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J F Redman

Publications and source records attributed to J F Redman.

At least 55 records · Page 3Linked to original sources
PubMed1990

Stimulation and priming of protein kinase C translocation by a Ca2+ transient-independent mechanism. Studies in human neutrophils challenged with platelet-activating factor and other receptor agonists.

N-Formyl-methionyl-leucyl-phenylalanine (fMLP) and leukotriene B4 stimulate human polymorphonuclear neutrophils (PMN) to translocate protein kinase C from the cytosol to plasmalemma as judged by their abilities to increase PMN binding of and receptor numbers for [3H]phorbol dibutyrate [( 3H]PDB) (O'Flaherty, J.T., Jacobson, D.P., Redman, J.F., and Rossi, A.G. (1990) J. Biol. Chem. 265, 9146-9152). Platelet-activating factor (PAF) had these same effects. Moreover, two potent PAF analogs (but not an inactive analog) increased [3H]PDB binding; a PAF antagonist blocked responses to PAF without altering those to fMLP; and PMN treated with PAF became desensitized to PAF while retaining sensitivity to fMLP. Indeed, PMN incubated with 1-100 nM PAF for 5-40 min had markedly enhanced [3H]PDB binding responses to fMLP. PAF thus acted through its receptors to stimulate and prime protein kinase C translocation. Its effects, however, did not necessarily proceed by a standard mechanism: Ca2(+)-depleted PMN failed to raise Fura-2-monitored cytosolic Ca2+ concentrations [( Ca2+]i), yet increased [3H]PDB binding and receptor numbers almost normally after PAF challenge. PAF also primed Ca2(+)-depleted PMN to fMLP. Nevertheless, [3H]PDB binding responses to PAF were blocked in PMN loaded with Ca2+ chelators, viz. Quin 2, Fura-2, or 5,5'-dimethyl-1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Exogenous Ca2+ reversed Quin 2 inhibition, and a weak chelator 4,4'-difluoro-BAPTA, lacked inhibitory actions. The chelators similarly influenced fMLP and leukotriene B4. Thus, PMN can by-pass [Ca2+]i to translocate protein kinase C. They may achieve this using a regulatable pool of Ca2+ that evades conventional [Ca2+]i monitors or a signal that needs cell Ca2+ to form and/or act. This signal may mediate function in Ca2(+)-depleted cells, the actions of [Ca2+]i-independent stimuli, cell priming, and protein kinase C movements that otherwise seem [Ca2+]i-induced.

Calcium↗
PubMed1990

Translocation of protein kinase C in human polymorphonuclear neutrophils. Regulation by cytosolic Ca2(+)-independent and Ca2(+)-dependent mechanisms.

[3H]Phorbol dibutyrate [( 3H]PDB) rapidly and reversibly binds to human polymorphonuclear neutrophils (PMN). Ca2+/diacylglycerol/phospholipid-dependent protein kinase C appeared to be the receptor for this binding because: a diacylglycerol, dioctanoylglycerol, competed with [3H]PDB for PMN binding sites; a blocker of protein kinase C-phospholipid interactions, sphinganine, inhibited PMN binding of [3H]PDB; and changes in cytosolic Ca2+ apparently regulated PMN binding of the label. Relevant to the last point, disrupted PMN contained 9 X 10(5) phorbol diester receptors/cell, whereas intact PMN had only 1.6 X 10(5) such receptors that were accessed by the ligand. This number fell to 1.0 X 10(5) in Ca2(+)-depleted PMN and rose to 2.5 X 10(5) in cells stimulated with the Ca2+ ionophore, ionomycin. This ionomycin effect lasted for greater than 16 min, correlated temporally with changes in cytosolic Ca2+, did not occur in Ca2(+)-depleted PMN, and was blocked by sphinganine. A second ionophore, A23187, likewise induced Ca2(+)-dependent rises in [3H]PDB binding. These results fit the standard model, wherein rises in cytosolic Ca2+ cause protein kinase C to translocate from cytosol to plasmalemma and thereby become more available to [3H]PDB. In contrast, two humoral agonists, N-formyl-Met-Leu-Phe (fMLP) and leukotriene (LT)B4, had actions that did not fit this model. They stimulated PMN to increase the availability of PDB binding sites by a sphinganine-sensitive mechanism, but their actions differed from those of ionophores. They induced biphasic (t = 15 and 60 s) increases in [3H]PDB binding while eliciting monophasic (t = 15 s), short-lived (t less than 1 min) rises in cytosolic Ca2+. In Ca2(+)-depleted PMN, moreover, fMLP and LTB4 stimulated slow (t greater than or equal to 30 s), monophasic, prominent rises in [3H]PDB binding and binding site number without appreciably altering cytosolic Ca2+. We suggest, therefore, that fMLP and LTB4 translocate protein kinase C using two sequential mechanisms. The first involves Ca2+ transients and thus produces abrupt (t = 15 s), rapidly reversing responses. The second mechanism uses an unrelated signal to effect a more slowly evolving (t = 60 s) movement of protein kinase C to plasmalemma. Hence, the standard model does not explain all instances of protein kinase C translocation, and a cytosolic Ca2(+)-independent signal contributes to the regulation of protein kinase C as well as those responses elicited by the effector enzyme.

Binding, Competitive↗
PubMed1990

Mechanisms involved in the bidirectional effects of protein kinase C activators on neutrophil responses to leukotriene B4.

Three protein kinase C (PKC) activators (PMA, mezerein, and a diacylglycerol) had bidirectional effects on human polymorphonuclear neutrophil (PMN) degranulation responses to leukotriene (LT) B4. Lower concentrations of the three agents enhanced, whereas higher concentrations inhibited, release of lysozyme and beta-glucuronidase stimulated by the arachidonic acid metabolite. Contrastingly, the activators inhibited but never enhanced LTB4-induced Ca2+ transients. We examined the causes for these varying effects. Each PKC activator reduced PMN specific binding of [3H]LTB4. Scatchard analyses revealed that PMA (greater than or equal to 0.16 nM) decreased the number of high affinity LTB4 receptors. The receptor losses correlated closely with inhibition of Ca2+ transients. PMN pretreated with 0.5 nM PMA for 5 min retained approximately 50% of their high affinity LTB4 receptors. These cells responded to 10 nM LTB4 with reduced but still substantial rises in cytosolic Ca2+, enhanced PKC mobilization, and increased granule enzyme release. The latter two effects appeared calcium-dependent because sequential exposure to PMA and LTB4 did not synergistically stimulate PKC mobilization or degranulation in PMN that were: 1) Ca2(+)-depleted; 2) challenged with 5 nM PMA; or 3) treated with LTB4 for 5 min before PMA. Each of the latter treatments completely interfered with the extent or timing of LTB4-induced Ca2+ transients. Accordingly, we suggest that the response-specific, bidirectional effects of PKC activators on LTB4 result from two opposing mechanisms. First, PKC activators down-regulate LTB4 high affinity receptors and thereby reduce those PMN responses that are not elicited by activated PKC (i.e., Ca2+ transients). Second, LTB4, by elevating cytosolic Ca2+, increases the amount of PKC mobilized by PKC activators and thereby promotes PKC-dependent responses (e.g., degranulation). The two mechanisms may be pertinent to the bidirectional effects of PKC activators on various other agonists. Furthermore, PKC, by down-regulating receptors, may serve as a physiologic stop signal for terminating function and producing a poststimulatory state of desensitization.

Calcium↗
PubMed1990

Cyclical binding, processing, and functional interactions of neutrophils with leukotriene B4.

Leukotriene (LT) B4 activates human polymorphonuclear neutrophils (PMN) by binding to plasmalemmal receptors. It stimulates PMN to raise cytosolic calcium and degranulate. Both responses end within 15-30 sec. However, in less than 15 sec, LTB4-treated PMN lose the ability to respond further to LTB4; decrease the affinity and number of high affinity receptors available for binding LTB4; sequester LTB4 in plasmalemma-associated sites that are inaccessible to a releasing buffer regimen; and begin internalizing LTB4. Over the next 90 min, the cells increasingly internalize LTB4 and convert it to less potent metabolites; release the metabolites; recover LTB4 binding sites; and become fully sensitive to LTB4. Contrastingly, during the entire 90 min incubation with LTB4. PMN retained the capacity to bind and respond normally to a second stimulus, platelet-activating factor. We therefore suggest the following model. LTB4 receptors, when ligand-bound, initiate function but rapidly lose this capacity as they lower their ligand binding affinity and sequester, internalize, or otherwise uncouple from transducing elements. These LTB4 receptor changes contribute to terminating PMN responses and producing a stimulus-selective state of desensitization. During the desensitization period, PMN progressively process and metabolize LTB4. This removes LTB4 from the environment, thereby allowing PMN to recover functional receptors for and sensitivity to the ligand.

Calcium↗
PubMed1990

Simplified technique for scrotal pouch orchiopexy.

The author details the technique of the scrotal pouch orchiopexy. As described, the operation has been used in more than 200 consecutive orchiopexies with no scrotal hematomas, testicular atrophy, or retraction of the testes.

Child↗
PubMed1990

Female urologic diagnostic techniques.

With the exception of stress incontinence, the most common urologic problems unique to female patients are vesicovaginal fistulas and urethral diverticula. The author describes modifications of a Foley catheter both to facilitate distention of the vagina for vaginoscopy and for urethrography and use of the visual urethrotome for urethroscopy.

Colposcopes↗
PubMed1990

Techniques of genital examination and bladder catheterization in female children.

The physical examination of the female child should not be considered complete until there has been an examination of the external genitalia, but without an effective technique and finesse, this examination can become an ordeal for everyone involved. The examination usually can be conducted with the child in a frog-leg position on the mother's lap. Catheterization can be performed with the child similarly positioned without using gloves, an examination light, or preparatory washing of the genitalia.

Child↗
PubMed1990

Techniques to enhance the ileal conduit.

There is a need for operations by which the complications of ileal conduits can be prevented or corrected. The author details techniques to ensure the formation of a short conduit, to shorten a conduit through a peristomal incision, and to correct ileocutaneous stomal stenosis.

Adult↗
PubMed1989

Bidirectional effects of protein kinase C activators. Studies with human neutrophils and platelet-activating factor.

Protein kinase C (PKC) (Ca2+/phospholipid-dependent enzyme) activators stimulated human neutrophils to reduce the availability of high affinity receptors for platelet-activating factor. These effects were concentration dependent, irreversible, temperature sensitive, and antagonized by a PKC blocker. The activators also inhibited 1-O-alkyl-65% hexadecyl, 25% octadecyl-2-acetyl-sn-glycero-3-phosphocholine (PAF)-induced Ca2+ transients; this inhibition correlated precisely with receptor depletion. Contrastingly, PKC activators could enhance as well as inhibit PAF-induced degranulation. Inhibition of degranulation occurred only at concentrations of the activators which depressed high affinity PAF binding by greater than 75%. Cells treated with lesser activator concentrations responded to PAF with reduced but still substantial rises in cytosolic Ca2+, markedly increased degranulation, and markedly increased PKC mobilization. The last two responses, however, failed to occur in cells that were (a) calcium depleted, (b) treated with high activator concentrations (which inhibited virtually all PAF binding and PAF-induced Ca2+ transients), or (c) treated with PAF 5 min before a PKC activator (PAF-induced rises in cytosolic Ca2+ reversed in less than 5 min). Thus, activated PKC down-regulates high affinity PAF receptors. This tends to reduce neutrophil responses to PAF. On the other hand, PAF, perhaps by raising cytosolic Ca2+, acts synergistically with PKC activators in mobilizing PKC. This may tend to enhance function but seems capable of influencing only those responses that are elicited by PKC activators (e.g. degranulation but not Ca2+ transients). The complex and bidirectional effects of PKC activators on other receptor-mediated, calcium mobilizing agonists in various cell types may reflect these opposing mechanisms.

Calcium↗
PubMed1988

Rare penile anomalies presenting with complication of circumcision.

Two rare penile anomalies, scaphoid megalourethra and 180-degree torsion of the penis, which presented as complications of circumcision are reported. Complications of circumcision of this type may be prevented by careful inspection of the penis prior to circumcision, by delaying circumcision if a penile abnormality is noted, and by careful visualization during all aspects of the procedure.

Circumcision, Male↗
PubMed1988

Bilateral cysts of tunica albuginea of testes.

A case is presented of a patient with bilateral cysts of the tunica albuginea. An orchiectomy had been accomplished on the right side, with confirmation of cysts of the tunica albuginea. Cysts of the contralateral testicle were diagnosed by testicular ultrasound examination. This case represents the first reported instance of bilateral cysts of the tunica albuginea.

Cysts↗
PubMed1988

Mesoaortic compression of the left renal vein (the so-called nutcracker syndrome): repair by a new stenting procedure.

Compression of the left renal vein (LRV) between the superior mesenteric artery and the aorta has been termed the nutcracker syndrome. Although often asymptomatic, this syndrome may result in varicocele, ovarian vein syndrome, and rarely LRV hypertension, pelviureteral varices, hematuria, and flank pain. Previous surgical approaches have included nephrectomy, variceal ligation, nephropexy, or renocaval reimplantation. We report a new LRV stenting procedure that provided relief for a young woman incapacitated by daily left flank pain and microscopic hematuria. Phlebography of the LRV revealed mesoaortic compression associated with a pressure gradient of 12 mm Hg and preferential outflow down large pelviureteral varices. At operation compression of the LRV was corrected with an external stent of reinforced polytetrafluoroethylene. The patient was asymptomatic and free of hematuria for 9 months after operation and follow-up phlebography documented normal renocaval flow, elimination of the pressure gradient, and reduction of the pelviureteral varices. This represents the first description in the vascular surgical literature of this venous compression syndrome, which has been recognized in previous urologic and radiologic reports reviewed herein. Vascular surgeons should be cognizant of the nutcracker syndrome, and we recommend this new stenting procedure as a more simple and physiologic therapy than previous approaches to this problem.

Adolescent↗