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Biomedical subjects

C Johns

Publications and source records attributed to C Johns.

At least 19 recordsLinked to original sources
PubMed2001

Role of the B(2) receptor of bradykinin in insulin sensitivity.

The biological actions of bradykinin (BK) are attributed to its B(2) type receptor (B(2)R), whereas the B(1)R is constitutively absent, inducible by inflammation and toxins. Previous studies in B(2)R gene knockout mice showed that the B(1)R is overexpressed, is further upregulated by hypertensive maneuvers, and assumes some of the hemodynamic functions of the B(2)R. The current experiments were designed to further clarify the metabolic function of the B(2)R and to explore whether the upregulated B(1)R can also assume the metabolic function of the missing B(2)R. One group of B(2)R-/- mice (n=9) and one of B(2)R+/+ controls (n=8) were treated for 3 days with captopril (which produced a similar blood pressure-lowering response in both groups) and studied with the hyperinsulinemic euglycemic clamp. The knockout mice had fasting and steady-state blood glucose levels similar to those of the wild-type mice but a had tendency to higher fasting insulin levels (at 27.8+/-5.2 versus 18+/-2.9 mU/L, respectively). However, they had significantly higher steady-state insulin levels (749+/-127.2 versus 429.1+/-31.5 mU/L, P<0.05) and a significantly lower glucose uptake rate (31+/-2.4 versus 41+/-2.3 mg/kg per minute, P<0.05) and insulin sensitivity index (4.6+/-0.9 versus 10+/-0.7 P<0.001). Analysis of B(1)R and B(2)R gene expression by reverse transcription-polymerase chain reaction in cardiac muscle, skeletal muscle, and adipose tissues revealed significantly higher B(1)R mRNA level in the knockouts versus wild-type (P<0.05) at baseline and a further significant upregulation in mRNA by 1.8- to 3.2-fold (P<0.05) after insulin infusion. We conclude that absence of B(2)R confers a state of insulin resistance because it results in impaired insulin-dependent glucose transport; this is probably a direct B(2)R effect because, unlike the hemodynamic autacoid-mediated effects, it cannot be assumed by the upregulated B(1)R.

Animals↗
PubMed2001

Familial aggregation of sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS).

Despite reports of familial clustering of sarcoidosis, little empirical evidence exists that disease risk in family members of sarcoidosis cases is greater than that in the general population. To address this question, we estimated sarcoidosis familial relative risk using data on disease occurrence in 10,862 first- and 17,047 second-degree relatives of 706 age, sex, race, and geographically matched cases and controls who participated in the multicenter ACCESS (A Case-Control Etiology Study of Sarcoidosis) study from 1996 to 1999. Familial relative risk estimates were calculated using a logistic regression technique that accounted for the dependence between relatives. Sibs had the highest relative risk (odds ratio [OR] = 5.8; 95% confidence interval [CI] = 2.1-15.9), followed by avuncular relationships (OR = 5.7; 95% CI = 1.6-20.7), grandparents (OR = 5.2; 95% CI = 1.5-18.0), and then parents (OR = 3.8; 95% CI = 1.2-11.3). In a multivariate model fit to the parents and sibs data, the familial relative risk adjusted for age, sex, relative class, and shared environment was 4.7 (95% CI = 2.3-9.7). White cases had a markedly higher familial relative risk compared with African-American cases (18.0 versus 2.8; p = 0.098). In summary, a significant elevated risk of sarcoidosis was observed among first- and second-degree relatives of sarcoidosis cases compared with relatives of matched control subjects.

Adolescent↗
PubMed2001

Early thymocyte development is regulated by modulation of E2A protein activity.

The E2A gene encodes the E47 and E12 basic helix-loop-helix (bHLH) transcription factors. T cell development in E2A-deficient mice is partially arrested before lineage commitment. Here we demonstrate that E47 expression becomes uniformly high at the point at which thymocytes begin to commit towards the T cell lineage. E47 protein levels remain high until the double positive developmental stage, at which point they drop to relatively moderate levels, and are further downregulated upon transition to the single positive stage. However, stimuli that mimic pre-T cell receptor (TCR) signaling in committed T cell precursors inhibit E47 DNA-binding activity and induce the bHLH inhibitor Id3 through a mitogen-activated protein kinase kinase-dependent pathway. Consistent with these observations, a deficiency in E2A proteins completely abrogates the developmental block observed in mice with defects in TCR rearrangement. Thus E2A proteins are necessary for both initiating T cell differentiation and inhibiting development in the absence of pre-TCR expression. Mechanistically, these data link pre-TCR mediated signaling and E2A downstream target genes into a common pathway.

Animals↗
PubMed2001

Practical method for evaluation of linearity and effective pathlength of on-capillary photometric detectors in capillary electrophoresis.

The optical characteristics of on-capillary photometric detectors for capillary electrophoresis were evaluated and five commercial detectors were compared. Plots of sensitivity (absorbance/concentration) versus absorbance obtained with a suitable testing solution yield both the linear range and the effective path length of the detector. The detector linearity is a crucial parameter when using absorbing electrolytes, such as for indirect photometric detection, and especially for highly absorbing electrolyte probe ions. The upper limits of the linear ranges (determined as 5% decline in sensitivity) for five commercial detectors ranged from 0.175 to 1.2 AU. The effective pathlength reflects the quality of the optical design of the detector and is equal to the capillary internal diameter only for a light beam passing exactly through the capillary centre, but becomes progressively shorter for imperfect optical designs. The determined effective pathlength for the five investigated detectors ranged from 49.7 to 64.6 microm for a 75 microm I.D. capillary.

Electrophoresis, Capillary↗
PubMed2001

Vasoactive potential of the b(1) bradykinin receptor in normotension and hypertension.

The B(1) type receptor of bradykinin (Bk B(1)R) is believed to be physiologically inert but highly inducible by inflammatory mediators and tissue damage. To explore the potential participation of the Bk B(1)R in blood pressure (BP) regulation, we studied mice with deleted Bk B(2)R gene with induced experimental hypertension, either salt-dependent (subtotal nephrectomy with 0.5% NaCl as drinking water) or renin/angiotensin-dependent (renovascular 2-kidney-1-clip). Compared with the wild-type controls, the B(2)R gene knockout mice had a higher baseline BP (109.7+/-1.1 versus 101.1+/-1.3 mm Hg, P:=0.002), developed salt-induced hypertension faster (in 19.3+/-2.3 versus 27.7+/-2.4 days, P:=0.024), and had a more severe end point BP (148+/-3.7 versus 133+/-3.1 mm Hg, P:<0.05). On the contrary, renovascular hypertension developed to the same extent (149.7+/-4.3 versus 148+/-3.6 mm Hg) and in the same time frame (14+/-2.2 versus 14+/-2.1 days). A bolus infusion of a selective B(1)R antagonist at baseline produced a significant hypertensive response (by 11.4+/-2 mm Hg) in the knockout mice only. Injection of graded doses of a selective B(1)R agonist produced a dose-dependent hypotensive response in the knockout mice only. Assessment of tissue expression of B(1)R and B(2)R genes by reverse transcription-polymerase chain reaction techniques revealed significantly higher B(1)R mRNA levels in the B(2)R knockout mice at all times (normotensive baseline and hypertensive end points). At the hypertensive end points, there was always an increase in B(1)R gene expression over the baseline values. This increase was significant in cardiac and renal tissues in all hypertensive wild-type mice but only in the clipped kidney of the renovascular knockout mice. The B(2)R gene expression in the wild-type mice remained unaffected by experimental manipulations. These results confirm the known vasodilatory and natriuretic function of the Bk B(2)R; they also indicate that in its absence, the B(1)R can become upregulated and assume some of the hemodynamic properties of the B(2)R. Furthermore, they indicate that experimental manipulations to produce hypertension also induce upregulation of the B(1)R, but not the B(2)R, in cardiac and renal tissues.

Animals↗
PubMed2001

Concordance of murine quantitative trait loci for salt-induced hypertension with rat and human loci.

To investigate the genetic control of salt-induced hypertension, we performed a quantitative trait locus analysis on male mice from a reciprocal backcross between the salt-sensitive C57BL/6J and the normotensive A/J inbred mouse strains after they were provided with water containing 1% salt for 2 weeks. Genome-wide scans performed on these mice and analyzed with a combination of conventional marker-based regressions and a novel simultaneous search for pairs revealed six significant quantitative trait loci associated with salt-induced blood pressure, two of which were interacting loci. These six loci, named Bpq1-6 for blood pressure quantitative trait loci, mapped to D1Mit334, D1Mit14, D4Mit164, D5Mit31, D6Mit15, and D15Mit13. Furthermore, five of these six loci were concordant with hypertension loci in rats, and four were concordant with hypertension loci in humans, suggesting that quantitative trait loci mapping in model organisms can be used to guide the search for human blood pressure genes.

Analysis of Variance↗
PubMed2001

New isoelectric buffers for capillary electrophoresis: N-carboxymethylated polyethyleneimine as a macromolecular isoelectric buffer.

Isoelectric buffers are attractive for electrophoresis because of their low conductivity, and their compatibility with indirect photometric detection in capillary electrophoresis (CE) where they do not interfere with the detection by exhibiting competitive displacement of the UV-absorbing probe ion. N-carboxymethylated polyethyleneimine (CMPEI) was prepared by introducing a half molar equivalent of carboxylate groups onto a polyethyleneimine backbone. Its isoelectric point determined by conductometric titration and from the pH of its dilute aqueous solution is approx. 6.8, which allows isoelectric buffering at a lower pH compared to histidine (pI7.7). Although the isoelectric point is somewhat diffuse, as expected for a polymeric compound, it exhibits a buffering capacity at a pI point of about twice that of histidine. Studies of electroosmotic flow (EOF) profile at various pH values in fused silica capillaries showed that CMPEI adsorbs onto the fused silica wall and reverses the EOF at pH < 6.5. CMPEI was applied as a buffer in an electrolyte containing 0.5 mM of the anionic dye tartrazine used as the probe for indirect detection of anions. The separation system exhibited a stable baseline, no system peaks, separation efficiencies of up to 195,000 theoretical plates, and detection limits down to 0.2 microM or 2 amol of injected analyte.

Journal Article↗
PubMed2001

Depending on the intent and emphasis of the supervisor, clinical supervision can be a different experience.

The paper proposes that clinical supervision can be a very different experience for the practitioner depending on the intent and emphasis of the supervisor. Utilizing Habermas's typology of knowledge constituted interests (1971), clinical supervision can be viewed as a dialectic between technical and emancipatory interests. The rhetoric and spirit of supervision would suggest an emancipatory approach yet the reality is that when supervision is accommodated with bureaucratic cultures, the technical interest will be dominant, especially when supervisors are in line-management roles to practitioners. This raises issues around the nature and role of clinical leadership, and ways of bridging the tension between emancipatory and technical interests.

Humans↗
PubMed2001

Papillary muscle contribution to ventricular ejection in normal and hypertrophic ventricles: a transesophageal echocardiographic study.

BACKGROUND: The interrelationship between left ventricular (LV) volume, stroke volume, and papillary muscle (PM) volume have not been studied. These volumes are relevant in understanding LV ejection mechanics in normal chambers and ascertaining whether differences exist between normal and hypertrophied LV chambers. METHODS AND RESULTS: PM basal areas were measured in short-axis transesophageal echocardiographic views and lengths were measured in long-axis views. PM volume was estimated by the formula for volume of a cone: 1/3 x PM base area x PM length. The formula for LV volume was as follows: LV volume = 2/3 x LV area x LV length. Of the initial 82 subjects with normal LV function studied by TEE, data on 71 are presented in this report. Thirty-two patients had normal LV size and wall thickness, and 39 had LV hypertrophy (LVH). PM volume/LV volume % in end-diastole (ED) and end-systole (ES) in normal muscles was 3.1 +/- 1.0 and 9.6 +/- 4.9, respectively. In LVH, the respective values were 5.1 +/- 2.0 (P < 0.05) and 13.5 +/- 4.9 (P < 0.05). For those with severe LVH, the values were 7.1 +/- 2.5 (P < 0.001) and 15.9 +/- 4.1 (P < 0.001), respectively, for ED and ES. Similar trends were seen in the PM volume/stroke volume relationships in normal and hypertrophic ventricles. CONCLUSIONS: PMs are larger and form a larger fraction of LV volume in LVH than in normal muscles. In patients with severe LVH, the contribution of PMs to ventricular ejection is more pronounced. PMs may, therefore, play a larger role in LV ejection in LVH than in normal ventricles (i.e., hypertrophied PM enhance the pump efficiency of LV ejection).

Adult↗
PubMed2001

The caring dance.

As nursing and health care practice enter the new Millennium, practitioners are increasingly urged to pay attention to evidenced based practice to justify what they do. Yet the truth is, that within the caring dance, practitioners need to connect with more ancient sources of wisdom. Failure to do so leads to a life out of balance and a failure to dance well and fulfil the fundamental role of being a nurse. The paper draws exclusively on the work of Blackwolf and Gina Jones, as an example of such ancient wisdom to inform and inspire the caring dance.

Attitude of Health Personnel↗
PubMed2001

Effects of ANG II on bradykinin receptor gene expression in cardiomyocytes and vascular smooth muscle cells.

Bradykinin has vasodilatory and tissue-protective effects exerted via its B(2) type receptor, whereas the B(1) receptor is constitutively absent but inducible by inflammation and toxins. In previous studies, we found that B(2) receptor gene knockout mice exhibit overexpression of the B(1) receptor, which assumes a vasodilatory function and is further upgraded in renovascular hypertension. The present study was designed to explore the effects of excess angiotensin II (ANG II) on B(1) receptor and B(2) receptor gene expression in mouse cardiomyocytes and rat vascular smooth muscle cells (VSMC) in vivo (after a 3-day infusion of 30 ng/min ANG II in 11 wild-type and in 13 genetically engineered mice with deleted B(2) receptor gene) and in vitro (ANG II added in rat VSMC culture in the presence or absence of AT(1) or AT(2) receptor antagonist). Expression of B(1) and B(2) receptor mRNA was assessed by reverse transcriptase-polymerase chain reaction. ANG II infusion caused upregulation by 30% of the already significantly overexpressed B(1) receptors in cardiomyocytes of the B(2) receptor gene knockout mice, but in the wild-type mice it upregulated only the B(2) receptor mRNA by 47%. The addition of ANG II in VSMC culture produced a time-dependent induction of B(1) and upregulation of B(2) receptor gene expression, maximal at 3 h (by fivefold), declining almost to baseline by 24 h. The addition of losartan completely blocked this effect, whereas the AT(2) blocker PD-123319 made no difference, indicating that this is an AT(1)-mediated effect of ANG II. The data indicate that excess ANG II in subpressor doses in vivo upregulates expression of the B(2) receptor, but in its absence, the already overexpressed B(1) receptor is further upregulated, evidently assuming a counterregulatory response; in vitro, it transiently upregulates both bradykinin receptors.

Angiotensin II↗
PubMed2001

Effects of antisense oligodeoxynucleotide targeting of the alpha(2B)-adrenergic receptor messenger RNA in the central nervous system.

The results of previous studies with genetically engineered mice have suggested that an intact central alpha(2B)-adrenergic receptor (alpha(2B)-AR) subtype mediates the development and maintenance of salt-induced hypertension. In the present study, we sought to further define the role of this receptor by injecting antisense oligodeoxynucleotides (AS-ODNs), targeting a selected sequence of the alpha(2B)-AR mRNA, into the lateral cerebral ventricle of rats that had undergone prior subtotal nephrectomy and dietary salt loading. Cell culture studies showed that these AS-ODNs could block alpha(2B)-AR protein generation. Before AS-ODN injection, blood pressure (BP) averaged 133+/-5 mm Hg during the daytime and rose to 165+/-4 mm Hg during the nighttime activity hours (P<0.001 versus baseline average of 120+/-2 mm Hg). The injection of AS-ODNs during the early afternoon prevented the BP rise and was associated with a significant fall in heart rate (from 385+/-12 to 306+/-15 bpm, P<0.05) and symptoms of sedation that lasted for several hours, with a peak at 3 to 6 hours and full recovery by 24 hours. At that time, a second injection produced identical effects in all rats (n=9). Control rats (n=10) that received scrambled ODN injections had no changes in BP or heart rate patterns, and neither group had evidence of neurotoxicity, indicating that these effects are specifically due to translational inhibition of central alpha(2B)-AR. We conclude that a fully functional central alpha(2B)-AR is necessary for the induction of salt-dependent hypertension.

Animals↗
PubMed2001

The ability of helical CT to preoperatively stage endometrial carcinoma.

OBJECTIVE: This study evaluated helical CT as an imaging modality for preoperative staging of endometrial carcinoma. MATERIALS AND METHODS: Three radiologists retrospectively and independently reviewed the preoperative helical CT scans of 25 consecutive patients with endometrial carcinoma. The presence or absence of deep myometrial invasion and the presence or absence of cervical involvement were evaluated on helical CT and compared with pathologic findings at hysterectomy. RESULTS: Helical CT has a sensitivity of 83% and a specificity of 42% for the detection of deep myometrial invasion (stage IC). Helical CT has a sensitivity of 25% and a specificity of 70% for the detection of cervical involvement (state II). These results compare poorly with those of MR imaging (sensitivity 92%, specificity 90% for the detection of deep myometrial invasion; sensitivity 86%, specificity 97% for the detection of cervical involvement). CONCLUSION: Helical CT is insensitive and nonspecific compared with MR imaging for the preoperative staging of endometrial carcinoma. MR imaging remains the imaging modality of choice.

Aged↗
PubMed2000

Indirect photomeric detection of anions in capillary electrophoresis using dyes as probes and electrolytes buffered with an isoelectric ampholyte.

The use of highly absorbing anionic dyes as probes and isoelectric ampholytes as buffers in background electrolytes (BGEs) combined with the use of a light emitting diode (LED) as a light source has been studied for ultrasensitive indirect photometric detection in capillary electrophoresis (CE). Potential dyes and buffers were evaluated based on characteristics relevant to indirect photometric detection principles, such as the electrophoretic mobility of the probe dye, its solubility and adsorption behaviour, and the isoelectric point and buffering capacity of the ampholytic buffer. Two dyes, tartrazine and naphthol yellow S, and histidine as the ampholytic buffer, were selected for detailed investigation. Purification of the probes was vital to avoid anionic impurities interfering with the detection. For the electrolytes containing a purified probe (0.5 mM) and histidine as the isoelectric buffer (p/ 7.7), hydroxypropylmethyl cellulose (approximately 0.05%) was effective in suppression of the electroosmotic flow (EOF). Analytical method performance characteristics were determined. For both probes, experimentally determined mobilities were generally close to literature values, excellent peak shapes and separation efficiencies of up to 298 000 theoretical plates were obtained, and detection limits were generally at the sub-microM level. For the naphthol yellow S-histidine BGE, linearity and reproducibility were also evaluated, with excellent linearity being observed over a range of 5-500 microM, and reproducibility (relative standard deviation, RSD) less than 1% for migration times and 2-8% for normalised peak areas. The approach developed was applied successfully to several real samples including tap water, mineral waters, and beer.

Anions↗
PubMed2000

Echocardiography of the coronary sinus in adults.

The coronary sinus (CS) is a small tubular structure just above the posterior left atrioventricular junction. The CS can be imaged in several different echocardiographic views. Using zoom M-mode recordings of the CS in apical two-chamber view, CS caliber can be sharply imaged and easily measured during different phases of the cardiac cycle. We have recently shown that the CS narrows during atrial contraction in persons with sinus rhythm, but does not narrow at all if atrial fibrillation is present. Attenuation of CS narrowing occurs in patients with congestive heart failure and inferior vena cava plethora. Maximal CS caliber occurs during ventricular systole. Patients with poor left ventricular systolic function show mild CS dilatation. Greater CS dilatation is present in patients with persistent left superior vena cava, and huge dilatation when this anomaly is accompanied by absence of a right superior vena cava. Injection of sonicated saline into a left and then a right arm vein is diagnostically useful in confirming these two venous anomalies. Pulsed-wave Doppler of the CS can be recorded in the parasternal right heart inflow view. From this and from the CS cross-section area it may be possible to estimate coronary blood flow.

Adult↗
PubMed2000

Role of the postsynaptic alpha(2)-adrenergic receptor subtypes in catecholamine-induced vasoconstriction.

Catecholamines induce direct vasoconstriction mediated by postsynaptic alpha-adrenergic receptors (alpha-ARs) of both the alpha(1) and alpha(2) type. To evaluate the contribution of each alpha(2)-AR subtype (alpha(2A), alpha(2B), and alpha(2C)) to this function, we used groups of genetically engineered mice deficient for the gene to each one of these subtypes and compared their blood pressure (BP) responses to their wild-type counterparts. Blood pressure responses to a bolus of norepinephrine (NE) were assessed before and after sequential blockade of alpha(1)-ARs with prazosin and alpha(2)-ARs with yohimbine. The first NE bolus elicited a brief 32 to 44 mm Hg BP rise (p < 0.001 from baseline) in all six groups. Prazosin decreased BP by 23 to 33 mm Hg in all groups, establishing a new lower baseline. Repeat NE at that point elicited lesser but still significant (p < 0.001) brief pressor responses between 32% and 45% of the previous BP rise in five of the six groups. Only the alpha(2A)-AR gene knockouts differed, responding instead with a 20-mm Hg fall in BP, a significant change from baseline (p < 0.001) and different from the pressor response of their wild-type counterparts (p < 0.001). The addition of yohimbine produced no further BP change in the five groups, but it did produce a small 7. 5-mm Hg fall (p < 0.05) in the alpha(2A)-AR knockouts. Norepinephrine bolus during concurrent alpha(1) and alpha(2)-AR blockade produced significant (p < 0.001) hypotensive responses in all subgroups, presumably attributable to unopposed stimulation of beta(2)-vascular wall ARs. We conclude that the alpha(2)-AR-mediated vasoconstriction induced by catecholamines is attributable to the alpha(2A)-AR subtype because mice deficient in any one of the other subtypes retained the capacity for normal vasoconstrictive responses. However, the alpha(1)-ARs account for the major part (as much as 68%) of catecholamine-induced vasoconstriction.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2000

Working with Alice: a reflection.

Reflective practice has become established within educational programmes and in clinical supervision. Yet what does it mean to be a reflective practitioner? This paper seeks to give some meaning to this concept by drawing on a story I wrote in my reflective journal one evening. My reflection on this event draws out key issues of practice and reflection that enable me to gain insight and apply to future practice within a reflexive learning spiral.

Attitude of Health Personnel↗