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J K Harrison

Publications and source records attributed to J K Harrison.

At least 91 records · Page 5Linked to original sources
PubMed1993

Genomic analysis and expression patterns reveal distinct genes for endothelial and brain nitric oxide synthase.

Constitutively active nitric oxide synthases (NOS) are a unique class of NADPH-dependent, calcium/calmodulin-dependent enzymes that catalyze the conversion of L-arginine to nitric oxide and L-citrulline. However, little is known about the molecular similarities or differences between the two prototypical constitutive NOS enzymes, endothelial NOS (ECNOS) and brain NOS (bNOS). The aims of this study were to begin characterizing the gene structure and tissue distribution of messenger RNAs (mRNAs) for ECNOS and bNOS and to examine the immunological resemblance of the proteins by Western blotting. Full-length complementary DNAs (cDNAs) encoding bovine ECNOS and rat bNOS hybridized, under high stringency, to different-sized fragments of endonuclease-digested bovine, rat, and human genomic DNA. In addition, more than one fragment was detected with both cDNAs, suggesting that ECNOS and bNOS genes contained multiple introns. Tissue distribution of ECNOS mRNA (4.4 kb) and bNOS mRNA (9.5 kb) in the rat was detected by Northern blotting. Patterns among tissue extracts were strikingly different, with ECNOS mRNA being most abundant in aorta, heart, lung, kidney, adrenal gland, spinal cord, and urogenital tissues and bNOS mRNA most prominent in brain regions, intestine, stomach, spinal cord, adrenal gland, and aorta. Interestingly, ECNOS cDNA detected two equally abundant RNA transcripts (4.4 and 4.0 kb) in most brain regions tested, suggesting an alternative splicing of the ECNOS pre-mRNA. Western blotting, using an ECNOS monoclonal antibody, recognized ECNOS protein from native bovine endothelial cells, cultured bovine endothelial cells, and COS cells transfected with ECNOS cDNA but did not recognize purified bNOS.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1993

Ontogeny of type 1 angiotensin II receptor gene expression in the rat.

To determine whether the expression of the type 1 angiotensin II receptor (AT1) gene is developmentally regulated and whether the regulation is tissue specific, AT1 mRNA levels were determined by Northern blot analysis in livers and kidneys from fetal, newborn, and adult rats, using a 1133-bp rat AT1 cDNA. In the liver, AT1 mRNA levels increased fivefold from 15 d gestation to 5 d of age. Liver AT1 mRNA levels at 5 d of age were similar to those of adult rats. In the kidney, AT1 mRNA levels were higher in immature than in adult animals. The intrarenal distribution of AT1 mRNA was assessed by in situ hybridization to a 35S-labeled 24 residues oligonucleotide complementary to rat AT1 mRNA. In the adult, AT1 mRNA was present in glomeruli, arteries, and vasa recta, whereas in the newborn AT1 mRNA was observed also over the nephrogenic area of the cortex. We conclude that: (a) fetal kidney and liver express the AT1 gene; (b) the AT1 gene expression is developmentally regulated in a tissue-specific manner; (c) during maturation, localization of AT1 mRNA in the kidney shifts from a widespread distribution in the nephrogenic cortex to specific sites in glomeruli, arteries, and vasa recta, suggesting a role for the angiotensin receptor in nephron growth and development.

Age Factors↗
PubMed1993

Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone.

GH-releasing hormone (GHRH), acting through the GHRH receptor (GHRH-R), plays a pivotal role in the regulation of GH synthesis and secretion in the pituitary. It is possible that GHRH may serve other roles in other tissues. Here we report the cloning of a cDNA encoding a human GHRH-R from an acromegalic pituitary cDNA library. The isolated cDNA encodes a 423-amino acid protein that has seven putative transmembrane domains characteristic of G-protein-coupled receptors. It is a member of the secretin family of G-protein-coupled receptors and has 47%, 42%, 35%, and 28% identity with receptors for vasoactive intestinal peptide, secretin, calcitonin, and PTH, respectively. Transient expression of this cDNA in COS cells induced saturable, high affinity, GHRH-specific binding and also stimulated intracellular cAMP accumulation in response to physiological concentrations of GHRH. A specific GHRH antagonist blocked both binding and second messenger response. Northern analysis indicated that GHRH-R mRNA was most abundant in extracts of pituitary and was not detected in other tissues.

Acromegaly↗
PubMed1992

Molecular cloning and expression of a cDNA encoding endothelial cell nitric oxide synthase.

Endothelium-derived relaxing factor (EDRF), identified as nitric oxide (NO), is derived from a guanidino nitrogen of L-arginine via its metabolism by nitric oxide synthase (NOS). Herein, we report the molecular cloning of a cDNA encoding the constitutive calcium-calmodulin (Ca2+/CaM)-regulated nitric oxide synthase (ECNOS). A full-length ECNOS clone was isolated by screening a bovine aortic endothelial cell cDNA library using a fragment of rat brain NOS (bNOS) cDNA. This cDNA has an open reading frame of 3615 nucleotides encoding a 1205-amino acid protein. Membranes prepared from COS cells transfected with the ECNOS cDNA demonstrated NADPH- and Ca2+/CaM- dependent conversion of L-, but not D-, arginine to NO and citrulline that was inhibited by NG-nitro-L-arginine methyl ester. Comparison of the deduced amino acid sequence of ECNOS to the bNOS and macrophage NOS (Mac-NOS) sequences revealed 57 and 50% identity, respectively. In addition, ECNOS contains a unique N-myristylation consensus sequence (not shared by bNOS or Mac-NOS) that may explain its membrane localization.

Amino Acid Oxidoreductases↗
PubMed1992

Left ventricular filling and ventricular diastolic performance after percutaneous balloon mitral valvotomy.

The time course of left ventricular (LV) filling and LV diastolic performance were examined in 27 consecutive patients in sinus rhythm before and acutely after balloon mitral valvotomy (BMV). The mitral valve area acutely increased from 1.1 +/- 0.3 to 2.1 +/- 0.8 cm2. Simultaneous pressure-volume data were obtained using digital subtraction left ventriculography and LV micromanometer pressure before and 10 minutes after BMV. The time constant of LV isovolumic relaxation was unchanged after BMV (50 +/- 10 ms before BMV vs 47 +/- 13 ms after BMV). In addition, values before and after BMV for LV end-diastolic volume (123 +/- 29 vs 125 +/- 36 ml), end-diastolic pressure (11 +/- 4 vs 12 +/- 4 mm Hg) and diastolic filling time (337 +/- 126 vs 338 +/- 152 ms) were not altered by the procedure. After BMV the peak diastolic filling rate (403 +/- 143 vs 469 +/- 302 ml/s) was maintained despite a 36% reduction in left atrial filling pressure. There was a trend toward earlier occurrence of the peak filling rate (196 +/- 127 vs 146 +/- 148 ms, p = 0.08). The percentage of diastolic filling in the first third of diastole, however, was similar (42 +/- 9 vs 48 +/- 16%) before and after the procedure. Thus, the time course of LV filling is not significantly altered acutely after BMV, but is maintained at reduced left atrial filling pressure. Neither LV relaxation or LV chamber compliance are altered acutely after BMV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Use of balloon occlusion to improve visualization of anomalous pulmonary venous return in an adult with cor triatriatum.

Cor triatriatum, although rare in adults, is often associated with anomalous pulmonary venous return. Accurate diagnosis of the pulmonary venous return and its anatomic connections is essential in planning proper surgical correction. This case illustrates the advantage of selective pulmonary artery angiography in obtaining accurate detail of the pulmonary venous anatomy from digital subtraction levophase images. Selective right and left pulmonary angiography was performed using a balloon catheter to simultaneously occlude the opposite pulmonary artery. This technique was well tolerated and greatly enhanced visualization of the anomalous pulmonary venous connections, allowing proper planning for corrective surgery.

Angiography, Digital Subtraction↗
PubMed1992

Ergonovine maleate testing during cardiac catheterization: a 10-year perspective in 3,447 patients without significant coronary artery disease or Prinzmetal's variant angina.

The utility of ergonovine testing for coronary artery spasm was assessed in 3,447 patients with angiographically insignificant (less than 50% diameter stenosis) or no coronary artery disease. No patients clinically had Prinzmetal's variant angina. Overall, 4% had a positive ergonovine test result, defined by spasm causing greater than or equal to 75% focal stenosis. Complications related to ergonovine use occurred in 11 patients (0.03%). In a training sample of 1,136 patients (studied between 1980 and 1984), two independent predictors of spasm were found by using multivariate analysis: the amount of visible coronary artery disease on the coronary angiogram (p less than 0.0001) and a smoking history (p = 0.001). A model to predict spasm based on these variables was validated in a test group of 2,311 patients who received ergonovine from 1985 to 1989. This model allowed the identification of a subset of 400 patients in the validation sample who had a 10% positive test rate compared with a 2% positive test rate in the remaining patients. These results should permit clinicians who use provocative testing in the catheterization laboratory to reserve testing for the subset of this group of patients most likely to have abnormal findings.

Angina Pectoris, Variant↗
PubMed1992

Polymerase chain reaction analysis of renin in rat aortic smooth muscle.

Controversy exists whether vascular smooth muscle cells in vivo synthesize renin, thereby providing a critical component of the hypothesized vascular renin-angiotensin system. To examine this question, we enzymatically isolated and pooled the medial layer of thoracic aortas from Sprague-Dawley rats that were either untreated or enalapril treated for 3 days, isolated messenger RNA (mRNA), and performed Northern blot analysis with rat complementary DNA (cDNA) probes for renin, cathepsin D, and cathepsin E. Renin mRNA was detected in kidney but was not detected in aortic smooth muscle from the untreated or enalapril-treated groups. Cathepsin E mRNA was detected in enalapril-treated aorta and kidney, and cathepsin D mRNA was detected in all tissues examined. cDNA was synthesized and subjected to polymerase chain reaction analysis by using primers corresponding in sequence to regions conserved throughout the aspartic proteinases. Cathepsins D and E were amplified from kidney and aortic cDNA. Renin was less consistently amplified from the aortic cDNA and was much less abundant than cathepsin E or cathepsin D. These results suggest that 1) renin mRNA is present in aortic smooth muscle cells in vivo in quantities detectable only after multiple rounds of polymerase chain reaction amplification, 2) renin mRNA is not upregulated in aortic smooth muscle after converting enzyme inhibition, and 3) cathepsins D and E are the predominant aspartic proteinases in aortic smooth muscle.

Animals↗
PubMed1992

Ejection load changes in aortic stenosis. Observations made after balloon aortic valvuloplasty.

To investigate complementarity and competitiveness between the intrinsic and extrinsic components of the total left ventricular systolic load, hemodynamic data from 18 elderly subjects with severe aortic stenosis were analyzed before and after balloon dilation of the stenosed aortic valve. Multisensor micromanometric pressure measurements allowed calculation (simplified Bernoulli equation) of the ejection velocity and aortic input impedance spectra. Despite a 32% increase in the aortic valve area (from 0.56 +/- 0.04 to 0.74 +/- 0.05 cm2 [mean +/- SEM], p < 0.01), the peak left ventricular systolic pressure fell by only 12% (from 189 +/- 10 to 167 +/- 8 mm Hg, p < 0.01). This was accompanied by an increase in the impedance at the same cardiac output. In a subset of patients (n = 9) in whom the peak aortic systolic pressure rose after valvuloplasty (from 115 +/- 10 to 128 +/- 12 mm Hg, p < 0.01), a 40% increase in the aortic valve area was accompanied by a marked increase in the aortic input impedance. In this subset, the steady component of the aortic input impedance increased by 24% (from 960 +/- 96 to 1,188 +/- 134 dyne.sec/ml, p < 0.05), and the characteristic impedance increased by 25% (from 106 +/- 13 to 132 +/- 19 dyne.sec/ml, p < 0.05). Because of an increased aortic impedance acutely following the procedure, the total left ventricular systolic load after balloon dilation of the stenotic valve was only slightly decreased despite a significant increase in aortic valve area. This represents an example of complementarity and competitiveness between the intrinsic and extrinsic components of the total systolic ventricular load. It may explain why improvement in left ventricular performance may be modest acutely following balloon aortic valvuloplasty.

Aged↗
PubMed1992

Critical mitral stenosis causing ischemic hepatic failure. Successful treatment by percutaneous balloon mitral valvotomy.

We report a 52-year-old patient with severe mitral stenosis who developed new onset atrial fibrillation, low output congestive heart failure and fulminant ischemic hepatic failure with subsequent severe coagulopathy. Percutaneous mitral valvotomy resulted in dramatic clinical improvement with complete resolution of liver function. This case illustrates the potential life-saving role for percutaneous balloon mitral valvotomy in treating critically ill patients who are unable to undergo thoracotomy due to coexisting medical illness.

Atrial Fibrillation↗
PubMed1991

Effectiveness of percutaneous balloon mitral valvotomy during pregnancy.

During pregnancy, medically refractory congestive heart failure due to mitral stenosis continues to present a clinical challenge and optimal management remains controversial. Thirteen women underwent balloon mitral valvotomy for control of functional class III or IV congestive heart failure due to mitral stenosis during pregnancy. The mean gestational age at the time of valvotomy was 25 +/- 6 weeks. Percutaneous balloon mitral valvotomy was performed successfully in all patients. No maternal or fetal mortality occurred. The mean mitral valve area assessed by Doppler echocardiography increased from 0.9 +/- 0.3 cm2 before to 2.1 +/- 0.3 cm2 after valvotomy. The mean mitral valve gradient decreased from 20 +/- 7 to 4 +/- 2 mm Hg. This was associated with a decrease in the pulmonary artery systolic pressure from 62 +/- 24 to 32 +/- 14 mm Hg. Currently, 12 of the 13 patients have delivered at an average gestational age of 38 +/- 0.5 weeks. Symptoms of congestive heart failure improved in all women and all were in New York Heart Association functional class I at the time of delivery. One patient is still pregnant and symptom free. Eleven singlet pregnancies resulted in the birth of full-term, healthy infants (mean birth weight 3.2 kg). The woman carrying a twin pregnancy improved from New York Heart Association class IV to class I after balloon mitral valvotomy but delivered prematurely at 32 weeks. The premature twin infants weighed 1.0 and 1.5 kg and died from respiratory failure at 48 hours. Percutaneous balloon mitral valvotomy can be performed safely during pregnancy and is effective in relieving symptoms of severe congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Determinants of one-year outcome from balloon aortic valvuloplasty.

Balloon aortic valvuloplasty (BAV) has been a therapeutic alternative treatment for severe symptomatic aortic stenosis. Previous studies have been unable to predict 1-year outcome because of limited acute and follow-up clinical, invasive and echocardiographic data. The purpose of this study was to predict long-term outcome based on comprehensive data obtained at the time of valvuloplasty and at 3 and 6 months after the procedure. Of 170 consecutive patients undergoing BAV, 108 (mean age 78 years) were at least 1 year from their procedure. Prospective clinical, micromanometer hemodynamic, digital ventriculographic and echocardiographic/Doppler data were collected at baseline and immediately after the procedure. Echocardiographic data were also obtained at 3 and 6 months. With use of Cox model analysis, major events (defined as cardiac death [n = 30], aortic valve replacement [n = 21] or repeat BAV [n = 13]) were predicted by advanced age, baseline heart failure class, and baseline echocardiographic-determined diastolic left ventricular diameter. Only baseline left ventricular ejection fraction proved to be a significant predictor of cardiac death (p = 0.002) in a multivariate model. Absolute values after BAV (stroke work, first derivative of left ventricular pressure, valve area, end-systolic volume, Fick cardiac output, transvalvular gradient) and acute changes measured by catheterization or echocardiography did not provide additional predictive information over that of post procedure ejection fraction. Similarly, echocardiographic valve area and transvalvular gradient at 3 months added no further prognostic data. With an ejection fraction greater than or equal to 45% (n = 63), cardiac survival at 1 year was 80%, irrespective of age, sex, congestive heart failure class or severity of coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Comparison of intravascular ultrasound, external ultrasound and digital angiography for evaluation of peripheral artery dimensions and morphology.

Validation of catheter-based intravascular ultrasound imaging has been based on comparisons with histology and digital angiography, each of which may have limitations in the assessment of arterial size and morphology. External, high-frequency ultrasound can accurately determine vessel dimensions and morphology and because, like ultravascular ultrasound, it also provides cross-sectional arterial ultrasound images, it may be a more appropriate technique for the in vivo comparison of arterial dimensions and morphology determined by intravascular ultrasound. Thus, intravascular ultrasound, external 2-dimensional ultrasound, Doppler color-flow imaging and digital angiography were compared for assessment of arterial dimensions and wall morphology at 29 femoral artery sites in 15 patients. Intravascular ultrasound and the other 3 imaging modalities correlated well in determination of lumen diameter (2-dimensional, r = 0.98, standard error of the estimate [SEE] = 0.14; Doppler color flow, r = 0.91, SEE = 1.11; angiography, r = 0.95, SEE = 0.91) and cross-sectional area (2-dimensional, r = 0.97, SEE = 0.04; Doppler color flow, r = 0.92, SEE = 0.14; angiography, r = 0.96, SEE = 0.08). However, lumen size measured by Doppler color flow was consistently smaller than that measured by the other 3 imaging modalities. Intravascular ultrasound detected arterial plaque at 15 sites, 5 of which were hypoechoic (soft) and 10 hyperechoic with distal shadowing (hard). Plaque was identified at 12 of 15 sites by Z-dimensional imaging (p = 0.30 vs intravascular ultrasound), but at only 6 of 15 sites by angiography (p = 0.003 vs intravascular ultrasound), only 1 of which was thought to be calcified plaque.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Surgical aortic valvuloplasty using the Cavitron Ultrasonic Surgical Aspirator: an invasive hemodynamic follow-up study.

Valve repair and calcium debridement in patients with calcific aortic stenosis, using the Cavitron Ultrasonic Surgical Aspirator (CUSA), results in a reduction in the aortic valve gradient while potentially avoiding long-term problems inherent to prosthetic valves. Invasive followup data in these patients has not previously been reported. Ten patients in whom CUSA debridement was performed underwent cardiac catheterization prior to and 8.0 +/- 2.5 months following the procedure. Compared to baseline, the aortic valve area significantly increased from 0.75 +/- 0.2 to 1.1 +/- 0.3 cm2 (p = 0.009) and the mean gradient was significantly reduced from 54 +/- 21 to 27 +/- 21 mmHg (p = 0.02) at followup. No significant change was noted in cardiac output, ejection fraction, left ventricular end systolic or diastolic volumes or left ventricular end diastolic pressure. However, 6 patients were found to have at least one grade worsening of aortic regurgitation. The development of increased aortic insufficiency in many patients after CUSA aortic valve debridement will likely limit this procedure's clinical utility.

Aged↗