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Biomedical subjects

A J Baker

Publications and source records attributed to A J Baker.

At least 73 records · Page 4Linked to original sources

Orthotopic liver transplantation reverses the adverse nutritional changes of end-stage liver disease in children.

The changes in growth and body composition after orthotopic liver transplantation (OLT) were studied in 61 children [median age at OLT 3.49 y (range: 0.04-14.5 y), 26 boys and 35 girls] who had survived > or = 1 y post-OLT. Height, weight, midarm circumference (MAC), triceps skinfold thickness (TSF), and subscapular skinfold thickness (SSF) were measured at OLT, 3 and 6 mo later, then annually up to 5 y. SD scores (SDS) were derived from population standards. Results are reported as mean SDS +/- SEM. At OLT the children were short and malnourished (height: -0.98 +/- 0.22; weight -0.82 +/- 0.18; MAC: -1.77 +/- 0.21; TSF: -1.27 +/- 0.17; SSF: -1.49 +/- 0.17). By 3 mo post-OLT, there was a sustained improvement in MAC (-0.73 +/- 0.22), TSF (-0.48 +/- 0.18), and SSF (-0.50 +/- 0.18). Weight SDS (-0.48 +/- 0.20) improved by 6 mo without significant change in height SDS. The three children with Alagille syndrome were smaller (height, weight, and MAC) than children with other diagnoses but did show catch-up growth. Fulminant hepatic failure was not associated with growth failure before or after OLT. Infants (n = 14) were smaller and more malnourished at OLT (smaller skinfold thicknesses and lower weight SDS) than those who received transplants at an older age. By 1 y post-OLT, the only persisting difference was in TSF. Abnormal liver function at 1 y post-OLT (n = 8) and repeated episodes of steroid-treated rejection (n = 13) were associated with worsening height and weight SDS. The use of tacrolimus for graft salvage from rejection (n = 6) was not associated with growth failure. In conclusion, end-stage liver disease has a more adverse effect on MAC, TSF, and SSF than on height and weight, but a marked and rapid improvement occurred post-OLT. Children who were most severely malnourished and growth restricted at the time of OLT showed the greatest catch-up growth after OLT.

Adolescent↗

Structural conservation and variation in the mitochondrial control region of fringilline finches (Fringilla spp.) and the greenfinch (Carduelis chloris).

We sequenced the entire control region and portions of flanking genes (tRNA(Phe), tRNA(Glu), and ND6) in the common chaffinch (Fringilla coelebs), blue chaffinch (F. teydea), brambling (F. montifringilla), and greenfinch (Carduelis chloris). In these finches the control region is similar in length (1,223-1,237 bp) and has the same flanking gene order as in other birds, and contains a putative TAS element and the highly conserved CSB-1 and F, D, and C boxes recognizable in most vertebrates. Cloverleaf-like structures associated with the TAS element at the 5' end and CSB-1 at the 3' end of the control region may be involved with the stop and start of D-loop synthesis, respectively. The pattern of nucleotide and substitution bias is similar to that in other vertebrates, and consequently the finch control region can be subdivided into a central, conserved G-rich domain (domain II) flanked by hypervariable 5'-C-rich (domain I) and 3'-AT-rich (domain III) segments. In pairwise comparisons among finch species, the central domain has unusually low transition/transversion ratios, which suggests that increased G + T content is a functional constraint, possibly for DNA primase efficiency. In finches the relative rates of evolution vary among domains according to a ratio of 4.2 (domain III) to 2.2 (domain I) to 1 (domain II), and extensively among sites within domains I and II. Domain I and III sequences are extremely useful in recovering intraspecific phylogeographic splits between populations in Africa and Europe, Madeira, and a basal lineage in Nefza, Tunisia. Domain II sequences are highly conserved, and are therefore only useful in conjunction with sequences from domains I and III in phylogenetic studies of closely related species.

Animals↗

Hepatitis GB virus-C/hepatitis G virus infection in liver disease.

Hepatitis GB virus-C (HGBV-C)/hepatitis G virus (HGV) infection was investigated in 106 children with liver disease (54 boys and 52 girls, mean age 7.3 years); 12 with chronic hepatitis C virus infection, 29 with positive hepatitis B surface antigen, nine with idiopathic fulminant hepatic failure, seven with graft dysfunction after liver transplantation associated with autoimmune features, 20 with cryptogenic liver disease, and 29 with autoimmune liver disease. HGV RNA detected by reverse transcription polymerase chain reaction was found to be positive in 4/106 patients (3.8%). Risk factors were identified in three patients, including blood transfusion and/or medical treatment in Eastern Europe. The prevalence was higher than that of blood donors but lower than that of 2 adult patients with liver disease. HGV is not associated with any specific disease group and does not seem to be a major aetiological agent of liver disease in childhood in the UK.

Adolescent↗

Liver transplant for giant cell hepatitis with autoimmune haemolytic anaemia.

Giant cell hepatitis (CGH) with autoimmune haemolytic anaemia (AHA) is a distinct entity with an aggressive course. Immunosuppression may help early disease. A case is reported of a child with GCH and AHA with early disease recurrence after liver transplantation for end stage liver disease.

Anemia, Hemolytic, Autoimmune↗

Neonatal presentation of Caroli's disease.

A neonatal presentation of Caroli's disease with severe cardiac and progressive renal pathology is described. The availability of small paediatric endoscopes ensured early diagnosis. Despite aggressive medical management, the baby died with severe bleeding complications before potentially life saving multiple organ transplantation could take place.

Arterial Occlusive Diseases↗

Force decline during muscle relaxation promotes calcium release to the cytosol.

During relaxation of skeletal muscle, an initial rapid decline of intracellular Ca2+ concentration ([Ca2+]i) (phase 1), is followed by a brief phase in which the decline of [Ca2+]i is markedly slowed or even reversed (phase 2). Phase 2 appears as a prominent "bump" on records of the time course of declining [Ca2+]i during relaxation. The goal of this study was to test the hypothesis that phase 2 represents a release of Ca2+ to the cytosol that occurs with net cross-bridge detachment during relaxation. The experimental approach was to measure [Ca2+]i with indo 1 in stimulated bullfrog semitendinosus muscles and to determine if phase 2 was diminished during relaxation of contractions in which cross-bridge interactions had been reduced by two different methods: 1) stretching muscles to reduce the overlap between actin and myosin filaments or 2) decreasing stimulus duration. The results showed that, when either method was used to reduce cross-bridge interactions during contraction, then the size of phase 2 during relaxation was also decreased. Phase 2 was eliminated during relaxation of contractions in which cross-bridge interactions had been reduced to a lower contraction force approximately 30% of maximum. These findings are consistent with the hypothesis that the phase 2 of [Ca2+]i decline represents a release of Ca2+ to the cytosol that occurs with net cross-bridge detachment during relaxation. This conclusion is consistent with previous studies that suggest that cross-bridge detachment lowers the affinity of troponin for Ca2+.

Actins↗

Ketamine concentrations during cardiopulmonary bypass.

PURPOSE: To describe the serum concentrations of ketamine following a clinically relevant dosing schedule during cardiopulmonary bypass (CPB). METHODS DESIGN: Prospective case series. SETTING: Tertiary care teaching hospital. PATIENTS: Six patients undergoing coronary artery bypass grafting and over age 60 yr. INTERVENTION: Following induction of anaesthesia each patient received a bolus of ketamine 2 mg.kg-1 followed by an infusion of 50 micrograms.kg-1.min-1 which ran continuously until two hours after bypass. MAIN OUTCOME MEASURES: Ketamine serum concentrations were measured at five minutes after bolus, immediately following aortic cannulation, 10 and 20 min on CPB, termination of CPB, termination of the drug infusion and three and six hours after infusion termination. RESULTS: At the time of aortic cannulation, ketamine concentrations were 3.11 +/- 0.81 micrograms.ml-1, these levels decreased by one third with the initiation of CPB. By the end of CPB the concentrations had returned to levels roughly equivalent to those observed at the time of aortic cannulation. Following cessation of the infusion, ketamine concentration declined in a log-linear fashion with a half-life averaging 2.12 hr. (range 1.38-3.09 hr). CONCLUSION: This dosage regimen maintained general anaesthetic concentrations of ketamine throughout the operative period. These levels should result in brain tissue concentrations in excess of those previously shown to be neuroprotective in animals. Thus we conclude that this infusion regimen would be reasonable to be use in order to assess the potential neuroprotective effects of ketamine in humans undergoing CPB.

Aged↗

Cytosolic and mitochondrial [Ca2+] in whole hearts using indo-1 acetoxymethyl ester: effects of high extracellular Ca2+.

Assessment of free cytosolic [Ca2+] ([Ca2+]c) using the acetoxymethyl ester (AM) form of indo-1 may be compromised by loading of indo-1 into noncytosolic compartments, primarily mitochondria. To determine the fraction of noncytosolic fluorescence in whole hearts loaded with indo-1 AM, Mn2+ was used to quench cytosolic fluorescence. Residual (i.e., noncytosolic) fluorescence was subtracted from the total fluorescence before calculating [Ca2+]c. Noncytosolic fluorescence was used to estimate mitochondrial [Ca2+]. In hearts paced at 5 Hz (N = 17), noncytosolic fluorescence was 0.61 +/- 0.06 and 0.56 +/- 0.07 of total fluorescence at lambda 385 and lambda 456, respectively. After taking into account noncytosolic fluorescence, systolic and diastolic [Ca2+]c was 673 +/- 72 and 132 +/- 9 nM, respectively, noncytosolic [Ca2+] was 183 +/- 36 nM and increased to 272 +/- 12 when extracellular Ca2+ was increased from 2 to 6 mM. This increase in noncytosolic [Ca2+] was inhibited by ruthenium red, a blocker of Ca2+ uptake by mitochondria. We conclude that cytosolic and mitochondrial [Ca2+] can be determined in whole hearts loaded with indo-1 AM by using Mn2+ to quench cytosolic fluorescence.

Animals↗

Phylogenetic relationships within the Alcidae (Charadriiformes: Aves) inferred from total molecular evidence.

The Alcidae is a unique assemblage of Northern Hemisphere seabirds that forage by "flying" underwater. Despite obvious affinities among the species, their evolutionary relationships are unclear. We analyzed nucleotide sequences of 1,045 base pairs of the mitochondrial cytochrome b gene and allelic profiles for 37 allozyme loci in all 22 extant species. Trees were constructed on independent and combined data sets using maximum parsimony and distance methods that correct for superimposed changes. Alternative methods of analysis produced only minor differences in relationships that were supported strongly by bootstrapping or standard error tests. Combining sequence and allozyme data into a single analysis provided the greatest number of relationships receiving strong support. Addition of published morphological and ecological data did not improve support for any additional relationship. All analyses grouped species into six distinct lineages: (1) the dovekie (Alle alle) and auks, (2) guillemots, (3) brachyramphine murrelets, (4) synthliboramphine murrelets, (5) true auklets, and (6) the rhinoceros auklet (Cerorhinca monocerata) and puffins. The two murres (genus Uria) were sister taxa, and the black guillemot (Cepphus grylle) was basal to the other guillemots. The Asian subspecies of the marbled murrelet (Brachyramphus marmoratus perdix) was the most divergent brachyramphine murrelet, and two distinct lineages occurred within the synthliboramphine murrelets. Cassin's auklet (Ptychoramphus aleuticus) and the rhinoceros auklet were basal to the other auklets and puffins, respectively, and the Atlantic (Fratercula arctica) and horned (Fratercula corniculata) puffins were sister taxa. Several relationships among tribes, among the dovekie and auks, and among the auklets could not be resolved but resembled "star" phylogenies indicative of adaptive radiations at different depths within the trees.

Alleles↗

Population differentiation and evolution in the common guillemot Uria aalge.

Common (Uria aalge) and Brünnich's guillemots (U. lomvia) are colonial seabirds that nest in temperate to arctic oceans throughout the Northern hemisphere. They are very similar in the characteristics of ecology, demography and life history that are thought to determine the extent of differentiation among populations, yet geographic variation in morphology is notably greater in common guillemots. Despite evidence of strong natal philopatry, previous analyses of allozymes and the mitochondrial cytochrome b gene revealed little genetic differentiation among North Atlantic colonies of Brünnich's guillemots. To determine if the more extensive morphological variability in common guillemots reflects greater genetic variability, we sequenced part of the cytochrome b gene for 160 common guillemots from 10 colonies distributed throughout the Northern hemisphere. Genotype frequencies and phylogenetic relationships among genotypes both indicated that Atlantic and Pacific populations are genetically distinct. Genetic divergence among genotypes suggested that differentiation of these populations has resulted from separation by Pleistocene glaciers and the Bering Landbridge, as well as by currently unsuitable breeding habitat in the Arctic Ocean. Cytochrome b genotype frequencies also differed among Atlantic colonies, and appeared to define a cline similar to that described for morphological characters. Analyses of sequence variation suggested that this variation probably results from secondary contact between two refugial populations from the Pleistocene glaciations, rather than from isolation by distance or selection. In contrast, the Atlantic population of Brünnich's guillemots appears to have arisen through recent expansion of a single homogeneous refugial population.

Animals↗

Ca(2+)-force relationship of frog skeletal muscle: a dynamic model for parameter estimation.

A simple mathematical model describing the dynamic connection between Ca2+ and force generation in intact skeletal muscle from the frog has been developed from isometric force responses to cytosolic Ca2+ concentration ([Ca2+]c) transients during tetanic and twitch contractions. The main element of the model is a two-state cross-bridge cycle characterized by the fractional rate of cross-bridge attachment (f(app)) and the fractional rate of cross-bridge detachment (g*). While g* is constant, f(app) is time varying and regulated by both [Ca2+]c and force. Having only four adjustable parameters, the model is mathematically unique, thereby allowing precise parameter estimation from the dynamic Ca2+ and force data. The model should be useful for developing insights into the relative importance for force generation and relaxation of 1) the size and shape of the Ca2+ transient, 2) the sensitivity of the fractional rate of cross-bridge attachment to both the [Ca2+]c and the force responses, and 3) the fractional rate of cross-bridge detachment, which is insensitive to both Ca2+ and force.

Animals↗

Influence of the intra-aortic balloon pump on the transcranial Doppler flow pattern in a brain-dead patient.

BACKGROUND: Confirmation of clinical brain death with transcranial Doppler (TCD) has been described. With the introduction of mechanical assist devices, it is important to know how these devices influence TCD measurements. CASE DESCRIPTION: A patient who fulfilled the clinical criteria for brain death after cardiac arrest is described. An intra-aortic balloon pump (IABP) was necessary to maintain hemodynamic stability. A TCD examination was performed as an adjunct to the clinical diagnosis of brain death. A pattern of reversal of blood velocity typical of brain death was observed. With the IABP functioning, an increase of mean forward flow velocity without appreciable increase in the net flow velocities was seen. The results of the TCD measurements with the IABP functioning are not in concordance with values reported in the literature that confirm the clinical diagnosis of brain death. CONCLUSIONS: Application of TCD in a patient with an IABP could lead to false interpretation of results if the TCD mean velocities are not registered with the IABP on standby or if the net flow velocities are not calculated.

Blood Flow Velocity↗

Sequential changes in insulin-like growth factor I (IGF-I) and IGF-binding proteins in children with end-stage liver disease before and after successful orthotopic liver transplantation.

Pediatric end-stage liver disease (ESLD) leads to poor linear growth and wasting. After orthotopic liver transplantation (OLT), catch-up growth occurs unpredictably and with a delay. The bulk of circulating insulin-like growth factor I (IGF-I) and its major circulating binding protein, IGF-binding protein-3 (IGFBP-3), is derived from the liver. We hypothesized that growth failure in ESLD, both before and after OLT, may result from abnormalities in the IGF-IGFBP axis. Serum IGF-I, IGFBP-1, and insulin were measured by RIA, and IGFBP-3 was determined by immunoradiometric assay in 26 children with ESLD (mean of 3.7 samples pre-OLT and 4.2 samples post-OLT per patient) and 30 age-matched controls. In addition, serum IGFBPs were visualized by Western ligand blotting. IGFBP-3 and IGFBP-2 were also observed by immunoblotting with specific antisera. IGFBP-3 protease activity was determined by protease gels using recombinant human IGFBP-3 label as substrate. Anthropometric measurements were performed according to standard techniques. Pre-OLT, IGF-I (32.7 +/- 4.8 micrograms/L), and IGFBP-3 (1.11 +/- 0.10 mg/L) were significantly lower than control values [IGF-I, 168.3 +/- 16.5 micrograms/L (P = 0.0001); IGFBP-3, 2.57 +/- 0.17 mg/L (P = 0.0001)]. Post-OLT, IGF-I (179.2 +/- 19.7 micrograms/L; P = NS) rose to control levels, whereas IGFBP-3 (3.49 +/- 0.14 mg/L; P = 0.002) became significantly greater than the control value. IGFBP-1 was significantly higher pre-OLT (78.9 +/- 9.6 micrograms/L; P = 0.0001) than post-OLT (45.7 +/- 6.9 micrograms/L), and both were significantly higher than control values (18.5 +/- 2.5 micrograms/L; P = 0.0001 vs. pre-OLT and P = 0.0002 vs. post-OLT). There was a trend toward higher insulin levels both pre-OLT (15.5 +/- 1.8 mU/L) and post-OLT (12.5 +/- 1.4 mU/L) compared with control values (9.7 +/- 1.1 mU/L; P = 0.06 vs. pre-OLT). IGFBP-1 was negatively correlated with serum insulin post-OLT (P = 0.008), but there was no correlation pre-OLT. Western ligand blotting confirmed the changes in IGFBP-3 pre- and post-OLT. Immunoblotting demonstrated a reduction in all mol wt forms of IGFVBP-3 pre-OLT. Protease assays demonstrated the appearance of IGFBP-3 proteolysis only at a time coincidental with the operative stress of OLT; overall, there was no difference in protease activity pre- and post-OLT. IGFBP-2 was unchanged post-OLT compared with pre-OLT, although levels were higher than control values. Mid-upper arm circumference and triceps skin fold thickness SD score 3 months post-OLT and weight SD score 1 yr post-OLT were significantly higher than those at OLT. In conclusion, IGF-I and IGFBP-3 are reduced, and IGFBP-1 and IGFBP-2 are increased in children with ESLD. After OLT, IGF-I levels return to normal, but marked abnormalities in IGFBPs remain. These changes may help to explain at least in part the growth failure seen in pediatric ESLD both before and after successful OLT.

Adolescent↗

Differential effects of malnutrition, bile duct ligation and galactosamine injection in young rats on serum levels and gene expression of IGF-binding proteins.

Hepatic gene expression and circulating levels of IGF-binding proteins (IGFBP)-1 to -4 were examined in two rat models of liver disease employing acute hepatitis or chronic structural damage. The study comprised four groups: group 1 (n = 6) was injected intraperitoneally with saline and food was available ad libitum (AL), group 2 (n = 6) underwent bile duct ligation (BDL), group 3 (n = 6) was injected with 400 mg galactosamine (GAL), group 4 (n = 6) was sham-operated and pair-fed to group 2 (PF). All were killed by decapitation at day 7. Serum IGF-I, by RIA, was significantly (P < 0.05) lower in the BDL group (458 +/- 37 micrograms/l) and PF group (451 +/- 51 micrograms/l) compared with the AL group (643 +/- 77 micrograms/l) and GAL group (720 +/- 67 micrograms/l). Immunoblotting showed raised IGFBP-2 levels in all groups compared with AL (BDL, 167 +/- 14% of AL; GAL, 173 +/- 13%; PF, 149 +/- 9%). IGFBP-3 was decreased in the GAL (56 +/- 11%) and PF groups (66 +/- 5%) but increased in the BDL group (154 +/- 29%). IGFBP-4 was decreased in the GAL (76 +/- 11%) and PF groups (47 +/- 5%) but unchanged in the BDL group (90 +/- 10%). By Northern analysis, IGFBP-1 mRNA expression was increased in the GAL (321 +/- 51%) and PF groups (263 +/- 12%) but reduced in the BDL group (68 +/- 8%). IGFBP-2 expression increased in all groups (PF, 836 +/- 19%; BDL, 683 +/- 121%; GAL, 372 +/- 68%) and was highest in the BDL and PF groups. IGFBP-3 expression was reduced in all groups (BDL, 57 +/- 16%; GAL, 52 +/- 12% PF, 51 +/- 13%). IGFBP-4 expression was reduced in the GAL (30 +/- 4%) and PF (28 +/- 5%) groups but unchanged in the BDL group (76 +/- 9%). Marked changes in gene expression of IGFBPs occurred in both models of liver disease, together with serum changes, which were different from each other and from malnutrition alone.

Animals↗

Flightless brown kiwis of New Zealand possess extremely subdivided population structure and cryptic species like small mammals.

Using allozymes and mtDNA sequences from the cytochrome b gene, we report that the brown kiwi has the highest levels of genetic structuring observed in birds. Moreover, the mtDNA sequences are, with two minor exceptions, diagnostic genetic markers for each population investigated, even though they are among the more slowly evolving coding regions in this genome. A major unexpected finding was the concordant split in molecular phylogenies between brown kiwis in the southern South Island and elsewhere in New Zealand. This basic phylogeographic boundary halfway down the South Island coincides with a fixed allele difference in the Hb nuclear locus and strongly suggests that two morphologically cryptic species are currently merged under one polytypic species. This is another striking example of how molecular genetic assays can detect phylogenetic discontinuities that are not reflected in traditional morphologically based taxonomies. However, reanalysis of the morphological characters by using phylogenetic methods revealed that the reason for this discordance is that most are primitive and thus are phylogenetically uninformative. Shared-derived morphological characters support the same relationships evident in the molecular phylogenies and, in concert with the molecular data, suggest that as brown kiwis colonized northward from the southern South Island, they retained many primitive characters that confounded earlier systematists. Strong subdivided population structure and cryptic species in brown kiwis seem to have evolved relatively recently as a consequence of Pleistocene range disjunctions, low dispersal power, and genetic drift in small populations.

Animals↗

Loss of response to beta-adrenoceptor agonists during the maturation of human monocytes to macrophages in vitro.

We have previously reported that human airway macrophages do not respond to the beta-adrenoceptor agonist isoprenaline. The airway macrophage is known to be derived from the blood monocyte. In this study we have assessed the effect of beta-adrenoceptor stimulation on human monocytes matured into macrophages in vitro, to determine whether the lack of response previously observed in the airway macrophage may be a consequence of differentiation. The release of thromboxane B2 (TXB2) from freshly isolated monocytes stimulated by opsonized zymosan (OPZ) was inhibited by 39.3 +/- 5.5% in the presence of isoprenaline (10(-7) M). However, the response was lost in the monocyte-derived macrophage (MDM), where isoprenaline (10(-7) M) caused only 4.0 +/- 9.3% inhibition of OPZ-stimulated TXB2 release. In contrast forskolin (10(-5) M) inhibited MDM TXB2 release by 36.4 +/- 17.3%, indicating that the adenylyl cyclase was functional. Measurement of adenylyl cyclase activity showed that there was a reduction in the basal level, 17.03 +/- 4.1 to 7.9 +/- 4.6 cyclic AMP pmol/min/mg protein, and NaF (10(-2) M)-induced activity, 116.3 +/- 32.1 to 21.9 +/- 12.6 cyclic AMP pmol/min/mg protein, between freshly isolated monocytes and MDMs, respectively. In addition, there was no change in MDM basal adenylyl cyclase activity on exposure to isoprenaline. Thus we have demonstrated the loss of beta-adrenoceptor function during the maturation of human monocytes to macrophages in vitro, despite a functional adenylyl cyclase system. In this respect the monocyte-derived macrophage is like the airway macrophage.

Acetylglucosaminidase↗

Cerebral microemboli during coronary artery bypass using different cardioplegia techniques.

Larger numbers of microemboli detected by transcranial Doppler echocardiography have been linked to adverse neuropsychological outcome after coronary artery bypass grafting. Differences in neurologic outcome have been attributed to different cardioplegia techniques. Transcranial Doppler-detected microembolic events were recorded during coronary artery bypass grafting using different cardioplegia techniques. Patients received cold antegrade (n = 20), warm antegrade (n = 17), or warm retrograde (n = 20) cardioplegia. Continuous monitoring was divided into stages: aortic cannulation, initiation of cardiopulmonary bypass, aortic cross-clamping, aortic declamping and decannulation until chest closure. Rate of embolic events and number of total and immediate embolic events were tabulated. Total embolic events ranged from 22 to 2,072 per patient and were similar among groups. The rate and total at each stage were similar. Total embolic events were highest during aortic clamping; the rate was highest at initiation of bypass. The immediate embolic events were higher in the warm retrograde group than both antegrade groups at aortic declamping. In summary, a high total and rate of embolic events were detected and differences between cardioplegia techniques were detected.

Coronary Artery Bypass↗