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Biomedical subjects

J Pollard

Publications and source records attributed to J Pollard.

At least 19 recordsLinked to original sources
PubMed1998

Ex vivo gene therapy prevents chronic graft vascular disease in cardiac allografts.

OBJECTIVE: We hypothesized that ex vivo hyperbaric transfection of antisense oligodeoxynucleotides for blockade of intercellular adhesion molecule-1, an important mediator of cell adhesion and T-cell co-stimulation, would reduce chronic graft vascular disease in cardiac allografts. METHODS: PVG hearts underwent ex vivo transfection with antisense, reverse antisense intercellular adhesion molecule-1 oligodeoxynucleotide (80 micromol/L), or saline solution at 3 atm pressure for 45 minutes at 4 degrees C and were transplanted heterotopically into ACI recipients with or without treatment with intercellular adhesion molecule-1 (1A29) or leukocyte function associated antigen-1 (WT.1) monoclonal antibodies. Transfection efficiency was confirmed with fluorescein isothiocyanate-labeled oligodeoxynucleotides and fluorescent microscopy. Efficacy of intracellular adhesion molecule-1 blockade was assessed with the use of immunohistochemistry. Graft reperfusion injury was evaluated at 6 to 24 hours by neutrophil infiltration (myeloperoxidase [MPO]), cardiac edema (%wt/wt), and histologic injury (percent contraction band necrosis). Grafts from recipients treated with cyclosporine A (5 mg/kg per day, days 0 to 9) were scored for chronic graft vascular disease on postoperative day 90 ranging from 0 (no involvement) to 4 (>50% vascular occlusion). RESULTS: Transfection was highly efficient (fluorescein isothiocyanate-labeled oligodeoxynucleotides in 48%+/-5% of total myocardial nuclei) and effective at blocking intracellular adhesion molecule-1 expression (positive area in allografts taken on postoperative day 3 was reduced from 100%+/-0% to 52%+/-14%, n=4). Blockade with antisense oligodeoxynucleotides versus monoclonal antibodies was less effective at preventing reperfusion injury while more effective at reducing chronic graft vascular disease (score 0.98+/-0.48, p < 0.05). Reverse antisense oligodeoxynucleotides and vector control (antisense oligodeoxynucleotide infusion without pressure) groups failed to demonstrate this beneficial effect. CONCLUSION: Hyperbaric transfection of antisense oligodeoxynucleotides proved highly efficient, effective at blockade of intracellular adhesion molecule-1, and demonstrated a sequence-specific reduction in chronic graft vascular disease. This highly targeted alteration of donor organ immunogenicity may have an important future role in clinical immunosuppressive strategies.

Animals↗
PubMed1998

Microvascular and cellular responses in the optic nerve of rats with acute experimental allergic encephalomyelitis (EAE).

The optic nerve of rats with EAE was examined at various times to determine the integrity of the blood-brain barrier (BBB) and to assess monocyte-macrophage, T cell, and microglial responses. In naive control animals, leakage of horseradish peroxidase (HRP) and the presence of cells expressing major histocompatibility complex (MHC) class II antigen were evident in the meninges of the retrobulbar optic nerve. In rats with EAE, microglia in the region of the lamina cribrosa and in the regions adjacent to the meninges became activated from day 7 to 8 postinduction (pi). HRP leakage was also evident in the region of the lamina cribrosa from day 7 to 8 pi. On day 8 pi, infiltration of inflammatory cells and Monastral blue leakage were apparent in the myelinated region of the optic nerve. The intensity of these cellular and vascular changes peaked at day 12 pi, when signs of clinical disease became manifest. Monocytes-macrophages expressing MHC class II and the ED1 antigen, together with lymphocytes expressing the alphabetaT cell receptor, constituted the major proportion of cells associated with inflammatory lesions. Thus: (i) the inherent weakness of the BBB as well as the presence of both antigen (myelin) and MHC class II+ cells in the retrobulbar optic nerve are likely susceptibility factors for the frequent involvement of this region in EAE and multiple sclerosis; and (ii) activation of microglia occurs early in the pathogenesis of experimental optic neuritis.

Animals↗
PubMed1998

Microvascular and cellular responses in the retina of rats with acute experimental allergic encephalomyelitis (EAE).

The microvascular and cellular responses in the retina during acute EAE were characterized using whole-mount preparations. The earliest detectable event was the accumulation of monocytes and T cells within veins on day 7 postinduction (pi). Mild breakdown of the blood-retinal barrier (BRB), activation of microglia and infiltration of monocytes and T cells into the retinal parenchyma were first evident on days 7 to 8 pi. Monocyte adhesion to the vessel wall and breakdown of the BRB were colocalized in the same vessel segments and occurred predominantly in veins. The marked difference in response observed in the retina versus the myelinated region of the optic nerve suggests that two types of inflammatory cascades are initiated. A mild response, characterised by very low numbers of T cells and monocytes and an absence of expression of MHC class II by resident microglia, is initiated when only small amounts of the encephalitogenic antigen are present in the perivascular space or associated with perivascular antigen-presenting cells. A full blown inflammatory reaction, as observed in the optic nerve, is initiated in the presence of substantial amounts of encephalitogenic antigen. This severe response is characterised by the infiltration of large numbers of CD4+, CD8+ T cells and ED1+ monocytes, and by abundant MHC class II expression by resident microglia as well as other cell types. Thus, MHC class II expression by resident microglia may be a possible effective amplifier mechanism if the encephalitogenic antigen is encountered in the tissue parenchyma.

Animals↗
PubMed1997

Effects of increased ICAM-1 on reperfusion injury and chronic graft vascular disease.

BACKGROUND: The purpose of this study was to assess the impact of increased donor cardiac intercellular adhesion molecule (ICAM-1) expression on both reperfusion injury and chronic graft vascular disease after transplantation. METHODS: Hearts were harvested from donor rats before and after pretreatment with lipopolysaccharide at -24 hours, underwent 45 minutes of cold ischemia, and were transplanted into ACI recipients with or without anti-ICAM-1 monoclonal antibody treatment. Grafts were procured early for analysis of ICAM-1 expression and reperfusion injury or the recipients were treated with cyclosporin A (to allow long-term graft acceptance) for postoperative days 0 through 9 with procurement on postoperative day 90 to histologically score for chronic graft vascular disease. RESULTS: Lipopolysaccharide-pretreated PVG heart grafts showed increased ICAM-1 expression by Northern blot and immunohistochemical analysis leading to increased reperfusion injury as assessed by neutrophil infiltration (myeloperoxidase), cardiac edema (percentage wet weight), and histologic injury (percentage area of contraction band necrosis), which was reversed by recipient treatment with anti-ICAM-1 monoclonal antibody. After administration of cyclosporin A, 5 mg/kg for 10 days, lipopolysaccharide-treated grafts had significantly worse chronic graft vascular disease scores (2.56 +/- 0.57 versus 1.84 +/- 0.75; p < 0.05 by Mann-Whitney U test). CONCLUSIONS: The induction donor inflammatory state before harvest leading to increased cardiac ICAM-1 expression promotes reperfusion injury and chronic graft vascular disease after transplantation in this rodent heterotopic heart model.

Animals↗
PubMed1997

T-cell antigen receptor transmembrane peptides modulate T-cell function and T cell-mediated disease.

This study describes a novel method of inhibiting T-cell function by the use of peptides rationally designed from the T-cell antigen receptor (TCR) alpha-chain transmembrane sequence involved with TCR receptor assembly. The most effective peptide (core peptide, CP) modulating in vitro and in vivo T-cell function contained nine amino acids two of which, lysine and arginine, were hydrophilic and separated by four hydrophobic amino acids. CP without chemical modification or conjugation was able to enter non-T and T cells. Conjugation of CP at the carboxyl terminus with palmitic acid resulted in a greater inhibition of T-cell interleukin-2 (IL-2) production in vitro than peptide alone. When examined for effects in vivo, CP reduced clinical signs of inflammation in three T cell-mediated disease models including adjuvant-induced arthritis, experimental allergic neuritis, and cyclophosphamide-induced diabetes in NOD/Lt(F) mice. This peptide or its analogues has potential as a therapeutic agent in human inflammatory and autoimmune disorders.

Amino Acid Sequence↗
PubMed1996

Inflammatory infiltrates in sural nerve biopsies in Guillain-Barre syndrome and chronic inflammatory demyelinating neuropathy.

Prompted by observations in experimental autoimmune neuritis we reanalyzed immunohistochemically the inflammatory infiltrates in sural nerve biopsies of 22 cases with Guillain-Barre syndrome (GBS) and 13 cases with chronic inflammatory demyelinating polyneuropathy (CIDP). Endoneurial infiltration of CD3+ T cells was found in 20 cases of GBS (median 5.5 cells/mm(2)) and in 10 cases of CIDP (5 cells). Epineurial T cells were present in all GBS cases (19.5 cells) and in 11 CIDP cases (21 cells). CD68+ macrophages were abundant in these neuropathies and often occurred in endoneurial perivascular clusters. In GBS subgroups the number of endoneurial T cells was significantly higher in patients with hypoesthesia and abnormal electrophysiological findings in the sural nerve. In CIDP hypoesthesia was associated with significantly higher numbers of macrophages. Our study also indicates that other factors including the time point of biopsy or previous corticosteroid treatment may influence the inflammatory cell profile. Quantifying cell infiltration may aid in establishing the diagnosis of an immunoneuropathy in patients with mild and noncharacteristic pathology.

Adult↗
PubMed1995

Effects of an antiperspirant with emollients on foot-sweat accumulation and blister formation while walking in the heat.

BACKGROUND: Friction blisters are a common injury in sports activities and military operations. Blisters can compromise performance, so it is important to devise preventive strategies to reduce these injuries. OBJECTIVE: This study investigated the influence of an antiperspirant with emollient additives on frequency and severity of friction blisters, hot spots, and irritant dermatitis. METHODS: Twenty-three healthy men walked on a treadmill (1.39 m/sec, 1% grade) in a warm environment (28 degrees C, 25% relative humidity) carrying a total mass of 21 +/- 1 kg. For 4 consecutive days before the walk, the subjects' feet were treated with either (1) an antiperspirant (20% aluminum zirconium tetrachlorohydrex glycine concentration plus water) with emollient additives, (2) emollient additives alone (placebo control), or (3) nothing (nontreated). In two separate trials (1 month apart) each participant received the antiperspirant treatment and both control treatments (emollient [placebo] and no treatment). RESULTS: No differences were seen among treatment conditions for sweat accumulation (p = 0.86), blister incidence (p = 0.36), hot spot incidence (p = 0.83), or blister severity (p = 0.31). Irritant dermatitis was not reported in any of the treatment conditions. CONCLUSION: The use of an antiperspirant with emollients reduces irritant dermatitis but does not reduce total foot-sweat accumulation, blister or hot spot incidence, or blister severity.

Adult↗
PubMed1990

Synaptic analysis of amacrine cells in the turtle retina which contain tyrosine hydroxylase-like immunoreactivity.

This study examined amacrine cells in the retina of the turtle Pseudemys scripta elegans, which were labelled using an antiserum directed against tyrosine hydroxylase (an enzyme participating in catecholamine synthesis). These cells were investigated using both light and electron microscopy. Labelled somata were located in the inner nuclear layer near the border of the inner plexiform layer. The dendritic arborizations of these neurons were tristratified and arborized in strata 1 and 3 and near the border between strata 4 and 5. Serial tangential sections taken through the entire inner plexiform layer of a 1 mm-2 region in mid-peripheral retina were examined. All of the synapses associated with labelled profiles were counted and classified. The majority (84%) of the synapses involving labelled processes represented output, while the remaining 16% represented synaptic input. The synaptic output of the labelled processes was as follows: 87% onto unlabelled amacrine cells, 4% onto ganglion cells, 9% onto unidentified cell processes. None of the synaptic output from labelled processes was onto bipolar cells. The synaptic input to these labelled cells was from bipolar cells (29%) and from unlabelled amacrine cells (71%). A well labelled amacrine cell was serially sectioned and examined at the ultrastructural level to analyze its synaptic connectivity. Immunoreaction product was located diffusely throughout the cytoplasm and in large vesicles. The synaptic organization of the cell was directed primarily toward output. The labelled processes were postsynaptic and presynaptic to unlabelled amacrine cell processes in strata 1 and 3 and at the border between strata 4 and 5. Synaptic input from bipolar cells was seen exclusively near the border between strata 4 and 5. Labelled processes were presynaptic to ganglion cell processes in stratum 1 and at the border between strata 4 and 5, but not in stratum 3. Quantitative studies suggested that amacrine cell inputs and outputs were evenly distributed across the dendritic arborization, while bipolar cell inputs and outputs to ganglion cells were concentrated on the distal parts of the dendritic arborization. No labelled processes were seen in the outer plexiform layer, indicating that the cells with tyrosine hydroxylase-like immunoreactivity in the turtle retina were true amacrine cells and not interplexiform cells.

Animals↗
PubMed1990

Hereditary sensory neuropathy type II without trophic changes.

Three cases with sensory peripheral neuropathies are reported. Case 1 presented with scoliosis, and cases 2 and 3 presented with abnormal gait. None had trophic limb changes, evidence of weakness, or a tendency to self-mutilation and each had normal motor studies on neurophysiological testing. Sural nerve biopsies showed a severe loss of myelinated fibres and case 3 had evidence of denervation on muscle biopsy. These cases are presented as examples of hereditary sensory neuropathy type II. They are unusual in that they do not have trophic changes.

Adolescent↗
PubMed1988

Ventricular ectopic activity with diuretic therapy.

The arrhythmogenic potential of diuretic-induced hypokalemia in patients with uncomplicated hypertension has been controversial. Thirty-two hypertensive patients with previous diuretic-induced hypokalemia, normal 24-hour ambulatory ECG monitoring, and normal exercise testing were treated with 100 mg hydrochlorothiazide (HCTZ) daily (Group 1) to induce hypokalemia or with a combination of HCTZ with amiloride (Group 2) to attempt to maintain plasma potassium levels in the normal range during diuretic therapy. Those Group 1 patients (Group 1A) with increased ventricular ectopic activity (VEA) during HCTZ therapy were subsequently potassium-repleted with amiloride and with supplemental potassium chloride to evaluate the effect of these treatments on VEA. One Group 1 patient died suddenly after 12 days of HCTZ therapy. Autopsy findings suggested an arrhythmic death. Six Group 1 patients who had increased VEA with HCTZ treatment had reductions in VEA with amiloride or supplemental potassium chloride. Group 2 patients did not have a significant increase in VEA. Thus, diuretic therapy appears to cause VEA primarily by electrolyte changes that are induced.

Adult↗
PubMed1986

[Neurologic manifestations of ciguatera. 3 cases with a neurophysiologic study and examination of one nerve biopsy].

Ciguatera is the commonest form of poisoning resulting from eating fish in the tropics. It has been recognised since the 15th century. The disease is due to the formation of ciguatoxin by a dinoflagellate, Gambierdiscus toxicus, loosely attached to algae growing on coral reefs. The toxin, which is harmless to the fish, is ingested by small herbivorous fish and passes up the food chain as these are eaten by carnivores. The toxic effects include gastroenteritis, itching of the skin, peripheral neuropathy and central nervous system dysfunction. Though most cases are mild, occasionally the disease is severe and even fatal. There is no effective specific treatment. Three cases, of which one died and which exhibited both peripheral and central nervous system involvement, are described. Histological changes in sural nerve fibers are described. There was striking oedema of the adaxonal Schwann cell cytoplasm. These histological changes are very similar to those seen following the injection of scorpion and spider venoms into the peripheral nerve of experimental animals. Both these venoms and ciguatoxin increase the permeability of the membrane to sodium.

Adult↗
PubMed1985

Phytanic acid oxidase deficiency in childhood.

Tables 2 and 5 summarize the major clinical and biochemical findings in these patients. Cases 1 and 2 resemble clinically the previous cases of children reported as suffering from infantile phytanic acid storage disease, Zellweger's disease, or neonatal adrenoleucodystrophy. Cases 3 and 4 differ strikingly from these and from one another. Numerous questions remain unanswered, but it seems likely that these patients have in common defects in peroxisomal function which are related but not identical. Why some patients with phytanic acid oxidase deficiency do not have significant elevation of serum phytanic acid is not known. These results, however, make it clear that a normal serum phytanic acid level does not exclude phytanic acid oxidase deficiency. In children with a progressive neurological illness, with liver disease, retinal disease, unexplained neuropathy or deafness, detailed studies of fatty acid metabolism are indicated, including lipoproteins, serum phytanic acid, C26:C22 long-chain fatty acid ratios, serum pipecolic acid and phytanic acid oxidase levels. Electron microscopy of liver biopsy specimens should be considered. Phytanic acid oxidase may prove a useful marker for some of these illnesses, and its usefulness could extend to prenatal diagnosis and assist in genetic counselling.

Abnormalities, Multiple↗
PubMed1983

51Cr release cytotoxicity radioimmunoassay to detect immune cytotoxic reactions to rat Schwann cells in vitro.

Monolayers of rat Schwann cells incubated with 51Cr were used as targets for a cytotoxicity assay employing rabbit antiserum to galactocerebroside (R anti-GalC). Specific 51Cr release was demonstrated which was heat sensitive and complement-dependent. The assay was readily performed, reproducible and quantitative, and should prove useful in assessing anti-Schwann cell cytotoxic activity of experimental and human serum.

Animals↗
PubMed1979

Health effects of urban air pollution. Special consideration of areas at 1,500 m and above.

Urban air pollution, when sufficiently severe, can cause death in humans; these deaths occur preponderantly among those with increased susceptibility. Pollution--carbon monoxide and oxidants in particular--is capable of aggravating preexisting chronic heart and lung diseases. Pollution and tobacco (especially cigarette) smoke act synergistically in a causative role in chronic bronchitis and in an aggravating role in emphysema. Susceptibility to the effects of urban air pollution varies widely, with the most susceptible being fetuses, the newborn, the elderly, the infirm, those with chronic heart and lung diseases, and those who smoke. The carbon monoxide standards for sea level are probably too lenient for an altitude of 1,500 m and above. Using a broad definition of health, which takes into account concepts such as quality of life and social and mental well-being, few metropolitan residents would deny that their health is compromised by air that is malodorous, that irritates mucous membranes, and that obscures beautiful scenery.

Adult↗
PubMed1979

Hyperexcitability of motor and sensory neurons in neuromyotonia.

Two members of a family with a neuropathy resembling Charcot-Marie-Tooth disease were unable to relax their muscles after voluntary contraction. Muscle spasm often outlasted voluntary contraction by 30 seconds or more before subsiding into myokymia and fasciculations. The posture of the hand during muscle spasm resembled that of tetany, and Trousseau's and Chvostek's signs were present although no abnormality of calcium or magnesium metabolism could be demonstrated. Muscle spasms ceased during medication with carbamazepine, 600 mg daily. Nerve stimulation, electromyography, and regional neuromuscular blockade with curare indicated that the condition originated in peripheral nerve, while microneurographic recordings showed that sensory as well as motor fibers were hyperexcitable. Sural nerve biopsy revealed axonal degeneration involving myelinated and unmyelinated fibers. It was concluded that the neural hyperexcitability is caused by a membrane defect resulting in a low threshold for excitation throughout the length of the axon.

Adult↗