Interleukin-13 induces PSGL-1/P-selectin-dependent adhesion of eosinophils, but not neutrophils, to human umbilical vein endothelial cells under flow.

Selective eosinophil accumulation is a hallmark of diseases such as asthma. In a model of chronic eosinophilic inflammation, we have previously shown that the tethering step in eosinophil adhesion is mediated by PSGL-1 binding to P-selectin. The Th2-associated cytokine IL-13 is of potential importance in allergic disease.

Expression of urokinase, plasminogen activator inhibitors and urokinase receptor in pregnant rhesus monkey uterus during early placentation.

We have investigated plasmin mediated proteolysis associated with trophoblast invasion during early stages of pregnancy in the rhesus monkey. In situ hybridization and immunocytochemical localization were used to define the cellular and tissue distribution of urokinase plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1) and 2 (PAI-2) and urokinase receptor in early monkey placenta and uterus. Our results indicate: (1) uPA is expressed in proliferating and invasive cytotrophoblast located in chorionic villi as well as in extravillous trophoblast associated with uterine arterioles.

Analysis of ciliary beat pattern and beat frequency using digital high speed imaging: comparison with the photomultiplier and photodiode methods.

Background: The aim of this study was to determine the relationship of the power and recovery stroke of respiratory cilia using digital high speed video imaging. Beat frequency measurements made using digital high speed video were also compared with those obtained using the photomultiplier and modified photodiode techniques.

Method: Ciliated epithelium was obtained by brushing the inferior nasal turbinate of 20 healthy subjects.

MEK kinase 3 directly activates MKK6 and MKK7, specific activators of the p38 and c-Jun NH2-terminal kinases.

Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) activates the c-Jun NH2-terminal kinase (JNK) pathway, although no substrates for MEKK3 have been identified. We have examined the regulation by MEKK3 of MAPK kinase 7 (MKK7) and MKK6, two novel MAPK kinases specific for JNK and p38, respectively. Coexpression of MKK7 with MEKK3 in COS-7 cells enhanced MKK7 autophosphorylation and its ability to activate recombinant JNK1 in vitro.

Regulation of extracellular-signal regulated kinase and c-Jun N-terminal kinase by G-protein-linked muscarinic acetylcholine receptors.

Extracellular signal-regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs, or stress-activated protein kinases) are activated by diverse extracellular signals and mediate a variety of cellular responses, including mitogenesis, differentiation, hypertrophy, inflammatory reactions and apoptosis. We have examined the involvement of Ca2+ and protein kinase C (PKC) in ERK and JNK activation by the human G-protein-coupled m2 and m3 muscarinic acetylcholine receptors (mAChR) expressed in Chinese hamster ovary (CHO) cells. We show that the Ca2+-mobilizing m3 AChR is efficiently coupled to JNK and ERK activation, whereas the m2 AChR activates ERK but not JNK.

Proteinuria induces tubular cell turnover: A potential mechanism for tubular atrophy.

Background: Proteinuria and tubular atrophy have both been closely linked with progressive renal failure. We hypothesized that apoptosis may be induced by tubular cell exposure to heavy proteinuria, potentially leading to tubular atrophy. Apoptosis was studied in a rat model of "pure" proteinuria, which does not induce renal impairment, namely protein-overload proteinuria.

High-frequency respiratory input impedance measurements in infants assessed by the high speed interrupter technique.

High-frequency input impedance (Z(f)) measurements, including antiresonances, provide useful noninvasive information on airway geometry and especially airway wall mechanics in the canine and human adult respiratory system. A knowledge of airway wall mechanics would be particularly important in understanding flow limitation phenomena in infants. High-frequency Z(f) has not been measured in infants above 256 Hz, because the high impedance of the infantile respiratory system would be expected to result in low amplitudes of oscillatory flow at higher frequencies.

Differences in airway wall compliance as a possible mechanism for wheezing disorders in infants.

High-frequency input impedance measurements (Z(f)) provide useful noninvasive information on airway geometry and especially airway wall mechanics in the canine and human adult respiratory system. Using the high-speed interrupter technique (HIT), we have shown that it is possible to measure high-frequency Z(f) in infants up to 900 Hz, including antiresonant phenomena which are known to be related to wave propagation velocity. This implies that the first antiresonant frequency (far,1) is a function of airway wall compliance.

p21WAF1 is dynamically associated with JNK in human T-lymphocytes during cell cycle progression.

We have examined the regulation of the c-Jun NH2-terminal kinase (JNK) subfamily of mitogen-activated protein kinases (MAPKs) in response to inhibition of DNA replication during the cell cycle of human T-lymphocytes. In this study, we demonstrate that JNK is rapidly activated following release of T-lymphocytes from G1/S-phase arrest and that this activation precedes resumption of DNA synthesis upon S-phase progression. We also show that activation of JNK correlates with dissociation of the cyclin-dependent protein kinase (CDK) inhibitor, p21WAF1, from JNK1.

Delivery systems: the science.

Different delivery devices may be chosen and the prescribing physician requires information on those suitable for patients of different age, together with the reproducibility of the dose inhaled from the chosen device. A large number of different devices are currently available for inhalation therapy. Although the dose of a drug inhaled by a patient from a device may vary by up to 400%, such information is not usually available to the prescribing doctor.

Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro.

Hyperglycemia is an independent risk factor for the development of diabetic microvascular disease. Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is a potent cytokine family that induces angiogenesis and markedly increases endothelial permeability. VPF is produced by many cell types, including vascular smooth muscle (VSM) cells, and has been implicated in the pathogenesis of neovascularization and endothelial dysfunction in diabetes.

Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo.

We previously reported the isolation of cDNAs encoding two mammalian mitogen-activated protein kinase (MAPK)/extracellular-regulated kinase (ERK) kinase kinases, designated MEKK2 and MEKK3 (Blank, J.L., Gerwins, P.

Selectins and their counter receptors: a bitter sweet attraction.

Selectins are adhesion receptors expressed by leucocytes, platelets, and endothelial cells. They mediate the initial binding of leucocytes to vascular endothelium in the post-capillary venules. This is an essential first step in leucocyte migration into tissue.

Immunohistochemical and hysteroscopic assessment of postmenopausal women with uterine bleeding whilst taking Tibolone.

The gonadomimetic steroid Tibolone, is currently widely used for the treatment of menopausal symptoms. Up to 20% of women have been reported to have episodes of bleeding whilst on therapy. We investigated 37 cases who experienced bleeding episodes whilst on Tibolone and compared these to six cases who experienced no bleeding whilst on therapy and who underwent similar investigations in the course of a clinical study.

A study of the dimerization of Rous sarcoma virus RNA in vitro and in vivo.

The Rous sarcoma virus dimer linkage site (DLS) has been located by electron microscopy at position 511 +/- 28 nucleotides. We have studied the dimerization of RNAs encompassing the first 634 nucleotides of Rous sarcoma virus and conclude that there are at least two dimerization signals. One is located between nucleotides 531 and 634 and may involve Watson-Crick pairing of an imperfect inverted repeat.

A cross-over trial comparing once daily levobunolol with once and twice daily timolol.

The intraocular pressure (IOP) lowering efficacy of once-daily levobunolol 0.5% was compared with timolol 0.5% twice-daily and timolol 0.

Genetic hypertension. A direct link to salt.

The basis of one type of inherited hypertension has been discovered-it is caused by mutations in the gene for the beta subunit of a renal sodium channel.

Serum and platelet-derived growth factor-induced expression of vascular permeability factor mRNA by human vascular smooth muscle cells in vitro.

1. Endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation are key events in the pathogenesis of atherosclerosis. Vascular permeability factor (VPF), an endothelial-cell-specific multifunctional cytokine, was recently described, and has the potential to contribute to the development of endothelial dysfunction.

Glucose-induced changes in Na+/H+ antiport activity and gene expression in cultured vascular smooth muscle cells. Role of protein kinase C.

Increased Na+/H+ antiport activity has been implicated in the pathogenesis of hypertension and vascular disease in diabetes mellitus. The independent effect of elevated extracellular glucose concentrations on Na+/H+ antiport activity in cultured rat vascular smooth muscle cells (VSMC) was thus examined. Amiloride-sensitive 22Na+ uptake by VSMC significantly increased twofold after 3 and 24 h of exposure to high glucose medium (20 mM) vs.

Neonatal extra corporeal membrane oxygenation (ECMO).

Extra corporeal membrane oxygenation (ECMO) is a novel, but invasive, form of life support developed from cardio pulmonary by pass technology. The technique has been used successfully in mature infants with severe respiratory failure since 1975. Where persistent pulmonary hypertension is a complicating problem the improved oxygenation resulting from the use of ECMO has a therapeutic role.

A targeted antithrombotic conjugate with antiplatelet and fibrinolytic properties which reduces in vivo thrombus formation.

Objective: Potent therapy that could be locally delivered to inhibit blood factor-vessel wall interaction and which would remain localised to the site of damage may avoid the side effects of systemic drugs in the treatment of disorders such as subacute thrombosis of saphenous vein grafts and intravascular stents. We therefore assessed the feasibility of developing a targeted antithrombotic conjugate by covalently cross-linking urokinase to a monoclonal antibody to platelet glycoprotein IIb/IIIa (M735) and a monoclonal antibody against damaged endothelium (P14G11).

Methods: Conjugation was carried out using N-succinimidyl-3-(2-pyridyldithio) propionate as the cross-linking reagent.

Respiratory viruses and exacerbations of asthma in adults.

Objective: To study the role of respiratory viruses in exacerbations of asthma in adults.

Design: Longitudinal study of 138 adults with asthma.

Setting: Leicestershire Health Authority.

Retrobulbar phenol injection in blind painful eyes.

Retrobulbar phenol injection was used as a neurolytic to manage blind chronically painful eyes in ten patients. The cause of the blind painful eye was absolute glaucoma in eight of the ten eyes. We used 1.

Improved detection of rhinoviruses in nasal and throat swabs by seminested RT-PCR.

A seminested RT-PCR (nRT-PCR) was used to detect picornavirus (PV) RNA in cell cultures inoculated with rhinoviruses (HRVs) and enteroviruses (EVs). PCR tests in which a primary "touchdown" PCR was followed by secondary reactions using PV or HRV specific primers were able to differentiate HRVs of 48 serotypes from EVs. PVnRT-PCR and HRVnRT-PCR were then used to test nasal and throat swabs from adult subjects with naturally acquired respiratory virus infections.