentiation towards the mature B‐cell stage.
Effects of cyclosporin A and a rapamycin derivative (SAR943) on chronic allergic inflammation in sensitized rats
Authors: Eynott Paul R. , Salmon Michael , Huang Tung‐Jung , Oates Timothy , Nicklin Paul L. , Chung K. Fan 
Published: June 2003

SummaryImmunomodulators such as cyclosporin A (CsA) and SAR943 (32‐deoxorapamycin) inhibit single allergen‐induced allergic inflammation such as eosinophilic and lymphocytic infiltration and mRNA expression for interleukin (IL)‐4 and IL‐5. We examined the effects of CsA and SAR943, administered orally, on asthmatic responses in a rat model of chronic allergic inflammation. Sensitized Brown‐Norway (BN) rats were exposed to ovalbumin (OVA) aerosol every third day on six occasions. CsA (5 mg/kg/day), SAR943 (2·5 mg/kg/day) or vehicle (Neoral™) was administered orally, once a day, from days 10 to 21 (a total of 12 doses). We measured eosinophilic and T‐cell inflammation in the airways, proliferation of airway cells by incorporation of bromodeoxyuridine (BrdU) and bronchial responsiveness to acetylcholine. CsA had no effects, while SAR943 inhibited airway smooth muscle (ASM, P < 0·05) and epithelial cell (P < 0·01) BrdU incorporation, and the number of CD4+ T cells (P < 0·05), without effects on BHR. ASM thickness was not significantly increased following chronic allergen exposure. Therefore, CsA and SAR943 have no effect on chronic eosinophilic inflammation, while SAR943, but not CsA, had a small effect on the proliferation of ASM and epithelium.
Induction of interleukin‐12 production in mouse macrophages by berberine, a benzodioxoloquinolizine alkaloid, deviates CD4+ T cells from a Th2 to a Th1 response
Authors: Kim Tae S. , Kang Bok Y. , Cho Daeho , Kim Seung H. 
Published: June 2003

SummaryIn this study we investigated whether berberine‐mediated induction of interleukin‐12 (IL‐12) production in antigen‐presenting cells could regulate a cytokine profile of antigen‐primed CD4+ T helper (Th) cells. Pretreatment with berberine induced IL‐12 production in both macrophages and dendritic cells, and significantly increased the levels of IL‐12 production in lipopolysaccharide‐stimulated macrophages and in CD40 ligand‐stimulated dendritic cells. Importantly, berberine pretreatment of macrophages increased their ability to induce interferon‐γ (IFN‐γ) and reduced their ability to induce IL‐4 in antigen‐primed CD4+ T cells. Berberine did not influence the macrophage cell surface expression of the class II major histocompatibility complex molecule, the co‐stimulatory molecules CD80 and CD86, and intracellular adhesion molecule‐1. Addition of neutralizing anti‐IL‐12p40 monoclonal antibody to cultures of berberine‐pretreated macrophages and CD4+ T cells restored IL‐4 production in antigen‐primed CD4+ T cells. The in vivo administration of berberine resulted in the enhanced induction of IL‐12 production by macrophages when stimulated in vitro with lipopolysaccharide or heat‐killed Listeria monocytogenes, leading to the inhibition of the Th type 2 cytokine profile (decreased IL‐4 and increased IFN‐γ production) in antigen‐primed CD4+ T cells. These findings may point to a possible therapeutic use of berberine or medicinal plants containing berberine in the Th type 2 cell‐mediated immune diseases such as allergic diseases.
Effects of functional Toll‐like receptor‐4 mutations on the immune response to human and experimental sepsis
Authors: Feterowski Carolin , Emmanuilidis Klaus , Miethke Thomas , Gerauer Klaus , Rump Martina , Ulm Kurt , Holzmann Bernhard , Weighardt Heike 
Published: June 2003

SummaryGenetically determined responsiveness to microbial stimuli such as lipopolysaccharide (LPS) may affect the pathophysiology of human sepsis. The D299G mutation in human Toll‐like receptor‐4 (TLR4) impairs LPS signalling in homozygous and heterozygous individuals. To investigate whether the presence of the TLR4(D299G) mutation may correlate with the development or outcome of sepsis following major visceral surgery the presence of TLR4(D299G) mutation was analysed in 307 Caucasian patients (154 without and 153 with sepsis). Sepsis was caused in 84% of patients by polymicrobial infection. The presence of the mutant TLR4 did not significantly correlate with development or outcome of sepsis. Serum levels of tumour necrosis factor, interleukin (IL)‐10, and IL‐6 at sepsis onset did not significantly differ between patients carrying wild‐type and mutant TLR4. Moreover, studies in a murine model of polymicrobial septic peritonitis demonstrated that TLR4‐deficiency did neither influence the systemic cytokine response nor the development of organ injury. The results suggest that the signalling capacity of TLR4 as affected by loss‐of‐function mutations does not influence human or experimental sepsis caused by polymicrobial infection. Thus, in polymicrobial infection, other innate immune receptors may compensate for TLR4 defects.
Immature dendritic cells possess a sugar‐sensitive receptor for human mannan‐binding lectin
Authors: Downing Ian , Koch Claus , Kilpatrick David C. 
Published: June 2003

SummaryMannan‐binding lectin (MBL) is a collectin synthesized by the liver and secreted into the bloodstream. It has a receptor for microbial structures in its C‐type lectin domain and a separate receptor(s) located within its collagen‐like region for autologous phagocytic cells. Here we demonstrate that human peripheral blood adherent cells (monocytes) and monocyte‐derived dendritic cells are a source of MBL, and that a novel calcium‐dependent and sugar‐specific MBL receptor is up‐regulated in immature (CD1a‐positive) dendritic cells. These findings suggest a previously unsuspected autologous function for MBL, perhaps a regulatory role within the immune system.
Limited role of charge matching in the interaction of human immunoglobulin A with the immunoglobulin A Fc receptor (FcαRI) CD89
Authors: Pleass Richard J. , Dehal Prabhjyot K. , Lewis Melanie J. , Woof Jenny M. 
Published: June 2003

SummaryHuman immunoglobulin A (IgA) mediates protective effector mechanisms through interaction with specific cellular Fc receptors (FcαRI). Two IgA Fc interdomain loops (Leu257–Leu258 in the CH2 domain and Pro440–Phe443 in the CH3 domain) have previously been identified as critical for binding to FcαRI. On the receptor, the interaction site for IgA has been localized to the EC1 domain. The essential FcαRI residues involved are Tyr35, Tyr81 and Arg82, with contributions also from Arg52 and to a lesser extent from His85 and Tyr86. The basic nature of the side chains of some of the receptor residues implicated in ligand binding suggested that charge matching might play some role in the interaction. To address this possibility, we have generated five IgA1 mutants with point substitutions in acidic residues lying close to the putative interaction site and assessed their abilities to bind FcαRI on human neutrophils. Mutants E254A, E254L and E437A displayed affinities for FcαRI comparable to that of wild‐type IgA1, while mutants D255A and D255V had only slightly reduced affinities for the receptor. Therefore, electrostatic interactions appear unlikely to play a significant role in the IgA–FcαRI interaction. Moreover, the lack of effect of mutations in residues adjacent to those previously implicated in binding, reaffirms the importance of the interdomain loops in FcαRI binding.
Differential regulation of interleukin‐12 p40 and p35 induction via Erk mitogen‐activated protein kinase‐dependent and ‐independent mechanisms and the implications for bioactive IL‐12 and IL‐23 responses
Authors: Goodridge Helen S. , Harnett William , Liew Foo Y. , Harnett Margaret M. 
Published: June 2003

SummaryBioactive interleukin (IL)‐12 is a 70 000‐molecular weight (MW) heterodimeric cytokine comprising p40 and p35 chains. However, p40 can also form homodimers that antagonize bioactive IL‐12 or heterodimerize with p19 to form IL‐23, which exhibits overlapping yet distinct functions to that of IL‐12. We now define distinct signalling mechanisms that regulate lipopolysaccharide (LPS)‐mediated induction of IL‐12 p40 and p35 in macrophages and which may therefore provide therapeutic targets for precise and specific fine‐tuning of cytokine responses. Thus, whilst LPS‐induced p38 mitogen‐activated protein kinase (MAPkinase) activation is required for the induction of both p40 and p35 subunits, Erk MAPkinase signalling mediates negative feedback regulation of p40, but not p35, production. Such Erk MAPkinase activation is downstream of calcium influx and targets LPS‐induced IL‐12 p40 transcription by suppressing the synthesis of the transcription factor, interferon regulatory factor‐1 (IRF‐1). In contrast, negative regulation of the p35 subunit of IL‐12 occurs via a calcium‐dependent, but Erk‐independent, mechanism, which is likely to involve nuclear factor (NF)‐κB signalling. Finally, the importance of both Erk and p38 MAPkinases in differentially regulating IL‐12 p40 and p35 production is underscored by each being targeted by ES‐62, a product secreted by parasitic filarial nematodes to polarize the immune system towards an anti‐inflammatory phenotype conducive to their survival.
Pentacapsula neurophila sp.n. (Multivalvulida) from the central nervous system of striped trumpeter, Latris lineata (Forster)
Authors: Grossel G W , Dykova I , Handlinger J , Munday B L 
Published: June 2003

AbstractStriped trumpeter, Latris lineata, are being experimentally cultured by the Tasmanian Aquaculture and Fisheries Institute at Taroona, Tasmania. Fish surviving over 30 days post‐hatching have frequently developed nervous aberrations associated with a severe granulomatous meningoencephalomyelitis. The myxozoan parasite Pentacapsula neurophila sp.n. was revealed as the parasite causing the disease in the striped trumpeter juveniles. Measurements made of isolated spores indicated that the organism was distinct from all previously described Pentacapsula species. This is the first report of a marine myxozoan parasite of the genus Pentacapsula in Australian waters.
Blood pressure independent association of microalbuminuria and left ventricular hypertrophy in hypertensive men
Authors: Dell'omo G. , Giorgi D. , Di Bello V. , Mariani M. , Pedrinelli R. 
Published: June 2003

Abstract.  Dell'Omo G, Giorgi D, Di Bello V, Mariani M, Pedrinelli R (Università di Pisa, Pisa, Italy). Blood pressure independent association of microalbuminuria and left ventricular hypertrophy in hypertensive men. J Intern Med 2003; 254:–.Background.  Rather unique amongst the prognostic predictors, microalbuminuria (MA, albuminuria: 15–200 μg min−1) is associated with several cardiovascular risk factors including left ventricular hypertrophy (LVH). The relationship, usually assumed to reflect an increased blood pressure (BP) load on the heart and the kidney, may, however, represent more than a haemodynamic correlate.Methods.  To evaluate this possibility, we related MA to left ventricular mass index (LVMI) and other functional and structural echocardiographic parameters, office and 24‐h BP, weight, lipids and smoking status in 330 never treated nondiabetic hypertensive men.Results.  The risk of MA increased linearly by ascending quartiles of LVMI and was 2.3‐fold higher in the presence of LVH after adjustment for age, left atrial size, mean fractional shortening. Systolic BP, either office or 24 h, and smoking status were the only additional independent predictors in multivariate logistic regression models. The BP‐adjusted risk of MA was about twofold higher in patients with LVH, either concentric or eccentric, and neutral in those with concentric remodelling compared with normal geometry.Conclusions.  The association between elevated LVMI and MA independent of several other potential confounders, systolic BP in particular, is consistent with the existence of cardiac albuminuric factors, possibly of hormonal nature, which are to be identified more precisely. The extent to which LVH explains the predictive power of MA for morbid events independent of the BP load remains unknown.
Raloxifene, conjugated oestrogen and endothelial function in postmenopausal women
Authors: Duschek E. J. J. , Stehouwer C. D. A. , De Valk‐De Roo G. W. , Schalkwijk C. G. , Lambert J. , Netelenbos C. 
Published: June 2003

Abstract.  Duschek EJJ, Stehouwer CDA, de Valk‐de Roo GW, Schalkwijk CG, Lambert J, Netelenbos C (VU University Medical Center, Amsterdam; Sophia Hospital, Zwolle; The Netherlands). Raloxifene, conjugated oestrogen and endothelial function in postmenopausal women. J Intern Med 2003; 254: 85–94.Objectives.  To study the long‐term effects of raloxifene, a potential designer oestrogen, and oestrogen monotherapy on endothelial function in healthy postmenopausal women.Design.  A 2‐year double‐blind, randomized and placebo‐controlled study in an Academic Medical Center. Fifty‐six hysterectomized but otherwise healthy postmenopausal women randomly received raloxifene hydrochloride 60 mg day−1 (n = 15) or 150 mg day−1 (n = 13), conjugated equine oestrogen (CEE) 0.625 mg day−1 (n = 15), or placebo (n = 13).Main outcome measures.  Endothelial function as estimated from brachial artery flow‐mediated, endothelium‐dependent vasodilation and nitroglycerine‐induced endothelium‐independent vasodilation, and plasma levels of the endothelium‐derived regulatory proteins, von Willebrand factor (vWF) and endothelin (ET).Results.  Raloxifene 60 mg did not significantly affect endothelial function. As compared with placebo, at 6 months of therapy, raloxifene 150 mg and CEE were associated with a mean increase in vWF of 25.5% point (95% CI 3.6–47.3) and 26.6% point (95% CI 6.9–46.3), respectively. At 24 months of therapy, raloxifene 150 mg was associated with a mean decrease in ET of 0.96 pg mL−1 (95% CI −1.57 to −0.36). Raloxifene nor CEE significantly affected endothelium‐dependent and/or ‐independent vasodilation.Conclusions.  Our results suggest that long‐term therapy with raloxifene or oral CEE does not affect endothelium‐dependent vasodilation in healthy postmenopausal women. Raloxifene 150 mg day−1 might have both positive and negative effects on endothelium. The clinical significance of these findings remains to be investigated.
Effects of low‐dose warfarin and aspirin versus no treatment on stroke in a medium‐risk patient population with atrial fibrillation
Authors: Edvardsson N. , Juul‐Möller S. , Ömblus R. , Pehrsson K. 
Published: June 2003

Abstract. Edvardsson N, Juul‐Möller S, Ömblus R, Pehrsson K (Sahlgrenska University Hospital, Malmö University Hospital, Bristol‐Myers Squibb Bromma; and Karolinska University Hospital; Stockholm, Sweden). Effects of low‐dose warfarin and aspirin versus no treatment on stroke in a medium‐risk patient population with atrial fibrillation. J Intern Med 2003; 254: 95–101.Objectives. To assess the optimal stroke prevention treatment for patients with atrial fibrillation (AF) and a low–medium risk (≤4%) of stroke.Design. A total of 668 patients with persistent or permanent AF, without an indication for full dose and with adequate rate control on sotalol, were randomized to warfarin 1.25 mg + aspirin 75 mg daily (W/A, 334 patients) or no anticoagulation (C, 334 patients). The mean follow‐up period was 33 months. The protocol intended to verify a 37% relative risk reduction provided a 4% stroke incidence in the C group.Results. The stroke incidence was less in the W/A group, although the reduction was not statistically significant (W/A 9.6% versus C 12.3%). Four haemorrhagic strokes were identified, two in each group. Secondary end‐points were transient ischaemic attacks (TIA) (W/A 3.3% versus C 4.5%), all cause mortality (W/A 9.3% versus C 10.8%), cardiovascular morbidity (W/A 17.7% versus C 22.2%) and the combination of stroke + TIA (W/A 11.7% versus C 16.5%). Bleedings were documented in 19 versus four patients (W/A 5.7% versus C 1.2%) (P = 0.003), although none fatal. Sinus rhythm (SR) was recorded occasionally in 68 patients (W/A 9.6% versus C 10.8%). The stroke incidence tended to be higher in those with SR than without, 16.2% versus 10.4%.Conclusions. Our results were inconclusive, but consistent with a small beneficial effect of W/A for reduction of stroke and major vascular events in AF patients at moderate risk. The low‐dose regiment produced, however, a significantly increased risk of bleedings. Documented SR occasionally recorded may represent a subpopulation that warrants full dose warfarin.
Sleep and endocrinology
Authors: Steiger A. 
Published: June 2003

Abstract.Steiger A (Max Planck Institute of Psychiatry, Munich, Germany). Sleep and endocrinology (Minisymposium). J Intern Med 2003; 254: 13–22.A bidirectional interaction between sleep electroencephalogram and endocrine activity is well established in various species including humans. Various hormones (peptides and steroids) participate in sleep regulation. A keyrole was shown for the reciprocal interaction between sleep‐promoting growth hormone‐releasing hormone (GHRH) and sleep‐impairing corticotropin‐releasing hormone (CRH). Changes in the GHRH : CRH ratio result in changes of sleep‐endocrine activity. It is thought that the change of this ratio in favour of CRH contributes to aberrances of sleep during ageing and depression (shallow sleep, blunted GH and elevated cortisol). Besides GHRH, ghrelin and galanin enhance slow wave sleep. Somatostatin is another sleep‐impairing factor. Neuropeptide Y acts as a CRH antagonist and induces sleep onset. There are hints that CRH promotes rapid eye movement sleep (REMS). In animals prolactin enhances REMS. In humans vasocactive intestinal polypeptide (VIP) appears to play a role in the temporal organization of sleep as, after VIP, the non‐REMS–REMS cycle decelerated. Cortisol appears to enhance REMS. Finally, gonadal hormones participate in sleep regulation. Oestrogen replacement therapy and CRH‐1 receptor antagonism in depression are beneficial clinical applications of sleep‐endocrine research.
Insomnia, metabolic rate and sleep restoration
Authors: Bonnet M. H. , Arand D. L. 
Published: June 2003

Abstract.Bonnet MH, Arand DL (Wright State University, Kettering Medical Center, and Wallace Kettering Neuroscience Institute, Dayton, OH, USA). Insomnia, metabolic rate and sleep restoration (Minisymposium). J Intern Med 2003; 254:–.Studies have shown occasional evidence of increased physiological activity in patients with primary insomnia. We hypothesized that metabolic rate, as measured by overall oxygen use (), might be a more general index of increased physiological activity. An initial experiment found elevated both at night and during the day in patients with primary insomnia as compared with matched normal sleepers. A second experiment found significant but more modest increases in in patients with Sleep State Misperception Insomnia [who complain of poor sleep but who had normal sleep by electroencephalographic (EEG) criteria]. In a third experiment, normal young adults were given caffeine 400 mg three times per day (TID) for 1 week as a means of increasing and possibly producing other symptoms of insomnia. Participants developed many symptoms consistent with those seen in patients with primary insomnia (poor sleep, increased latency on the Multiple Sleep Latency Test, increasing fatigue despite physiological activation, and increased anxiety on the Minnesota Multiphasic Personality Inventory (MMPI)). In a final experiment, physiological arousal was again produced by caffeine to determine if sleep with elevated arousal would be less restorative. All subjects (Ss) slept for 3.5 h after being given 400 mg of caffeine. During 41 h of sleep deprivation that followed, there was no significant condition difference for the Multiple Sleep Latency Test or mood measures. The results provided only weak support for the idea that sleep is less restorative after physiological arousal.