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Biomedical subjects

C Eng

Publications and source records attributed to C Eng.

At least 37 records · Page 2Linked to original sources
PubMed1994

Cowden syndrome and Lhermitte-Duclos disease in a family: a single genetic syndrome with pleiotropy?

Cowden syndrome is an autosomal dominant condition of multiple hamartomas. Patients with this phakomatosis have an increased risk of breast cancer and thyroid tumours. Lhermitte-Duclos disease is usually a sporadic condition of cerebellar ganglion cell hypertrophy, ataxia, mental retardation, and self-limited seizure disorder. We describe a three generation family with Cowden syndrome and Lhermitte-Duclos disease. Karyotyping performed on the peripheral lymphocytes of the proband and her affected mother showed a 46,XX complement. Single strand conformational polymorphism analysis failed to show any germline p53 mutations as a cause of the syndrome in this family.

Adult↗
PubMed1994

Mutations of the RET proto-oncogene in the multiple endocrine neoplasia type 2 syndromes and Hirschsprung disease.

Distinct point mutations in the RET proto-oncogene are the cause of the inherited multiple endocrine neoplasia type 2 syndromes (MEN 2), and the congenital gut disorder Hirschsprung disease. The site and type of these mutations suggests that they have differing effects on the activity of the receptor tyrosine kinase encoded by RET. The normal function of the RET receptor tyrosine kinase has yet to be determined. However, this has been investigated by the inactivation of the RET gene in transgenic mice. The developmental abnormalities apparent in these mice, together with the observation that the major tissues affected in MEN 2 and Hirschsprung disease have a common origin in the embryonal neural crest, suggest that RET encodes a receptor for a developmental regulator involved in the genesis of a variety of neural crest derivatives, and in the organogenesis of the kidney.

Animals↗
PubMed1993

Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A.

Multiple endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome that affects tissues derived from neural ectoderm. It is characterized by medullary thyroid carcinoma (MTC) and phaeochromocytoma. The MEN2A gene has recently been localized by a combination of genetic and physical mapping techniques to a 480-kilobase region in chromosome 10q11.2 (refs 2,3). The DNA segment encompasses the RET proto-oncogene, a receptor tyrosine kinase gene expressed in MTC and phaeochromocytoma and at lower levels in normal human thyroid. This suggested RET as a candidate for the MEN2A gene. We have identified missense mutations of the RET proto-oncogene in 20 of 23 apparently distinct MEN 2A families, but not in 23 normal controls. Further, 19 of these 20 mutations affect the same conserved cysteine residue at the boundary of the RET extracellular and transmembrane domains.

Amino Acid Sequence↗
PubMed1993

The role of gene mutations in the genesis of familial cancers.

The simplest molecular mechanism of hereditary tumorigenesis is represented by retinoblastoma (RB). Knudson's model specifies that, in hereditary RB, the first mutation in an allele of the RB gene exists in the germline. A subsequent somatic mutation in the second normal RB allele releases RB formation in the eye. This mechanism of loss of function of both normal tumor suppressor gene copies applies to other hereditary cancer syndromes as well, including multiple endocrine neoplasia type 1, neurofibromatosis type 2, Li-Fraumeni syndrome, and probably familial breast/ovarian syndrome. In some syndromes, e.g. familial adenomatous polyposis and multiple endocrine neoplasia type 2, the mechanism may be slightly different. Loss of function of only one allele of the susceptibility locus appears to be sufficient to promote a proliferative advantage in target tissues. In many of these inherited cancer syndromes, variable expression and variable penetrance of phenotypes exist. Allelism, existence of a multigene complex, or modulation of expression by modifier genes may explain the phenomena.

Animals↗
PubMed1993

Effect of captopril on postischemic myocardial expansion.

The effects of captopril on systolic function and diastolic myocardial expansion were assessed in an open-chest multiple occlusion model of myocardial stunning. Captopril was given as a 0.25 mg/kg bolus followed by a continuous infusion at 0.25 mg/kg/h for the duration of the stunning protocol, which was initiated 30 min after the bolus dose was given. The coronary artery was occluded for 5 min and reperfused for 10 min. This procedure was performed 12 times. Regional systolic function and end-diastolic length (EDL) in both the stunned region and normal zone were measured by sonomicrometry. Heart rate (HR) and left ventricular diastolic blood pressure (LVDP) were not significantly different between untreated (n = 11) and captopril-treated (n = 10) groups. The mean aortic pressure (MAP) in the captopril-treated group was approximately 10 mm Hg lower than in the untreated group, p < 0.05. Systolic function as determined by the percentage systolic shortening was significantly decreased to approximately 20% of baseline (preocclusion) function in both untreated and captopril treated groups as a result of the stunning procedure, p < 0.001. However, there was an important treatment effect on diastolic expansion of stunned myocardium. In the untreated group, the stunned myocardium underwent a 5-7% relative increase in end-diastolic length (expansion), p < 0.05. In the captopril-treated group, this expansion process was abolished. We conclude that in a multiple occlusion model of myocardial stunning, captopril had no effects in preserving systolic function but had favorable attributes in dilation and expansion of postischemic myocardium.

Animals↗
PubMed1992

Increase in myofilament separation in the "stunned" myocardium.

This study explores the effects of ischemic reperfusion injury on the radial separation distance between thick and thin myofilaments. The left anterior descending coronary artery was occluded for 5 mins and reperfused for 10 mins twelve times repetitively in 6 dogs. At the end of a final 90 min reperfusion period, the hearts were fixed by perfusion with glutaraldehyde, and subepicardial and subendocardial tissue from both normal and ischemic areas were prepared for transmission electron microscopy. Quantitative analysis of inter-filament distance (IFD) was performed on micrographs of transverse sections. The center-to-center IFD was calculated from the numerical density of thick filaments at the A band level using a hexagonal array conversion formula. Sarcomere length was measured on micrographs of longitudinal sections. The results showed that center-to-center thick IFD in the stunned subendocardium was 43.9 +/- 0.8 nm which was significantly greater than the control distance of 40.6 +/- 0.4 nm (P less than 0.001) from normal zone tissue. Thick IFD in the subepicardium was also significantly different: 43.4 +/- 0.6 nm in the stunned tissue as compared with 39.0 +/- 0.7 nm in the non-ischemic tissue (P less than 0.001). Sarcomere length in the normally perfused subendocardium was 2.01 +/- 0.07 micron and was increased to 2.20 +/- 0.08 micron in the stunned subendocardium (P less than 0.005). Sarcomere length in the normal and the stunned subepicardium was also different: 2.02 +/- 0.04 vs. 2.10 +/- 0.09 micron (P less than 0.005). The significant increase in spatial separation between the contractile filaments may affect optimal cross-bridge force generation at the molecular level.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗
PubMed1992

Thoracic epidural anesthesia via the caudal approach in children.

We investigated the feasibility of performing thoracic epidural anesthesia via the caudal approach in 20 children (age 62 +/- 38 months and weight 18.5 +/- 7.3 kg; mean +/- standard deviation). Based on external landmarks, a predetermined length of 24-G epidural catheter (Concord Portex 20/24 microcatheter system) with stylet was passed into the epidural space through a 20-G intravenous catheter inserted through the sacrococcygeal ligament, and a radiograph of the abdomen and chest was obtained. The radiographically determined catheter tip position was within two vertebrae of the target position in 17 of 20 subjects. In one subject, it was impossible to advance the catheter more than 10 cm. The other two malpositioned catheters were successfully reinserted. Intraoperative caudal anesthesia and postoperative pain relief were satisfactory in all 20 subjects. We have found it possible to use the caudal approach to thoracic epidural anesthesia in children as old as 10 yr. Ease of removal of the stylet, ease of injection, and negative aspiration and test doses predict successful placement and obviate the need for routine radiographic confirmation of catheter position.

Anesthesia, Caudal↗
PubMed1992

The influence of propofol with and without nitrous oxide on cerebral blood flow velocity and CO2 reactivity in humans.

The cerebrovascular response to CO2 has been reported to be preserved during propofol anesthesia, but no comparison with awake control values has been made, and the additional influence of N2O has not been investigated. Using the noninvasive technique of transcranial Doppler ultrasonography, this study investigated the cerebrovascular response to varying levels of PaCO2 while awake and during anesthesia with propofol and propofol/N2O. Seven adults without systemic diseases undergoing nonneurologic surgery were studied. A pulsed-wave Doppler monitor was used to measure the mean middle cerebral artery flow velocity (Vmca) during varying levels of PaCO2 (25-55 mmHg) under the following conditions: 1) awake; 2) propofol 2.5 mg.kg-1 bolus followed by continuous infusion of 150 micrograms.kg-1.min-1; and 3) propofol as in the condition above plus 70% N2O. During the awake study condition, hypocapnia was induced by voluntary hyperventilation, and hypercapnia was induced with rebreathing of 7% CO2 in a closed circuit. During the anesthetized study conditions, hypocapnia and hypercapnia were induced by adjustment of minute ventilation. A minimum of five to six simultaneous Vmca and PaCO2 measurements were obtained under each of the study conditions. Systemic blood pressure was monitored via a radial arterial catheter, and phenylephrine was administered if mean arterial blood pressure decreased below 60 mmHg (phenylephrine was used in three of five patients in the propofol-N2O group). Linear regression and analysis of covariance were used for statistical analysis of Vmca-PaCO2 relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Collagen loss in the stunned myocardium.

BACKGROUND: This study was performed to biochemically assess and quantify the previously observed ultrastructural alterations in the collagen matrix of stunned myocardium. METHODS AND RESULTS: The stunned myocardium was produced in 13 mongrel dogs by a series of 12 coronary artery occlusions of 5 minutes followed by 10-minute reperfusion periods, with a final reperfusion period of 90 minutes. Regional systolic function in the stunned myocardium was 17% of control. Relative end-diastolic length in the stunned region increased up to 8%. There was a nonuniform transmural loss of collagen. Hydroxyproline in the stunned endocardium was not different from control. The stunned midwall and epicardium demonstrated 12.5% (p less than 0.05) and 14.6% (p less than 0.005) decreases, respectively. All transmural layers in the stunned myocardium had significant increases in collagenase activity before procollagenase activation, averaging a 73.6% increase (p less than 0.025). Complete activation of all procollagenase forms with aminophenylmercuric acetate revealed no differences in fully activated collagenase between the stunned and normal regions. The lysosomal enzymes, elastase and cathepsin G, were not different between stunned and normal zone tissue. These results would tend to exclude exogenous sources of protease in the stunned myocardium at the 90-minute final reperfusion time frame. Collagen fibers were isolated from the stunned and normal zone tissue and underwent dansyl chloride reaction. Stunned collagen fibers had 9% greater dansyl labeling, suggesting greater numbers of exposed N-terminal amino acid residues on the fiber and compatible with greater enzymatic cleavage activity on the stunned collagen matrix. Tissue water content was consistently greater in the stunned region compared to the normal: a uniform transmural increase of approximately 1.7%. CONCLUSIONS: The stunned myocardium is characterized by both systolic dysfunction and diastolic expansion or dilatation. Endogenous procollagenase is activated by the ischemic process leading to degradation of the extracellular matrix. The underlying mechanisms may be relevant in ischemic enlargement of the heart and cardiomyopathy.

Animals↗
PubMed1991

Reciprocal strains in the normal and ischemic myocardium and their relation to the size of the ischemic region.

Previous studies have reported "bulging" of the ischemic zone and reciprocal shortening of the normal zone during the isovolumetric contraction period. This study examines the interaction and relation of these reciprocal strains during the isovolumetric contraction period. Normal zone and ischemic zone segment length data were acquired at 1 ms intervals during acute ischemia in 10 open chest dogs. The relation of ischemic zone and normal zone segment length was inversely linear in the isovolumetric contraction period during steady state ischemia and during preload reduction (mean correlation coefficient 0.92). The slope derived from the regression analysis was the same as that determined from the first and last data points of the isovolumetric contraction period (correlation coefficient between the regression versus two-point slope 0.96). This slope was used to calculate the size of the ischemic area based on the hypothesis that the isovolumetric normal zone shortening quantitatively accounted for the ischemic zone bulging during the isovolumetric contraction period, with the percent risk region serving as a weighing factor. The calculated risk region correlated with the anatomic risk region (r = 0.83, p less than 0.01; n = 9) and was independent of preload. During the isovolumetric contraction period, left ventricular short-axis diameter shortened approximately 0.2%; 80% of the ischemic zone lengthening occurred during this period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Isolation and characterization of insoluble collagen of dog hearts.

A procedure for isolating insoluble heart collagen has been developed. The method involves the use of defined optimal conditions of sonication that yield no thermal denaturation of the triple-helical structure nor disruption of the primary structure of the collagen molecules; this is followed by extraction of isolates with nondenaturing agents. The amino acid residues of the isolates are then reacted with dansyl chloride to allow determination of amino-terminal residues and quantification of the collagen. The method has several advantages over existing procedures: (i) There is no other method available for isolation of undenatured insoluble heart collagen in almost pure form (consists of 96% of type I collagen) and in a good yield. Sonication of tissue at or below 4 degrees C for a total of 120 s (15 s sonication repeated 8 times at 120-s intervals) yielded insoluble collagen fibers with 90% yield and a 20-fold purification as determined by the increase in Hyp content of the isolates. Extraction of these isolates with 0.6 M KCl and 1 M NaCl at 4 degrees C resulted in a 22-fold purification with 70% yield, while the classical extraction method with nondenaturing reagents yielded only 5-fold purification. (ii) There has been little study of the derivatization of an insoluble protein (collagen) with dansyl chloride. The Lys residues of collagen could be recovered as epsilon-Dns-Lys in 84% yield from a reverse-phase C-18 column by high-performance liquid chromatography. This assay allows measurement of 0.1-100 nmol epsilon-Dns-Lys. (iii) The method generates direct information concerning the quantity of collagen and its nature with respect to amino groups.

Animals↗
PubMed1990

Elevated creatine kinase and malignancy.

Increased serum levels of CK isoenzymes variously signal heart, brain, or skeletal muscle damage. They may also be markers for advanced tumors with poor prognosis.

Biomarkers, Tumor↗
PubMed1989

ACE inhibitors in acute and chronic ischaemia: current status and future promise.

1. Myocyte loss, reactive hypertrophy, dynamic ischaemia with 'stunning', and ventricular wall remodelling are all involved in the initiation and progression of myocardial failure which is ischaemic in origin. 2. The effects of ACE inhibitors to reduce preload and afterload has potentially salutary effects in these settings. Moreover, sulphyl containing ACE inhibitors may have further actions in reducing free radicals and their damage in the acute phases of these events. 3. These promising initial studies warrant further exploration.

Acute Disease↗