Responses to angiotensin with and without angiotensin-converting enzyme inhibition in the canine left anterior descending coronary artery.
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Angiotensin I↗
Biomedical subjects
K M Taylor
Publications and source records attributed to K M Taylor.
13C NMR studies of the enzyme-product complex of Bacillus subtilis chorismate mutase.
The chorismate mutase reaction is a rare enzyme-catalyzed 3,3-sigmatropic rearrangement of chorismate to prephenate. Bacillus subtilis chorismate mutase was overproduced and purified from Escherichia coli XL1-Blue (pBSCM2) using a modification of the procedure of Gray et al. (Gray, J. V., Grolinelli-Pimpaneau, B., & Knowles, J. R. (1990) Biochemistry 29, 376-383); the modification leads to minimal contaminating prephenate dehydratase activity (< 0.001%). The native molecular mass of B. subtilis chorismate mutase was determined by gel filtration to be approximately 44 kDa, indicative of a homotrimer of the 14.5-kDa subunits as determined by electrospray mass spectrometry. 13C NMR was used to study the structure of [U-13C]prephenate bound at the active site of B. subtilis chorismate mutase. All the enzyme-bound 13C NMR resonances of [U-13C]prephenate were assigned, and where possible, 1JC,Cs were quantified; [1,3,5,8-13C]prephenate and [2,6,9-13C]prephenate, prepared respectively from [1,3,5,8-13C]chorismate and [2,6,9-13C]chorismate, aided the 13C NMR resonance assignments. Enzyme-bound prephenate exhibits remarkably different chemical shifts relative to free prephenate; the chemical shift changes range from -6.6 ppm for the C6 resonance to 5.6 ppm for the C5 resonance, suggesting a strong perturbation of the C5-C6 bond. 13C NMR studies of model compounds at various pH values and in various solvents suggest that the observed 13C chemical shift changes of enzyme-bound prephenate cannot be rationalized solely on the basis of changes in the pKas of the carboxylic acid groups or hydrophobic solvation at the active site.(ABSTRACT TRUNCATED AT 250 WORDS)
Bacillus subtilis↗
Expression of the human neuropeptide tyrosine Y1 receptor.
Neuropeptide tyrosine (NPY) is the predominant peptide in the innervation of many human tissues and is considered to play a role in the regulation of blood flow, gastrointestinal secretion and motility, and renal function. Three NPY receptors have been identified (Y1, Y2, and Y3) and the cDNAs encoding the human Y1 and bovine Y3 receptors have recently been cloned. We have demonstrated the expression of the Y1 receptor subtype in several fetal and adult human tissues, including the colon, kidney, adrenal gland, heart, and placenta. A single transcript was identified (approximately 2.2 kb) and localized in tissue sections by in situ hybridization. In the colon the receptor is expressed in the mucosa and basal glands, as well as the myenteric and submucous plexuses. Y1 receptor mRNA was detected in renal collecting ducts, loop of Henle, and juxtaglomerular apparatus and in the syncytiotrophoblast layer of placental villi. Fetal aorta and adult intramyocardial, colonic, and renal blood vessels also exhibited receptor expression, localized to the intima as well as the media. The distribution of Y1 receptor expression correlates with that of NPY-immunoreactive nerves and the apparent actions of NPY in the intestine, kidney, and heart. Although the placenta is devoid of nerves, an NPY-like transcript was detected in the villous trophoblast layer. The results indicate a tissue-specific regulation of NPY Y1 receptor expression.
Adult↗
Cardiopulmonary bypass impairs small intestinal transport and increases gut permeability.
Gastrointestinal damage occurs in 0.6% to 2% of patients after cardiopulmonary bypass (CPB), and carries a mortality of 12% to 67%. The incidence of subclinical gastrointestinal damage may be much greater. We examined the effects of nonpulsatile, hypothermic CPB on intestinal absorption and permeability in 41 patients. Bowel mucosal saccharide transport and permeation were evaluated using 100 mL of an oral solution containing 3-O-methyl-D-glucose (0.2 g), D-xylose (0.5 g), L-rhamnose (1.0 g), and lactulose (5.0 g) to assess active carrier-mediated, passive carrier-mediated, transcellular, and paracellular transport, respectively, with a 5-hour urine analysis. Patients were studied before, immediately after, and 5 days after CPB. Immediately after CPB there was a decrease in urinary excretion of 3-O-methyl-D-glucose (from 34% +/- 2.2% to 5.2% +/- 0.7%; p < 0.0001), D-xylose (from 25.4% +/- 1.4% to 4.1% +/- 0.8%; p < 0.0001), and L-rhamnose (from 8.3% +/- 0.6% to 2.6% +/- 0.4%; p < 0.0001). The permeation of 3-O-methyl-D-glucose and D-xylose returned to normal levels 5 days after CPB, but that of L-rhamnose remained significantly below pre-CPB values at 6.6% +/- 0.5% (p = 0.004). However, the permeation of lactulose increased after CPB (from 0.35% +/- 0.04% to 0.59% +/- 0.1%; p = 0.018), and the lactulose/L-rhamnose gut permeability ratio increased markedly (from 0.045 +/- 0.04 to 0.36 +/- 0.08; normal = 0.06 to 0.08; p = 0.004). Patients who had a CPB time of 100 minutes or more had a greater increase in gut permeability (p = 0.049).(ABSTRACT TRUNCATED AT 250 WORDS)
3-O-Methylglucose↗
Aprotinin therapy in cardiac operations: a report on use in 41 cardiac centers in the United Kingdom.
Aprotinin, a serine protease inhibitor, has recently been shown to reduce blood loss in cardiac surgical patients. Data on the safety and efficacy of aprotinin therapy administered to 671 cardiac surgical patients in 41 United Kingdom cardiac surgical units have been submitted to interim analysis. The patients studied were in high-risk categories for excessive bleeding, including 457 redo operations and 79 patients with active infective endocarditis. Overall mortality was 12% in redo cases and 5.1% in first-time operations. Adverse events were reported in only 20 patients (3%). Median blood loss at 24 hours after operation was 400 mL, and median transfusion volume throughout the operative and postoperative period was 2 units. These data confirm that the use of aprotinin therapy in high-risk cardiac surgical patients is associated with a low incidence of adverse events.
Adolescent↗
Angiosarcoma of the heart causing cardiac rupture: a rare cause of hemopericardium.
Cardiac rupture as a complication of primary cardiac tumors has rarely been reported in the literature. The diagnosis is difficult to establish preoperatively, but echocardiography may provide the best assessment of cardiac damage. We found a loculated pericardial effusion on two-dimensional echocardiography, a finding that has been documented in two of the previous four case reports. A case of right atrial rupture is reported with review of other cases from the literature.
Heart Neoplasms↗
Perioperative approaches to coagulation defects.
Cardiac surgical procedures are known to be associated with coagulation defects and disordered hemostasis. Excessive perioperative and postoperative bleeding and the need for considerable volumes of blood and blood product transfusions are well recognized. The risks of blood transfusion with high donor-exposure levels have focused attention on blood conservation as a priority in reducing the complications of cardiac operations. Hemostatic defects may be related to patient-inherent coagulopathies, preexisting associated pathology, and preoperative drug therapy. In addition, hemostatic defects are induced during the operation itself. Two principal therapeutic approaches to this complex problem have evolved. Although different, these approaches are not mutually exclusive and may be used complementarily. The first is autotransfusion and the second is hemostatic drug therapy. Although many drugs have been tried, including antifibrinolytic agents (epsilon-aminocaproic acid, tranexamic acid), platelet-preserving agents (prostacyclin, dipyridamole), and desmopressin, the only drug that has shown significant and consistent efficacy in reducing bleeding in cardiac surgery patients is the serine protease inhibitor aprotinin. Aprotinin has been shown to be highly effective in reducing blood loss and blood and blood product transfusion requirements in high-risk patients. Clinical experience with aprotinin therapy in cardiac patients and specific issues such as dosage regimens and the target automated clotting time levels in patients on high-dose aprotinin therapy are outlined. Indications for the use of aprotinin and the balance between risk and benefit are discussed.
Aprotinin↗
Quantitative immunohistochemical assessment of bovine myocardial innervation before and after cryosurgical cardiac denervation.
OBJECTIVE: The aim was to determine the relative distribution and possible origins of peptide containing nerves in the bovine heart before and after functional extrinsic denervation established by cryosurgery. METHODS: A quantitative immunohistochemical technique was used. RESULTS: In the intact heart, myocardial nerve fibres and fascicles displaying immunoreactivity for the general neural marker protein gene product 9.5 had an atrial to ventricular gradient in density. The right atrium was the most densely innervated region and a major proportion of the total myocardial innervation, visualised by protein gene product 9.5 immunoreactive nerves, showed neuropeptide tyrosine (45%) and tyrosine hydroxylase (20%) immunofluorescence staining, while nerves immunoreactive for vasoactive intestinal polypeptide and calcitonin gene related peptide formed relatively minor subpopulations (representing less than 2% and 0.5%, respectively, of the total fluorescent myocardial innervation). Following cryoablation there was a significant reduction in the percentage fluorescent area of protein gene product 9.5 immunoreactive nerves throughout the heart, of greater than 90% of the control values. There were highly significant reductions in the percentage fluorescent area of nerves showing immunoreactivity to neuropeptide tyrosine, tyrosine hydroxylase, and calcitonin gene related peptide, to 1.01, 0.92, and 0.05%, respectively, of the intact myocardial innervation. The distribution of vasoactive intestinal polypeptide immunoreactive nerves was more variable and displayed an equivocal response to cardiac cryoablation. CONCLUSIONS: The majority of nerves showing immunoreactivity to neuropeptide tyrosine, tyrosine hydroxylase, and calcitonin gene related peptide are of extrinsic origin, while vasoactive intestinal polypeptide immunoreactive nerves may have intrinsic as well as extrinsic origins. The distribution and apparent origins of immunohistochemically defined nerves in the bovine heart are similar to those observed in the human heart which suggests that the calf may be an appropriate model for comparative studies.
Animals↗
Hematologic scoring system in early diagnosis of sepsis in neutropenic newborns.
The hematologic profiles of 1000 newborns were prospectively examined to identify infants with neutropenia (N = 170) according to the system of Manroe et al. (J Pediatr 1979;95:89-98) and to evaluate a hematologic scoring system (Rodwell et al. J Pediatr 1988;112:761-7) as a screening test for sepsis. Neutropenia was more commonly of noninfectious than infectious origin (83.5% vs. 16.5%; P < 0.001). On the initial test a positive screen (scores > or = 3) identified 26 of 28 infants with sepsis or probable infection (sensitivity 93%; specificity 82%; positive and negative predictive values 50 and 98%, respectively). Corresponding values for an elevated immature:total neutrophil ratio were 100, 75, 43 and 100%. Overall mortality with neutropenia was 15% and was higher with an infectious than a noninfectious etiology (39% vs. 11%, P < 0.001) despite early antibiotic therapy. The combination of a neutrophil count < or = 500/mm3 and scores > or = 3 or an elevated immature:total neutrophil ratio identified a poor prognostic group: 67% (8 of 12) and 70% (7 of 10) infants, respectively, with these findings died, 6 in the infected group. The hematologic scoring system or immature:total neutrophil ratio in combination with the degree of neutropenia provides valuable diagnostic and prognostic information which could be applied to identification of possible candidates for granulocyte transfusions or other experimental treatments.
Bacterial Infections↗
Thrombolytic therapy in paroxysmal nocturnal haemoglobinuria complicated by hepatic vein thrombosis.
Hepatic vein thrombus is a common and often fatal complication of paroxysmal nocturnal haemoglobinuria. Rapid diagnosis with ultrasound, computed tomography or venography is required to improve the prognosis. Although heparin is often the initial therapy of choice, thrombolytic agents may be more beneficial in the early management.
Budd-Chiari Syndrome↗
Intractable chest pain in cardiomyopathy: treatment by a novel technique of cardiac cryodenervation with quantitative immunohistochemical assessment of success.
A novel method of cardiac denervation by cryoablation has been developed experimentally. The technique uses liquid nitrogen delivered under pressure to ablate the principal sources of cardiac innervation--namely, the adventitia surrounding the aorta, pulmonary arteries, and veins. The technique has been verified experimentally both in vivo by physiological means and in vitro by quantitative immunohistochemistry and the measurement of myocardial noradrenaline concentrations. A 35 year old woman presented with intractable precordial pain, normal epicardial coronary arteries, and hypertrophic cardiomyopathy. Her symptoms were refractory to maximal medical treatment and she was thought to be unsuitable for either conventional myocardial revascularisation, autotransplantation, or allografting with the concomitant risk of transplant coronary artery disease. She therefore underwent cardiac denervation by the method developed in the laboratory. There was quantitative immunohistochemical evidence of extrinsic cardiac denervation associated with a considerable improvement in her symptoms. This improvement persisted during a follow up period of over 16 months.
Adult↗
Magnetic resonance imaging and P300 (event-related auditory evoked potentials) in the assessment of postoperative cerebral injury following coronary artery bypass graft surgery.
Cerebral injury following coronary artery bypass grafting (CABG) surgery was investigated with magnetic resonance imaging (MRI) and P300, a long-latency endogenous evoked potential associated with psychological processing of stimulus information. Twelve patients were studied before and after surgery. Prior to surgery, MRI abnormalities were found in all but one patient. After surgery, five patients had new abnormalities, mainly deep white-matter lesions (DWML). Postoperative P300 latency was significantly increased in six patients. P300 topographical distribution showed a shift from predominantly posterior cerebral regions to frontal regions in most patients. Postoperative P300 and MRI deficits were found in three of the five patients. One of the patients with marked MRI change (DWML in caudate nucleus) did not show P300 deficit.
Adult↗
Test and teach. Number Seventy. Diagnosis: Transient myeloproliferative disorder in a child with Down's syndrome.
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Blood Cell Count↗
Discordant neutrophil alkaline phosphatase activity and cytogenetic response in chronic myeloid leukemia treated with alpha-interferon.
Decreased neutrophil alkaline phosphatase (NAP) synthesis is a classical feature of Philadelphia (Ph) positive chronic phase chronic myeloid leukemia (CML). Whether this aberration is an integral leukemic property of the cell or results from mediation by other factors is unclear. During alpha-interferon (alpha-IFN) based therapy the relationship between Ph chromosome suppression and NAP synthesis was examined. Four categories of response were observed in 19 patients studied sequentially. Significantly, persistent low NAP activity was observed in one patient in complete cytogenetic remission, while a second group of 7 patients demonstrated normal NAP activity in spite of persistence of the Ph chromosome in 100% of metaphases. In the absence of various clinical influences that can modulate NAP activity in chronic phase CML, the results reinforce the observation that the BCR/ABL fusion gene product is not a key factor influencing NAP activity in CML.
Adult↗
Use of X-linked clonal analysis in acute promyelocytic leukemia.
X-linked clonal analysis (XLCA) either using Glucose-6-phosphate dehydrogenase (G-6-P-D) polymorphisms or restriction fragment length polymorphisms (RFLP) and methylation analysis has provided considerable understanding of haematologic malignancy. Acute Promyelocytic Leukemia (APL) is characterized by a unique cytogenetic translocation t(15;17), frequent achievement of remission without a preceding phase of marrow hypocellularity after induction chemotherapy and a high rate of clinical response to all-trans retinoic acid (ATRA). In limited studies XLCA has provided insight into the pathogenesis and mechanism of drug action in this disease.
Humans↗
Possible errors in the measurement of retinal lesions.
PURPOSE: To determine the accuracy of the measurement of structure in the retina from fundus photographs. METHOD: A model eye was developed to measure the retinal image size of the Zeiss fundus camera. A x 10 microscope objective with a focal length of 16.41 mm was used together with a microscope graticule. RESULTS: Under emmetropic conditions the difference between the calculated and the measured magnification was 8.6%. The total change in magnification from myopia to hyperopia was -24.63% to +18.1%. When the camera position was altered with respect to the model eye by +/- 5 mm under myopic conditions the change in magnification was -4.5% and +6.8%. In the hyperopic condition the change was -5.6% to +4.6%. CONCLUSIONS: Measuring the size of structure in the retina from photographs may therefore prove to be inaccurate but in some circumstances determining the percentage change in size may prove more reliable.
Animals↗
Changes in pericardial morphology and fibrinolytic activity during cardiopulmonary bypass.
The presence of pericardial adhesions at resternotomy not only increases the operation time but also increases the risk of serious damage to the heart, great vessels, and extracardiac grafts. The reported prevalence of damage is 2% to 6%. The fibrinolytic activity of pericardial tissue may be a crucial factor in determining the extent of adhesion formation following primary operation. Ten patients undergoing cardiac operations were studied to assess the plasminogen activating activity of homogenates of pericardial tissue samples. Samples were taken at three times during the operation and the plasminogen activating activity was measured by means of a standard fibrin plate technique. Tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor-1, and plasminogen activator inhibitor-2 were also measured by means of enzyme-linked immunosorbent assays. Compared with its initial levels (median 2.06 IU/cm2, range 1.28 to 6.48 IU/cm2), the plasminogen activating activity of pericardial biopsy tissue was significantly reduced at 75 minutes (median 0.64 IU/cm2, range 0.12 to 2.44 IU/cm2, p < 0.01) and at 135 minutes (median 1.45 IU/cm2, range 0.12 to 4.39 IU/cm2, p < 0.05). The major plasminogen activator present was tissue-type plasminogen activator. Compared with its initial levels (median 2.34 ng/ml, range 1.03 to 6.42 ng/ml), subsequent tissue-type plasminogen activator values were also significantly reduced at 75 minutes (median 0.83 ng/ml, range 0.75 to 5.13 ng/ml, p < 0.005) and at 135 minutes (median 1.24 ng/ml, range 0.75 to 6.67 ng/ml, p < 0.05). Low levels of urokinase-type plasminogen activator were found in 5 of 10 patients. However, neither plasminogen activator inhibitor-1 nor plasminogen activator inhibitor-2 was detected. Examination with a light microscope showed both increasing pericardial mesothelial damage and increasing features of acute inflammatory changes with time. This study shows that plasminogen activating activity is present in pericardial tissue and that tissue-type plasminogen activator is the major plasminogen activator. The observed inflammatory changes and concomitant damage to the pericardial mesothelium, and the significant reductions in pericardial tissue-type plasminogen activator and plasminogen activating activity seen during cardiac operations, may be important factors contributing to the early development of pericardial adhesions.
Adult↗
Retinal vessel circulation patterns visualized from a sequence of computer-aligned angiograms.
PURPOSE: To present a computer method that can be used to combine the images from a sequence of fluorescein angiograms of the retinal microcirculation so that a composite image can be generated and a color image illustrating circulation at all points in the vascular network can be computed. This should enable more accurate comparison of retinal vascular occlusions that occur during cardiopulmonary bypass surgery. METHODS: Photographic negatives of the macular region from two angiographic sequences, one taken before surgery and the other taken just before the end of bypass, were digitized, background shade corrected, and registered. Composite images were generated as minimum projection images and the filling images generated from parameters of a smooth curve fit to the filling data at every point. RESULTS: The composite images showed a filling pattern that more accurately reflected the maximum fluorescence at every point than any single image. The images generated from the filling data provide a new way to visualize and quantify changes in the retinal circulation. CONCLUSIONS: The technique demonstrates that problems arising from selection of a single frame from a filling sequence can be overcome by combining images. The technique used to generate the color-coded filling image should prove useful for any image sequence in which differential filling is of interest.
Blood Flow Velocity↗