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Biomedical subjects

J Egan

Publications and source records attributed to J Egan.

At least 55 records · Page 3Linked to original sources
PubMed1996

An agent cleaving glucose-derived protein crosslinks in vitro and in vivo.

Glucose and other reducing sugars react with proteins by a nonenzymatic, post-translational modification process called nonenzymatic glycosylation or glycation. The sugar-derived carbonyl group adds to a free amine, forming a reversible adduct which over time rearranges to produce a class of products termed advanced-glycation end-products (AGEs). These remain irreversibly bound to macromolecules and can covalently crosslink proximate amino groups. The formation of AGEs on long-lived connective tissue and matrix components accounts largely for the increase in collagen crosslinking that accompanies normal ageing and which occurs at an accelerated rate in diabetes. AGEs can activate cellular receptors and initiate a variety of pathophysiological responses. They modify an appreciable fraction of circulating low-density lipoproteins preventing uptake of these particles by their high-affinity tissue receptors. Advanced glycation has also been implicated in the pathology of Alzheimer's disease. Because AGEs may form by a pathway involving reactive alpha-dicarbonyl intermediates, we investigated a potential pharmacological strategy for selectively cleaving the resultant glucose-derived protein crosslinks. We now describe a prototypic AGE crosslink 'breaker', N-phenacylthiazolium bromide (PTB), which reacts with and cleaves covalent, AGE-derived protein crosslinks. The ability of PTB to break AGE crosslinks in vivo points to the importance of an alpha-dicarbonyl intermediate in the advanced glycation pathway and offers a potential therapeutic approach for the removal of established AGE crosslinks.

Amyloid beta-Peptides↗
PubMed1996

Duration of protection from clinical hepatitis A disease after vaccination with VAQTA.

Recent papers examining the expected persistence of anti-hepatitis A virus antibody following vaccination with inactivated hepatitis A vaccine have estimated that geometric mean antibody levels will remain above cut-off levels for 10-30 years. However, the methodology used in these papers did not take into account any estimates of variability between subjects. In this paper data from the persistence of antibody after the administration of another vaccine, VAQTA (hepatitis A vaccine, inactivated; MSD), were used to develop further models of antibody decay. Using individual subject estimates instead of group means allowed the estimation of time to negativity for various percentiles of the population (including the median), and the construction of confidence intervals on estimates of time to negativity. Data from studies of subjects who seroreverted to negativity, and subsequently received a booster dose, were also considered to show that subjects who lose detectable antibody are likely to remain protected from hepatitis A disease by persistent immune memory and rapid anamnestic response soon after exposure to hepatitis A virus. The estimates of duration of protection suggest that VAQTA will provide protection for many years, first through presence of antibody and further through an anamnestic response based on persistent immune memory.

Hepatitis A↗
PubMed1996

Pancreatic thread protein is mitogenic to pancreatic-derived cells in culture.

BACKGROUND & AIMS: Pancreatic thread proteins (PTPs) are acinar cell products and members of the regenerating gene (reg) family. reg expression increases during islet regeneration, is depressed during aging-related islet dysfunction, and may be important in beta-cell growth and maintenance. The aim of this study was to examine the genetic expression of reg in pancreatic-derived cells in vitro and the mitogenic effect of PTP/reg protein on these cells. METHODS: reg gene expression was measured by Northern analysis in three rat pancreatic cell lines: ARIP (ductal), AR42J (acinar), and RIN (beta-cell). PTP/reg protein was isolated from bovine and human pancreas. Cells were cultured with PTP/reg for 72 hours, and thymidine incorporation was measured. RESULTS: reg messenger RNA was detected in AR42J but not in ARIP or RIN. PTP/reg protein was mitogenic to RIN and ARIP in a dose-related fashion but not to AR42J. It was not mitogenic to cultured mature rat islets. CONCLUSIONS: reg messenger RNA is expressed in acinar but not in beta-cell or ductal pancreatic cell lines. PTP/reg protein was mitogenic to both beta-cell and ductal cell lines but not to mature, nondividing islets. This supports the hypothesis that PTP/reg protein is an acinar cell-derived mediator of beta-cell growth and may be involved in modulating the duct-to-islet axis.

Animals↗
PubMed1995

Right lower lobe herniation after domino heart-lung transplantation.

We report 2 cases of trapping and incarceration of the right lower lobe in the left hemithorax after heart-lung transplantation with bicaval anastamoses (domino donors). This occurred despite confirmation of the normal anatomy at the time of implantation, before lung inflation. In 1 case this complication resulted in a right lower lobectomy 7 days after transplantation due to infarction and infection of the right lower lobe. These cases illustrate the importance of reexamining the anatomy after lung inflation, before chest closure.

Adult↗
PubMed1995

Randomized, prospective study of cyanoacrylate injection, sclerotherapy, or rubber band ligation for endoscopic hemostasis of bleeding canine gastric varices.

The purpose of this randomized, nonblinded study was to compare the effectiveness, safety, and technical ease of three different endoscopic techniques for the treatment of bleeding gastric varices in a canine model. Twenty dogs with large, bleeding gastric varices underwent endoscopic hemostasis with rubber band ligation, sclerotherapy, and cyanoacrylate injection. The time and number of attempts required to achieve definitive hemostasis were evaluated for each technique, and each method was assessed for ease of use. Ulceration rates, ulcer size and depth, and stigmata of ulcer hemorrhage were assessed at 1 week. Intravariceal sclerotherapy was the fastest and easiest to perform. Rubber band ligation was intermediate in technical ease, but it caused the largest and deepest ulcers and had the highest rates of stigmata of ulcer hemorrhage and secondary bleeding. Cyanoacrylate injection was the most cumbersome endoscopic method to perform. All three treatments were effective for controlling gastric variceal bleeding. Intravariceal sclerotherapy had the most favorable results overall because of its technical ease, efficacy, and modest complication rates.

Animals↗
PubMed1995

A comparison of conventional culture and three rapid methods for the detection of Salmonella in poultry feeds and environmental samples.

Three rapid methods, an impedance method (Malthus 2000 Analyzer), a colorimetric DNA hybridization method (Gene-Trak) and a post-enrichment enzyme-linked immunosorbent assay (Salmonella-Tek) were compared with conventional culture for the detection of Salmonella in poultry feeds, and in fluff and dust samples from poultry housing. The percentage positive samples for Salmonella by each of the methods were 25.5% for conventional culture, 38.4% for the Malthus, 28.9% for the Gene-Trak and 28.5% for the Salmonella-Tek. By any method 60/153 (39.2%) of the samples tested were positive on confirmed culture.

Animal Feed↗
PubMed1994

Benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo (BPPV) is a peripheral vestibular disorder affecting the posterior semicircular canal. It is most often idiopathic in nature, though it has been known to occur in patients following head injury, Meniere's disease, acoustic neuroma and viral neuronitis. Two basic theories of the pathology of BPPV include cupulolithiasis and canalithiasis. Diagnosis is made by instituting the Hallpike-Dix maneuver to elicit the positional vertigo and nystagmus. While many patients suffer from BPPV on a limited basis, treatment options are available for those individuals with recurrent episodes and permanent BPPV, including surgery and conservative medical exercises and maneuvers. Nursing care is aimed toward teaching the exercises and maneuvers and assisting the patient to adjust the individual lifestyle movements that may precipitate an attack.

Diagnosis, Differential↗
PubMed1994

Acridine orange diagnosis of Plasmodium falciparum: evaluation after experimental infection.

The value and role of the acridine orange/microhematocrit tube method (quantitative buffy coat [QBC] analysis) in the diagnosis of malaria remains controversial. To establish the true sensitivity of this test in comparison with the thick blood film, we studied 49 subjects who were experimentally infected with Plasmodium falciparum in 10 malaria vaccine and infectivity trials. Diagnosis was made by the acridine orange staining method 1-3 days earlier than by the thick blood film in 23 subjects (47%) and at the same time as the thick blood film in 20. On the other hand, diagnosis was made by thick blood film earlier than by the acridine orange staining method in six individuals. There were no false positive results using acridine orange among 584 specimens studied. Diagnosis was made using acridine orange at a parasitemia of less than 11 parasites/microliters of blood in 65% of cases. Where available, the acridine orange assay is clearly preferable in terms of speed and accuracy to the thick blood film for diagnosis with parasitemias of less than 150/microliters of blood, and perhaps as important, for ruling out infection with P. falciparum in a symptomatic patient.

Acridine Orange↗
PubMed1993

Altered growth hormone (GH) secretion in vivo and in vitro in the diabetes-prone BB/Worcester rat.

Diminished concentrations of growth hormone (GH) have been observed in the male BB/Wor rat with diabetes mellitus (DM). The precise mechanism(s) responsible for the altered GH levels is not entirely understood. We have therefore employed independent techniques to investigate potential alterations in: 1) the peripheral metabolism of the hormone; 2) GH release by somatotropes; and 3) hypothalamic regulation of GH secretion. An extra group of insulin-untreated animals was included for the studies of acute DM. The results demonstrate diminished circulating mean concentrations of GH (35 +/- 4 vs. 16 +/- 4 micrograms/l; mean +/- SEM; control vs. animal with DM; P = 0.006) due to impaired GH secretion. In particular, there was a decrease in the mass of GH secreted per burst (230 +/- 22 vs. 136 +/- 34 micrograms/l; P = 0.04) and in the GH secretory rate (24 +/- 4 vs. 9 +/- 3 micrograms/l/min; P < 0.01). No differences in the secretory burst frequency, (5.3 +/- 0.3 vs. 5.2 +/- 0.5 #/8-h; P = 0.68), secretory half-duration (10 +/- 2 vs. 17 +/- 2 min; P = 0.09), or serum GH half-life (8 +/- 1 vs. 6 +/- 1 min; P = 0.13) were observed. In vitro studies of acutely dispersed somatotropes obtained from rats with DM demonstrated increased sensitivity to GHRH (1 nM), as detected by a greater mean hemolytic plaque area following exposure to an EC50 dose of the secretagogue (14.3 +/- 3.3 vs. 17.4 +/- 3.5 microns 2 x 10(3); P = 0.049), and diminished sensitivity to SRIH (1 nM) inhibition of GH release following exposure to an EC50 dose of the secretagogue (10.0 +/- 1.2 vs. 14.9 +/- 2.3 microns2 x 10(3); P = 0.026). The number of the pituitary cells (18.0 +/- 2.8 vs. 15.3 +/- 1.0 x 10(5) cells; P = 0.38) as well as the number of somatotropes (7.3 +/- 1.4 vs. 7.6 +/- 0.9 x 10(5) cells; P = 0.87) were indistinguishable between experimental groups. Hypothalamic gene transcript levels for GH-releasing hormone (GHRH) and somatotropin release-inhibiting hormone (SRIH) were evaluated by in situ hybridization histochemistry to assess cellular synthetic activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1992

The effects of selective matrix degradation on the short-term compressive properties of adult human articular cartilage.

The effects of proteoglycan and collagen digestion on the transient response of human articular cartilage when tested in unconfined compression were determined. Small cylindrical specimens of cartilage, isolated from the femoral head of the hip joint and from the femoral condyles of the knee joint, were subjected to a suddenly applied compressive load using a test apparatus designed to yield a transient oscillatory response. From this response values of the elastic stiffness and the viscous damping coefficient were determined. Cathepsin D and cathepsin B1 were used to digest the proteoglycan in some specimens, while in other specimens leukocyte elastase was used to attack the non-helical terminal regions of the Type II tropocollagen molecules and possibly the Type IX collagen molecule and thereby disturb the integrity of the collagen mesh. The results showed that proteoglycan digestion alone reduced the viscous damping coefficient but it did not significantly alter the elastic stiffness as determined from the oscillatory response. In contrast, the action of elastase reduced both the damping coefficient and the elastic stiffness of the cartilage. The results demonstrated the role of proteoglycans in regulating fluid transport in cartilage and hence controlling the time-dependent viscous properties. The elastic stiffness was shown to be dependent on the integrity of the collagen fibre network and not on the proteoglycans.

Aged↗
PubMed1991

Bone weakness after the removal of plates and screws. Cortical atrophy or screw holes?

Bone weakness leading to refracture is a recognised complication of the removal of rigid fixation plates. We have used partially demineralised rabbit tibiae to simulate atrophic changes and to determine whether weakness is due to atrophy or to residual screw holes. Partial demineralisation and a screw hole each reduced maximum bending moment. However, energy absorbing capacity was little affected by demineralisation, but was reduced to 50% by a single drill hole. Residual screw holes are a considerably more important cause of bone weakness after plate removal than is cortical atrophy.

Animals↗