Resuscitation of preterm infants in Nigeria - A national survey on practice.

Introduction and Aims: Preterm births constitute a major clinical problem associated with significant morbidity and mortality in the perinatal, neonatal, and childhood periods. Decisions around initiating and/or continuing resuscitation and treatment of preterm infants (PI) both at birth and afterwards need careful consideration. While the developed countries have published guidelines for the resuscitation and care of the PI, this is not the case in developing countries where availability of resources and the absence of a published guidelines impacts on practice. Our study was therefore carried out to access the practice and decision-making that surrounds the resuscitation of PIs by neonatologists and neonatal nurses working in neonatal intensive care units (NICU) across Nigeria. Subjects and Methods: We conducted an online national survey on neonatal care providers working in level 2 and level 3 neonatal units (NICU) across Nigeria. Around 190 participants were selected from the six geopolitical zones of the country and they were asked about current practices relating to resuscitation and stopping life-sustaining treatment as well as estimated survival rates at different gestational ages (GA). Results: In total, 138 clinicians responded to our survey. Of this, 73% completed the survey. Majority (83%) of the respondents worked in government-funded public hospitals while the remaining 17% worked in the private hospitals. 74% of the respondents' report having a guideline on the PI. Resuscitation practice varied amongst different neonatologists and neonatal nurses with 48% of the clinicians providing resuscitation at 23-26 weeks and the remainder providing resuscitation at a GA >26 weeks with a median GA threshold for initiating resuscitation at 27 weeks. From an institutional perspective, 75% of PIs <26 weeks were resuscitated in public hospitals while the remaining 25% were resuscitated in private hospital, however this is not statistically significant (P = 0.385). In situations when the GA is unknown, we found a median fetal weight of 700 g as the threshold for providing active treatment. We noticed wide variations in responses on the estimated survival rates of the PIs, however a common finding is the increased chances of survival with increasing GA. Also, PIs across all GAs had higher chances of survival in public hospitals than in private hospitals, however, this is not statistically significant (P = 0.385-0.956). The major factor influencing a clinicians' decision to limit resuscitation was the "risk of poor quality of life" (50%) and the prevalent way of palliating the newborn amongst respondents is by stopping life-sustaining treatment (34%). Conclusion: Our survey revealed considerable variation in resuscitation practices amongst different neonatal care providers. Having a framework that will formulate and publish a national guideline based on factors like local survival rates, societal norms, and resources and ensuring that it is adopted by all NICUs will generate greater consistency of care.

Striae reconstructed, a full thickness skin model that recapitulates the pathology behind stretch marks.

OBJECTIVE: Stretch marks are disfiguring skin lesions that often cause problems of self-esteem, but little effort has been put to studying this pathology. We therefore analysed cell cultures of dermal fibroblasts isolated from a striae albae, to thereafter reconstruct a full thickness skin model. METHODS: Human Dermal Fibroblasts (HDF) were isolated from a striae distensae (SD) lesion and from the adjacent non-lesioned skin. The dermis of two full thickness skin models was reconstructed with either striae- or normal-HDF, while the epidermis was in both reconstructed with Normal Human Epidermal Keratinocytes. RESULTS: Main observations and pertinent data: Gene expression analysis of cell cultures revealed a generalized decomposition of the Extra Cellular Matrix (ECM), since collagens type I and III, lysyl oxidase (LOX), biglycan, lumican and fibronectin were downregulated, while MMP3 was increased together with a decrease of its natural inhibitors (TIMP1, TIMP2 and PAI-1). These findings were statistically corroborated for key ECM elements at the protein level (COL1, MMP1 and TGFB1). Interestingly, striae albae fibroblasts retained a pro-inflammatory phenotype, as suggested by increased gene expression of CXCL8, HAS1 and TNFA. We next reconstructed a full thickness skin model (Striae Reconstructed) with dermal fibroblasts from striae albae. Gene expression analysis showed that the Striae Reconstructed elicited not only ECM decomposition, but also skin ageing, as indicated by the upregulation of P16, PTGS2 and SOD2. Discussion points: Although the epidermis was constructed with normal human epidermal keratinocytes, the Striae Reconstructed presented epidermal atrophy and a dramatic increase of ß1-integrin at the epidermal-dermal junction providing, for the first time to our knowledge, a rationale showing that the key cell player behind stretch marks are dermal fibroblasts rather than epidermal keratinocytes. CONCLUSION: New knowledge: Taken together, our findings shed new light into the aetiology of stretch marks and indicate that the Striae Reconstructed, a new model for in vitro testing and drug screening, may open new avenues for the treatment of stretch marks.

OBJECTIFS: Les vergetures sont des lésions cutanées défigurantes qui posent souvent des problèmes d'estime de soi, mais peu d'efforts ont été consacrés dans l'étude de cette pathologie. Nous avons donc analysé des cultures cellulaires de fibroblastes dermiques isolés d'un stria alba, afin de reconstruire ensuite un modèle de peau avec une pleine épaisseur. METHODES: Des fibroblastes dermiques humains (FDH) ont été isolés d'une lésion de Stria distensae (SD) et d'une peau adjacente sans lésion. Le derme de deux modèles de peau de pleine épaisseur a été reconstruit avec du HDF striae- ou normal, tandis que l'épiderme était reconstruit avec des kératinocytes humains normaux. RESULTATS: Principales observations et données pertinentes: L'analyse de l'expression génique de cultures cellulaires a révélé une décomposition généralisée de la matrice extra-cellulaire (MEC) car les collagènes de types I et III, la lysyl oxydase, le biglycane, le lumican et la fibronectine étaient régulés négativement, tandis que la MMP3 augmentait ses inhibiteurs naturels diminuaient (TIMP1, TIMP2 et PAI-1). Ces résultats ont été corroborés statistiquement pour les éléments clés de la MEC au niveau de la protéine (COL1, MMP1 et TGFB1). Il est intéressant de noter que les fibroblastes de Striae albae ont conservé un phénotype proinflammatoire, comme le suggère l'augmentation de l'expression des gènes de CXCL8, HAS1 et TNFA. Nous avons ensuite reconstruit un modèle de peau de pleine épaisseur (Stria Reconstructed) avec des fibroblastes dermiques de Striae albae. L'analyse de l'expression génique a montré que la reconstruction de Striae induisait non seulement la décomposition de la MEC, mais également le vieillissement de la peau, comme l'indique la régulation à la hausse de P16, PTGS2 et SOD2. Points de discussion : Bien que l'épiderme ait été construit avec des kératinocytes humains normaux, les stries reconstruites présentaient une atrophie épidermique et une augmentation spectaculaire du taux de ß1-intégrine au niveau de la jonction épidermo-dermique, fournissant pour la première fois une explication rationnelle qui démontre que les cellules principales impliquées dans la pathologie de la Striae sont les fibroblastes et non les kératinocytes. CONCLUSION: Nouvelles connaissances: Ensemble, nos résultats donnent une nouvelle lumière sur l'étiologie des vergetures et indiquent que le Striae Reconstructed, un nouveau modèle de test in vitro et de dépistage du médicament, pourrait être une avancée pour le traitement des vergetures.

The three α1-adrenoceptor subtypes show different spatio-temporal mechanisms of internalization and ERK1/2 phosphorylation.

We analyzed the kinetic and spatial patterns characterizing activation of the MAP kinases ERK 1 and 2 (ERK1/2) by the three α1-adrenoceptor (α1-AR) subtypes in HEK293 cells and the contribution of two different pathways to ERK1/2 phosphorylation: protein kinase C (PKC)-dependent ERK1/2 activation and internalization-dependent ERK1/2 activation. The different pathways of phenylephrine induced ERK phosphorylation were determined by western blot, using the PKC inhibitor Ro 31-8425, the receptor internalization inhibitor concanavalin A and the siRNA targeting ß-arrestin 2. Receptor internalization properties were studied using CypHer5 technology and VSV-G epitope-tagged receptors. Activation of α1A- and α1B-ARs by phenylephrine elicited rapid ERK1/2 phosphorylation that was directed to the nucleus and inhibited by Ro 31-8425. Concomitant with phenylephrine induced receptor internalization α1A-AR, but not α1B-AR, produced a maintained and PKC-independent ERK phosphorylation, which was restricted to the cytosol and inhibited by ß-arrestin 2 knockdown or concanavalin A treatment. α1D-AR displayed constitutive ERK phosphorylation, which was reduced by incubation with prazosin or the selective α1D antagonist BMY7378. Following activation by phenylephrine, α1D-AR elicited rapid, transient ERK1/2 phosphorylation that was restricted to the cytosol and not inhibited by Ro 31-8425. Internalization of the α1D-AR subtype was not observed via CypHer5 technology. The three α1-AR subtypes present different spatio-temporal patterns of receptor internalization, and only α1A-AR stimulation translates to a late, sustained ERK1/2 phosphorylation that is restricted to the cytosol and dependent on ß-arrestin 2 mediated internalization.

Different ß-adrenoceptor subtypes coupling to cAMP or NO/cGMP pathways: implications in the relaxant response of rat conductance and resistance vessels.

BACKGROUND AND PURPOSE: To analyse the relative contribution of ß1 -, ß2 - and ß3 -adrenoceptors (Adrb) to vasodilatation in conductance and resistance vessels, assessing the role of cAMP and/or NO/cGMP signalling pathways. EXPERIMENTAL APPROACH: Rat mesenteric resistance artery (MRA) and aorta were used to analyse the Adrb expression by real-time-PCR and immunohistochemistry, and for the pharmacological characterization of Adrb-mediated activity by wire myography and tissue nucleotide accumulation. KEY RESULTS: The mRNAs and protein for all Adrb were identified in endothelium and/or smooth muscle cells (SMCs) in both vessels. In MRA, Adrb1 signalled through cAMP, Adrb3 through both cAMP and cGMP, but Adrb2, did not activate nucleotide formation; isoprenaline relaxation was inhibited by propranolol (ß1 , ß2 ), CGP20712A (ß1 ), and SQ22536 (adenylyl cyclase inhibitor), but not by ICI118,551 (ß2 ), SR59230A (ß3 ), ODQ (soluble guanylyl cyclase inhibitor), L-NAME or endothelium removal. In aorta, Adrb1 signalled through cAMP, while ß2 - and ß3 -subtypes through cGMP; isoprenaline relaxation was inhibited by propranolol, ICI118,551, ODQ, L-NAME, and to a lesser extent, by endothelium removal. CL316243 (ß3 -agonist) relaxed aorta, but not MRA. CONCLUSION AND IMPLICATION: Despite all three Adrb subtypes being found in both vessels, Adrb1, located in SMCs and acting through the adenylyl cyclase/cAMP pathway, are primarily responsible for vasodilatation in MRA. However, Adrb-mediated vasodilatation in aorta is driven by endothelial Adrb2 and Adrb3, but also by the Adrb2 present in SMCs, and is coupled to the NO/cGMP pathway. These results could help to understand the different physiological roles played by Adrb signalling in regulating conductance and resistance vessels.

Morphine metabolism in the opium poppy and its possible physiological function. Biochemical characterization of the morphine metabolite, bismorphine.

We identified a novel metabolic system of morphine in the opium poppy (Papaver somniferum L.). In response to stress, morphine is quickly metabolized to bismorphine consisting of two morphine units, followed by accumulation in the cell wall. This bismorphine binds predominantly to pectins, which possess high galacturonic acid residue contents, through ionical bonds. Our newly developed method using artificial polysaccharides demonstrated that bismorphine bridges are formed between the two amino groups of bismorphine and the carboxyl groups of galacturonic acid residues, resulting in cross-linking of galacturonic acid-containing polysaccharides to each other. The ability of bismorphine to cross-link pectins is much higher than that of Ca2+, which also acts as a cross-linker of these polysaccharides. Furthermore, we confirmed that cross-linking of pectins through bismorphine bridges leads to resistance against hydrolysis by pectinases. These results indicated that production of bismorphine is a defense response of the opium poppy. Bismorphine formation is catalyzed by anionic peroxidase that pre-exists in the capsules and leaves of opium poppies. The constitutive presence of morphine, together with bismorphine-forming peroxidase, enables the opium poppy to rapidly induce the defense system.

Molecular design of a new class of spin-labeled ribonucleosides with N-tert-butylaminoxyl radicals.

We designed a new type of spin-labeled nucleosides with an N-tert-butylaminoxyl radical which is introduced to the nucleobase directly. Purine and pyrimidine ribonucleosides containing the aminoxyl radical such as 1a-d, 2, 3, and 4 were synthesized to investigate the stability and behavior of the N-tert-butylaminoxyl radical on a nucleobase. Lithiation of tri-O-silylated 6-chloropurine ribonucleoside (5) followed by reaction with 2-methyl-2-nitrosopropane (MNP) gave the key compound 6a, which was further converted to 6b-d. Oxidation of the obtained 6a-d and their triols (7a-d) with Ag(2)O led to formation of the corresponding stable spin-labeled nucleosides (8a-d and 1a-d), which were confirmed by EPR spectroscopy. Similarly, the precursors of spin-labeled pyrimidines (13, 20, and 23) were synthesized by site-selective lithiation of tri-O-protected pyrimidine derivatives (9, 18, and 21) followed by the reaction with MNP and deprotection. An EPR study showed that the aminoxyl radicals (2, 3, and 4) were stable and that their hyperfine structures were dependent on the position of the radical. Electron densities of pyrimidine also affected hyperfine structures.

Sylvian fissure and medial temporal lobe structures in patients with schizophrenia: a magnetic resonance imaging study.

Volumes of the medial temporal lobe structures (i.e. the amygdala, hippocampus, and parahippocampal gyrus), Sylvian fissure, and inferior horn of the lateral ventricle relative to the cerebral hemisphere were measured in 24 patients with schizophrenia and 23 normal controls using magnetic resonance imaging. The patients had significantly larger Sylvian fissures and inferior horns bilaterally than the controls. In the patients the right Sylvian fissure size showed a significant positive correlation with the duration of illness. Moreover, earlier onset of illness was significantly correlated with decreased volume of the left medial temporal lobe structures. These results replicate previous finding of inferior horn enlargement and suggest the significance of the Sylvian fissure and the medial temporal lobe structures in pathophysiology of schizophrenia.

Synthesis and properties of a new class of nucleosides with spin source.

Novel spin-labeled ribonucleosides 1-5 were synthesized to investigate stability and behavior of N-tert-butyl aminoxyl radical on nucleobase. Site selective lithiation of tri-O-protected ribonucleosides followed by the reaction with 2-methyl-2-nitrosopropane (MNP) resulted in introduction of N-tert-butylhydroxylamino group into various positions of purine or pyrimidine nucleus. Oxidation of the obtained hydroxylamines with Ag2O led to formation of 1-5. EPR study showed that the unpaired electron of the aminoxyl radical was delocalized into the nucleobase and hyperfine structures were dependent on the position of the radical.

Two cases of tinea corporis by infection from a rabbit with Arthroderma benhamiae.

The first cases of tinea corporis with Arthroderma benhamiae in Japan are reported. A 7-year-old girl and a 30-year-old mother in Shimane prefecture suffered from dermatophyte infections on the neck, shoulder, arms and leg. Three isolates from the two patients and a rabbit by which they supposedly were infected, were identified as Trichophyton mentagrophytes. On the bases of mating tests using the tester strains of both the African race and the Americano-European race of A. benhamiae, they were identified as A. benhamiae African race mating type (-). Our results are the first to indicate that both races of A. benhamiae exist in Japan.

Insight into acid-mediated asymmetric spirocyclization in the presence of a chiral diol.

Asymmetric spirocyclization based on intramolecular conjugate addition using a combination of a Lewis acid and an optically active cyclohexane-1,2-diol has been studied in connection with 1) the effect of substituents on the cyclohexane-1,2-diol and 2) the effect of substituents on the substrate. This reaction was found to be both thermodynamically and kinetically controlled under restricted conditions.

A novel method of preparing amine-modifying C-4' oxidized nucleotide.

A novel method of preparing C-4' oxidized nucleotide, a monomeric model of an alkali labile lesion (1) has been studied. The C-4' selenated 4a and 4b were found to be effective in preparing 3, a monomeric model of 1, by the reaction with NBS (N-bromosuccinimide). The successive reaction of 3 with amine at room temperature afforded the alpha,beta-unsaturated gamma-methylene-gamma-lactam (2) in good yield.

[A case of systemic lupus erythematosus with pulmonary hypertension].

A 15 year-old girl was admitted to the hospital because of fever, polyarthlargia, dry cough, dyspnea, butterfly rash and multiple oral aphthas. The diagnosis of systemic lupus erythematosus (SLE) was made based on renal disorders, pancytopenia, positive antinuclear antibody and positive for antibodies to double-stranded DNA. On admission, she developed progressive dyspnea with highly active SLE. The patient was complicated with both pulmonary hypertension (PH) and interstitial pneumonitis (IP), judging from increased pulmonary sound by an auscultation, interstitial shadows especially at bilateral lower lung and enlarged shadow of right atrium in a chest rentgenogram, ground glass pattern of bilateral middle to lower lung in a chest computed tomographic scan, increased pulmonary artery pressure, 53 mmHg, by an ultrasound cardiograph (UCG). Combination of methylprednisolone pulse therapy, cyclosporin A and plasma exchanges was effectively administered, which resulted in improvement of disease activity of SLE, IP and PH. However, two months later, although disease activity of SLE was completely reduced, recurrence of PH by UCG and multiple pulmonary embolism (PE) which was observed by a chest rentgenogram and a pulmonary blood flow scintigraphy was further complicated. Administration of cyclophosphamide pulse therapy and warfarin therapy improved both PE and PH. The patient had PH at the different clinical course of SLE; 1) PH maybe induced by severe IP at the active phase of SLE and 2) PH brought about from multiple PE at the inactive phase of SLE. Thus, the case is thought to be suggestive of elucidating the pathogenesis of PH of several systemic autoimmune diseases including SLE.

Conocimientos y actitudes sobre el SIDA entre los funcionarios penitenciarios / Awareness and attitudes to aids amongst prision staff

Este trabajo describe la evaluación de los cambios de actitudes y conocimientos en una muestra de funcionarios penitenciarios después de una experiencia de educación para la salud que consistió en un programa de sesiones de formación sobre el sida. En este trabajo participaron 110 funcionarios/as. La metodología de valoración de los resultados responde a un diseño cuasi-experimental, con un pre-test y un post-test, mediante un contraste de 2 (Chi-cuadrado), se ha podido establecer si existían diferencias en la información asimilada antes y después de haber asistido al curso. Los resultados señalan, que aunque la muestra explorada por nosotros en esta experiencia dispuso de información detallada sobre los mecanismos de contagio de las enfermedades que les preocupaban, el miedo al contagio siguió influyendo sobre la actitud del trabajador ante ellas. Este hecho puede explicar que, después de las sesiones de formación, el 90 por ciento de nuestra muestra declarase conocer los mecanismos de transmisión del Sida, y en torno al 50 por ciento eligiese alternativas inadecuadas a preguntas sobre situaciones de riesgo de contagio expresando comportamientos irracionalmente precavidos. Los resultados sobre transmisión de información, confirman una alta efectividad; los resultados sobre asimilación de esa información y su traslado a la conducta real son más pobres. Concluimos con esta experiencia que informar no es suficiente para cambiar actitudes, aunque sea un paso previo necesario (AU)

Primary ileal plasmacytoma arising in mixed low- and high-grade B-cell lymphoma of mucosa-associated lymphoid tissue type.

We report an extremely rare case of primary ileal plasmacytoma accompanied by mixed low- and high-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The radiographic and macroscopic features of the tumor were characterized by two constricting lesions in the ileum. Histologic examination of the resected specimen showed that one constrictive lesion was plasmacytoma and the other MALT lymphoma was low and high grade. The plasmacytoma seemed to have differentiated from the MALT lymphoma.

Additive combination of actarit and methotrexate in the treatment of refractory rheumatoid arthritis.

Abstract The objective of this study was to evaluate the efficacy and safety of an additive combination of a disease-modifying antirheumatic drug (DMARD) actarit and low-dose methotrexate (MTX) in patients with active rheumatoid arthritis (RA) unresponsive to MTX. Thirty-four patients with active RA, who had been unsuccessfully treated with MTX for at least 3 months were enrolled on a 24-week course of actarit (300 mg/day) and MTX (2.5-10 mg/week). Disease activity was evaluated by physical global assessments using conventional measures (Japan Rheumatism Association), and the American College of Rheumatology (ACR) criteria of improvements in RA. Thirty-two patients completed this study. No severe adverse drug reactions were seen. Patients whose RA did not respond to MTX alone responded to the combination therapy, with a significant improvement in the duration of morning stiffness, grip strength, swollen joint counts, patient's articular pain score, modified health assessment questionnaire (M-HAQ) score, score of both patient's and physician's global assessments, and C-reactive proteins (CRP). Sixteen patients (50.0%) and 9 patients (31.0%) showed a significant improvement in overall conventional measures, and ACR response criteria, respectively, and 60.0% of RA patients who received MTX for more than 1 year showed improvement in ACR definition. Patients who responded to the combination treatment within the first 12 weeks showed persistent improvement for the remaining part of the 24 week period. Our results indicate that the additive combination of actarit and MTX is safe, and without serious adverse effects, and has an excellent efficacy in patients with active and refractory RA.

[A case of mixed connective tissue disease with microscopic polyarteritis nodosa associated with perinuclear-antineutrophil cytoplasmic antibody and anti-glomerular basement membrane].

A 46-year-old female was admitted to our hospital due to general fatigue, systemic edema and dyspnea with history of systemic sclerosis (SSc). The patient was diagnosed as mixed connective tissue disease (MCTD) based on Raynaud phenomenon, a high anti-RNP antibody level and clinical symptoms and laboratory findings suggesting SSc, dermatomyositis (DM) and systemic lupus erythematosus (SLE). After the admission, both alveolar hemorrhage and a rapidly progressive glomerulonephritis (RPGN) also developed and laboratory findings showed a positive remark of myeloperoxydase-antineutrophil cytoplasmic antibody (MPO-ANCA) and anti-glomerular basement membrane (GBM) antibody. She was therefore re-diagnosed as microscopic polyarteritis nodosa (microscopic PAN) combined with MCTD and treatment with high dose prednisolone and steroid pulse therapy dramatically improved general conditions and lung symptoms, but maintenance dialysis was persistent because of irreversible renal failure. However, 3 months after the admission, she died of acute exacerbation of interstitial pneumonitis that was unresponsive to steroid pulse therapy. Autopsy revealed interstitial pneumonitis with alveolar hemorrhage and crescentic glomerulonephritis (CrGN), in which immunofluorescent microscopy showed no deposition in agreement with pauciimmune type. The histological findings supported the diagnosis; primary microscopic PAN combined with MCTD, which is a quite rare case, to our knowledge. Furthermore, co-existence of MPO ANCA and anti-GBM antibody, clinical and histological findings of the case also lead us to reconsider the relevance of these antibodies to pathogenesis and/or categories of microscopic PAN and Goodpasture's syndrome.

Hepatocyte growth factor is a potent trigger of neutrophil adhesion through rapid activation of lymphocyte function-associated antigen-1.

Recruitment of neutrophils into tissue occurs in several pathologic processes such as inflammation, atherosclerosis, thrombosis, and ischemia. In inflammation, the adherence of neutrophils to the endothelium depends on neutrophil integrins. Integrin-mediated adhesion is tightly regulated, ie, integrins do not function if neutrophils are not triggered by certain activation stimuli. We investigated the role of hepatocyte growth factor (HGF) in the adhesion of neutrophils to endothelial cells in inflammation. Our results showed that (a) HGF induced not only lymphocyte function-associated antigen-1 (LFA-1)-mediated adhesion of neutrophils to endothelial cells but also transmigration of neutrophils in a concentration-dependent manner; (b) HGF functionally transformed neutrophil integrin LFA-1 to active form and reduced surface L-selectin expression level; (c) HGF induced F-actin polymerization and cytoskeletal rearrangement within seconds; (d) genistein, a tyrosine kinase inhibitor, as well as wortmannin, a phosphoinositide 3 (PI 3)-kinase inhibitor, inhibited both F-actin polymerization and LFA-1-mediated adhesion of neutrophils to endothelial cells; and (e) neutrophils in cutaneous inflamed tissue highly expressed HGF and serum levels of HGF were elevated in patients with Behçet's disease, which is associated with neutrophilic vasculitis and marked neutrophil accumulation. Our results indicate that HGF plays a pivotal role in integrin-mediated adhesion and transmigration of neutrophils to sites of acute inflammation through cytoskeletal rearrangement activated by tyrosine kinase and PI 3-kinase signaling.

Heparan sulfate proteoglycan on endothelium efficiently induces integrin-mediated T cell adhesion by immobilizing chemokines in patients with rheumatoid synovitis.

OBJECTIVE: To clarify the role of heparan sulfate proteoglycan (HSPG) and chemokines in integrin-mediated T cell adhesion to endothelial cells in the synovium of patients with rheumatoid arthritis (RA). METHODS: Endothelial cells were purified from RA synovium. Expression of heparan sulfate, chemokines, and adhesion molecules on the endothelium was assessed by immunohistochemical analysis or flow cytometry. The effects of chemokines and heparan sulfate on T cell adhesion to RA endothelium were estimated with relevant antibodies and signaling inhibitors. Production of chemokines from synovial T cells was detected by Northern blotting and enzyme-linked immunosorbent assay. RESULTS: The endothelium in RA synovium highly expressed HSPG. The soluble form of chemokines, macrophage inflammatory protein 1beta (MIP-1beta), induced T cell adhesion to the endothelial cells. When MIP-lalpha and MIP-1beta were immobilized on RA endothelial cells, a more efficient integrin-mediated adhesion of T cells was induced compared with their soluble form. The induced T cell adhesion was reduced by pretreatment with either heparitinase, anti-MIP-lalpha antibody, or anti-MIP-lbeta antibody, indicating that these chemokines were bound to heparan sulfate on the cells. T cell adhesion was also inhibited by pertussis toxin, wortmannin, and cytochalasin B. MIP-lalpha and MIP-1beta were found on vessels in RA synovium in vivo, which were spontaneously produced from T cells purified from RA synovium. CONCLUSION: Endothelial cells in RA synovium characteristically express HSPG, which is involved in T cell integrin triggering by "posting" chemokines, which are produced by synovial T cells, and by "relaying" them to their receptors on T cells, which activate G protein-dependent phosphoinositide 3-kinase and actin-dependent integrin triggering.