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S Joseph

Publications and source records attributed to S Joseph.

At least 19 recordsLinked to original sources
PubMed1992

Thrombin promotes actin polymerization in U937 human monocyte-macrophage cells. Analysis of the signalling mechanisms mediating actin polymerization.

The U937 human monocyte-macrophage cell line was used to examine the effect of thrombin, an ill-defined chemoattractant, on the polymerization of actin, a process essential for cell motility. In differentiated macrophage-like U937 cells, thrombin (0.5-50 units/ml) caused a rapid dose-dependent increase in the formation of filamentous (F-) actin, detected by the staining of F-actin with the fluorescent toxin, 7-nitrobenz-2-oxa-1,3-diazole-phallacidin. In contrast with other chemoattractants such as N-formylmethionyl-leucylphenylalanine or C5a, actin polymerization in response to thrombin occurred via a pertussis-toxin-insensitive G1-(inhibitory G-protein) independent signalling pathway. Further, this response was not affected by the Ca2+ chelator EGTA or by the specific protein kinase C (PKC) inhibitor RO-31-8220. The response to thrombin was not mimicked by the Ca2+ ionophore ionomycin or by the direct PKC activator phorbol 12-myristate 13-acetate. The thrombin response was, however, inhibited by the non-specific protein kinase inhibitor staurosporine. The present results suggest that in U937 cells thrombin stimulates the formation of F-actin via a signalling pathway independent of (i) the activation of PKC, (ii) the mobilization of intracellular Ca2+ and (iii) the activation of Ca(2+)-dependent protein kinases, but dependent on the activation of an undefined staurosporine-sensitive protein kinase.

Actins↗
PubMed1992

Evaluation of two rapid tests for the diagnosis of Chlamydia trachomatis genital infections.

The performance of two new enzyme immunoassays (EIA) for the detection of Chlamydia trachomatis in a practice setting was compared. A consecutive series of 207 female patients seen at an inner-city sexually transmitted disease clinic were tested by cell culture, the Kodak SureCell (SC) and Abbott TestPack Chlamydia (TP) EIAs. In addition 210 male patients, selected by physicians on the basis of the fact that multiple urethral samples could be obtained, were tested by cell culture and SC. The prevalence of infection was 19% in the females and 12.5% in males. The sensitivity, specificity, positive predictive value and negative predictive value for the SC and TP were 88%, 95%, 81%, 97% and 59%, 99%, 95%, 91%, respectively, in the female population. The sensitivity of the SC was significantly greater than that of the TP (p less than or equal to 0.002). The performance values of the SC in men (in the same order) were 64%, 96%, 71% and 95%, respectively. The SC in male patients and the TP in female patients had low sensitivity. The sensitivity of the SC in female patients was significantly higher than that of the TP. However, the SC yielded more false positive results. To determine the utility of these tests in a practice setting further studies are required.

Adolescent↗
PubMed1992

The identity of IgE receptors (Fc epsilon RII) that mediate cellular activation of human macrophages: evidence against a role for CD23.

There is now compelling evidence that macrophages bind IgE, and are involved in several IgE-dependent responses. The CD23 antigen mediates a mitogenic response in "primed" B-lymphocytes, although its expression is not confined to B cells, and CD23 is inducably expressed in many cells including macrophages. CD23 is also known to bind IgE, a property that leads to inhibition of the mitogenic response in B cells. In the present review, the possibility that CD23 mediates IgE-dependent responses in macrophages has been re-examined, and it is proposed that the functional receptor for IgE on macrophages may be quite separate from the CD23 antigen.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1992

Activation of bovine endothelial thromboxane receptors triggers release of prostacyclin but not EDRF.

OBJECTIVE: The aim was to examine the capacity of U46619 (a stable thromboxane A2 mimetic) to mediate release of endothelium derived relaxing factor (EDRF) from bovine aortic endothelial cells, and compare the response to the U46619 dependent release of prostacyclin (PGI2). METHODS: Bovine aortic endothelial cells (AG4762) were cultured in vitro on microcarrier beads, which were then loaded onto a column and perfused. The cells were challenged with U46619, bradykinin, or the Ca2+ ionophore ionomycin in the perfusate, and measurements made of the release of 6-oxo-PGF1 alpha (the stable hydrolysis product of PGI2, measured by radioimmunoassay) and EDRF (bioassay). Cells were also cultured on glass cover slips, loaded with Fura 2-AM, and measurements made of the rise in intracellular Ca2+ after challenge with U46619, bradykinin or ionomycin. RESULTS: U46619 triggered release of 6-oxo-PGF1 alpha but not EDRF from AG4762 cells, contrasting with bradykinin which released both 6-oxo-PGF1 alpha and EDRF. Ionomycin had little or no capacity to mimic and trigger release of 6-oxo-PGF1 alpha, although ionomycin mediated large increases in intracellular Ca2+. In contrast, staurosporine (a putative inhibitor of protein kinase C) substantially inhibited the U46619 and bradykinin dependent release of 6-oxo-PGF1 alpha. CONCLUSIONS: In contrast to bradykinin linked receptors on AG4762 endothelial cells, which are coupled to the release of both prostacyclin and EDRF, activation of thromboxane A2 receptors on these cells selectively triggers release of PGI2 but not EDRF. Further, based on the distinct effects of ionomycin and staurosporine, it appears that agonist stimulated PGI2 release from these cells is mediated predominantly by protein kinase C, rather than by rises in intracellular Ca2+. This observation contrasts with previously described mechanisms of PGI2 release from endothelium obtained from other sources.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

In vitro selection of active hairpin ribozymes by sequential RNA-catalyzed cleavage and ligation reactions.

In vitro selection methods provide rapid and extremely powerful tools for elucidating interactions within and between macromolecules. Here, we describe the development of an in vitro selection procedure that permits the rapid isolation and evaluation of functional hairpin ribozymes from a complex pool of sequence variants containing an extremely low frequency of catalytically proficient molecules. We have used this method to analyze the sequence requirements of two regions of the ribozyme-substrate complex: a 7-nucleotide internal loop within the ribozyme that is essential for catalytic function and substrate sequences surrounding the cleavage-ligation site. Results indicate that only 3 of the 16,384 internal loop variants examined have high cleavage and ligation activity and that the ribozyme has a strong requirement for guanosine immediately 3' to the cleavage-ligation site.

Base Composition↗
PubMed1992

Differential sensitivities of the prostacyclin and nitric oxide biosynthetic pathways to cytosolic calcium in bovine aortic endothelial cells.

1. Bovine aortic endothelial cells were cultured in vitro, and shown to release both prostacyclin (PGI2; Kact = 24.1 nM) and endothelium-derived relaxing factor (EDRF, NO; Kact = 0.7 nM) in a concentration-dependent manner when exposed to bradykinin. 2. The bradykinin-dependent release of PGI2 (but not EDRF) was inhibited by 1 microM isoprenaline or 5 microM forskolin, and the inhibitory effect of isoprenaline could be reversed by the beta 2-adrenoceptor antagonist, ICI 118551. In contrast, isoprenaline had no capacity to inhibit PGI2 release stimulated by exogenous arachidonic acid. 3. Exposure of cells to bradykinin increased the cytosolic concentration of Ca2+ ions ([Ca2+]i; Kact = 4.8 nM), and the effect was inhibited by both 1 microM isoprenaline and 5 microM forskolin. 4. In similar experiments, exposure of cells to ionomycin also increased [Ca2+]i and the values of [Ca2+]i were calibrated in terms of the ionomycin concentration. In subsequent experiments involving exposure of endothelial cells to selected concentrations of ionomycin, it was possible to show that the biosynthesis of NO was triggered at ionomycin concentrations about one tenth of the required for PGI2 biosynthesis and that these corresponded to a [Ca2+]i threshold of 350 nM for PGI2 release while that for EDRF release was less than 200 nM. 5. These differences in Ca2+ ion sensitivity explain the selective inhibition of bradykinin-stimulated PGI2 biosynthesis (to the exclusion of NO biosynthesis) by isoprenaline or forskolin, both of which attenuate bradykinin-dependent increases in [Ca2+]i.

Adrenergic beta-Antagonists↗
PubMed1992

Crisis support and psychiatric symptomatology in adult survivors of the Jupiter cruise ship disaster.

The aim of the present study was to explore the relationship between crisis support and psychiatric symptomatology among adult survivors in the year following the Jupiter cruise ship disaster. Evidence is presented that support decreases over the following year, and that higher levels of crisis support are strongly related to better psychological outcome. Crisis support is shown to retain its association with symptomatology even when satisfaction with support is partialled out. These data are discussed with reference to the debate over the relative importance of received vs. perceived support.

Adaptation, Psychological↗
PubMed1991

Thrombin signalling in U937 human monocytic cells is coupled to inositol phosphate formation but not to thromboxane B2 synthesis nor to inhibition of adenylate cyclase: distinct differences in thrombin signalling between U937 cells and platelets.

The blood coagulation factor, human thrombin has been shown to have chemotactic and mitogenic effects on mononuclear phagocytic inflammatory cells. In the present study, we have used the U937 human monocytic cell line to explore the signal transduction mechanisms utilised by thrombin in these cells. In U937 cells differentiated into a macrophage-like phenotype, thrombin stimulated the formation of inositol trisphosphate (IP3) and the mobilisation of intracellular Ca2+ [( Ca2+]i) via a mechanism which was partially sensitive to pertussis toxin. Thrombin failed, however, to evoke thromboxane (Tx) B2 synthesis in the differentiated cells. In contrast, the chemotactic peptide N-formyl-L-methionylleucyl-L-phenylalanine (FMLP) stimulated TxB2 synthesis under conditions where it evoked increases in IP3 formation and [Ca2+]i mobilisation, via a pertussis toxin-sensitive mechanism, comparable in extent to those mediated by thrombin. Thrombin also failed to cause inhibitory guanine nucleotide binding protein (Gi)-mediated inhibition of adenylate cyclase activity in U937 cell membranes. These results indicate that U937 cells express receptors for thrombin which are in part coupled via a pertussis toxin-sensitive guanine nucleotide binding protein to phospholipase C activation, the formation of IP3 and the mobilisation of [Ca2+]i. However, the failure of thrombin to stimulate TxB2 synthesis or cause Gi-mediated inhibition of adenylate cyclase in U937 cells contrasts with its effects in human platelets and other thrombin-responsive cells. These results suggest that the thrombin receptor or receptor-effector coupling mechanism(s) in mononuclear cells is functionally distinct from the thrombin receptor or receptor-effector coupling mechanism(s) present in other thrombin-responsive cells.

Adenylate Cyclase Toxin↗
PubMed1991

Syringohydromyelia: radiological evaluation of 82 patients in a developing country.

A series of 82 patients presenting with syringohydromyelia and confirmed at operation were studied by conventional radiological techniques and computed tomography (CT). Cord collapse was demonstrated in 71% of the patients with wide bony canals and only 11% of patients with normal bony canals. It was most reliably shown with high resolution CT. Intrathecal CT metrizamide myelography (CTMM) failed to demonstrate contrast percolation into many cavities shown in the plain scans. Obliteration of the subarachnoid space at C1-2 levels appreciated in the plain scans strongly indicated coexisting tonsillar herniation, making CTMM unnecessary. In almost all patients, CTMM was found to be non-contributory if the high resolution plain CT scan failed to reveal cord cavitation.

Adolescent↗
PubMed1991

Impact of portable pulse oximetry on arterial blood gas test ordering in an urban emergency department.

STUDY OBJECTIVE: To determine the impact of portable pulse oximetry on physician use of arterial blood gas tests (ABGs) in an urban emergency department. DESIGN: Prospective, controlled clinical trial. SETTING: The ED of the Regional Medical Center at Memphis, a publicly subsidized, 450-bed, acute care hospital staffed by residents and faculty of the University of Tennessee, Memphis. TYPE OF PARTICIPANTS: Rotating housestaff treating adult ED patients with a wide variety of medical and surgical problems. INTERVENTION: Introduction of a portable pulse oximeter for noninvasive measurement of blood oxygenation. MEASUREMENTS: Rates of ABG test ordering, housestaff reason(s) for ordering an ABG, and the incidence of adverse clinical outcomes before and after introduction of portable pulse oximetry. MAIN RESULTS: A total of 20,120 patient visits occurred during the four-month study. Before oximeter introduction, emergency physicians ordered 699 ABGs, 63% of which were indicated by explicit criteria. After oximeter introduction, 440 ABGs were ordered (a 37% decrease). Almost all of this decrease was due to fewer ABGs ordered to assess oxygenation (260 before vs 75 after; chi 2, P less than .001). These reductions were not explained by differences in total patient visits or case mix. Physicians decreased ordering of indicated ABGs by almost as great an extent as they reduced ordering of unindicated tests, suggesting they did not consistently distinguish between the two. However, decreased testing did not result in any serious adverse outcomes, defined as unanticipated respiratory or cardiac arrest in the ED, unanticipated arrest on the floor within 24 hours of admission, or death within two days of hospital discharge. CONCLUSION: Portable pulse oximetry can provide a simple, noninvasive way to determine oxygen saturation in the ED. Routine use of portable pulse oximetry may substantially reduce rates of ABG testing and associated patient charges without adversely affecting the quality of emergency care.

Adult↗
PubMed1991

Obstruction of the infrarenal portion of the abdominal aorta: results of treatment with balloon angioplasty.

Our experience in the treatment of stenoses of the infrarenal portion of the abdominal aorta with balloon angioplasty in 27 patients is reported. Clinical findings were lower limb claudication (all patients), impotence (eight patients), and blue-toe syndrome (two patients). The underlying disease was atherosclerosis in 24 patients and nonspecific aortoarteritis in three patients. Dilatation was successful in all patients. Embolic occlusions of the left common iliac artery (one patient) and left superficial femoral artery (one patient) were the only major complications. Claudication in the affected limb continued in the first patient; the second died when diagnostic angiography, performed 3 months after angioplasty, caused a severe atheroembolus. Of the other 25 patients, nine of the 10 followed up for 13-48 months and all seven followed up for 3-8 months were free of symptoms. Six of eight patients with sexual dysfunction had normal function after angioplasty. Seven patients still awaited follow-up and one was lost to follow-up. Our experience suggests that balloon angioplasty is an effective treatment of stenoses of the infrarenal portion of the abdominal aorta.

Adult↗
PubMed1991

Hydrolysed microspheres from cross-linked polymethyl methacrylate (Hydrogel). A new embolic material for interventional neuroradiology.

Highly hydrophilic, perfectly smooth and spherical microspheres have been synthetized. These non-biodegradable microspheres absorb water in varying degrees and can be injected easily through microcatheters due to their slippery and compressible characteristics. The material was successfully used for embolization of 4 vascular intracranial tumours and 2 spinal vascular lesions in the cervical region, by superselective delivery. Histopathology confirmed absolute inertness of the microspheres.

Adult↗
PubMed1990

Stimulation of human platelets by collagen occurs by a Na+/H+ exchanger independent mechanism.

In stimulated human platelets dense-granule secretion in response to the 'weak agonists' ADP, adrenaline, platelet activating factor and low concentrations of thrombin as well as Ca2+ mobilisation in response to thrombin are enhanced by a Na+/H+ exchanger. In the present study the role of this antiport in collagen stimulated human platelets was examined. While stimulation of platelets loaded with the fluorescent intracellular pH-sensitive dye, bis-carboxyethyl-5-(6)-carboxyfluorescein (BCECF) with thrombin resulted in the activation of the Na+/H+ exchanger, activation of this antiport did not occur in collagen-stimulated platelets. The lack of antiport activity in response to collagen using BCECF-loaded platelets correlated with the lack of any functional role of the antiport in collagen stimulated platelets. In the presence of a Na+/H+ exchange inhibitor, ethylisopropylamiloride, neither collagen-induced platelet aggregation or dense-granule secretion was affected. Furthermore, while the removal of extracellular Na+ (Na+ext), a condition that also prevents activation of the antiport, inhibited dense-granule secretion in response to a low concentration of thrombin, collagen-induced secretion was potentiated. This potentiatory effect could not be attributed to changes in either the membrane potential or in collagen-induced phospholipase C or protein kinase C activity. The present results indicate that in contrast to the 'weak agonists' (1) collagen-induced platelet activation does not require activation of the Na+/H+ exchanger and (2) Na+ext per se is an inhibitor of collagen-induced secretion.

Blood Platelets↗
PubMed1990

Corpus callosum lipoma with frontal encephalocele.

Computed tomographic and plain X-ray observations in a patient with corpus callosum lipoma associated with frontal encephalocele are reported. The rarity of the lesion and the specific diagnostic criteria on CT are emphasised.

Brain Neoplasms↗
PubMed1990

Aneurysmal form of aortoarteritis (Takayasu's disease): analysis of thirty cases.

The clinical and radiological features, and outcome of 30 patients including 22 females, with the aneurysmal form of aortoarteritis were analysed. The average age at diagnosis was 27.4 +/- 7.2 years. Features which indicated the diagnosis of aneurysmal aortoarteritis included young age, female sex, characteristic location, associated stenotic lesions and the presence of multiple aneurysms. There were 41 fusiform and 18 saccular aneurysms, mostly located in the descending aorta. Diffuse dilatation (n = 24) was seen mainly in the ascending aorta. Two patients had dissecting aneurysms, while one patient had an aneurysm of the left main coronary artery. Both these lesions are rare in aortoarteritis. The aneurysmal form was associated with a higher incidence of aortic incompetence (P less than 0.01) and elevated ESR (P less than 0.001) as compared to the more common non-aneurysmal form. The average follow-up period was 59.7 (+/- 48.1) months. The event-free survival rate was 82.9% at 5 years, similar to that seen in the non-aneurysmal form. These data should be useful to the clinician in the diagnosis and management of the aneurysmal form of aortoarteritis.

Adolescent↗