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Biomedical subjects

K Humphries

Publications and source records attributed to K Humphries.

At least 19 recordsLinked to original sources
PubMed2006

Longitudinal blood flow in shared (arteriovenous anastomoses) and non-shared cotyledons in monochorionic placentae.

OBJECTIVES: In this study we aimed to quantitate monochorionic twin placental blood flow in vivo through arterio-venous anastomoses (AVA) and corresponding vessels within normal cotyledons. METHODS: The topography of chorionic plate vasculature was mapped using colour Doppler in ten monochorionic diamniotic twin (MCDA) pregnancies. Cotyledonary flow was derived by insonation of chorionic veins draining normal (n=10) and paired control shared cotyledons (n=10). Venous volume flow was calculated from five determinations of vessel diameter and three of time average mean velocity (TAMV). Measurements were repeated every 2-4 weeks from 18 until 32 weeks' gestation. RESULTS: Blood flow through non-shared and shared cotyledons increased with gestation (p<0.0001). Median flow at 28 weeks through shared cotyledons was 16 ml/min (15-21) (median, interquartile range), lower than in shared cotyledons (31, 25-35) (p<0.001), as was median volume flow across gestation calculated as area under the curve (shared cotyledons 126 (122-167), control cotyledons 269 (214-274), p=0.01). However, velocity was similar, with the difference due to smaller vein diameters draining shared compared to normal cotyledons (mean 3.6mm (SD 0.8) vs. 4.5mm (0.8), p=0.004). Ex vivo quantitation of insonated cotyledons and of all cotyledons confirmed the difference in vein diameter in the placentae studied. CONCLUSIONS: Blood flow through shared cotyledons was lower across gestation than through paired normal cotyledons in the placenta studied due to the smaller diameter of the AVA vessels. The size of AVAs rather than simply their presence and direction may contribute to determining transfusional imbalance in monochorionic twins.

Arteriovenous Anastomosis↗
PubMed2005

Safety and efficacy of rosuvastatin therapy for the prevention of hyperlipidemia in adult cardiac transplant recipients.

BACKGROUND: Hyperlipidemia after orthotopic heart transplantation (OHT) is associated with immunosuppression. Many OHT patients have increased lipid levels above published guidelines despite treatment with high doses of statins. Treatment with rosuvastatin (ROS) in OHT patients has not yet been evaluated. Therefore, we assessed its efficacy and safety in an OHT population. METHODS: Twenty-one OHT recipients, median age 66 years, whose lipid levels were sub-optimal on the highest tolerated doses of statins, received ROS in addition to standard immunosuppression. Total cholesterol (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), liver transaminases (AST) and creatinine kinase (CK) were measured before and during treatment with ROS. RESULTS: After 6 weeks on an average ROS dose of 10 mg/day, a TC:HDL-C ratio of <4 was reached in 76% of patients, and 70% of patients reached an LDL-C level of <2.5 mmol/liter (100 mg/dl). TC decreased to <5.2 mmol/liter (200 mg/dl) in 80% of patients and TG decreased to <2 mmol/liter (175 mg/dl) in 61% of patients. Except for the HDL-C increase, all changes were statistically significant. The decrease in the median TC:HDL-C ratio between baseline and 6 weeks was also statistically significant (p = 0.001). There were no significant changes in CK or AST levels, and no clinical evidence of myositis. One patient developed myalgia and 2 were withdrawn from the study because of mild elevation of CK (<3-fold upper limit of normal [ULN]). CONCLUSIONS: In the setting of tertiary referral centers, ROS appears to be safe and effective in lowering LDL-C in OHT recipients in whom treatment with other statins failed to achieve target LDL-C. No evidence of liver or muscle dysfunction was noted. Long-term studies are needed to ascertain the effect of ROS therapy on incidence of coronary artery disease (CAD) in this population.

Aged↗
PubMed2003

A technique for the measurement of patellar tracking during weight-bearing activities using ultrasound.

A new fixation device, the femoral clamp, was developed in this study for the ultrasound measurement of patellar medio-lateral motion during sitting and squatting knee flexion/extension. Seventeen subjects, 6 males, 11 females, aged between 18 and 40 years were recruited for the test. Results showed that the patella moved medially then laterally from extension to flexion when sitting. Weight-bearing knee motion produced a more laterally tracked patella without the presence of the initial medial patellar translation. The tracking patterns of the patellae were similar regardless of knee movement direction. The patellar lateral position was greatly affected by the movement task (p < 0.0005), and was also influenced by gender for maximum medial position (p < 0.05). The reproducibility of the measurement was between 0.29 and 0.90 for the intra-rater and 0.34-0.75 for the inter-rater reliability. The accuracy of the ultrasound measurement was validated by interventional magnetic resonance (iMR) imaging of the patella and the mean error of the measurement was 1.4 +/- 3.2 mm. Although further research is needed to improve the accuracy and reliability of this method, it has demonstrated the feasibility of obtaining patellar tracking data during load-bearing activities.

Adult↗
PubMed2001

PKA, PKC, and AKAP localization in and around the neuromuscular junction.

BACKGROUND: One mechanism that directs the action of the second messengers, cAMP and diacylglycerol, is the compartmentalization of protein kinase A (PKA) and protein kinase C (PKC). A-kinase anchoring proteins (AKAPs) can recruit both enzymes to specific subcellular locations via interactions with the various isoforms of each family of kinases. We found previously that a new class of AKAPs, dual-specific AKAPs, denoted D-AKAP1 and D-AKAP2, bind to RIalpha in addition to the RII subunits. RESULTS: Immunohistochemistry and confocal microscopy were used here to determine that D-AKAP1 colocalizes with RIalpha at the postsynaptic membrane of the vertebrate neuromuscular junction (NMJ) and the adjacent muscle, but not in the presynaptic region. The labeling pattern for RIalpha and D-AKAP1 overlapped with mitochondrial staining in the muscle fibers, consistent with our previous work showing D-AKAP1 association with mitochondria in cultured cells. The immunoreactivity of D-AKAP2 was distinct from that of D-AKAP1. We also report here that even though the PKA type II subunits (RIIalpha and RIIbeta) are localized at the NMJ, their patterns are distinctive and differ from the other R and D-AKAP patterns examined. PKCbeta appeared to colocalize with the AKAP, gravin, at the postsynaptic membrane. CONCLUSIONS: The kinases and AKAPs investigated have distinct patterns of colocalization, which suggest a complex arrangement of signaling micro-environments. Because the labeling patterns for RIalpha and D-AKAP 1 are similar in the muscle fibers and at the postsynaptic membrane, it may be that this AKAP anchors RIalpha in these regions. Likewise, gravin may be an anchor of PKCbeta at the NMJ.

A Kinase Anchor Proteins↗
PubMed2001

Development of three-dimensional power Doppler ultrasound imaging of fetoplacental vasculature.

To develop an off-line system for three-dimensional (3-D) ultrasound (US) reconstruction of fetoplacental vasculature using colour segmentation and reconstruction software and to determine sources of error in fully freehand ultrasound image acquisition. US images were acquired freehand with the Acuson Sequoia (5C 2-MHz transducer) using power Doppler. After digital transfer to a personal computer, CQ Analysis software (Kinetic Imaging Ltd, Liverpool, UK) was used to segment the colour information from these images, and the resulting 8-bit grey-scale images were used for 3-D rendering using commercial software (VoxBlast, Vaytek Inc., Fairfield, IA, USA). 2-D scanning, software and freehand acquisition accuracy were assessed using a linear test rig and distance and volume phantoms (Dansk Phantom Service Ltd); 2-D scanning accuracy was within 1.3%, and software reconstruction accuracy within 1% for x and y planes and up to 3% for the z plane. Fully freehand acquisition was associated with a 12% to 18% mean percentage error in distance measurement in the plane of acquisition. Volumetric reconstruction inaccuracy was between 1.5% and 19.7% for precisely separated images and between 16.2% and 39.2% for fully freehand image acquisition. Rendered 3-D US vascular images clearly delineated vascular anatomy within the placenta and cord. Fully freehand 3-D US does have a role in off-line reconstruction of vascular anatomy, although variability in the z plane precludes its use for volumetric measurement. (E-mail: a.welsh@ic.ac.uk)

Female↗
PubMed2001

How long is too long?

Explore the source record for details and available documents.

Angioplasty, Balloon, Coronary↗
PubMed1999

Effect of time post mortem on the concentration of endotoxin in rat organs: implications for sudden infant death syndrome (SIDS).

The aim of the study was to test the following hypotheses: (i) that endotoxin injected 40 min prior to death can be detected in rat organs post mortem and (ii) that endotoxin levels do not change with increasing time post mortem. Rats were injected with or without endotoxin in buffered saline, 40 min prior to being killed. Endotoxin levels in rat organs were assessed using a Limulus amoebocyte assay. The effect of storage time post mortem was assessed by following various storage regimes at 25 degrees C and 8 degrees C. Significant differences (P = < 0.001) in endotoxin levels of all samples tested were found between rats injected with and without endotoxin. A significant increase in detectable endotoxin was observed between 0 h and 6 h post mortem in rats injected with or without endotoxin. No difference in detectable endotoxin levels in the kidney, liver and spleen was observed from 30 h to 102 h post mortem in rats injected with or without endotoxin. In rats injected with endotoxin, detectable endotoxin levels in the heart were raised between 0 h and 6 h, 6 h and 54 h, and 30 h and 78 h. Endotoxin injected into rats 40 min prior to death can be detected post mortem. For rats injected with saline or endotoxin prior to death levels in the kidney, liver and spleen were not affected by storage at 8 degrees C for 30-102 h, after initial storage at room temperature for 6 h. Levels of endotoxin detected in the hearts of rats injected with saline were not affected by storage up to 102 h. In rats injected with endotoxin prior to death, detectable levels in the heart were significantly affected by increasing time in storage.

Animals↗
PubMed1995

Stage- and lineage-specific expression of the HOXA10 homeobox gene in normal and leukemic hematopoietic cells.

There is growing evidence that the HOX homeobox-containing transcription factors are differentially expressed during hematopoiesis. We have previously demonstrated that the HOXA10 gene is expressed in unfractionated normal marrow and in immortalized leukemic cell lines with myelomonocytic features, but not in cell lines with lymphoid or erythroid features. To gain insights into the patterns of activation of this gene during hematopoietic differentiation, we have examined HOXA10 expression in CD34+ and CD34- subfractions of normal marrow and normal peripheral blood, as well as samples from patients with a variety of acute and chronic leukemias. HOXA10 is strongly expressed in CD34+ normal marrow cells, markedly downregulated in CD34- marrow cells, and inactive in mature neutrophils, monocytes, and lymphocytes. HOXA10 is expressed in all types of acute myelogenous leukemia (AML) with the notable exception of acute promyelocytic leukemia (AML-M3). HOXA10 message is observed in chronic myelogenous leukemia (CML) but appears to be reduced in accelerated phase and blast crisis, particularly lymphoid blast crisis. With rare exception, HOXA10 expression is not observed in samples of acute or chronic lymphoid leukemias. Normal marrow and patient samples appear to contain a single transcript which encodes a full-length homeobox-containing protein, while immortalized cell lines contain an additional alternatively spliced transcript. These studies indicate that HOXA10 expression is restricted to early stages of myeloid differentiation.

Base Sequence↗
PubMed1992

Erythropoietin-induced tyrosine phosphorylations in a high erythropoietin receptor-expressing lymphoid cell line.

Retroviral gene transfer of the murine erythropoietin receptor (EpR) cDNA into the pro-B-cell line, Ba/F3, was used to generate cells expressing high EpR levels. One of the resulting clones, Ba/F3 clone C5, contained 5 integrated copies of the gene and expressed, at the cell surface, a single affinity class of EpRs at 10 to 15 times the level present on spleen cells from phenylhydrazine-treated mice. Cross-linking studies with clone C5, using 125I-Ep, yielded the same two 105- and 88-Kd major species as that seen with typical erythroid cells. This was distinct from that obtained with EpR-transfected COS cells or L cells, which gave species of 88 and 65 Kd. This suggests that the biologically active EpR complex generated in this Ba/F3 cell line may closely resemble that present in native Ep-responsive erythroid progenitor cells. Tyrosine phosphorylation experiments showed that several proteins in clone C5 cells were rapidly phosphorylated on tyrosine residues in response to Ep, one being the EpR itself. The proportion of cell surface EpRs tyrosine phosphorylated in response to Ep was substantial, reaching a maximum of approximately 10% within 30 minutes of incubation at 37 degrees C. A comparison of Ep- and murine interleukin-3 (mIL-3)-induced tyrosine phosphorylation patterns in clone C5 cells showed that both growth factors stimulated the tyrosine phosphorylation of proteins with molecular weights of 135, 93, 70, and 55 Kd. This could suggest that the Ep and mIL-3 receptors are capable of using the same tyrosine kinase in these cells.

Animals↗
PubMed1992

Monitoring hemangioblastoma tumor burden using plasma erythropoietin levels.

We report a 39-year-old female patient with a hepatic hemangioblastoma, polycythemia and elevated plasma erythropoietin (Epo) levels. Following orthotopic liver transplantation (OLTx), her plasma Epo levels and hematocrit normalized but began to rise several months later. This rise correlated with the appearance of multiple lung metastases. The tumor was implicated as the source of excess Epo production using Northern analysis of a resected metastatic lung nodule. Based on our results, the measurement of plasma Epo levels in patients with Epo secreting tumors could be of general utility in assessing tumor burden.

Adult↗
PubMed1991

Analysis of splice junctions and in vitro and in vivo translation potential of the small, abundant B19 parvovirus RNAs.

Two parvovirus B19 cDNA libraries have been constructed; one from COS-7 cells transfected with a B19/pSVOd hybrid vector and the other from B19-infected human erythroid leukemic cells. We have used these libraries to investigate the expression of the abundant classes of polyadenylated B19 RNAs; the 700- and 800-nt class which terminates in the middle of the genome and the 500- and 600-nt class which contains an ORF from the extreme right-hand end of the genome. The 700- and 800-nt RNA species were not found in the COS cell library, suggesting that a variant polyadenylation signal (ATTAAA or AATAAC) in the middle of the genome is not efficiently recognized in these cells. In contrast, the 700- and 800-nt class was highly represented in the human library, confirming the use of this variant polyadenylation signal in the normal host cell of the virus. In COS cells the middle exon of the 500- and 600-nt class of RNA exhibited variability in both splice donor and acceptor sites. However, in human cells there were only two splice acceptor sites nt 1910 and 2030, and a single splice donor site nt 2183 for this exon. Antisera, prepared against a peptide derived from the 94-aa potential protein encoded by the 500- and 600-nt class of RNA, recognized, on a Western blot, a polypeptide of approximately 11 kDa that was translated in vitro from these cDNAs and in vivo in pSVOd/B19 transfected COS cells. Immunoprecipitation revealed that two proteins were made from this ORF, suggesting the use of internal translation initiation site(s). Another antisera, raised against a second peptide corresponding to an antigenic region of the potential protein encoded by the 700- and 800-nt class of RNA, failed to detect a 15-kDa protein by Western blotting or immunoprecipitation of labeled proteins both in vitro and in vivo in COS cells.

Amino Acid Sequence↗
PubMed1987

Electrochemical oxidation of 5-hydroxytryptophan in acid solution.

The electrochemical oxidation of 5-hydroxytryptophan (5-HTPP) in acid solution proceeds by an initial 1e-, 1H+ reaction to a radical intermediate. This radical can dimerize and three diastereomers of 4,4'-bis(5-hydroxytryptophan) have been isolated and characterized. The radical can also undergo further electrochemical oxidation (1e-, 1H+) to a quinoneimine intermediate. Nucleophilic attack by water on this quinoneimine, followed by further oxidation, gives tryptophan-4,5-dione. Nucleophilic attack by 5-HTPP on the quinoneimine gives a dimeric indolenine which undergoes a complex series of chemical and electrochemical reactions leading ultimately to 4-[4-(6-hydroxyquinolyl)]-5-hydroxytryptophan. Two diastereomers of the latter compound have been isolated and characterized.

5-Hydroxytryptophan↗
PubMed1986

Behavioral impairments related to cognitive dysfunction in the autoimmune New Zealand black mouse.

The possibility that autoimmunological disorders involving neuronal constituents as autoantigens can result in measurable behavioral impairments prompted the behavioral analysis of the New Zealand black (NZB) mouse strain, known to have high levels of brain-reactive antibodies. Sensorimotor competence and performance in tasks requiring learning and memory were assessed in 7-10-month-old NZB and contrasted with those of CFW mice. The NZB mice showed pronounced deficits in performance of passive and active shock avoidance responses. These deficits could not be accounted for by the slight sensorimotor disadvantage of NZB mice relative to CFW mice. No difference between the two mouse strains was seen in passive avoidance behavior at 1.5 months of age. It is concluded that NZB mice display a behavioral deficit related to cognitive dysfunction and that autoimmune mechanisms may be involved in the etiology of this deficit. Such behavioral disturbances produced by an autoimmune mechanism may have relevance for the neurological declines observed in aging, since the incidence of autoimmune disorders increases markedly in old age.

Animals↗
PubMed1985

Effect of assay conditions on cross reactivity of digoxin-like immunoreactive substance(s) with radioimmunoassay kits.

One or more digoxin-like immunoreactive substances (DLIS), most frequently present in serum of premature and full-term neonates. cross react to various extents with different digoxin immunoassay kit reagents. Mostly, this variation is attributed to the relative cross reactivity of DLIS with the antiserum in each kit. However, modification of standard assay procedures for digoxin can also greatly alter the relative cross reactivity of DLIS. Using sequential RIA kit methods for digoxin by 20 to 60% relative to the standard equilibrium RIA mode. Cross reactivity was decreased still more if the concentrations of antiserum (binding-site concentration) and tracer (125 l-labeled digoxin) were decreased, and conversely. Serum samples containing only digoxin, analyzed by the modified method, consistently yielded results well comparable with those obtained with the manufacturers' recommended procedures. We describe use of the different responses to digoxin and DLIS of standard and sequential radioimmunoassays and use of simultaneous equation to calculate the concentration of DLIS (in digoxin equivalents) in digoxin-containing samples.

Cross Reactions↗
PubMed1983

Individual BFU-E in polycythemia vera produce both erythropoietin dependent and independent progeny.

Erythropoietic progenitors from peripheral blood of normal individuals or patients with polycythemia vera (PV) were cultured in methylcellulose medium containing 2.5 U/ml of erythropoietin (Ep). After 7-9 days, colonies considered to be early stage large bursts were individually removed, resuspended in a small volume of fresh methylcellulose medium, and then divided between 2 dishes. To one of these secondary cultures, sufficient Ep was added to bring the concentration of Ep up to approximately 3 U/ml. To the other was added an equal volume of medium but no Ep. The final concentration of Ep in these cultures was determined to be less than 0.01 U/ml. Nine days later, both types of secondary cultures were scored for the presence of colonies containing 8 or more hemoglobinized erythroblasts. Of 90 primary colonies from 3 normal individuals assessed in this way, 59 gave secondary erythroid colonies in the high Ep cultures, while none gave secondary erythroid colonies in the low Ep cultures. Additional control experiments in which primary colonies from normal individuals were divided into duplicate high Ep cultures showed that on average, the procedure used divided primary colonies equally. Of 109 primary colonies from 5 PV patients that yielded secondary erythroid colonies in the high Ep cultures, 21 yielded no secondary erythroid colonies in the low Ep cultures. The other 88 yielded erythroid colonies in both, but the secondary colonies in the low Ep cultures were consistently smaller in size and significantly fewer in number. Similar results were obtained when primary colonies were generated in cultures to which no Ep was added. These findings indicate that primitive BFU-E in patients with PV can be subdivided into 2 populations: a minor population restricted to the production of erythroid colony-forming cells (Ep-dependent progenitors) that require Ep for their detection, and a major population that is not restricted in this way. In addition, these experiments show that most of the primitive BFU-E that generate Ep-independent progenitors also produce significant numbers of cells that are Ep-dependent.

Adult↗