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Biomedical subjects

C D Smith

Publications and source records attributed to C D Smith.

At least 235 records · Page 13Linked to original sources
PubMed1988

Modulation of inositol phospholipid metabolism by polyamines.

At low concentrations of Mg2+, incorporation of 32P from [gamma-32P]ATP into phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) in plasma membranes isolated from human polymorphonuclear leucocytes was enhanced 2-4-fold by the polyamines spermidine and spermine. Polyamines had no effects on inositol phospholipid phosphorylation at high concentrations of Mg2+. At 1 mM-Mg2+, [32P]PIP2 synthesis was maximally enhanced by 2 mM-spermine and 5 mM-spermidine, whereas putrescine only slightly enhanced synthesis. Spermine decreased the EC50 (concn. for half-maximal activity) for Mg2+ in [32P]PIP2 synthesis from 5 mM to 0.5 mM. Spermine did not modulate the Km for ATP for [32P]PIP or [32P]PIP2 synthesis. Spermine also decreased the EC50 for PI in [32P]PIP synthesis. In contrast, spermine elevated the apparent Vmax, without affecting the EC50 for PIP, for [32P]PIP2 synthesis. Spermine and spermidine also inhibited the hydrolysis of [32P]PIP2 by phosphomonoesterase activity. Therefore polyamines appear to activate inositol phospholipid kinases by eliminating the requirements for super-physiological concentrations of Mg2+. Polyamine-mediated inhibition of polyphosphoinositide hydrolysis would serve to potentiate further their abilities to promote the accumulation of polyphosphoinositides in biological systems.

1-Phosphatidylinositol 4-Kinase↗
PubMed1988

The surgical management of esophageal stricture in children. A century of progress.

Early in this century all procedures performed on the esophagus were accomplished through its lumen. Ingestion of caustics was common and resulted in dense strictures for which complicated and ingenious methods of dilation were advised. Because obstructions usually recurred, by-pass operations were devised with conduits of skin or segments of the gastrointestinal tract. Now, in contrast, when burns occur, intensive steroid therapy usually prevents all but localized areas of stricture. These areas, if short, can be treated with hydrostatic balloon dilation under fluoroscopic control. If longer or resistant to dilation, these strictures can be managed by incision and insertion of a colic patch with excellent long-term results. To a previous series of children who have had esophageal patch with a vascularized segment of colon, now added is an experience with a free segment of small intestine with vascular anastomosis to an artery and vein in the neck and another case of a free patch of pericardium to the esophageal stricture.

Burns, Chemical↗
PubMed1988

Changes in vascular vasopressin receptors and responsiveness in DOCA/NaCl-treated rats.

This study investigated the effects of treatment with desoxycorticosterone acetate and salt (DOCA/NaCl) on blood pressure, aortic vascular vasopressin receptors and in vitro vascular responsiveness in male rats. Four groups of animals were utilized in the study: a control group on normal tap water, a control group drinking a 1% NaCl solution; a DOCA/NaCl-treated group (1% NaCl in the drinking water); and a uninephrectomized (1K) DOCA/NaCl-treated group. DOCA/NaCl treatment for 4 weeks resulted in a significant elevation in blood pressure which was more pronounced in the uninephrectomized animal. The concentration of specific binding sites for vasopressin on the aorta were reduced in both the DOCA/NaCl-treated groups. However, the vascular responsiveness of the aorta to vasopressin was significantly reduced only in the hypertensive, uninephrectomized-DOCA/NaCl-(1K DOCA/NaCl) treated rat. Both the maximal contraction and the sensitivity was reduced in the 1K DOCA/NaCl group. The results of this study would suggest that the vascular alterations to vasopressin are probably post receptor mediated and result from the DOCA/NaCl-induced hypertension.

Animals↗
PubMed1988

The history of lupus erythematosus. From Hippocrates to Osler.

Hippocrates (460-375 BC) was the first to describe cutaneous ulcers under the heading of herpes esthiomenos. From what we can tell, Herbernus of Tours was the first to apply the term lupus to a skin disease in 916 AD. Following this, a number of terms including lupus, noli me tangere, and herpes esthiomenos were used to describe cutaneous ulcers. Willan (1757-1812) expanded the classification of skin diseases using the term herpes for vesicular diseases and lupus for destructive and ulcerative diseases of the face. The first clear description of lupus erythematosus was by Biett and was reported by his student Cazenave under the term erythema centrifugum in 1833. In 1846 Hebra, under the name of Seborrhea Congestiva described disc-shaped patches and introduced the butterfly simile for the malar rash. In 1851 Cazenave renamed erythema centrifugum, calling it lupus erythematosus and gave a classic description of discoid lupus erythematosus. In 1872 Kaposi subdivided lupus into the discoid and systemic forms and introduced the concept of systemic disease with a potentially fatal outcome. Hutchinson alluded to the photosensitive nature of the rash and may have provided the earliest description of what is now called annular subacute cutaneous lupus. In 1894 Payne used quinine in the treatment of patients with LE and postulated the presence of a vascular disturbance. In 1902, Sequira and Balean published a large series of patients with discoid and systemic LE and provided clinical and pathologic details of a young woman who died of glomerulonephritis. In 1904, Jadassohn published an exhaustive review of discoid and systemic LE, including clinical features and pathologic findings. Between 1895 and 1904 Sir William Osler published 29 cases of what was termed the erythema group of diseases. Perhaps his major contribution was to show that skin diseases could be accompanied by a variety of systemic manifestations. In retrospect most of his patients suffered from diseases other than SLE and it was only in his 1904 paper that two cases with SLE were described. He did not acknowledge this diagnosis in his cases and we share the viewpoint that his contribution to the study of SLE has been overemphasized.

History, 15th Century↗
PubMed1987

Nucleotide regulatory protein-mediated activation of phospholipase C in human polymorphonuclear leukocytes is disrupted by phorbol esters.

Polymorphonuclear leukocytes (PMNs) activate phospholipase C via a guanine nucleotide regulatory (G) protein. Pretreatment of the PMNs with pertussis toxin (PT) or 4-beta-phorbol 12-myristate 13-acetate (PMA) inhibited chemoattractant-induced inositol trisphosphate generation. To determine the loci of inhibition by PT and PMA, G protein-mediated reactions in PMN plasma membranes were examined. Plasma membranes prepared from untreated and PMA-treated PMNs demonstrated equivalent ability of a GTP analogue to suppress high affinity binding of the chemoattractant-N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe) to its receptor. The rate, but not the extent, of high affinity binding of GTP gamma[35S] to untreated PMN membranes was stimulated up to 2-fold by preincubation with 1 microM fMet-Leu-Phe. The ability of fMet-Leu-Phe to stimulate the rate of GTP gamma S binding was absent in membranes prepared from PT-treated PMNs, but remained intact in membranes from PMA-treated cells. Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) via phospholipase C could be activated in untreated PMN membranes by either fMet-Leu-Phe plus GTP or GTP gamma S alone at low concentrations of Ca2+ (0.1-1 microM). Membranes prepared from PT-treated PMNs degraded PIP2 upon exposure to GTP gamma S, but not fMet-Leu-Phe plus GTP. In contrast, membranes prepared from phorbol ester-treated PMNs did not hydrolyze PIP2 when incubated with GTP gamma S. Treatment with PT or PMA did not affect the ability of 1 mM Ca2+ to activate PIP2 hydrolysis in PMN membranes, indicating that neither treatment directly inactivated phospholipase C. Therefore, PT appears to block coupling of the chemoattractant receptors to G protein activation, while phorbol esters disrupt coupling of the activated G protein to phospholipase C. The phorbol ester-mediated effect may mimic a negative feedback signal induced by protein kinase C activation by diacylglycerol generated upon activation of phospholipase C.

Calcium↗
PubMed1987

A double-mix cementation for improved esthetics of resin-bonded prostheses.

An efficient technique is described for reducing incisal discoloration of abutment teeth without creating a cement line. One disadvantage is the need for both opaque and tooth-colored translucent resin cements, but the complex procedure can be facilitated by increasing the working time of the resin cements.

Cementation↗
PubMed1987

Clinical performance of sealed composite restorations placed over caries compared with sealed and unsealed amalgam restorations.

The 2-year clinical evaluations of paired occlusal restorations are presented. Each study participant received a sealed composite restoration placed over a carious lesion and either a traditional outline-form (unsealed) amalgam or an ultraconservative sealed amalgam restoration. Caries was removed before placement of both types of amalgam restorations. No important clinical differences developed among the three groups of restorations.

Adolescent↗
PubMed1987

Anti-endothelial cell antibodies: detection and characterization using a cellular enzyme-linked immunosorbent assay.

Anti-endothelial cell antibodies (AECA) have been detected in autoimmune diseases such as systemic lupus erythematosus (SLE) and scleroderma (PSS) but their role in pathogenesis is unknown. Immunofluorescence, immunohistochemistry, complement-dependent antibody lysis, and radioimmunoassay have been used in the past to detect AECA. We have developed a rapid, sensitive, and quantitative cellular enzyme-linked immunosorbent assay (ELISA) to detect and characterize AECA. Sera were obtained from 28 normal volunteers, 28 patients with SLE, and 14 patients with PSS. We also performed studies in 47 patients with various monoclonal gammopathies. Endothelial cells (EC) were obtained from human umbilical veins by standard methods and subcultured on 96-well tissue culture plates without fixation. EC were then sequentially incubated with sera, peroxidase-conjugated goat anti-human Ig (IgG, IgM, or IgA), and substrate. Optical density readings were converted to arbitrary units by developing a standard curve. Heavy-chain specific antibodies were used to determine the class of AECA binding to EC. IgG was purified by using protein A columns and digested with pepsin to obtain F(ab')2 fragments. The mean units of AECA from normals were 19.3 for IgG and 12.5 for IgM. SLE sera showed significant levels of IgM AECA (37 units, P less than 0.001) but not IgG (29 units, P less than 0.1). PSS sera showed significant levels of both IgM AECA (38 units, P = 0.001) and IgG AECA (42.7 units, P less than 0.005). IgA AECA were not detected in normal, SLE, or PSS sera. Blocking Fc receptors with rabbit IgG did not affect the titer of IgG or IgM AECA.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Surface↗
PubMed1986

A guanine nucleotide regulatory protein controls polyphosphoinositide metabolism, Ca2+ mobilization, and cellular responses to chemoattractants in human monocytes.

Previous studies demonstrated that oligopeptide chemoattractant receptors on PMN and macrophages exist in high and low affinity states which are interconvertible by guanosine di- and triphosphates. These observations suggest that guanine nucleotide regulatory (N) proteins play a role in phagocyte activation by chemotactic factors. The data presented here indicate that chemotactic factor receptors on monocytes utilize an N protein to activate phospholipase C and subsequent biologic responses by the cells. This conclusion is based on the findings that inactivation of an N protein of 41,000 m.w. by Bordetella pertussis toxin (PT) treatment abolishes monocyte responsiveness to chemoattractants but not to lectins, PMA, or the Ca2+ ionophore A23187. Treatment with PT inhibited IP3 production, Ca2+ mobilization, and cellular activation as assessed by chemotaxis and changes in forward light scattering in response to the chemoattractants by at least 80%. Therefore, a PT-sensitive N protein plays an important role in the activation of monocytes by chemoattractants.

Adenosine Diphosphate Ribose↗
PubMed1986

Receptor-coupled activation of phosphoinositide-specific phospholipase C by an N protein.

Cleavage of phosphatidylinositol 4,5-bisphosphate by phospholipase C results in the production of two important second messengers: inositol-1,4,5-trisphosphate and 1,2-diacylglycerol. Although several receptors promote this cleavage, the molecular details of phospholipase C activation have remained unresolved. In this study, occupancy of a Ca2+-mobilizing receptor, the oligopeptide chemoattractant receptor on human polymorphonuclear leukocyte plasma membranes, was found to lead to the activation of a guanine nucleotide regulatory (N) protein by guanosine 5'-triphosphate. The activated N protein then stimulated a polyphosphoinositide-specific phospholipase C by reducing the Ca2+ requirement for expression of this activity from superphysiological to normal intracellular concentrations. Therefore, the N protein-mediated activation of phospholipase C may be a key step in the pathway of cellular activation by chemoattractants and certain other hormones.

Adenosine Triphosphate↗
PubMed1986

Role of guanine nucleotide regulatory protein in polyphosphoinositide degradation and activation of phagocytic leukocytes by chemoattractants.

Leukocyte activation by chemoattractants provides an important model to study the biochemical mechanisms of stimulus-response coupling in these cells. Well-defined chemotactic factors induce readily quantifiable responses in phagocytic leukocytes. These include directed migration and the production and release of toxic substances including oxygen radicals and lysosomal enzymes. The development of radiolabeled synthetic oligopeptides with potent chemotactic activity allowed the demonstration of chemoattractant receptors on polymorphonuclear leukocytes (PMNs) as well as macrophages. In membrane preparations from these cells, these receptors exist in high- and low-affinity states which are regulated by guanosine di- and triphosphates. This suggested that chemoattractant receptors interact with guanine nucleotide regulatory proteins (N or G proteins). Although chemoattractants elicit a rapid but transient increase in intracellular cAMP levels, they neither stimulate nor inhibit membrane-bound adenylate cyclase, suggesting a novel role for N proteins in certain receptor-transduction mechanisms. Stimulation of phagocytes by chemoattractants is also associated with a rapid increase in cytosolic Ca2+ concentrations ([ Ca2+]i) which appears to result from the production of inositol 1,4,5-triphosphate (IP3) as a consequence of the diesteric cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2). Treatment of phagocytes with pertussis toxin (PT), which ADP-ribosylates and thereby inactivates certain N proteins, abolishes the cells' responsiveness to chemoattractants. More direct evidence for a role of a PT-sensitive N protein in leukocyte activation was provided by the demonstration that chemoattractants stimulate the hydrolysis of PIP2 in PMN membranes only in the presence of GTP. This receptor-mediated hydrolysis of PIP2 is not observed in plasma membranes prepared from PT-treated PMNs. Therefore, these studies suggest that occupancy of chemoattractant receptors activates a PT-sensitive N protein. The activated N protein shifts the Ca2+ requirement for phospholipase C activity from supraphysiological levels to ambient cytosolic Ca2+ concentrations. Cleavage of PIP2 results in the formation of the second messenger molecules, IP3 and 1,2-diacylglycerol, which can initiate cellular activation. These messengers also seem to activate responses which feed back to attenuate receptor stimulation of phospholipase.

Adenylyl Cyclases↗
PubMed1986

Model for leukocyte regulation by chemoattractant receptors: roles of a guanine nucleotide regulatory protein and polyphosphoinositide metabolism.

Binding of chemoattractants to their receptors on phagocytes activates a guanine nucleotide regulatory (N) protein through the substitution of GTP for GDP on N. The activated N protein in turn stimulates a membrane-associated phospholipase C by lowering the Ca2+ concentration required to activate this enzyme from supraphysiologic levels to ambient intracellular concentrations. The phospholipase C hydrolyzes phosphatidylinositol 4,5-bisphosphate into the Ca2+ mobilizer inositol 1,4,5-trisphosphate and the protein kinase C activator 1,2-diacylglycerol. In addition to promoting cellular activation, the products of this hydrolysis initiate processes which feed back to inhibit poly-phosphoinositide breakdown. The regulatory model proposed herein may be relevant to other receptors which stimulate polyphosphoinositide metabolism.

Adenylyl Cyclases↗
PubMed1986

Pneumatic reduction bag for treatment of gastroschisis and omphalocele. A 10-year experience.

In 1975, a new Silastic device was developed by the authors to be used in the staged reduction of viscera in newborns with giant gastroschisis or omphalocele. That device and their early experience were described in 1977. This article reports the results of use of this device over the past 10 years. Primary closure of gastroschisis and omphalocele is accomplished, if possible. If tension of the closure is too great, the pneumatic bag is attached and staged reduction accomplished over 7-8 days. The advantages of this device are: it is preformed and easily sterilized by autoclaving; it is strong enough to elevate the abdominal wall; the pneumatic sac eliminates bulky ligatures; when it is pulled through a slotted rod, the edges of the defect are opposed; and it is available in two sizes.

Abdominal Muscles↗