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PubMed2000

Translocational changes of localization of synapsin in axonal sprouts of regenerating rat sciatic nerves after ligation crush injury.

Time-dependent translocational changes of Synapsin I (SyI), a synaptic vesicle-associated phosphoprotein and its involvement in the axonal transport were investigated in the regenerating axonal sprouts. A weak SyI immunoreactivity (IR) was found in the axoplasm of normal axons. Rat sciatic nerves were crush-injured by ligating with 1-0 silk thread at the mid-thigh level and released from the ligation 24 h later. At various times after release, immunocytochemistry was performed. SyI was translocated from the proximal to the distal site of ligation and also involved in the sprouting of regenerating axons. The distribution patterns of SyI IR were changed in the crush-injured nerves. SyI immunoreactive thin processes were strongly appeared in the proximal region from 1 h after release. After 3 h, a very strong IR was expressed. The intense SyI immunoreactive thin processes were elongated distally and were changed the distribution pattern by time-lapse. After 12 h, strong immunoreactive processes were extended to the ligation crush site. At 1 day, a very intense IR was expressed. At 2 days, immunoreactive thin processes extended into the distal region over the ligation crush site and strong IR was observed after 3 days. SyI was accumulated in the proximal region at the early phases after release. These results suggest that SyI may be related to the translocation of vesicles to the elongated membranes by a fast axonal transport in the regenerating sprouts.

Animals↗
PubMed1992

An efficient method for blunt-end ligation of PCR products.

This report presents data demonstrating a simple method that can potentially be extended to a wide range of cloning strategies to increase the yield of insert-containing recombinants. The method requires that the ligation of an insert to a vector does not regenerate the original restriction enzyme recognition sequence. In the example presented, PCR products were blunt-end ligated to a SmaI-cut vector, in the presence of SmaI endonuclease. The addition of the restriction enzyme to the ligation reaction dramatically favored the ligation of insert to vector rather than vector self-ligation.

Cloning, Molecular↗
PubMed1990

CD-3-mediated activation of MAP-2 kinase can be modified by ligation of the CD4 receptor. Evidence for tyrosine phosphorylation during activation of this kinase.

The CD4R has been shown to exert variable effects on T cell activation responses. Depending on the manner of ligation, the CD4R has been demonstrated to have positive as well as negative effects on the generation of [Ca2+]i flux by the CD3R. Coaggregation of CD3 with CD4 enhanced Ca2+ flux while their independent ligation and aggregation diminished this response. To further elucidate these paradoxical CD4 effects, we studied induction of a microtubule-associated protein 2 kinase (MAP-2K) activity during ligation of the CD3R. Lymphoid MAP-2K activation by CD3 is an evanescent event that is dependent on phosphorylation of 43-kDa MAP-2K via a pathway that involves protein kinase C. Coaggregation of CD4 and CD3 with cross-linking antibodies and avidin enhanced the CD3-mediated MAP-2K response almost twofold. In contrast, independent ligation and cross-linking of CD4 reduced the CD3-induced MAP-2K response by approximately 50%. An important requirement for this inhibitory effect was that CD4 be ligated before stimulation with anti-CD3. The negative effect of anti-CD4 mAb was specific as other mAb failed to simulate this event. The PMA-induced MAP-2K response was not inhibited by anti-CD4. Intact 32P-labeled Jurkat and normal human T cells demonstrated the appearance of a single 43-kDa tyrosine phosphoprotein during stimulation with PMA and anti-CD3. When these crude cellular extracts were extensively fractionated across DEAE- and hydrophobic columns, MAP-2K was resolved into two peaks of activity, each containing a single tyrosine phosphoprotein around 43 kDa. In addition to tyrosine-specific labeling, mitogenic stimulation of normal human T cells also induced threonine-specific labeling of MAP-2K. These results imply that activation of lymphoid MAP-2K is a dual process requiring at least two independent kinases for optimal activity. Inasmuch as CD3 activates protein kinase C and CD4 is associated with a tyrosine kinase, pp56lck, we suggest that their coaggregation may create the conditions whereby MAP-2K may be activated by dual phosphorylation. Independent aggregation of these receptors may lead to physical separation and breakdown of this interactive mechanism.

Adult↗
PubMedDate not supplied

Effects of magnesium sulfate and nifedipine on regional cerebral blood flow during middle cerebral artery ligation in the rat.

The effects of magnesium sulfate and nifedipine on regional cerebral blood flow were compared after ligation of the middle cerebral artery in rats. Twenty-one rats were divided into 3 groups of 7 each. The groups were the magnesium group, the nifedipine group, and the control group. Animals were anesthetized with pentobarbital. The middle cerebral artery was ligated, and magnesium sulfate was infused at a rate of 16 mg/kg/min for 30 min in the magnesium group, and nifedipine was infused at a rate of 10 micrograms/kg/min for 45 min in the nifedipine group. Using [14C]-iodoantipyrine, regional cerebral blood flow was measured 1 hr after middle cerebral artery ligation in the ischemic cortex, contralateral cortex, thalamus, hypothalamus, pons, medulla and cerebellum. In the control group, the mean cerebral blood flow was 30.7 +/- 12.2 ml/min/100 g in the middle cerebral artery-ligated cortex, and 75.9 +/- 10.5 ml/min/100 g in the contralateral cortex. Nifedipine did not significantly alter the cerebral blood flow in any of the brain regions studied. However, in the magnesium group, the regional cerebral blood flow in the middle cerebral artery-ligated cortex was significantly higher (64.2 +/- 8.8 ml/min/100 g) than that recorded in the control and nifedipine groups, whereas the regional cerebral blood flow in the contralateral cortex was not significantly different from other groups. Our data showed that magnesium was effective and superior to nifedipine in improving blood flow in the ischemic area of the brain.

Animals↗
PubMed1990

[Experimental study on right ventricular function during left heart bypass--in a coronary septal branch ligation model].

Right heart failure (RHF) during left heart bypass (LHB) has been recognized clinically. Two hypotheses concerning RHF during LHB exist: one suggests that the cause is related to LHB itself, and another suggests that RHF existed prior to LHB. By using 16 mongrel dogs, the influence of LHB and ventricular septal ischemia on the right heart was studied experimentally. Under the extracorporeal circulation the coronary septal branch was dissected and a suture was hooked around the artery for the ligation. To maintain a constant right ventricular (RV) preload at 100 ml/kg/min, blood was drained from both the superior and inferior venae cavae, and was sent to the right atrium (RA) by a roller pump. Functional parameters of right heart, such as RA pressure, RV pressure, the first derivative of RV (RV dp/dt) and RV free wall contractile width, were measured while the LHB between left atrium and femoral artery was established. The measurements were done before and after the ligation of the septal branch, and were also done during LHB when the LHB ratio was changed from 0, 40, 60, 80, 100, 100, 80, 60, 40 and 0% of RV preload. RV free wall contractile width, measured by ultrasonic method, and the Max RV dp/dt were decreased significantly when LHB ratio was increased and both were increased when LHB ratio was decreased. When the septal branch was ligated, the contractile width was decreased significantly. The max RV dp/dt was also decreased but not significantly. When the LHB was performed after ventricular septal branch ligation, the trend of the RV functional changes was similar to that before ligation.

Animals↗
PubMed1989

Circle of Willis blood velocity and flow direction after common carotid artery ligation for neonatal extracorporeal membrane oxygenation.

The velocity and direction of blood flow in the circle of Willis arteries were measured in three infants who underwent right common carotid artery ligation for extracorporeal membrane oxygenation treatment. Within 15 minutes of common carotid artery ligation, blood flow was detected in one infant's right middle cerebral artery; however, the velocity was reduced to 50% of the preextracorporeal membrane oxygenation level. The velocity remained 50% to 70% lower than normal during the 88 hours of extracorporeal membrane oxygenation therapy. In the other two infants, the velocity changes were less severe. By 2 to 10 weeks after weaning from extracorporeal membrane oxygenation, the velocities in the left cerebral arteries were increased to 116% to 217% of the corresponding right cerebral vessels. Following common carotid artery ligation, a retrograde direction of flow was noted in the first (A1) segment of the right anterior cerebral artery and in the right posterior communicating artery, whereas the direction of flow was normal in the corresponding vessels on the left. After common carotid artery ligation, the vertebrobasilar and the contralateral internal carotid systems appear to be the main sources of reperfusion of the right cerebral hemisphere via the circle of Willis. Furthermore, because of the known variants of the circle anatomy, a noninvasive pulsed Doppler method could be used to evaluate the flow patterns in the circle of Willis arteries, both before and after common carotid artery ligation for extracorporeal membrane oxygenation.

Arteriovenous Shunt, Surgical↗
PubMed1988

Functional diversity among putative E2 isozymes in the mechanism of ubiquitin-histone ligation.

The covalent ligation of the 8.6-kDa protein ubiquitin to histones within transcriptionally poised regions is believed to participate in the localized regulation of chromatin structure. This unique post-translational modification is thought to be distinct from similar cytosolic reactions in requiring ubiquitin-activating enzyme (E1) and one or more putative ubiquitin carrier proteins (E2) but not isopeptide ligase (E3). Apparently homogeneous preparations of the E2 isozymes were tested for their ability to catalyze the E3-independent conjugation of ubiquitin to linker histone H1 and core histones H2A, H2B, H3, and H4 in the presence of catalytic amounts of E1. Significant rates of nonprocessive core histone monoubiquitination were catalyzed by the E2(14kDa), E2(20kDa), and E2(32kDa) isozymes but not by either E2(17kDa) or E2(24kDa). The former three E2 isozymes also supported slow rates of direct multiple ubiquitination to secondary ligation sites on the histones. Rate studies for the monoubiquitination of H2A and H2B revealed that: 1) E2(14kDa) catalyzed a second order reaction with respect to histone concentration; 2) E2(32kDa)-mediated ligation proceeded by hyperbolic kinetics, yielding Km values of 2.8 and 12 microM for H2A and H2B, respectively; and 3) E2(20kDa) exhibited complex kinetics composed of both second order and hyperbolic pathways, the latter having Km values of 0.83 and 1.5 microM for H2A and H2B, respectively. Pulse-chase kinetics suggested that both ubiquitin thiol esters formed to E2(20kDa) were catalytically competent in H2A ligation. The active E2 isozymes also catalyzed the processive multiple ubiquitination of calf thymus H1. Other rate studies determined that Kd values for binding of the active E2 species to E1 ternary complex were 0.1 nM for E2(14kDa), 0.4 nM for E2(32kDa), and 3.6 nM for E2(20kDa). The data indicate that E2(20kDa) and E2(32kDa) are specific but mechanistically distinct ligation enzymes responsible for the conjugation of ubiquitin to nucleosomal proteins.

Histones↗
PubMed1988

Resonance Raman spectroscopic evidence for heme iron-hydroxide ligation in peroxidase alkaline forms.

Horseradish peroxidase will convert from a five-coordinate high-spin heme at neutral pH to a six-coordinate low-spin heme at alkaline pH. Though alkaline forms of other heme proteins such as hemoglobin and myoglobin are known to contain a heme-ligated hydroxide, alkaline horseradish peroxidase has been considered not to contain a ligated hydroxide. Several alternatives have been proposed which would be stronger field ligands than a hydroxide ion. In this report we provide resonance Raman evidence, using Soret excitation, that alkaline horseradish peroxidase does in fact contain a heme iron-ligated hydroxyl group. The band was located for isoenzymes C and A-1 by its sensitivity to 18O substitution and confirmed with 54Fe, 57Fe, and 2H. An isoenzyme of turnip peroxidase was investigated and found to also contain a ligated hydroxide at alkaline pH. The observed peroxidase Fe(III)-OH frequencies are 15-25 cm-1 higher than the corresponding frequencies of alkaline methemoglobin and metmyoglobin and correlate with changes in spin-state distribution. This is explained in the context of hydrogen bonding to a distal histidine which results in increased ligand field strength facilitating the formation of low-spin hemes. It has been demonstrated that the ferryl/ferric redox potential of horseradish peroxidase is markedly lowered at alkaline pH (Hayashi, Y., and Yamazaki, I. (1979) J. Biol. Chem. 254, 9101-9106). These observations are rationalized in terms of oxidation of a ligated ferric hydroxyl group facilitated through base catalysis by a distal histidine.

Heme↗
PubMed1995

Divergent induction of apoptosis and IL-8 secretion in HT-29 cells in response to TNF-alpha and ligation of Fas antigen.

Colonic epithelial cell injury is the common manifestation of inflammatory diseases of the bowel. One form of epithelial injury is apoptosis. In our study, we investigated the mechanism leading to apoptosis in HT-29 cells in response to TNF-alpha and ligation of Fas Ag. HT-29 displayed a dual response to TNF-alpha and Fas Ag ligation: in combination with IFN-gamma, HT-29 cells underwent apoptosis, whereas independently, these factors stimulated secretion of IL-8. We used this model of immune-mediated epithelial cell injury to elucidate the signals leading to apoptosis in response to TNF-alpha and Fas Ag ligation compared with the signals leading to induction of IL-8 secretion. The model was further used to distinguish signaling differences between TNF-alpha receptors and the Fas Ag in this cell line. The experiments presented here demonstrate that Fas Ag ligation alone led to production of IL-8 by colonic epithelial cells and represented another function mediated by Fas Ag in addition to apoptosis. This study shows that the pathways leading to cell death and IL-8 production in response to Fas Ag ligation and TNF-alpha were similar with regard to their requirements for new gene expression, protein synthesis, and protein kinase activity. Specifically, new gene expression and protein synthesis were not necessary for TNF-alpha- and Fas Ag-mediated apoptosis, but were necessary for TNF-alpha- and Fas Ag-mediated IL-8 secretion. Tyrosine protein kinase phosphorylation was necessary to signal secretion of IL-8 in response to both agonists but it was not necessary for apoptosis. In spite of the similarities between these two agonists, the kinetics of apoptosis via Fas Ag were significantly more rapid than through the TNF-alpha receptor and serve to distinguish these two signals.

Apoptosis↗
PubMed1995

Effects of vascular pedicle ligation on blood flow in canine semitendinosus muscle.

Blood flow to the semitendinosus muscle was studied in 12 dogs after ligation of either the proximal or distal vascular pedicle and elevation of the muscle from its normal position. Using 15-micron-diameter radioactive microspheres, flow was measured at rest, 6 and 18 days after muscle elevation and pedicle ligation. Mean blood flow in the proximal region of the muscle 6 and 18 days after ligation of the caudal gluteal (proximal) pedicle was not significantly different from mean blood flow calculated in the middle and distal regions of the muscle. There was also no significant difference in mean blood flow among proximal, middle, and distal regions of the muscle, 6 and 18 days after ligation of the distal caudal femoral (distal) pedicle. There was significantly (P < 0.05) increased blood flow between group-A (ligation of caudal gluteal artery) and group-C (operated-control) muscles, 6 and 18 days after surgery. There was no loss of muscle fiber striations or nuclei, or presence of fibrous tissue that might have indicated ischemic necrosis in any of the experimental groups. These results indicate that the entire semitendinosus muscle can be sustained by the blood flow from either of its 2 vascular pedicles, which reinforces its potential as a muscle flap.

Animals↗
PubMed1994

Components of a system that ligates cyclin to ubiquitin and their regulation by the protein kinase cdc2.

Cyclin B, a positive regulatory subunit of the cdc2 protein kinase complex, is synthesized across the cell cycle and then rapidly degraded at the end of mitosis. Degradation of cyclin B is triggered by increased levels of active cdc2 and is required for exit from mitosis. It was shown previously that cyclin degradation is carried out by the ubiquitin system, but the components responsible for the specificity and regulation of cyclin-ubiquitin ligation have not been identified. The formation of ubiquitin-protein conjugates usually requires the sequential action of three enzymes: a ubiquitin-activating enzyme (E1), a ubiquitin-carrier protein (E2), and a ubiquitin-protein ligase (E3). In this work we employed a fractionation approach to identify the components of a clam oocyte system responsible for specific ubiquitination of cyclin and to determine which components are regulated by cdc2. Experimental conditions were established under which a fusion protein containing an amino-terminal fragment of cyclin B is ligated to ubiquitin only in extracts from M-phase but not from interphase cells. Fractionation of M-phase extracts by DEAE-cellulose and high speed centrifugation yielded three fractions that were all required for cell cycle stage-specific cyclin-ubiquitin ligation. Only one of these fractions could be replaced by a previously known enzyme of the ubiquitin system, E1. A second fraction contained a novel species of E2, termed E2-C, which acts in the ligation of ubiquitin to cyclin but not to other endogenous proteins. A third component is associated with particulate material. Whereas E2-C from either M-phase or interphase extracts is active, the particulate component is active only in M-phase. Incubation of the particulate fraction from interphase cells with the protein kinase cdc2 activates it for cyclin-ubiquitin ligation, after a lag of about 30 min. These findings suggest that the particulate fraction may contain an E3 enzyme that acts on cyclin, as well as additional factors activated by cdc2.

Animals↗
PubMed1993

Tubal ligation, hysterectomy, and risk of ovarian cancer. A prospective study.

OBJECTIVE: To assess whether tubal ligation and hysterectomy affect subsequent risk of ovarian cancer. DESIGN: Prospective cohort study with 12 years of follow-up. SETTING: United States, multistate. PARTICIPANTS: A total of 121,700 female registered nurses who were 30 to 55 years of age in 1976; the follow-up rate was 90% as of 1988. MAIN OUTCOME MEASURE: Ovarian cancer of epithelial origin confirmed by medical record review. RESULTS: We observed a strong inverse association between tubal ligation and ovarian cancer, which persisted after adjustment for age, oral contraceptive use, parity, and other ovarian cancer risk factors (multivariate relative risk [RR], 0.33; 95% confidence interval [CI], 0.16 to 0.64). The association was similar when we assessed tubal ligation status at the baseline questionnaire and excluded cases in the first 4 years to eliminate any possible short-term decrease in risk due to screening of the ovaries during ligation surgery. We noted a weaker inverse association between simple hysterectomy and ovarian cancer (RR, 0.67; 95% CI, 0.45 to 1.00). Neither vasectomy nor condom use by a partner was associated with risk of ovarian cancer. CONCLUSIONS: These data indicate that tubal ligation, and perhaps hysterectomy, may substantially reduce risk of epithelial ovarian cancer.

Adult↗
PubMed1993

Ligation of synthetic activated DNA substrates by site-specific recombinases and topoisomerase I.

The FLP protein of the 2-microns plasmid of Saccharomyces cerevisiae is a conservative site-specific recombinase that is involved in the amplification of the plasmid. This recombination reaction proceeds via the covalent attachment of the protein to the 3'-phosphoryl group at the site of the breaks through a phosphotyrosine linkage. We have recently developed an assay that measures FLP-mediated strand ligation independent of FLP-mediated cleavage and covalent attachment to the DNA. The substrate for ligation was produced by FLP-induced cleavage of the FLP recognition site followed by digestion with Pronase and was shown to contain (at least) a tyrosine residue at the 3'-PO4 terminus adjacent to the FLP cleavage sites. We have now synthesized artificial substrates that bear a tyrosine residue on the 3'-PO4 of an appropriate oligonucleotide and find that this substrate is ligated as efficiently as the previous ligation substrates that were isolated after FLP cleavage of the substrate. Analogous substrates for other members of the integrase family of recombinases (lambda integrase protein, P1-Cre protein) as well as for mammalian topoisomerase I are also active as ligation substrates with their cognate protein. This class of activated substrates should be useful in the study of breakage and reunion reactions involving DNA.

Animals↗
PubMed1996

Ligation of CD69 induces apoptosis and cell death in human eosinophils cultured with granulocyte-macrophage colony-stimulating factor.

Peripheral blood (PB) eosinophils rapidly undergo apoptosis and cell death in vitro unless cultured in the presence of cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) in which their survival is prolonged for up to 10 days. CD69 is a type II membrane antigen expressed by cytokine-activated, but not freshly isolated, PB human eosinophils. We have examined the effect of ligation of CD69 by specific monoclonal antibody (MoAb) on the viability of human eosinophils cultured with recombinant human (rh)GM-CSF. Eosinophils were purified by immunomagnetic selection and cultured with GM-CSF (10(-10) mol/L). Eighteen hours after the start of culture, a panel of CD69 MoAb or controls (anti-CR3 or isotype-matched control MoAb) were added. Viability was assessed by trypan blue exclusion and apoptosis by morphologic assessment, DNA laddering, and flow cytometric analysis of eosinophil red autofluorescence. Up to 50% of the eosinophils had undergone apoptosis 48 hours after addition of anti-CD69 MoAb compared with less than 10% apoptosis for CR3 or the isotype matched control. The majority of apoptotic eosinophils excluded trypan blue at 48 hours post CD69 ligation. More apoptotic eosinophils were observed at later time-points and this was associated with loss of viability. At 120 hours post-addition of the anti-CD69 MoAb MLR3, 24% +/- 10.6% eosinophils were viable compared with 84% +/- 3.4% for the CR3 control (P < .001). A F(ab)2 fragment of CD69 MoAb P8, also induced apoptosis in GM-CSF cultured eosinophils. A more rapid induction of eosinophil apoptosis was obtained with CD69 MoAb immobilized via their Fc portions on protein-A coated plastic 96 well plates. Ligation of CD69 or CR3 resulted in the release of comparable quantities of eosinophil peroxidase at 48 hours post-ligation. These levels of EPO were consistent with the viability of these cells at 48 hours as assessed by exclusion of trypan blue. Finally, a neutralizing MoAb to TGF beta 1 had no effect on CD69-dependent apoptosis induction nor were there detectable quantities of TGF beta 1 in supernatants from GM-CSF--cultured eosinophils ligated with CD69 or control MoAb. These results suggest that eosinophils cultured with GM-CSF can be induced to undergo apoptosis as a result of cell signalling mediated by perturbation of CD69. This may represent an important physiologic mechanism for eosinophil removal in vivo.

Antigens, CD↗
PubMed1996

[Minilaparotomy tubal ligation in the immediate post-partum after vaginal delivery. A retrospective analysis of 253 cases in the maternity service of the Yaounde University Hospital Center (Cameroon)].

The authors report the results of a retrospective study of 253 cases of tubal ligation collected between January 1985 and December 1989 in the maternity unit of the Yaounde Teaching hospital. The tubal ligations were done through minilaparotomy with local anesthesia using the technique of Pomeroy. The frequency of tubal ligation evaluated at 3,8 per cent did not change during the period of this study. The authors note that the majority of patients in this study wished a tubal ligation only when they have 5 or more surviving children. We had no post-operative death, but our complication rate of 1,6 % can be improved upon by paying more attention to operative details. The authors conclude that because of poorly equipped medical infrastructures in the context of developing countries tubal ligation through minilaparotomy should be promoted as a contraceptive method in family planning programs.

Adult↗
PubMed1997

CD38 ligation in human B cell progenitors triggers tyrosine phosphorylation of CD19 and association of CD19 with lyn and phosphatidylinositol 3-kinase.

CD38 is a 45-kDa transmembrane glycoprotein highly expressed in lymphoid progenitors. Ligation of CD38 with specific Abs inhibits growth and induces apoptosis in human immature B cells. CD38 ligation also triggers tyrosine phosphorylation of syk, c-cbl, and phospholipase C-gamma and activates phosphatidylinositol 3-kinase (PI3-K). In the present study, we investigated whether the cell surface membrane molecules used in B cell receptor-mediated signaling, such as Ig alpha, Ig beta, and CD19, could be involved in the CD38-mediated signaling cascade. In the B cell receptor-negative immature B cell lines RS4;11, 380, and REH, Ig alpha and Ig beta were expressed exclusively in the cytoplasm and were not tyrosine phosphorylated after CD38 ligation. By contrast, CD19 was markedly tyrosine phosphorylated and was associated with lyn and PI3-K. PI3-K activation appears to be directly linked to the growth-arresting effects of CD38 ligation, which are reduced by PI3-K inhibitors. Ligation of either CD38 or CD19 resulted in a similar pattern of protein tyrosine phosphorylation; both signaling pathways caused tyrosine phosphorylation of c-cbl. Levels of CD38 surface expression were not affected by prolonged incubation with anti-CD19 Ab, while CD19 expression markedly decreased. These results indicate that CD19 is a major component of the CD38 signaling cascade in B cell precursors, serving as a cell surface membrane docking site for cytoplasmic kinases. CD38 and CD19 are not physically linked, but activate an overlapping set of kinases in human immature B cells.

ADP-ribosyl Cyclase↗
PubMed1997

CD38 ligation results in activation of the Raf-1/mitogen-activated protein kinase and the CD3-zeta/zeta-associated protein-70 signaling pathways in Jurkat T lymphocytes.

CD38 ligation with the specific mAb IB4 induced early and late signaling events in Jurkat T cells, as judged by the transient induction of tyrosine phosphorylation of phospholipase C-gamma1, c-Cbl, zeta-associated protein (ZAP)-70, Shc, extracellular signal-regulated protein kinase-2 (Erk-2) as mitogen-activated protein (MAP) kinase, and increased expression of the activation Ag CD69. In addition, CD38 ligation induced Ras-dependent events such as Erk-2 mobility shift and increased Erk-2 kinase activity. Further evidence that Erk-2 activation is regulated by CD38 ligation was obtained indirectly with the observed induction of Raf-1, Lck, and Sos-1 mobility shifts, processes that are believed to be dependent, at least in part, on MAP kinase activation. Using a protein tyrosine kinase inhibitor, herbimycin A, or a protein kinase C inhibitor, Ro-31-8220, we found that the anti-CD38-induced Erk-2 activation is both protein tyrosine kinase and protein kinase C dependent. CD38 ligation also resulted in increased CD3-zeta tyrosine phosphorylation and its association with ZAP-70. CD38 ligation in a Jurkat Lck-deficient mutant, JCam1, failed to induce substrate tyrosine phosphorylation and activation of Erk-2. These data indicated that in Jurkat T cells, CD38 receptor triggering results in Lck-regulated activation of both Raf-1/MAP kinase and CD3-zeta/ZAP-70/phospholipase C-gamma1 signaling pathways.

ADP-ribosyl Cyclase↗
PubMed1997

A comparison of postoperative complications from pressure-ridge Molteno implants versus Molteno implants with suture ligation.

BACKGROUND AND OBJECTIVES: The pressure-ridge Molteno implant incorporates a ridge on the proximal episcleral plate to limit aqueous outflow during the immediate postoperative period. This modification is intended to decrease the high incidence of postoperative hypotony and flat anterior chambers following Molteno tube implantation, while avoiding the pressure spikes that can occur with suture ligation of the Molteno tube. This study was devised to compare postoperative intraocular pressure control and complications associated with pressure-ridge Molteno implantation versus a standard Molteno implantation with suture ligation of the tube. PATIENTS AND METHODS: Thirty eyes were prospectively randomized to receive either a pressure-ridge, double-plate Molteno implant or a standard, double-plate Molteno Molteno implant with suture ligation of the tube. RESULTS: Postoperative intraocular pressure was significantly higher at day 1 and week 2 in the suture-ligation implant group, although the final pressure at 12 weeks was not different between the two groups. Six of 15 eyes from the pressure-ridge implant group experienced shallow or flat anterior chambers with hypotony, whereas 5 of 15 eyes from the suture-ligation implant group had significant postoperative pressure spikes. CONCLUSION: Because the ridge effect is unpredictable, further modifications are necessary to prevent postoperative hypotony.

Female↗