Covenants of work and grace: themes of recovery and redemption in polio narratives.
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Adult↗
Biomedical subjects
D J Wilson
Publications and source records attributed to D J Wilson.
Resolution of posttransplant hypertension after liver transplantation despite impaired glomerular filtration.
Hypertension developing after transplantation is characterized by widespread vasoconstriction including the kidney. Late resolution (mean, 29 +/- 4 months) of posttransplant hypertension has been observed in 15 (Group I) of 278 subjects monitored after liver transplantation. These studies were undertaken to define the systemic and renal changes associated with resolution, as compared with a group matched for age, sex, and time after transplant who remained hypertensive (Group II; N = 15) or a group who never developed hypertension (Group III; N = 23). Blood pressure during resolution paralleled changes in the systemic resistance index, which fell from 3,052 +/- 548 to 1,872 +/- 205 dyne/s.cm5/m2 (P < 0.01). GFR and RBF remained low, despite the resolution of hypertension, and renal vascular resistance did not change. Circulating endothelin levels remained above normal in all transplant recipients (Group I, 11.9 +/- 3.0 versus normal subjects, 7.0 +/- 1.1 pg/mL; P < 0.05), and urinary prostacyclin excretion was suppressed (880 +/- 120 versus 2,247 +/- 187 ng/day; P < 0.01). No hormonal differences were apparent between transplant groups. These results demonstrate the capacity for systemic vasodilation to occur after transplantation, independent of vascular tone in the kidney. They further suggest that renal vasoconstriction and impaired GFR alone are not sufficient to explain de novo hypertension after transplantation.
Adult↗
MRI and clinical study of an easy and safe technique of suprascapular nerve blockade.
Suprascapular nerve block is used with increasing frequency by anaesthetists and rheumatologists in the management of shoulder pain from a variety of disorders. In the classical technique, the needle is introduced into the supraspinous fossa perpendicular to the blade of the scapula and then is moved to enter the scapular notch, with the risk of pneumothorax or damage to the suprascapular nerve or vessels. However, it is not necessary to locate the scapular notch in order to perform this block. Introducing the needle parallel to the blade, i.e. away from the direction of the lung and the suprascapular nerve and vessels, and injecting the solution into the floor of the supraspinous fossa is an easy and safe technique. We report the results of a MRI and clinical study that confirm the efficacy of this approach.
Adult↗
Immunolocalization of integrins in the human retina.
PURPOSE: Integrins are cell surface proteins that participate in interactions between cells and with extracellular matrix. Binding of integrins to their ligands influences cell activities including proliferation, migration, and differentiation. Expression of integrin subunits from three different subfamilies were examined in human retina. METHODS: Integrins were detected in frozen sections of two human retinas with an avidin-biotin-complex immunohistochemical technique, using nine different monoclonal antibodies specific for alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, alpha v, beta 1, beta 2, and beta 3. One retina was from a patient who had conjunctival squamous cell carcinoma, and the other was from uninvolved regions of an eye with a choroidal melanoma. RESULTS: All integrins tested were detectable in consistent patterns in two retinas. All except alpha 2 and alpha 4 were stained vibrantly in retinal and choroidal vessels. All alpha subunit staining of vessels showed overlap or close proximity to beta 1 staining. In addition to vessels, beta 1 was also present in the internal limiting membrane; alpha 2, alpha 3, alpha 4, alpha 5, and beta 2 were all found throughout much of the neural retina, albeit with distinctive staining patterns. Other than in association with vessels, alpha 6 and alpha v were not detected in neural retina, and beta 3 was only weakly detected in the nerve fiber layer; alpha 4 and beta 2 were expressed in the retinal pigment epithelium; beta 1 and beta 2 were strongly expressed in drusen present in one of the eyes. CONCLUSION: Nine integrin subunits have been found to have unique distributions in adult human retina. An understanding of the distribution in normal retina can serve as a useful contrast to patterns of staining associated with retinal diseases.
Antibodies, Monoclonal↗
Immunolocalization of integrins in proliferative retinal membranes.
PURPOSE: Integrins are cell surface adhesion molecules that serve as receptors for extracellular matrix components or for other cells. Integrins help regulate processes such as cell proliferation, migration, and differentiation. These processes are thought to have fundamental roles in the pathogenesis of proliferative retinal membranes in diseases such as proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Therefore, the authors sought to determine the expression pattern of integrins in human proliferative membranes. METHODS: Tissue was obtained from two patients with PVR, two with PDR, and one subretinal neovascular membrane from a patient with presumed ocular histoplasmosis. Integrins were detected with an avidin-biotin-complex immunohistochemical technique using nine different monoclonal antibodies specific for alpha subunits 2, 3, 4, 5, 6, and V, and beta subunits 1, 2, and 3. RESULTS: All integrin subunits studied were detectable to varying degrees in proliferative membranes. beta 1 and alpha 6 were especially prominent at the edges of most PVR and PDR membranes. Pigmented cells expressed up to nine different integrin subunits, in contrast to normal RPE cells, which immunostained for only alpha 4 and beta 2. Proliferative diabetic retinopathy vessels expressed all nine integrin subunits examined, including alpha 4, which was poorly expressed in vessels of nondiabetic retinas. CONCLUSIONS: Integrin subunits are readily detectable in pathologic membranes. Both PVR and PDR are associated with altered integrin expression in vascular endothelium and pigmented cells. The distribution of integrins at the edge of a membrane suggests a role in the growth or contraction of the membrane, presumably by participating in the interaction between cells and substances such as vitreous collagen. Therefore, integrin antagonists may hold promise for the treatment of proliferative retinopathies.
Adult↗
Superficial temporal-artery aneurysm.
We report finding at surgery a histopathologically-confirmed superficial temporal-artery aneurysm. To our knowledge, this is the first report of this type of aneurysm in the ophthalmic literature. The ophthalmologist must include this condition in the differential diagnosis of a pulsatile and tender temporal artery, especially when a history of trauma is present.
Aneurysm↗
Platelet-derived growth factor ligands and receptors immunolocalized in proliferative retinal diseases.
PURPOSE: Platelet-derived growth factor (PDGF) and its receptors could contribute to the development of proliferative retinal membranes, because PDGF is angiogenic and is both mitogenic and chemotactic for retinal pigment epithelial (RPE) and glial cells, components of membranes. The authors sought to determine whether PDGF ligands and their receptors were present in proliferative retinal membranes. METHODS: To localize PDGF ligands and receptors, the authors examined normal postmortem control retinas, intact eyes with proliferative vitreoretinopathy (PVR) or proliferative diabetic retinopathy (PDR), and membranes removed by vitrectomy from patients with PVR, epimacular proliferation, PDR, or PVR with PDR of previous onset. Sections were stained with antibodies specific for each PDGF ligand and receptor, using an avidin-biotin-complex immunohistochemical technique. To correlate PDGF receptor beta (PDGFR beta) and ligand immunostaining, sections were doubled labelled with antibodies specific for either PDGF-A or PDGF-B. RESULTS: Ligands. In the normal retina and choroid, staining for the A-chain was limited to vascular cells. Only the nerve fiber layer and vessels were positive for the B-chain. In diseased tissue, PDGF-A immunoreactivity was detected as intense staining ( ) of all but one of the proliferative retinal membranes; some RPE cells were positive for PDGF-A, especially in the eye with PDR. PDGF-B was also present in many proliferative retinal membranes but not in RPE cells. Receptors. In the normal retina and choroid, both PDGFR alpha and PDGFR beta were detected only in vessels. In proliferative retinal membranes, both receptors were detected in vessels. Long strands of RPE-like cells at the edges of PVR membranes were strongly positive for PDGFR beta but negative or +/-, respectively, for PDGFR alpha. Double-label assays showed that PDGFR beta was often colocalized with each PDGF ligand, especially in pigmented cells. CONCLUSIONS: PDGF ligands and receptors are widespread in proliferative retinal membranes of different origin. Because PDGFR beta and PDGF-B were colocalized in many of the same cells, the potential for autocrine and paracrine stimulation of cell migration and growth exists. These results are consistent with a role for PDGF ligands and receptors in the pathogenesis of different proliferative retinopathies.
Adolescent↗
Evaluation of whole blood flow cytometric detection of platelet bound fibrinogen on normal subjects and patients with activated platelets.
Activated platelets can be detected by measuring platelet-bound fibrinogen in a whole blood, flow cytometric assay, using a fluorescently-conjugated polyclonal antibody. Fibrinogen binding to unstimulated platelets from normal subjects was low in this assay, as was expression of the CD63 antigen. Single cell counting of samples prepared for flow cytometric analysis showed platelet aggregates do not form during the assay procedure. Immune complexes were not seen, and fibrinogen binding to the platelets was unaffected by the CD32 MAb, IV.3. Artefactual activation of the unfixed samples could be minimised by control of phlebotomy, time and temperature of incubation. Variations in platelet count in the range 140-430 x 10(9) 1(-1) and in plasma fibrinogen in the range 2-6 g 1(-1) did not affect the assay results. Comparison of fibrinogen binding with expression of CD63 antigen on normal platelets, stimulated with agonists in vitro, demonstrated that fibrinogen binding detects an earlier stage of platelet activation. Platelet bound fibrinogen was shown to be sensitive in detecting small numbers of activated platelets in clinical samples in twelve patients on intensive care, four undergoing haemofiltration. The patients had a significantly higher median percentage of circulating platelets with bound fibrinogen (p < 0.005), but fibrinogen binding was significantly lower (p < 0.02) in response to 10(-5) M ADP, compared to twelve age-matched normal controls.
Adult↗
A clinicopathologic correlative study of noncontact transscleral Nd:YAG cyclophotocoagulation.
We studied the histopathologic changes of three eyes enucleated two weeks, eight weeks, and 17 months, respectively, after noncontact Nd:YAG cyclophotocoagulation. The histologic findings at two weeks were destruction of the nonpigmented and pigmented ciliary body epithelium, occlusion of the capillaries of the ciliary processes, and ciliary body stromal necrosis in the region of the processes. Hyperplasia of the pigmented and nonpigmented epithelium, fibrosis and near total atrophy of the ciliary processes, and partial atrophy of the ciliary muscles were present at eight weeks and 17 months. We concluded that application of treatment 1.0 to 1.5 mm posterior to the corneoscleral limbus selectively destroys the pars plicata, and that, histologically, the mechanism for reducing intraocular pressure appears to be destruction of ciliary processes with reduction of aqueous formation.
Aged↗
Flow cytometric detection of the redistribution of the glycoprotein Ib-IX complex on thrombin-stimulated platelets is dependent on the type of antibody conjugate used.
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Antibodies, Monoclonal↗
A low-affinity human granulocyte-macrophage colony-stimulating factor/murine erythropoietin hybrid receptor functions in murine cell lines.
To identify domains in hematopoietic growth factor receptors that are important for signal transduction, a hybrid receptor (GMER) was constructed by splicing the DNA of the entire extracellular and transmembrane domains of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha 2 subunit (GMR) to the cytoplasmic domain of the murine erythropoietin receptor (mEpoR). The hybrid receptor was introduced into the interleukin-3 factor-dependent murine hematopoietic cell line Ba/F3. Cells that expressed high receptor numbers were selected by cell sorting using phycoerythrin-labeled human GM-CSF. Immunoprecipitation of GMER from Ba/F3 cells showed a band with an Mr of 105,000 daltons. Human GM-CSF binding to Ba/F3 cells that expressed GMER showed a kd of 3.0 nmol/L and 475 binding sites/cell, while the same cells that expressed GMR had 300 sites/cell and a kd of 3.5 nmol/L. The proliferative response to GM-CSF of Ba/F3 cells that expressed GMER showed 1/2 maximal cell growth (as measured by 3H-thymidine incorporation) at a GM-CSF concentration of 2.5 x 10(-8) mol/L. When cultured in human GM-CSF, Ba/F3-GMER cells expressed cell surface glycophorin. Similar results were obtained with Ba/F3 cells transfected with the mEpoR and cultured in erythropoietin. Expression of GMR plus the human GM-CSF receptor beta chain in the same cell line also resulted in human GM-CSF stimulated proliferation; however, cell surface glycophorin was not detected. These data show that a low-affinity GM-CSF/Epo hybrid receptor can promote GM-CSF-dependent proliferation and can induce the expression of glycophorin, an erythroid-specific protein.
Animals↗
Budd-Chiari syndrome due to hepatic venous web: rapid color Doppler diagnosis.
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Adult↗
Antero-posterior skeletal patterning is not dependent on continuity of the apical ectodermal ridge in the chick wing bud.
The mechanism of antero-posterior specification of limb skeletal pattern is still controversial. If, as proposed by the ZPA model, a diffusible morphogen does exist, its route of passage across the limb field has not been resolved. To investigate the contribution of the apical ectodermal ridge (AER) to the control of antero-posterior pattern formation, we examined the consequences of small wounds made to the AER. The wound response was investigated by means of resin histology and scanning electron microscopy; subsequent limb development and cartilage pattern were examined in whole-mount preparations. Although regrowth of the bilaminate dorsal and ventral ectoderm over the wound occurred within 15 h, the more highly differentiated pseudostratified columnar epithelium of the AER did not reform, and there was subsequent retardation of limb outgrowth at the wound site. At 10-11 days of development, the appearance of the limbs allowed them to be placed into one of three categories; presence of supernumerary elements, accentuation of an inter-digital cleft, or normal. The first of these categories included limbs in which digit 3 had bifurcated such that the sum of the parts of the resultant digital skeleton was greater than that which forms in a normal limb. Since in all of the experimental limbs all skeletal elements were present, we propose that continuity of the AER is not a pre-requisite for antero-posterior skeletal pattern formation in the chick wing.
Animals↗
Coagulation effects of cyclosporine in liver transplantation.
Thromboembolic complications have been described in graft recipients receiving cyclosporine (CS). Whether these individuals have a hypercoagulable state when compared to healthy controls was evaluated. Recalcification times (RT) of saline-incubated citrated whole blood and endotoxin-incubated whole blood of both control and transplant patients were determined. There was no difference between the RT saline or RT endotoxin groups in both patient groups. These data suggest that CS alone has no procoagulant effects, but that additional factors such as endotoxin and/or graft-induced antigen production may provoke the thrombotic complications.
Blood Coagulation↗
Prothrombotic effects of endothelin-2 (ET-2).
In this report we demonstrate that ET-2, in addition to its powerful vasoconstrictor properties and its role in hypertension, is capable of creating a hypercoagulable (prothrombotic) state. This study was facilitated by the utilization of a sensitive modified recalcification time (MRT) test that can measure coagulation at all points in the coagulation spectrum. The MRT was determined on aliquots (1 ml) of citrated blood which were added to saline (MRTS), to 10 micrograms of endotoxin (MRTE), and to 10 pg of ET-2 (MRT ET-2). The mean values of MRTS, MRTE, and MRT ET-2 were 4.3 +/- 0.8, 3.7 +/- 1.0, and 3.9 +/- 0.8 min, respectively. There was a statistically significant difference between MRTE vs. MRTS and MRT ET-2 vs. MRTS using the two-tailed t-test (p < 0.02 and p < 0.005, respectively).
Blood Coagulation↗
Procoagulant property of platelet activating factor (PAF).
Platelet-activating factor (PAF) is known to activate platelets and thus promote clot formation in most mammalian species including humans. In this communication, the ability of PAF to hasten the overall coagulation process by measuring the recalcification time (RT) is described. Assessment of the RT in vitro indicated that the RT was significantly reduced by PAF (p < 0.001). This information adds a new dimension to the role of PAF in coagulation and also provides an exciting lead to the development of drugs for controlling the state of accelerated coagulation by pharmacologic means.
Blood Coagulation↗
Effect of ethylene oxide sterilization on human demineralized bone.
Demineralized human bone used as an autologous bone graft substitute is ethylene oxide sterilized, which is reported to reduce the bone's osteoinductive potential. To determine the minimum sterilization time required and the effect of ethylene oxide on bone's osteoinductive capacity and chemical structure, samples were exposed to ethylene oxide for different times (5-240 min). Results showed that 1 h exposure sterilized the bone (assessed by Attests). This exposure time reduced the bone's osteoinductive potential and caused surface ultrastructural changes. These findings raise questions concerning the suitability of ethylene oxide for sterilizing demineralized human bone.
Animals↗
Procedures for mastitis diagnosis and control.
Procedures for mastitis diagnosis and control include culturing individual cow and bulk tank milk samples, antibiotic susceptibility testing, and evaluation of somatic cell count reports and clinical mastitis treatment records. Integrated use of such procedures is necessary for effective mastitis diagnosis and control.
Animals↗