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Biomedical subjects

A Chester

Publications and source records attributed to A Chester.

At least 19 recordsLinked to original sources
PubMed2000

RNA editing: cytidine to uridine conversion in apolipoprotein B mRNA.

RNA editing is a post-transcriptional process that changes the informational capacity within the RNA. These processes include alterations made by nucleotide deletion, insertion and base conversion. A to I and C to U conversion occurs in mammals and these editing events are catalysed by RNA binding deaminases. C to U editing of apoB mRNA was the first mammalian editing event to be identified. The minimal protein complex necessary for apoB mRNA editing has been determined and consists of APOBEC-1 and ACF. Overexpression of APOBEC-1 in transgenic animals caused liver dysplasia and APOBEC-1 has been identified in neurofibromatosis type 1 tumours, suggesting that RNA editing may be another mechanism for tumourigenesis. Several APOBEC-1-like proteins have been identified, including a family of APOBEC-1-related proteins with unknown function on chromosome 22. This review summarises the different types of RNA editing and discusses the current status of C to U apoB mRNA editing. This knowledge is very important in understanding the structure and function of these related proteins and their role in biology.

APOBEC-1 Deaminase↗
PubMed1998

Differential distribution of angiotensin AT2 receptors in the normal and failing human heart.

Cardiac expression of angiotensin II (Ang II) AT1 and AT2 receptor subtypes is species dependent, and changes in their relative proportion may influence myocardial hypertrophy and fibrosis. Regional differences in the distribution of Ang II receptors in the normal and failing human heart were assessed using 125I-(Sar1,Ile8)Ang II binding and quantitative autoradiography. Receptor subtypes were distinguished by their affinity for selective nonpeptide antagonists (losartan and PD123319) and sensitivity to dithiothreitol. Ventricular and atrial tissues displayed a heterogeneous distribution of ligand binding sites. AT2 receptors predominated, representing 70% to 77% of the sites in normal and noninfarcted myocardium. Endocardial, interstitial, perivascular and infarcted regions in the ventricles of patients with end-stage ischemic heart disease or dilated cardiomyopathy exhibited a significantly greater density (P < .001) of high affinity AT2 binding sites (Kd = 0.57 nmol/liter) compared with adjacent noninfarcted myocardium. Regions displaying the relative increase in AT2 binding sites corresponded to areas of fibroblast proliferation and collagen deposition, shown by picrosirius red staining. AT1 binding sites were localized to nerves, occurred at relatively low density in coronary vessels and represented only 23% to 29% of myocardial 125I-(Sar1,Ile8)Ang II binding sites. The border zone between infarcted and noninfarcted myocardium characteristically contained numerous microvessels, exhibiting perivascular AT2 receptors and endothelial angiotensin converting enzyme activity, as demonstrated by binding of 125I-351A. Specific myocardial AT2 receptor mRNA transcripts (approximately 3 kb) were identified and exhibited alternative splicing of untranslated 5' exons. The differential distribution of cardiac Ang II receptor subtypes and selective increase in binding to AT2 sites in the diseased heart suggest that cells bearing the AT2 receptor represent a significant target for Ang II, possibly contributing to its growth-related actions.

Adolescent↗
PubMed1997

The use of a highly informative CA repeat polymorphism within the abetalipoproteinaemia locus (4q22-24).

Abetalipoproteinaemia is a rare autosomal-recessive disorder caused by a defect in the large subunit of the microsomal triglyceride transfer protein (MTP) which is required for the assembly and secretion of apolipoprotein B-containing lipoproteins. We report here the use of a polymorphic CA dinucleotide repeat in intron 10, MTPIVS10, of the large subunit of the human MTP protein in the analysis of a pregnancy in a consanguineous family, in which abetalipoproteinaemia was suspected, although prenatal diagnosis was subsequently refused. The mutation in the family has been identified as a novel four-nucleotide insertion/duplication of exon 17 between nucleotides 2349 and 2350 of the cDNA sequence of the MTP gene. However, the marker, MTPIVS10, can be used as an alternative to the time-consuming mutation detection techniques.

Abetalipoproteinemia↗
PubMed1997

Altered endothelial and smooth muscle cell reactivity caused by University of Wisconsin preservation solution in human saphenous vein.

PURPOSE: We have investigated the effect of University of Wisconsin (UW) solution at different temperatures on endothelial and smooth muscle cell function of the human saphenous vein to define the efficacy of UW solution as a preservation solution for saphenous vein conduits. METHODS: Saphenous vein segments from 38 patients undergoing coronary artery bypass surgery were examined with an isolated organ bath technique to monitor changes in vessel reactivity. RESULTS: Endothelial-dependent relaxations to acetylcholine were attenuated after incubation in UW solution at both 4 degrees C and 28 degrees C (p < 0.05, n = 10). In contrast, relaxations to sodium nitroprusside were unchanged after incubation in UW solution at both temperatures (n = 8). The responses to 90 mmol/L KCl were increased at both 4 degrees C and 28 degrees C, respectively. Tyrode's: 27.2% +/- 3.1% and 23.8% +/- 3.0%, UW: 64.7% +/- 8.0% and 73.1% +/- 11% (p < 0.001). In addition, the responses to 5-HT were enhanced at 4 degrees C and 28 degrees C (p < 0.05). In contrast, responses to noradrenaline were enhanced only at 28 degrees C compared with the responses after incubations in Tyrode's solution (p < 0.05, n = 6). Furthermore U46619 (0.3 nmol/L to 1 nmol/L) responses were augmented at 4 degrees C (p < 0.05, n = 7). The potency (pD2) values for each agonist were not significantly different after incubations in UW solution. CONCLUSIONS: We conclude that UW solution produces attenuation of acetylcholine relaxations and temperature-dependent increased reactivity of smooth-muscle cell function in the isolated human saphenous vein. These studies document the complex interactions brought about by UW solution on the different components of the vascular wall that need to be elucidated further if this solution is to attain a place in vascular preservation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Influence of cooling on mesenteric vascular reactivity.

OBJECTIVES: Cardiopulmonary bypass has been shown to cause hypoperfusion of certain vascular beds leading to multiple system organ failure. It has been reported that the gut may be an important trigger. The underlying mechanism is not fully known, but vascular changes, particularly those due to cooling, could play a role. METHODS: We examined the effect of cooling (28 degrees C) and subsequent rewarming (37 degrees C) on the vascular reactivity of the rabbit mesenteric artery and abdominal aorta to a range of vasoactive substances using an in vitro organ bath apparatus. Cumulative concentration-responses of the agonists (noradrenaline, histamine, dopamine and potassium chloride) were examined at 37 degrees C, then repeated at 28 degrees C and then subsequently repeated after rewarming to 37 degrees C. RESULTS: All agonists were capable of inducing a constrictor response on the mesenteric artery and abdominal aorta. The results represent means +/- SEM. There was an increase in potency of noradrenaline at the lower temperature [from 5.6 +/- 0.1 (37 degrees C) to 6.0 +/- 0.1 (28 degrees C); Bonferroni-corrected P < 0.05; n = 10], which returned to normal [5.6 +/- 0.1 (37 degrees C)] following rewarming in the mesenteric artery. In contrast, there was a decrease in potency of noradrenaline in the aorta on cooling [6.5 +/- 0.1 (37 degrees C) to 6.2 +/- 0.1 (28 degrees C); Bonferroni-corrected P < 0.05; n = 8]. Neither histamine or dopamine showed any difference in potency at 28 degrees C or at 37 degrees C following rewarming in the mesenteric artery or aorta. There was no difference in the efficacy of the response of the mesenteric artery to noradrenaline as indicated by the maximum responses. However, the response to the highest dose of dopamine was increased on rewarming to 37 degrees C compared to control responses at 37 degrees C before cooling in the aorta [7.23 +/- 1.48 g vs 3.6 +/- 0.6 g; Bonferroni-corrected P < 0.05; n = 14]. Histamine contractions were attenuated at 28 degrees C and following rewarming to 37 degrees C in the mesenteric artery [5.5 +/- 0.5 g (37 degrees C) vs 2.2 +/- 0.2 g (28 degrees C); Bonferroni-corrected P < 0.05; n = 18], [5.5 +/- 0.5 g (37 degrees C) vs 2.32 +/- 0.5 g (37 degrees C rewarming); Bonferroni-corrected P < 0.05; n = 18]. CONCLUSIONS: We conclude that cooling elicits a heterogeneous responsiveness of the rabbit mesenteric artery and abdominal aorta to noradrenaline and dopamine which could have important implications for blood flow to mesenteric vascular beds during hypothermic cardiopulmonary bypass.

Adrenergic alpha-Agonists↗
PubMed1992

Acute effects of cyclosporin and cremophor EL on endothelial function and vascular smooth muscle in the isolated rat heart.

We studied the effects of cyclosporin dissolved in the vehicle used as an intravenous preparation, namely, cremophor EL, and cremophor alone on the basal coronary flow plus endothelial function and vascular smooth muscle response by examining their influence on 5-hydroxytryptamine (5-HT) and nitroglycerine (GTN) induced the changes in coronary flow in the isolated rat heart. A total of 72 rat hearts were perfused with a modified Langendorf preparation. There was a 12.8 +/- 3% reduction in the basal coronary flow after 60 minutes of perfusion with the drug-free buffer (p = ns). A dose of 50 ng/ml of cremophor or cyclosporin gave a similar reduction in the flow (cremophor 9.2 +/- 0.7%, cyclosporin 12.7 +/- 2%). However, at higher concentrations cremophor caused dose-dependent coronary vasodilation, while cyclosporin had the opposite effect. The maximum effect after 1000 ng/ml of cyclosporin was a 48.7 +/- 0.6% decrease, and after an equivalent dose of cremophor a 24.8 +/- 2.2% increase in the flow. The vasodilatory response to 5-HT and GTN remained unchanged after 60 minutes of perfusion with the drug-free buffer (5-HT, before 33.3 +/- 2.5%, after 37.7 +/- 4.2%; GTN, before 34.3 +/- 2.5%, after 33.7 +/- 1.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Concomitant occurrence of mucopolysaccharidosis IIIB and Glanzmann's thrombasthenia. Further evidence of a hyperactive alpha-N-acetylglucosaminidase-producing allele.

A daughter of first cousins had two extremely rare, recessive disorders: thrombasthenia (Glanzmann's disease, glycoprotein IIb/IIIa deficiency) and mucopolysaccharidosis IIIB, (Sanfilippo B syndrome, alpha-N-acetylglucosaminidase (NAG) deficiency). Normal alpha-N-acetylglucosaminidase activity was observed in two obligate heterozygotes (the proband's father and her maternal grandmother), suggesting that in addition to the normal and defective alleles, a third, hyperactive allele is also present in this family. Such a hyperactive allele seems to be quite prevalent in our area, and makes the biochemical identification of heterozygotes impossible if no extensive family surveys provide additional clues. There was no linkage between the two diseases, nor between any of them and several blood-groups and HLA-antigens tested for.

Acetylglucosaminidase↗
PubMed1989

Endothelin-1 is a potent long-lasting vasoconstrictor in dog peripheral vasculature in vivo.

Endothelin-1 (ET-1), a 21 amino acid peptide, has recently been identified and shown to produce a potent and prolonged constriction of mammalian blood vessels in vitro. We have studied the effect of local infusion of this peptide on resistance vessels in the hindlimb of the anesthetized greyhound dog. Incremental doses of ET-1 (3-200 pmol/min) were infused into the left femoral artery. Doses above 10 pmol/min produced a slowly progressive reduction in hindlimb blood flow in a dose dependent fashion, maximally reducing flow by 79.5% +/- 3.2 from 152.3 +/- 29.1 ml/min to 27.8 +/- 5.8 ml/min (+/- SEM, p less than 0.015), with a concomitant rise in vascular resistance. In the control vessel (right femoral artery) there were no statistically significant changes in blood flow observed. Onset time of the response to ET-1 was 3 min, whereas spontaneous recovery of the flow occurred at 30 min following cessation of the infusion. We demonstrated transient reversal of constriction in this arterial model during coinfusion with endothelin-1 (100 pmol/min) of dihydropyridine calcium channel blocking agent nicardipine (0.5-20 nmol/min), substance P (0.5-50 fmol/min), adenosine (10-10,000 pmol/min), and isosorbide dinitrate (0.001-0.1 mg/min).

Animals↗
PubMed1988

Neonatal screening for cystic fibrosis.

Two groups of patients with cystic fibrosis were compared. The screened group, detected with an improved neonatal screening assay for immunoreactive trypsin, developed fewer chest infections requiring treatment and gained more weight than the unscreened group. Early diagnosis by screening seems to affect early morbidity.

Body Weight↗
PubMed1986

Inhibition of wound healing by Corynebacterium parvum.

Corynebacterium parvum (C. parvum), an immunostimulant, was examined for its effects on wound healing in mice. Animals injected intraperitoneally with C. parvum, 1400 micrograms 48 hr prior to wounding had significantly decreased wound strength at 5, 7, 11, 14, and 21 days after wounding compared to saline-injected controls (P less than 0.05-P less than 0.001). Mice injected with C. parvum at 48 or 2 hr before wounding, synchronous with wounding and 2 or 48 hr after wounding had significantly decreased wound disruption strength of 11-day-old wounds (P less than 0.01-P less than 0.001). Formalin fixations of wound strips from C. parvum-treated animals were consistently weaker than similarly treated wound strips from controls (P less than 0.05-P less than 0.01). Histologic analysis of wounds from C. parvum-treated animals revealed decreased amounts of wound collagen and increased inflammatory reaction compared to saline-injected animals. While C. parvum can improve survival following injury or septic challenge, the potential for marked alterations in wound healing may limit its clinical application in surgical and trauma patients.

Animals↗
PubMed1985

Plasma warfarin concentrations after a massive overdose.

The plasma pharmacokinetics of warfarin were studied in a patient who took an overdose of warfarin (2000 mg by mouth), together with 25 X 10(4) units of heparin administered subcutaneously. The plasma warfarin level fell rapidly (half-life, 21.7 h), and there was no convincing evidence for dose-dependency in its disposition.

Heparin↗
PubMed1982

In vitro coagulant properties of venoms from Australian snakes.

The procoagulant properties of venous Australian snakes are limited to prothrombin activation. Venoms of Notechis scutatus, Tropidechis carinatus and Pseudechis porphyriacus require phospholipid, calcium and factor V to maximally activate normal prothrombin. Venoms of Pseudonaja textilis and Oxyuranus microlepidotus activate both normal prothrombin and the decarboxy form and do not require co-factors. The actions of the venom of Oxyuranus scutellatus are dependent on concentration.

Animals↗
PubMed1980

The nature of mannose-containing material which accumulates in cultured fibroblasts from patients with mannosidosis.

Fibroblasts from a patient with mannosidosis were grown in a medium containing a radioactive monosaccharide (D-[U-14C]mannose or N-acetyl-D-[1-14C]-glucosamine). An accumulation of radioactive material was observed. It was possible to prevent the accumulation to a certain degree by the addition of human liver alpha-D-mannosidase to the fibroblast medium. After six days of fibroblast culture the majority of the accumulated material had a molecular weight in the oligosaccharide range and was stationary during high-voltage electrophoresis. Paper chromatography of the stationary material separated three radioactive compounds with the same chromatographic mobilities as the oligosaccharides alpha-D-Man-(1 leads to 3)-beta-D-Man-(1 leads to 4)-D-GlcNAc (I), alpha-D-Man-(1 leads to 2)-alpha-D-Man-(1 leads to 3)-beta-D-Man-(1 leads to 4)-GlcNAc (II), and alpha-D-Man-(1 leads to 2)-alpha-D-Man-(1 leads to 2)-alpha-D-Man-(1 leads to 3)-beta-D-Man-(1 leads to 4)-GlcNAc (III) previously isolated from the urine of patients with mannosidosis. Degradation of the three radioactive compounds with jack bean alpha-mannosidase gave D-mannose and a disaccharide (containing D-mannose and N-acetyl-D-glucosamine). Thus the three main compounts observed in the fibroblasts from patients with mannosidosis are most probably identical to the oligosaccharides I--III.

Acetylglucosamine↗
PubMed1979

Tubular function in adult polycystic kidney disease.

Various tubular functions were assessed in 10 patients with polycystic kidney disease (PKD). Three relatively unique abnormalities were apparent in many of these patients -- an inability to maximally concentrate urine, a decrease in ability to lower urine pH after acute acid challenge, and an inability to excrete adequate amounts of ammonium during persistent acid challenge. The defects in urinary acidification and ammonium excretion in PKD have not been previously described.

Adult↗