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Biomedical subjects

J A Sullivan

Publications and source records attributed to J A Sullivan.

At least 73 records · Page 4Linked to original sources

Surgical repair of stenotic ostial lesions of the left main coronary artery.

Fourteen patients with isolated stenosis of the left coronary artery ostium underwent vein patch angioplasty. An anterior approach between the aorta and pulmonary artery to expose the left main coronary ostium was used in 12 of 14 patients. There were no deaths, and postoperative angiograms in 13 of the patients showed normal coronary ostial contour with normal runoff. Two perioperative myocardial infarctions were observed. Four of the 14 patients underwent an urgent operation. Isolated coronary ostial stenosis appears to be a distinct clinical entity occurring in younger patients, mostly female, and often with a short clinical course. Unstable pain and hemodynamics are observed. The common pathologic cause of the stenotic lesion is not clear.

Adult↗

Spatial and temporal characteristics of the increase in intracellular Ca2+ induced in cytotoxic T lymphocytes by cellular antigen.

The increase in intracellular Ca2+ concentration [( Ca2+]i) in cytolytic T lymphocytes in response to target cell binding was investigated by ratio image fluorescence microscopy. Ca2+ mobilization from intracellular stores occurred at a site distal to target cell contact and was transient. Extracellular Ca2+ influx resulted in an increase in [Ca2+]i that was prolonged and distributed more proximal to the target cell. Oscillations in [Ca2+]i were observed after target cell contact, although the periodicity was dependent on the presence of extracellular Ca2+. The Ag-specific reorientation of cytoplasmic granules occurred well after [Ca2+]i had begun to decline to a resting level, but was dependent on extracellular Ca2+. These studies indicate that the Ag-stimulated increase in [Ca2+]i exhibits considerable spatial and temporal variation, and that these characteristics are altered by the availability of extracellular Ca2+. The results also suggest that these changes in [Ca2+]i may play a role in the cytoplasmic events that accompany T cell-mediated cytolysis.

Animals↗

Spontaneous oscillations of intracellular calcium and growth hormone secretion.

A novel combination of two single cell assays allowed the simultaneous measurement of intracellular calcium concentration and hormone secretion in normal pituitary cells. [Ca2+]i was recorded using the fluorescent Ca2+ indicator fura-2 and digital imaging microscopy. This technique was combined with a reverse hemolytic plaque assay for growth hormone in order to identify somatotropes and quantitate the amount of hormone released. A dynamic profile of rhythmic calcium oscillations was found in spontaneously secreting somatotropes. Each somatotrope displayed a distinct frequency (one pulse every 5-30 s) and amplitude (range 50-450 nM) generated asynchronously from cell to cell. The amount of growth hormone (GH) released correlated directly with both the frequency and amplitude of calcium oscillations at the level of single GH cells. Furthermore, calcium excursions in somatotropes were rapidly suppressed by either (i) removal of extracellular calcium, (ii) somatostatin (1 mM), or (iii) the calcium channel blockers cobalt (2 mM) and verapamil (100 microM). These observations demonstrate that spontaneous calcium oscillations are characteristic for normal somatotropes. These oscillations are related to spontaneous hormone secretion and due to influx through calcium channels in the membrane. Somatostatin, the physiologic inhibitor of GH secretion, suppresses calcium transients. These findings suggest that the intracellular signaling information may be encoded both in the frequency and amplitude of calcium oscillations.

Animals↗

Dual stimulation of phospholipase activity in human monocytes. Role of calcium-dependent and calcium-independent pathways in arachidonic acid release and eicosanoid formation.

Human peripheral blood monocytes, prelabeled with [3H]arachidonic acid (AA), release labeled eicosanoids in response to soluble or particulate stimuli. Treatment with 12-O-tetradecanoate phorbol-13 acetate (20 nM), calcium ionophores, A23187 (2 microM) or ionomycin (1 microM), or serum-treated zymosan (300 micrograms) resulted in production of cyclooxygenase (CO) metabolites, 6-keto-PG-F1 alpha, thromboxane-B2, PGE2, PGF2 alpha, PGD2, PGB2, 12-L-hydroxy-5,8,10-heptadecatrienoic acid; 15-lipoxygenase products, including 15-hydroxyeicosatetraenoic acid (HETE); and unmetabolized AA. Labeled 5-lipoxygenase (LO) products, 5-HETE, and leukotriene-B4 were detected only after exposure to ionophore or serum-treated zymosan. The calcium dependence of 5-LO activation was confirmed in experiments where calcium was omitted from the incubation medium, and EGTA (0.5 mM) was added, as well as by direct measurement of increased intracellular calcium in phagocytosing monocytes. Combined or sequential treatment with two stimuli increased the release of unmetabolized AA without a commensurate augmentation of labeled metabolites, indicating that release of CO and LO metabolites does not necessarily reflect the extent of phospholipase activation. Quantitation of individual eicosanoids by RIA confirmed results by using radionuclides. These studies show the following. Activation of human monocyte phospholipase may be regulated by at least two pathways, one "12-O-tetradecanoate phorbol-13 acetate-like," which is largely independent of calcium, and another which is mediated by increased intracellular Ca2+ ("ionophore-like"). "Physiologic" stimulation of monocyte arachidonate release, such as that seen accompanying phagocytosis of opsonized particles, may occur via either a calcium-sensitive or calcium-insensitive pathway or both. Calcium may regulate eicosanoid formation at the level of phospholipase or 5-LO. Free AA, CO products, and 12- or 15-LO products are ordinarily released after phagocytosis, but leukotriene-B4, 5-HETE, or other 5-LO metabolites are produced only under conditions where calcium concentrations are optimal.

Arachidonic Acid↗

An experimental comparison of four hearing aid prescription methods.

Four hearing aid prescription methods were compared. A digital master hearing aid was used to produce the prescribed frequency gain characteristics. Measures of speech recognition and paired comparison judgments of relative speech intelligibility and speech quality were obtained at three output levels for each of the experimental frequency gain characteristics. No single prescriptive method emerged as being clearly superior. Relative performance of the four prescriptive methods varied as a function of output level. Similar results were observed for both speech recognition testing and paired comparison testing.

Adult↗

Relationship of free intracellular calcium to the cytolytic activity of Entamoeba histolytica.

Entamoeba histolytica adherence and destruction of host cells is required for in vivo pathogenicity; amebic in vitro adherence is mediated by a galactose- or N-acetyl-D-galactosamine-inhibitable surface lectin (Gal/GalNAc adherence lectin). Free intracellular Ca2+ concentration [( Ca2+]i) was measured in living amebae and target cells during amebic cytolysis of Chinese hamster ovary (CHO) cells and human polymorphonuclear neutrophils by utilizing the Ca2+ probe Fura-2 and computer-enhanced digitized microscopy. Motile E. histolytica trophozoites had oscillatory increases in [Ca2+]i in head or tail regions; however, there was no increase in regional or total amebic [Ca2+]i upon contact with a target CHO cell. Target CHO cells and polymorphonuclear neutrophils demonstrated marked irreversible increases in [Ca2+]i within 30 to 300 s following contact by an ameba (P less than 0.01); increased [Ca2+]i preceded the occurrence of nonspecific surface membrane permeability and death of the target cell. Target CHO cells contiguous on a monolayer to a cell contacted by an ameba experienced a rapid but reversible rise in [Ca2+]i (P less than 0.01) and were not killed. Galactose (40 mg/ml) totally abrogated the rise in target CHO cell [Ca2+]i that followed contact by amebae (P less than 0.01); immunoaffinity-purified amebic Gal/GalNAc adherence lectin (0.25 micrograms/ml) induced a rapid and reversible rise in CHO cell [Ca2+]i (P less than 0.01) which was inhibited by galactose. Amebic [Ca2+]i was not elevated following parasite adherence to target cells; a rapid and substantial rise in target cell [Ca2+]i occurred which was mediated, at least in part, by the Gal/GalNAc adherence lectin of the parasite and led to the death of target cells.

Adhesiveness↗

Cutaneous vascular spiders in cirrhotic patients: correlation with hemorrhage from esophageal varices.

Ninety-two consecutive male cirrhotic patients had esophagoscopy to determine the presence and size of varices, and a concomitant skin examination for assessment of cutaneous vascular spiders. Thirty-one subjects bled from varices within 10 days of the spider evaluation, and this group was compared to 61 individuals who never bled. Our results show that incidence of spiders (90%) and varices (91%) is nearly identical, that frequency of variceal bleeding is higher among subjects with spiders compared with those who lack these lesions (36% vs 11%, p less than 0.05), and that the spider profile may be useful to identify individuals who are at increased risk for variceal hemorrhage. Frequency of bleeding was 50% (p less than 0.01) when greater than 20 spiders were present and 63% (p less than 0.01) when multiple atypically located lesions were detected. Large spiders (greater than 15 mm) correlate best with large varices and have the strongest association with bleeding (80%, p = 0.0002). If evidence of benefit from prophylactic treatment of esophageal varices can be established, then elements of the spider profile may serve as a discriminating marker to assist in selection of appropriate patients for therapy.

Adult↗

Mechanical consequences of rod contouring and residual scoliosis in sublaminar segmental instrumentation.

The mechanical performance of contoured Luque rods in a neuromuscular model of spine deformity was examined to define an upper limit of deformity above which rod stresses would exceed the endurance limit for 316L stainless steel and therefore predict fatigue failure. Bovine constructs varying from 0-120 degrees scoliosis were loaded axially, with strain recordings obtained at the apex of the curve. Relatively low loads produced enough tensile stress to contemplate implant fatigue in all except the nondeformed (0 degrees) construct. Construct stiffness was found to decrease rapidly in spines with greater than 38 degrees deformity. In addition, data on patients who had suffered rod fracture from four different centers were found to compare favorably with experimental observations. We conclude that the vulnerability of Luque rod constructs to implant failure, from a mechanical standpoint, is greater than is generally assumed. Cross-linking of rods was found to increase stiffness. Methods to decrease tensile stresses in the implants and increase stiffness include external immobilization, larger diameter rods, and procedures to enhance correction.

Adolescent↗

Comparison of mammary serum antigen (MSA) and CA15-3 levels in the serum of patients with breast cancer.

Serum levels of mammary serum antigen (MSA) and CA15-3 were evaluated in 135 individuals in order to determine their single and combined value in the diagnosis and monitoring of breast cancer. Raised MSA levels (greater than 300 IU) were found in 68% of patients with Stage I and II breast cancer compared to only 3% having raised CA15-3 levels (greater than 40 U ml-1). Of 38 patients with Stage IV breast cancer, 95% had raised levels of MSA and CA15-3 combined with each test individually detecting 82% of those with Stage IV disease. No correlation was found between MSA and CA15-3 levels. Four patients being treated for breast cancer were followed over a 5-17 week period; MSA levels correlated with disease course in 3 and CA-15 in 2. The overall sensitivity, specificity and accuracy in detecting breast cancer were 76%, 91% and 96% for MSA; and 47%, 95% and 97% for CA15-3 respectively. When both tests were used together combined evaluation gave the highest sensitivity (84%) and specificity (100%). MSA seems to be superior to CA15-3 for early breast cancer diagnosis and a combination of the two tests gave the best results for metastatic disease.

Antigens, Neoplasm↗

Cytosolic calcium changes in individual neutrophils stimulated by opsonized and unopsonized Candida albicans hyphae.

Previous experiments suggest the critical central role of the neutrophil (PMN) respiratory burst in the prevention and containment of disseminated candidiasis. A rise in cytosolic free calcium concentrations ([Ca2+]i) has been documented as an early event after PMN stimulation which is involved in the subsequent genesis of microbicidal and inflammatory respiratory burst products. [Ca2+]i were therefore determined in individual PMN, loaded with the fluorescent calcium probe fura-2 as they attached to and spread over serum-opsonized or unopsonized Candida albicans hyphae, particles that are too big to be completely ingested. After contact between hyphae and PMN, the PMN rapidly spread over hyphal surfaces. Although both opsonized and unopsonized hyphae stimulated similar magnitudes of peak median increases in PMN [Ca2+]i, the kinetics of responses differed; median [Ca2+]i peaked within 1 min after contact with opsonized hyphae versus 4 min after contact with unopsonized hyphae. Moreover, a detectable calcium transient did not invariably follow contact and spreading of each individual PMN over a hyphal surface. In contrast to patterns seen after stimulation of PMN with opsonized zymosan, in which [Ca2+]i is greatest in the periphagosomal region, there was a more uniform distribution throughout the cytoplasm in PMN stimulated with the noningestable hyphae. These alterations in the early patterns and timing of PMN stimulation may reflect analogous differences in subsequent events which control the efficiency and specificity of microbicidal responses to uningestible hyphae and which also determine whether host tissues are damaged by the generation of toxic PMN activation products.

Benzofurans↗

Influence of type and opsonization of ingested particle on intracellular free calcium distribution and superoxide production by human neutrophils.

Intracellular free calcium concentration [( Ca2+]i) was measured with the fluorescent Ca2+ indicator Fura 2 within individual human neutrophils during the phagocytosis of several types of particles, including serum-treated zymosan (STZ), immunoglobulin G (IgG)-coated zymosan (IGZ), C3b-coated zymosan (C3Z), nontreated zymosan (Z), and serum-treated similarly sized latex particles (STL). STZ was coated with both IgG and C3b. IGZ was coated with only IgG, and C3Z was coated with only C3b. STL was coated with only C3b but to a lesser extent than C3Z. The ingestion of particles was greatest for STZ and somewhat lower for C3Z. Ingestion of IGZ and STL was much less than ingestion of C3Z. The relative efficiencies of the particles for inducing superoxide production were as follows: STZ greater than IGZ = C3Z greater than Z = STL. [Ca2+]i significantly increased from the resting level of approximately 70 to greater than 240 nM (P less than 0.01) during phagocytosis of the particles. The increment in [Ca2+]i was greater in the paraphagosomal region than in the cell body after the ingestion of STZ or IGZ. The mean peak [Ca2+]i values in the paraphagosomal cytoplasm of neutrophils ingesting one particle of STZ, IGZ, C3Z, Z and STL were 536.1 +/- 57.6, 424.7 +/- 55.8, 373.8 +/- 62.7, 272.3 +/- 31.5, and 270.8 +/- 38.0 nM, respectively, which showed good correlation (r = 0.97) with the efficiency of the particles for inducing superoxide production. Depletion of extracellular Ca2+ by EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N'N'-tetraacetic acid] attenuated both [Ca2+]i increase and superoxide production induced by particles. Thus [Ca2+]i increased after ingestion of several types of particles, and the subcellular pattern of [Ca2+]i was different depending on the type of particle ingested. Greater increases in paraphagosomal [Ca2+]i were closely associated with greater increases in superoxide production by neutrophils.

Benzofurans↗

Characterization of orbital lesions by surface coil MR imaging.

Surface coil MR imaging is an effective technique for evaluating orbital pathology. T1 and T2 weighting provides information not obtainable by CT and results in better characterization of some lesions. MR appears to be most useful for characterizing ocular pathology, specifically for differentiating retinoblastoma from benign diseases (Coat's disease and PHPV). MR can also be used to separate ocular tumors from associated subretinal fluid. With MR imaging, the signal intensities of lymphoma differ from those of benign inflammatory or infiltrative conditions such as pseudotumor or thyroid ophthalmopathy. Mucoceles, too, have a specific signal intensity pattern with T1 and T2 weighting. CT appears to be superior to MR for demonstrating densely calcified lesions or lesions of bone.

Eye Diseases↗

Experiments with a programmable master hearing aid.

A series of experiments is described tracing the development and application of adaptive paired-comparison testing to the prescriptive fitting of hearing aids. The equipment needed to implement the test procedures became progressively more complex with each new experiment, leading to the development of a digital master hearing aid.

Adult↗

Segmental spinal instrumentation with sublaminar wires. A critical appraisal.

Fifty-eight patients who had scoliosis or kyphosis of varying etiologies were followed for a minimum of two years (average, forty-four months) after segmental spinal instrumentation using sublaminar wires. In eight (19 per cent) of the patients who had been operated on for scoliosis one or both rods broke. The average time that had elapsed before the breakage was discovered was twenty-three months. None of the patients in whom a rod had broken had had postoperative immobilization or a first-stage anterior fusion, and only one had had supplementary grafting with banked bone. Instrumentation to the pelvis was also associated with a greater incidence of broken rods. The use of supplementary grafting with banked bone or the use of postoperative immobilization significantly decreased the loss of postoperative correction. Preliminary anterior spinal fusion helped prevent breakage of rods but not loss of correction. It was concluded that postoperative immobilization and use of large amounts of supplementary bone graft lead to better results when using this implant system.

Adolescent↗