Search PubMed⌕ Search

Biomedical subjects

J Fuller

Publications and source records attributed to J Fuller.

At least 91 records · Page 5Linked to original sources

Donor-specific cellular immunity in rejecting and long-term-surviving class I-disparate rat renal allograft recipients.

The effects of pre- and posttransplant immunization on graft survival, infiltrate intensity, and host in situ/systemic cellular immune responsiveness were examined for class I MHC-disparate rat renal allograft recipients. Naive, unsensitized PVG (RT1c) recipients of class I MHC disparate PVG.R1 (RT1.Aa on PVG background) orthotopic kidney transplants displayed long-term (greater than 50 days) survival (LTS) in a majority (41/52) of cases. Pretransplant immunization of recipients with a PVG.R1 skin graft most often resulted in rejection (mean survival greater than 21.3 days) with 8/15 rats surviving less than or equal to 2 weeks and only 3/15 with LTS. Pretransplant immunization with a skin graft from a fully MHC-disparate PVG.1A (RT1a on PVG background) donor resulted in acute rejection (mean = 6.1 days) with 0/8 rats surviving greater than or equal to 2 weeks. Donor-specific class I and II disparate (PVG.1A), and third-party (LEW) skin transplants applied on LTS (greater than 50 days) PVG.R1 kidney graft recipients showed typical 1st- and accelerated 2nd-set skin graft rejection, but had no effect on kidney graft survival. In contrast, 6/7 LTS PVG.R1 kidney graft recipients accepted PVG.R1 skin grafts indefinitely following their transient partial rejection. Histologic analysis of kidney allografts revealed the highest degree of mononuclear cell infiltrates in animals specifically sensitized by PVG.1A skin grafts prior to transplant. Donor class I-specific cytotoxic T lymphocyte precursor (pCTL) frequencies, as determined by limiting dilution assays, were increased and equivalent at 1 week posttransplant in kidney allograft cell eluates from nonrejecting naive recipients (1/127-1/2209) and rejecting presensitized animals (1/470-1/7848). LTS animals had decreased intragraft pCTL at greater than 50 days (1/2969-1/61875), as did LTS at greater than 50 days that received PVG.R1, PVG.1A, or LEW skin grafts posttransplant. In all groups, splenocyte pCTL frequencies were significantly lower than the corresponding values within the allograft. By comparison, no significant differences in intragraft or splenic proliferative T lymphocyte (pPTL) precursor frequencies were observed between any groups. These results indicate that unsensitized recipients of class I-disparate renal cells grafts are capable of maintaining graft survival in the early posttransplant period, despite the presence of significant in situ antidonor class I MHC-specific cellular immune responsiveness. These findings also indicate that long-surviving PVG recipients of class I-disparate renal allografts develop specific functional tolerance to donor class I alloantigens, that may be associated with a diminished frequency of anti-class I cytotoxic (but not proliferative) T cell precursors.

Animals↗

Home phototherapy.

Home phototherapy has both social and economic benefits: newborns diagnosed with neonatal bilirubin jaundice can leave the hospital with their mothers, and home treatment can realize a cost-savings of up to 50%. As pediatric home care expands, agencies may want to consider adding home phototherapy to their array of services.

Durable Medical Equipment↗

Use of wiring configuration and wiring codes for estimating externally generated electric and magnetic fields.

The relative locations and characteristics of the distribution lines feeding 434 residences in the Denver metropolitan area were recorded and classified according to the Wertheimer-Leeper code (WL code) as a part of an epidemiological study of the incidence of childhood cancer. The WL code was found to place the mean values of the fields in rank order. However, the standard deviations were approximately the same size as the means. Theoretical calculations indicate that a significant fraction of the low-power magnetic fields can be generated by the distribution lines, especially in the cases where the distribution lines are within 50 feet of the residence. Thus, the wiring code was shown to be a useful method for making a first-order approximation to predict long-term, low-level magnetic fields in residences.

Building Codes↗

A simple method for measurement of the haemoglobin binding capacity of canine haptoglobin.

The potential of a series of related compounds to induce haemolytic anaemia in dogs highlighted the need for a reliable and sensitive technique to identify changes in plasma haptoglobin concentration. An indirect method established for human samples was adapted for use with canine plasma. This method measures the haemoglobin binding capacity of plasma, which is directly proportional to the functional haptoglobin concentration. The efficacy of this technique was investigated on samples taken from Beagle dogs which had previously received small quantities of water intravenously. A substantial reduction in haemoglobin binding capacity was recorded before other haematological parameters were significantly affected. It was concluded that measurement of haemoglobin binding capacity by this method provides a valid reflection of haptoglobin status in the dog.

Animals↗

The preclinical toxicology of anisoylated plasminogen streptokinase activator complex.

The preclinical toxicological evaluation of anisoylated plasminogen streptokinase activator complex (APSAC) was designed with specific regard to the potential for immunogenic effects in animals arising from the high molecular weight of the complex. Animals were treated with multiples of the human dose by use of a dose regimen spanning that proposed clinically and in conventional repeat dose toxicity studies employing the maximum practicable dose level and duration. Few adverse effects were noted, despite the large doses administered with respect to the clinical dose. The thrombolytic activity of APSAC resulted in pronounced acute effects on blood coagulation times and fibrinogen levels in rats and dogs but there was little evidence of clinically relevant systemic toxicity in either species. Evidence of a possible effect on the liver was seen 24 hours after single doses much higher than the proposed human dose in the rat (40-fold higher) and dog (9-fold higher). No hepatic effects were apparent following repeated administration. The main adverse effect was focal acute myocarditis, which was seen only in rats of the Sprague Dawley strain. Administration of human plasminogen alone or in combination with streptokinase also produced this lesion, suggesting that plasminogen may play a central role in its appearance. Experiments in anaesthetised dogs showed APSAC to be devoid of undesirable haemodynamic effects. An intravenous acute toxicity study in rats with p-anisic acid, which is released on deacylation of APSAC, showed the levels of p-anisic acid which occur in humans to be of no toxicological significance. Finally, in a series of tests designed to investigate potential genetic toxicity, no mutagenic activity was detected.

Animals↗

Anesthetics change tissue proton NMR relaxation.

Previous studies have shown the treatment of experimental animals with therapeutic doses of pharmaceuticals in acute and chronic regimens has resulted in extensive (up to 33%) change in tissue proton NMR relaxation times. In this study, the effects of injectable anesthetics (Innovar, pentobarbital, ketamine and alpha-chloralose) were compared with inhalational anesthetics (halothane, enflurane and isoflurane). Proton NMR T1 and T2 relaxation times were obtained from excised tissues of anesthetized rats (6 each treatment). Sodium pentobarbital and alpha-chloralose showed no alterations, whereas Innovar produced increases in brain and kidney relaxation times and ketamine showed increases in the heart. More widespread and extensive changes were observed after 1.5 hours of inhalation anesthesia: liver, muscle and fat showed relaxation time decrease; heart, spleen and lung were increased. No change in water content, as measured by wet/dry ratios, was observed for any tissue. Therefore, intravenous anesthesia may be preferred to inhalational anesthesia for magnetic resonance imaging based on potential changes in tissue relaxation properties. In addition, the absence of a measurable effect on brain suggests that the mechanism for anesthesia does not involve major changes in brain water.

Anesthetics↗

Legionnaires' disease after heart transplantation.

The cases of 8 heart transplant recipients with legionnaires' disease are reviewed. The diagnosis in each patient was made by fluorescent antibody stains or direct culture of the sputum, transtracheal aspirate, or fine needle aspirate of the lung. All patients were successfully treated with erythromycin alone or in combination with rifampin. Radiographic and clinical variations of legionnaires' disease as seen in the immunocompromised host are presented.

Adolescent↗

Prostacyclin production in regions of arterial stenosis.

The effect of abnormal flow dynamics on prostacyclin (PGI2) production by intact endothelium is unknown. To investigate this we studied the effects of graded stenoses on vessel wall PGI2 production in dogs (n = 8) whose femoral and carotid arteries (n = 32) were narrowed by machine-milled clips, producing 1.0 cm segmental stenoses of 25%, 50%, 75%, and 90% diameter reduction. Three dogs were injected with Indium 111-labeled platelets and 12 vessels were scanned for platelet deposition. All stenotic vessels were excised at 6 weeks for histologic study (hematoxylin-eosin section and immunohistochemistry for factor VIII) and PGI2 radioimmunoassay (as the metabolite 6-keto PGF1 alpha). All vessels remained patent with no thrombus formation in any segment. Vessel imaging in platelet-labeled animals showed no significant deposition. Histologic analysis demonstrated an intact endothelial surface in the stenotic segments, confirmed by the demonstration of factor VIII production by these cells. PGI2 production (per unit surface area) by the arterial segments with greater than or equal to 50% stenosis markedly exceeded the PGI2 production by the normal proximal and distal segments (p less than 0.0002) and showed further significantly increased production with increasing degrees of stenosis (p less than 0.00001). The data indicate increased PGI2 production by normal endothelium in regions of arterial stenosis. The mechanism of this increase is unknown, but this endothelial "turn on" effect may serve to inhibit deposition of platelets and thrombus formation in the presence of disordered flow patterns.

Animals↗