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Biomedical subjects

C Ferguson

Publications and source records attributed to C Ferguson.

At least 73 records · Page 4Linked to original sources

Epidural analgesia.

The most frequently used postoperative analgesia techniques are intramuscular injection (IM) and patient controlled analgesia (PCA). Recently, the use of epidural catheter injection (EPI) has been done with success. This study was done to prospectively compare these three techniques for postoperative analgesia after extensive operations upon the colon and rectum. Patients were randomized to one of three analgesia groups--IM, intramuscular morphine sulfate; PCA, patient controlled morphine sulfate, and EPI, epidural morphine sulfate. Data collected included age, time to first bowel movement, amount of narcotic, number achieving 75 per cent of preoperative forced vital capacity, postoperative pruritus, headache, nausea and vomiting, respiratory depression, atelectasis or pneumonitis. A visual analog pain scale was used to evaluate postoperative pain severity (0, no; 1, partial; 2, marked, and 3, total relief). Sixty-eight patients were eligible for study (IM, 19; PCA, 22; EPI, 23, and excluded, four). The EPI group required significantly less daily narcotic compared with either the IM or PCA groups (17.0 +/- 6.12 milligrams; 67.8 +/- 26.8 milligrams; 40.5 +/- 20.6 milligrams, respectively, less than 0.05 ANOVA) and total narcotic (81.3 +/- 31.3 milligrams; 355.4 +/- 147.7 milligrams; 215.3 +/- 105.4 milligrams, respectively, p less than 0.05 ANOVA). EPI achieves excellent pain control in more patients with a significantly lower dose of narcotics and significantly fewer pulmonary complications. Therefore, epidural analgesia is the optimal method of postoperative analgesia after extensive abdominal operations.

Adult↗

Immunological approaches to the transmembrane topology and conformational changes of the carboxyl-terminal regulatory domain of yeast plasma membrane H(+)-ATPase.

Molecular genetic experiments have suggested that the carboxyl terminus of the Saccharomyces cerevisiae plasma membrane H(+)-ATPase is an inhibitory domain involved in the "in vivo" regulation of the enzyme by glucose metabolism. An antibody prepared against a fusion protein including the last 59 amino acids of the ATPase sequence has been affinity purified to yield a preparation which requires the 18 carboxyl-terminal amino acids for recognition. Antibody binding experiments show that the carboxyl-terminal domain of the ATPase can be selectively exposed by concentrations of the detergent Tween-20 which do not break down the permeability barrier of the plasma membrane to the antibody. Both enzyme-linked immunosorbent assay and immunofluorescence analysis demonstrate that the accessibility of the carboxyl-terminal domain in isolated plasma membranes depends on the physiological state of the cell being increased by glucose metabolism. Immunofluorescence analysis of isolated plasma membrane vesicles, using a dual labeling protocol with concanavalin A and antibody to reveal the orientation of individual vesicles, and colloidal gold immunoelectron microscopy of ultrathin cryosections of whole yeast cells separately demonstrate that the ATPase carboxyl terminus is located in the cytoplasmic compartment. The application of a mutant deleted of the epitope(s) recognized by the affinity purified carboxyl-terminal antibody eliminates the possibility of artifacts arising from nonspecific antibody binding. The accessibility properties and cytoplasmic location of the carboxyl-terminal domain appear to be consistent with its role as a negative regulator of the ATPase.

Blotting, Western↗

Domains of yeast plasma membrane and ATPase-associated glycoprotein.

In yeast homogenates the plasma membrane H(+)-ATPase and a major surface glycoprotein of about 115 kDa are present in two membrane fractions with peak densities in sucrose gradients of 1.17 and 1.22. Immunogold electron microscopy of frozen yeast sections indicates that the ATPase is exclusively (greater than 95%) present at the surface membrane. Therefore the two ATPase-containing fractions appear to correspond to different domains of the plasma membrane. The 115 kDa glycoprotein is tightly associated with the ATPase during solubilization and purification of the enzyme. However, in a mutant lacking the glycoprotein the activity of the plasma membrane H(+)-ATPase is similar to wild type, suggesting that this association is fortuitous. The ATPase and the glycoprotein are difficult to separate by electrophoresis and therefore binding of concanavalin A to the ATPase cannot be unambiguously demonstrated in wild-type yeast. By utilizing the mutant without glycoprotein it was shown that the ATPase band of 105 kDa binds concanavalin A.

Cell Membrane↗

Effects of inorganic lead on the differentiation and growth of cultured hippocampal and neuroblastoma cells.

Lead exposure has devastating effects on the developing nervous system, and has been implicated in variety of behavioral and cognitive deficits as well as neural morphological abnormalities. Since lead impacts many calcium-dependent processes, one likely mechanism of lead toxicity is its disruption of calcium dependent processes, among which is neuronal differentiation. We investigated the effects of inorganic lead on survival and several parameters of differentiation of cultured neurons. Three different cell types were used: Rat hippocampal neurons (a primary CNS cell type), B50 rat neuroblastoma cells (a transformed CNS-derived cell line), and N1E-115 mouse neuroblastoma cells (a transformed peripherally-derived cell line). Lead concentrations ranged from low nM to 1 mM. Lead effects differed considerably among the three cell types, with B50 cells least affected. Lead effects were generally multimodal, with fewest effects observed at intermediate concentrations. Lead inhibited neurite initiation in hippocampal neurons, but stimulated initiation in N1E-115 cells. In those cells that differentiated, lead increased dendrite numbers in hippocampal neurons and neurite numbers in N1E-115 cells. Lead exposure increased both the length and the degree of branching of axons in hippocampal neurons and the length of neurites in N1E-115 cells. We hypothesize that lead impacts multiple regulatory processes that influence neuron survival and differentiation, and that its effects show differing dose-dependencies. The differing responses of the different cell types to lead suggests that differentiation may be regulated in different ways by the three types of cells. Alternatively, or additionally, the cell types may differ in their ability to compensate for, sequester, or expel lead.

Animals↗

L-type calcium channels may regulate neurite initiation in cultured chick embryo brain neurons and N1E-115 neuroblastoma cells.

The intracellular free Ca2+ concentration, [Ca2+]i, plays an important role in regulating neurite growth in cultured neurons. Insofar as [Ca2+]i is partly a function of Ca2+ influx through voltage-sensitive calcium channels (VSCC), Ca2+ entry through VSCC should influence neurite growth. Vertebrate neurons may possess several types of VSCC. The most frequently described VSCC types are usually designated L, T and N. In most preparations, these VSCC types respond differently to certain pharmacological agents, including Cd2+, Ni2+, the dihydropyridines nifedipine and BAY K8644, and the aminoglycoside antibiotics. We used these agents to study the role of Ca2+ influx in regulating neurite initiation and length in cultures of chick embryo brain neurons and N1E-115 mouse neuroblastoma cells. In chick neurons, nifedipine and Cd2+ (less than 50 microM), which have been reported to inhibit L-type channels, reduced neurite initiation, but not mean neurite length. Ni2+ (less than 100 microM), reported to inhibit T-type channels, had no effect on either initiation or length. Low concentrations of most aminoglycosides (less than 300 microM), reported to inhibit N-type channels, had no effect on neurite initiation, but high concentrations of streptomycin (great than 300 microM), reported to inhibit both L- and N-type channels, reduced neurite initiation. BAY K8644, which enhances current flow through L-type channels, had no effect except at high concentration (50 microM), which inhibited initiation. N1E-115 neuroblastoma cells have been reported to contain L-type and T-type channels, but thus far no channel similar to the N-type has been described. In cultured N1E-115 cells, nifedipine (5 microM), Cd2+ (5 microM), and streptomycin (200 microM) reduced neurite initiation, while nickel (50 microM) and neomycin (100 microM) did not affect initiation. None of these agents altered neurite length. In N1E-115 cells, whole-cell voltage clamp recordings showed that nifedipine and Cd2+ inhibited L-type channels but not T-type channels, while Ni2+ inhibited T-type channels but not L-type channels. Streptomycin slightly inhibited L-type channels but enhanced current flow through T-type channels. Neomycin slightly inhibited both channel types. These data indicated that neurite initiation in these two cell types may be modulated by Ca2+ influx through L-type channels, but not T- or N-type channels. Neurite length was not significantly influenced by any of the agents tested, suggesting that Ca2+ influx through VSCC may not affect neurite elongation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Identification and localization of high molecular weight proteins in insect flight and leg muscle.

Thick and thin filaments in asynchronous flight muscle overlap nearly completely and thick filaments are attached to the Z-disc by connecting filaments. We have raised antibodies against a fraction of Lethocerus flight muscle myofibrils containing Z-discs and associated filaments and also against a low ionic strength extract of myofibrils. Monoclonal antibodies were obtained to proteins of 800 kd (p800), 700 kd (p700), 400 kd (p400) and alpha-actinin. The positions of the proteins in Lethocerus flight and leg myofibrils were determined by immunofluorescence and electron microscopy. p800 is in connecting filaments of flight myofibrils and in A-bands of leg myofibrils. p700 is in Z-discs of flight myofibrils and an immunologically related protein, p500, is in leg muscle Z-discs. p400 is in M-lines of both flight and leg myofibrils. Preliminary DNA sequencing shows that p800 is related to vertebrate titin and nematode twitchin. Molecules of p800 could extend from the Z-disc a short way along thick filaments, forming a mechanical link between the two structures. All three high molecular weight proteins probably stabilize the structure of the myofibril.

Amino Acid Sequence↗

The laryngeal mask airway in pediatric radiotherapy.

The use of the laryngeal mask airway, a new form of airway, is described in infants and young children receiving radiotherapy under general anesthesia. The laryngeal mask airway consists of a tube, at the distal end of which is attached an elliptically shaped cuff resembling a miniature face mask. The laryngeal mask is inserted blindly into the pharynx, and its cuff forms a low pressure seal around the larynx through which the patient can breathe spontaneously. No complications occurred during use of the laryngeal mask in 25 children who received 312 anesthetics. This experience suggests that the laryngeal mask airway has a valuable role in this situation and may contribute to the safety of anesthesia.

Anesthesia, General↗

Observations on the haemopoietic response to critical illness.

Peripheral blood cytopenias are common in patients receiving intensive care, particularly in those with multiple organ failure. To assess the contribution of bone marrow hypoplasia in such patients 44 bone marrow samples from 24 patients under intensive care were studied by standard morphological techniques and by the granulocyte-macrophage colony forming cell (GM-CFC) assay. Frequently observed morphological abnormalities in the bone marrow included the following: (i) a reduction in overall cellularity in seven patients, with a progressive decrease in most patients studied sequentially; (ii) an increase in the number of actively phagocytic macrophages; and (iii) a disruption of normal bone marrow architecture with the accumulation of intercellular hyaluronic acid glycosaminoglycan. Mean GM-CFC growth was significantly reduced when compared with that in a group of normal controls. In four of five patients studied sequentially GM-CFC growth became subnormal in association with a reduction in bone marrow cellularity. Inhibitory serum factors were not identified. These morphological abnormalities are similar to the changes observed in gelatinous degeneration of the bone marrow. In both situations disruption of the haemopoietic microenvironment, with the accumulation of hyaluronic acid proteoglycan, may be an important factor in the inhibition of haemopoietic progenitor cell growth. The proliferation of macrophages, by the release of a variety of cytokines or reactive oxygen intermediates, may also be implicated in impaired haemopoiesis and the development of disordered erythropoiesis.

Adolescent↗

Crystallization of p68 on lipid monolayers and as three-dimensional single crystals.

Two-dimensional crystals of p68, a Ca2+ -binding protein that has homology with members of the lipocortin/calpactin family, were obtained by interaction with a phospholipid monolayer. By measuring surface pressure at constant surface area, p68 was found to interact in a Ca2+ -dependent manner specifically with phosphatidylethanolamine, less so with phosphatidylserine and not at all with phosphatidylcholine. With dimyristoyl-phosphatidylethanolamine, two-dimensional crystalline arrays were formed. Image analysis of electron micrographs of these crystals, which diffracted to about 50 A, revealed p3 symmetry with a unit cell of about 178 A by 178 A; the protein densities showed a two-domain structure giving a cylindrical molecule of about 100 A by 35 A diameter packed as trimers. Three-dimensional microcrystals obtained without lipid or Ca2+ were suitable for electron microscopy and gave a tetragonal unit cell of about 256 A by 68 A. The implications of these observations on the structure and lipid specificity of p68 binding are discussed.

Annexin A6↗

Prediction of pancreatic necrosis by dynamic pancreatography.

Parenchymal necrosis has recently been recognized as the principal determinant of the incidence of secondary infection in acute pancreatitis. Because secondary infection of pancreatic necrosis accounts for more than 80% of all deaths from acute pancreatitis, a method for determining the presence or absence of parenchymal necrosis would offer considerable prognostic and therapeutic information. Thirty seven patients with unequivocal acute pancreatitis and five normal controls were prospectively studied with intravenous bolus, contrast-enhanced computed tomography (dynamic pancreatography). In the absence of pancreatic necrosis, there were no significant differences in parenchymal enhancement between any of the following patient groups: controls (5), uncomplicated pancreatitis (20), pancreatic abscess (7), or peripancreatic necrosis (4)(p less than 0.05). On the other hand, pancreatic parenchymal enhancement was significantly reduced or absent in all six patients with segmental or diffuse pancreatic necrosis (p less than 0.05). Postcontrast pancreatic parenchymal enhancement was also found to be inversely correlated with the number of Ranson signs (p less than 0.001). Dynamic pancreatography offers prognostic information and is a safe and reliable technique for predicting the presence or absence of pancreatic parenchymal necrosis.

Abscess↗

Electron microscopic study of crystals of the Xenopus laevis transcription factor IIIA-5S ribosomal RNA complex.

A novel method has been developed to grow crystals of the Xenopus laevis transcription factor IIIA-5S RNA complex directly on grids for examination by electron microscopy. Microcrystals were examined in negative stain and in thin sections to reveal a hexagonal lattice with unit-cell dimensions a = b = 87.1 +/- 4.4 A and c = 143.8 +/- 12.7 A. Optical diffraction patterns from micrographs were obtained about the major crystal axes extending to about 40-A resolution. A packing scheme is proposed for which there are three or six transcription factor IIIA-5S RNA complexes in the unit cell related by 3(1) symmetry along the long cell axis. This would require that the 5S RNA molecules are arranged end-to-end, with the terminal loops of adjacent molecules overlapping.

Animals↗

The ultrasonic features of an unusual cholesterol gallstone.

We describe a cholesterol gallstone with an unusual macroscopic appearance and only mild acoustic shadowing on ultrasonography with a 3.5 MHz transducer used in vivo; there was greater shadowing using 5.0 and 7.5 Mhz transducters in vitro.

Cholelithiasis↗

Metastatic osteosarcoma and multiple lung resection. A case report.

The existence of pulmonary metastases in patients presenting with osteosarcoma is known to indicate a poor prognosis. Lung resection of solitary lesions is now a standard treatment approach, but with limited successful long-term results. We report the progress of a 16-year-old girl with osteosarcoma of the proximal tibia who underwent 11 lung resections for pulmonary metastases over a two-year period, and who has since then been free of disease for seven years.

Adolescent↗