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Biomedical subjects

S Barker

Publications and source records attributed to S Barker.

At least 37 records · Page 2Linked to original sources

Cellular senescence after single and repeated balloon catheter denudations of rabbit carotid arteries.

The hypothesis that increased cellular proliferation in the vasculature may lead to replicative senescence has been tested in a model of neointima formation. We have used a biomarker of replicative senescence, senescence-associated beta-galactosidase (SA-beta-gal), to detect senescence in rabbit carotid arteries subjected to single and double balloon denudations. We found an accumulation of senescent cells in the neointima and media of all injured vessels, in contrast to the near absence of such cells in control vessels. The relative area occupied by SA-beta-gal-positive cells was higher in vessels subjected to double denudation than in those subjected to single denudation, both in the neointima (0.99% versus 0.06%, respectively; P:<0.001) and in the media (0.11% versus 0.01%, respectively; P:<0.02). The majority of SA-beta-gal-positive cells were vascular smooth muscle cells, and a minority were endothelial cells. SA-beta-gal-positive cells showed no evidence of apoptosis by use of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Our results indicate that the proliferative response that follows intraluminal injury to the artery leads to the emergence of senescent endothelial and smooth muscle cells. The demonstration that vascular cell senescence can occur in vivo suggests that this process may be involved in cardiovascular pathologies that have a proliferative component.

Angioplasty, Balloon↗

Acute pulmonary oedema: presenting symptom of multiple sclerosis.

Acute pulmonary oedema and headache are both common. The former is usually cardiogenic in origin. Severe headache of sudden onset in a young person may be suggestive of subarachnoid headache. We describe a 24-year-old man who presented with headache and pulmonary oedema, finally ascribed to multiple sclerosis. This is the first report of neurogenic pulmonary oedema as the first symptom of multiple sclerosis. We review the neuroanatomical basis and experimental evidence for neurogenic pulmonary oedema.

Adult↗

Glucocorticoid receptors in the euryhaline teleost Anguilla anguilla.

To determine the importance of glucocorticoids in the salt water adaptation of European yellow eel we have evaluated the concentration, affinity and physical properties of glucocorticoid receptors (GR) in gill from both sea water- (SW) and freshwater-adapted (FW) animals. Using ligand binding techniques we demonstrated that high affinity GR were present in both cytosolic and nuclear fractions obtained from whole gill. Isoelectric focusing (IEF) of branchial GR indicated the presence of two distinct species, with pI values of 6.1 and 6.7. The form at pI 6.7 sedimented with a Svedberg constant of 4S on glycerol density gradients while the pI 6. 1 sedimented in fractions corresponding to 9S. Treatment of the pI 6. 1 form with urea (4 M) resulted in generation of the form with pI 6. 7. The evidence thus suggested that the oligomeric urea-sensitive form (pI 6.1) contained a form of GR which, as a monomer, focused at pI 6.7. IEF revealed the same concentrations of the pI 6.7 form in both SW and FW. However, there was significantly more (3-fold) pI 6. 1 isoform in FW than in SW, and this form decreased gradually during the course of seawater transfer. A transient increase of the nuclear-bound GR was also observed during SW adaptation. The balance between these forms could represent a dynamic parameter with important implications regarding GR function and gill responses to cortisol in salt water adaptation in teleosts.

Adaptation, Physiological↗

The influence of external knee moments on the outcome of total meniscectomy. A comparison of radiological and 3-D gait analysis measurements.

Twenty one individuals who had undergone unilateral total meniscectomy, and had no significant antero-posterior (AP) laxity underwent three dimensional (3-D) gait analysis, bilateral radiological assessment of varus/valgus alignment and tibio-femoral osteoarthritis (TFOA). Average foot progression angle during the stance phase of gait was not related to knee adduction moment. The findings support the previously noted correlation between varus/valgus alignment and TFOA. The dynamic gait parameter of the adduction moment in early stance did not correlate with either hip-knee-ankle angle or TFOA, thus the expected influence of external moments on outcome after meniscectomy was not found. Thus the correlation between varus/valgus alignment and TFOA can not be explained by a simple loading algorithm.

Adolescent↗

Relationship between soluble intracellular endothelin-converting enzyme and endothelin-1 synthesis: effect of inhibitors of the secretory pathway.

The relationship between soluble and membrane-bound endothelin-converting enzyme (ECE) activity with the level of endothelin-1 (ET-1) synthesis was investigated in cultured endothelial cells. Escherichia coli lipopolysaccharide (LPS) was used to stimulate ET-1 synthesis, and brefeldin A, monensin, colchicine or cytochalasin B, which disrupt peptide biosynthetic pathways in a variety of ways, were tested for their ability to modify changes in ET-1 synthesis and ECE levels. LPS increased ET-1 secretion by more than twofold. Levels of soluble ECE activity, but not those of membrane-bound ECE activity, correlated with ET-1 synthesis. These results suggest the soluble ECE activity is likely to play a role in ET-1 biosynthesis.

Animals↗

Impact of hypoxemia on the performance of cerebral oximeter in volunteer subjects.

Adverse neurological events during hypoxic episodes in high-risk patients or in patients not thought to be at risk while undergoing procedures increase morbidity and mortality. The ability to reliably monitor cerebral oxygenation could serve as an indicator for the need of therapeutic intervention and it's overall effect. This study was designed to verify the reliability of the only commercially available continuous noninvasive monitor, the INVOS 3100 (Somanetics Corp., Troy, MI), in subjects with varying levels of hypoxemia. Six adult volunteer subjects were enrolled. After placement of electrocardiogram (EKG), noninvasive blood pressure (NIBP), pulse oximeter (SpO2), cerebral oximeter (rSO2), a 20 g radial artery catheter, and a 4 F oximetric jugular bulb catheter, the subjects were given hypoxic mixtures to breathe to varying levels of desaturation. Arterial and mixed venous blood was drawn for blood-gas analysis at each level of O2 saturation. The cerebral hemoglobin saturation value from the cerebral oximeter was compared to the combined brain saturation using the formula: estimated field saturation between the light source and the detector (fSO2) = 0.25 x the arterial oxygen saturation (SaO2) + 0.75 x the jugular bulb venous oxygen saturation (SjvO2), (fSO2 = 0.25 SaO2 + 0.75 SjvO2). Statistical analysis demonstrated a correlation of 0.67 between rSO2 and fSO2 and a bias of -3.1% with a precision of 12.1%. Minimal bias of 0.38% and precision of 6.22% were calculated for transitional error. We concluded from the study that rSO2 may serve as a reliable indicator of changes in brain oxygenation induced by hypoxemia.

Adult↗

Endothelin-2 synthesis is stimulated by the type-1 tumour necrosis factor receptor and cAMP: comparison with endothelin-converting enzyme-1 expression.

ABSTRACT The synthesis of the vasoconstrictor peptide endothelin-2 (ET-2) is dependent on hydrolysis of the biologically inactive intermediate big ET-2 by an endothelin-converting enzyme (ECE). Here, mechanisms inducing ET-2 synthesis have been investigated using the human renal adenocarcinoma cell line (ACHN). Synthesis of ET-2 by ACHN cells was inhibited by phosphoramidon (IC(50( congruent with11 microM). To determine whether ET-2 synthesis occurs in parallel with the metallopeptidase ECE-1, a putative processing peptidase for big ET-2, changes in the levels of their mRNAs were compared by semi-quantitative RT-PCR under conditions causing the upregulation of ET-2 synthesis. Tumour necrosis factor-alpha (TNFalpha), forskolin and a cell-permeable cAMP analogue (dibutyryl cAMP) caused concentration-dependent increases in ET-2 synthesis. Combination of forskolin or dibutyryl cAMP with TNFalpha produced a significantly greater increase in ET-2 production than these agents alone, indicating that adenylate cyclase and TNFalpha induce ET-2 synthesis by separate signalling pathways. Studies using receptor selective TNFalpha mutants, (125(I-TNFalpha binding and TNF receptor mRNA showed that type-1 TNF receptors mediate the ET-2 response to TNFalpha. PreproET-2 mRNA levels were increased by TNFalpha at 1 h and 2 h, but returned to control levels at 4 h. Treatment with forskolin significantly increased preproET-2 mRNA levels after 1 h and 4 h. ACHN cells expressed ECE-1b and ECE-1c, but not the ECE-1a isoform of this peptidase. RT-PCR for the combined isoforms ECE-1b/c/d showed TNFalpha to increase mRNA levels at 2 h and 4 h. Forskolin had no effect on ECE-1b/c/d mRNA levels. Thus, expression of ET-2 and ECE-1b/c/d mRNAs in ACHN cells do not display the co-ordinated regulation observed with typical peptide prohormone processing enzymes and their substrates.

Adenocarcinoma↗

Angiotensin II modulates the activity of the Na+/K+ATPase in eel kidney.

We have previously shown that angiotensin II (Ang II) has a role at the level of the eel gill chloride cell regulating sodium balance, and therefore osmoregulation; the purpose of the present study was to extend these findings to another important osmoregulatory organ, the kidney. By catalytic histochemistry Na(+)/K(+)ATPase activity was found in both sea water (SW)- and freshwater (FW)-adapted eel kidney, particularly at the level of both proximal and distal tubules. Quantitation of tubular cell Na(+)/K(+)ATPase activity, by imaging, gave values in SW-adapted eels which were double those found in FW-adapted eels (Student's t-test: P<0.0001). This was due to a reduced number of positive tubules present in FW-adapted eels compared with SW-adapted eels. By conventional enzymatic assay, the Na(+)/K(+)ATPase activity in isolated tubular cells from SW-adapted eels showed values 1.85-fold higher those found in FW-adapted eels (Student's ttest: P<0.0001). Perfusion of kidney for 20 min with 100 nM Ang II provoked a significant increase (1.8-fold) in Na(+)/K(+)ATPase activity in FW, due to up-regulation of Na(+)/K(+)ATPase activity in a significantly larger number of tubules (Student's t-test: P<0.0001). The effect of 100 nM Ang II in SW-adapted kidneys was not significant. Stimulation with increasing Ang II concentrations was performed on isolated kidney tubule cells: Ang II provoked a dose-dependent stimulation of the Na(+)/K(+)ATPase activity in FW-adapted eels, reaching a maximum at 100 nM (1.82-fold stimulation), but no significant effect was found in SW-adapted eels (ANOVA: P<0.001 and P>0.05 respectively). Isolated tubule cells stimulated with 100 nM Ang II showed a significant generation of inositol trisphosphate (InsP(3)) and an increment in calcium release from intracellular stores. In conclusion, our results suggest that tubular Na(+)/K(+)ATPase is modulated by environmental salinity, and that Ang II has a role in regulating its activity in FW-adapted eels, probably through an InsP(3)-dependent mechanism.

Angiotensin II↗

A novel diagnosis of left paraduodenal hernia through laparoscopy.

A congenital intraperitoneal hernia, also known as a "paraduodenal hernia," is an extremely rare cause of intestinal obstruction. These hernias, which are caused by variations in intestinal rotation, present with symptoms ranging from intermittent abdominal pain to acute obstruction. Preoperative diagnosis is rare, and conventional treatment is usually by laparotomy. Laparoscopic diagnosis and repair has recently been reported in Japan. We present as case of a left paraduodenal hernia diagnosed and treated laparoscopically and a review of the literature.

Abdominal Pain↗

NMR structure of C-terminally tagged gramicidin channels.

A biotin group was covalently attached to the C terminus of gramicidin A (gA) through a linker arm comprising a glycine residue with either one (gAXB) or two caproyl groups (gAXXB). High-resolution two-dimensional NMR spectroscopy was used to determine the structure of these modified gA analogues and [Lys16]gramicidin A (gA-Lys) in sodium dodecyl-d25 sulphate micelles. Gated gA ion channels based on linking a receptor group to these gA analogues have been used recently as a component in a sensing device. The conformations of the gA backbones and amino acid side chains of lysinated gA and biotinylated gA in detergent micelles were found to be almost identical to that of native gA, i.e. that of an N-terminal to N-terminal (head to head) dimer formed by two right-handed, single-stranded beta 6.3 helices. The biotin tail of the gAXB and gAXXB and the lysine extremity of gA-Lys appeared to lie outside the micelle. Thus it appears that the covalent attachment of functional groups to the C terminus of gA does not disrupt the peptide's helical configuration. Further, single channel measurements of all three gA analogues showed that functioning ion channels were preserved within a membrane environment.

Biotin↗

Ultrasonographic measurement of liver length in the small-for-gestational-age fetus.

OBJECTIVE: Our purpose was to measure fetal liver size in small-for-gestational-age fetuses diagnosed by ultrasonography and to determine whether the small abdominal circumference used to diagnose small for gestational age is the result of a small liver. STUDY DESIGN: Ninety-eight pregnant women who were diagnosed as having a fetus that was small for gestational age were included. All had a fetal ultrasonographic measurement of abdominal circumference <10th percentile for gestational age. Measurements were made of the length of the right lobe of the fetal liver within 2 weeks of delivery. The liver length measurements were compared with data collected from a normal population that had been previously published by the authors. The group of fetuses with liver length measurements <10th percentile for gestational age were compared with those with liver length measurements within normal limits. RESULTS: Liver length measurements were >10th percentile in 80 fetuses (82%). Eighteen fetuses (18%) had small liver lengths, and this group had significantly smaller antenatal ultrasonographic measurements of head, abdomen, and femur. They were smaller at birth with smaller placentas and they had a higher perinatal mortality rate. CONCLUSION: The small abdominal circumference measurement that is the mainstay of ultrasonographic diagnosis of small for gestational age is thought to be a reflection of fetal liver size. This study questions that assumption. The majority of small-for-gestational-age fetuses in this small study did not have small liver lengths. The small abdominal circumference measurement may reflect a reduction in size of other intra-abdominal organs, reduced amounts of fat, or possibly an elevated diaphragm because of poor lung growth.

Case-Control Studies↗

Perinatal predictors of growth at six months in small for gestational age babies.

Poor growth in childhood is associated with a number of later complications and early recognition may enable early intervention to improve outcomes. Approximately 20% of small for gestational age (SGA) babies remain small at two years. Most catch up growth occurs in the first 6 months and smallness at 6 months predicts later small size in the majority of cases. There are no previous reports of perinatal predictors of size at 6 months in SGA babies. The aim of this study was to identify the perinatal factors associated with small size at 6 months in infants who were SGA at birth (birthweight < 10th%). SGA infants had assessments of length, weight, and head circumference performed at three monthly intervals by the same researcher. Detailed perinatal data was collected in all cases. Abnormal size was defined as a length, weight or head circumference measurement < 10th% for 6 months corrected age. Infants were considered to show failure of catch-up growth if measurements at 6 months were further below the population mean than birth measurements. Two hundred and forty eight babies were recruited of whom 203 (82%) completed followup at 6 months. Forty (20%) babies were short, and in logistic regression shortness at 6 months was predicted by shortness at birth and male sex. Thirty one (16%) had weight < 10th% and low weight was predicted in logistic regression by early gestation at diagnosis of SGA (median 30.8 weeks in those who were under weight and 33.9 weeks in those of normal weight p < 0.0001). Thirty seven (18%) had a low head circumference which was predicted by small head size at birth. Three quarters of the babies who were short, underweight, or had low head circumference at 6 months also showed failure of catch-up growth. Shortness and small head circumference at 6 months were predicted by shortness and small head circumference at birth, especially in boys. Underweight was predicted by early detection of SGA antenatally. Most SGA babies who remained small at 6 months failed to show catch up growth after birth.

Adult↗

Statewide replication of predictive validation for the Multnomah Community Ability Scale.

The Multnomah Community Ability Scale is a 17 item instrument that case managers can use to rate levels of functioning for clients with severe mental illness. Prior work in a large urban community mental health center showed that the instrument predicted subsequent involuntary hospitalization. The current project involved some 2,487 clients of community mental health programs throughout Oregon. This replication study again showed that low scores on the instrument predicted subsequent psychiatric hospitalization.

Adolescent↗

A preliminary study determining the feasibility of electromagnetic tracking for kinematics at the ankle joint complex.

OBJECTIVE: To determine the feasibility of using electromagnetic tracking (EMT) for quantifying three-dimensional kinematics at the ankle joint complex (AJC). METHODS: AJC kinematics were recorded in 10 normal healthy adults, and 10 rheumatoid arthritis patients presenting with AJC instability and deformity who were undergoing footwear and orthotic intervention. RESULTS: Kinematics in normal subjects had strong face validity, curve shape showing moderate (n=9), good (n=8) or excellent (n=4) agreement with data from seven published studies. The range of motion about the x-axis (15.2 degrees ) was similar to reference values (17.0 degrees ), but our technique underestimated rotations about the y- (8.1 degrees vs 14.0 degrees ) and z-axes (7.7 degrees vs 12.2 degrees ). In the rheumatoid arthritis pronated foot group, eversion and internal rotation during the stance phase of gait were between 2 and 5 times greater than for normal subjects. The use of a corrective foot orthosis in this group restored normal kinematics, reducing maximum eversion and internal rotation by 57 and 68%, respectively. CONCLUSION: A new technique for measuring kinematics at the AJC is described. Based upon the findings of this pilot study, EMT may be useful for diagnosing AJC dysfunction and quantifying the mechanical efficacy of footwear and orthosis interventions.

Adult↗

The expression of endothelin-1 and endothelin-converting enzyme-1 (ECE-1) are independently regulated in bovine aortic endothelial cells.

The endopeptidase called endothelin-converting enzyme-1 (ECE-1) is thought to play a physiological role in endothelin-1 (ET-1) biosynthesis. For human ECE-1, differential splicing of messenger RNA (mRNA) results in the synthesis of three isoforms, termed ECE-1a, ECE-1b, and ECE-1c. The isoform(s) responsible for the hydrolysis of the biosynthetic intermediate big ET-1 in endothelial cells have yet to be assigned. To investigate whether the expression of mRNAs for preproET-1 and ECE-1 are regulated in parallel, a variety of conditions were used to compare levels of ET-1 synthesis by bovine aortic endothelial cells (BAECs) with levels of mRNA for preproET-1, ECE-1a, ECE-1c, and the combined ECE-1 isoforms (ECE-1a/b/c). Stimulation of BAECs with tumor necrosis factor-alpha or transforming growth factor-beta increased ET-1 synthesis, and treatment of BAECs with 2-chloroadenosine or staurosporine caused concentration-dependent reductions in ET-1 synthesis. Estimates of mRNA levels by reverse transcription-polymerase chain reaction (RT-PCR) with linear cycling conditions showed changes in preproET-1 expression to correlate well with ET-1 secretion. In contrast, RT-PCR analysis of ECE-1 expression by using primer pairs to measure ECE-1a, ECE-1c, or all the ECE-1 isoforms simultaneously showed no correlation between their mRNA levels and those of preproET-1. This indicates that under the conditions investigated, expression of ECE-1 is not coordinated with ET-1 synthesis in BAECs.

Animals↗