Search PubMed⌕ Search

Biomedical subjects

T R Graham

Publications and source records attributed to T R Graham.

At least 37 records · Page 2Linked to original sources
PubMed1995

Right ventricular failure in patients requiring left ventricular assistance.

Right ventricular failure may complicate isolated left ventricular assistance. In a series of 8 patients undergoing left ventricular assistance in postcardiotomy cardiogenic shock, right ventricular failure developed in 5, directly contributing to death in all cases despite initially satisfactory support. Difficulty in grafting a dominant right coronary artery was a common factor in all cases. Early consideration should be given to biventricular support under these circumstances.

Aged↗
PubMed1994

Left ventricular rupture associated with mitral valve replacement.

Rupture of the left ventricle during the immediate postoperative period is a serious, but uncommon complication of mitral valve replacement. This review article outlines the pathological findings, possible causative mechanisms and current management of this cardiac surgical catastrophe.

Aged↗
PubMed1994

Signal-mediated retrieval of a membrane protein from the Golgi to the ER in yeast.

The Saccharomyces cerevisiae Wbp1 protein is an endoplasmic reticulum (ER), type I transmembrane protein which contains a cytoplasmic dilysine (KKXX) motif. This motif has previously been shown to direct Golgi-to-ER retrieval of type I membrane proteins in mammalian cells (Jackson, M. R., T. Nilsson, and P. A. Peterson. 1993. J. Cell Biol. 121: 317-333). To analyze the role of this motif in yeast, we constructed a SUC2-WBP1 chimera consisting of the coding sequence for the normally secreted glycoprotein invertase fused to the coding sequence of the COOH terminus (including the transmembrane domain and 16-amino acid cytoplasmic tail) of Wbplp. Carbohydrate analysis of the invertase-Wbp1 fusion protein using mannose linkage-specific antiserum demonstrated that the fusion protein was efficiently modified by the early Golgi initial alpha 1,6 mannosyltransferase (Och1p). Subcellular fractionation revealed that > 90% of the alpha 1,6 mannose-modified fusion protein colocalized with the ER (Wbp1p) and not with the Golgi Och1p-containing compartment or other membrane fractions. Amino acid changes within the dily sine motif (KK-->QK, KQ, or QQ) did not change the kinetics of initial alpha 1,6 mannose modification of the fusion protein but did dramatically increase the rate of modification by more distal Golgi (elongating alpha 1,6 and alpha 1,3) mannosyltransferases. These mutant fusion proteins were then delivered directly from a late Golgi compartment to the vacuole, where they were proteolytically cleaved in a PEP4-dependent manner. While amino acids surrounding the dilysine motif played only a minor role in retention ability, mutations that altered the position of the lysines relative to the COOH terminus of the fusion protein also yielded a dramatic defect in ER retention. Collectively, our results indicate that the KKXX motif does not simply retain proteins in the ER but rather directs their rapid retrieval from a novel, Och1p-containing early Golgi compartment. Similar to observations in mammalian cells, it is the presence of two lysine residues at the appropriate COOH-terminal position which represents the most important features of this sorting determinant.

Amino Acid Sequence↗
PubMed1994

Clathrin-dependent localization of alpha 1,3 mannosyltransferase to the Golgi complex of Saccharomyces cerevisiae.

Posttranslational modification of yeast glycoproteins with alpha 1,3-linked mannose is initiated within a Golgi compartment analogous to the medial Golgi cisternae of higher eukaryotes. We have characterized the synthesis, posttranslational modification, and localization of the yeast alpha 1,3 mannosyltransferase (Mnn1p) using antibodies prepared against a segment of this protein expressed in bacteria. Mnn1p is initially synthesized as a 98.5-kD, type II integral membrane glycoprotein that is modified with both N- and O-linked oligosaccharides. It is subject to a slow, incremental increase in molecular mass that is dependent upon protein transport to the Golgi complex. Self-modification of Mnn1p with alpha 1,3 mannose epitopes, primarily on O-linked oligosaccharides, is at least partly responsible for the incremental increase in molecular mass. Mnn1p is a resident protein of the Golgi complex and colocalizes with guanosine diphosphatase to at least two physically distinct Golgi compartments by sucrose gradient fractionation, one of which may be a late Golgi compartment that also contains the Kex2 endopeptidase. Surprisingly, we found that a significant fraction of Mnn1p is mislocalized to the plasma membrane in a clathrin heavy chain temperature sensitive mutant while guanosine diphosphatase remains intracellular. A mutant Mnn1p that lacks the NH2-terminal cytoplasmic tail is properly localized to the Golgi complex, indicating that clathrin does not mediate Mnnlp Golgi retention by a direct interaction with the Mnn1p cytoplasmic tail. These results indicate that clathrin plays a broader role in the localization of Golgi proteins than anticipated.

Amino Acid Sequence↗
PubMed1994

Hepatic portal venous flow in patients undergoing tricuspid valve surgery.

OBJECTIVE: To determine the changes of flow in the hepatic artery and portal vein of patients undergoing tricuspid valve repair together with mitral valve replacement. DESIGN: Non-randomised parallel group study. SETTING: Tertiary referral centre. PATIENTS: 18 patients with mitral valve disease with or without tricuspid regurgitation (age range 46-73; six men) and six patients with coronary artery disease and normal left ventricular function (women age range 39-78; four men). INTERVENTIONS: Mitral valve replacement with or without modified De Vega repair of the tricuspid valve or coronary artery bypass surgery. MAIN OUTCOME MEASURES: Flow in the hepatic artery and portal vein as measured by duplex Doppler flowmetry before and two to four weeks after operation. RESULTS: Preoperative hepatic artery flow was less in patients with mitral valve disease than in patients with coronary artery disease (162.7(13.1) ml.min-1 v 242.5(6.6) ml.min-1, p < 0.05). Portal vein perfusion was significantly reduced only in patients with associated tricuspid regurgitation compared with (844(83) ml.min-1 v 1422(64) ml.min-1 p < 0.05). Hepatic perfusion was unaltered after operation in patients undergoing coronary artery bypass surgery (p > 0.05). Flow in the hepatic artery and portal vein was improved only in patients undergoing mitral valve replacement with associated tricuspid valve repair (p < 0.05). CONCLUSION: Abnormalities of hepatic perfusion can be measured non-invasively in all patients with mitral valve disease but especially in those with associated tricuspid regurgitation needing valve repair. These abnormalities improved two to four weeks after mitral valve surgery and tricuspid valve repair, suggesting that measurement of portal flow might be a useful means of assessing the severity of tricuspid regurgitation.

Adult↗
PubMed1994

Efficacy of urgent thoracotomy for trauma in patients attended by a helicopter emergency medical service.

Over a 12-month period the Helicopter Emergency Medical Service underwent 1084 missions attending casualties in the London area. Sixteen patients required an emergency thoracotomy for resuscitation, nine of which were performed at the scene and seven in the emergency department. The median injury severity score of these patients was 29.9 (SIR 11.8) of which 11 had suffered blunt injuries. Medical attention at scene was administered 16.2 min (SIR 4.0) following the London ambulance service receiving the emergency call. Significantly longer time was spent attending patients who had a scene thoracotomy (35.1 min SIR 16.4) compared with those in whom the thoracotomy was performed in the casualty department. No patient in this series survived resuscitative thoracotomy. It is suggested that scene thoracotomy be abandoned and emphasis placed upon the rapid transport of patients to an emergency facility. This enables other resuscitative measures in addition to thoracotomy to be applied effectively and concentrated over a brief period by a multidisciplinary team.

Adolescent↗
PubMed1994

Atrial fibrillation following myocardial revascularization.

Atrial fibrillation following coronary artery surgery is common, especially in elderly patients but despite numerous studies its pathophysiological basis is still incompletely understood. It is usually benign and self-limiting, but may be associated with haemodynamic compromise, prolonged hospitalization and embolic stroke. No risk factors (apart from age and preoperative beta-blocker withdrawal) have been shown to be associated with its occurrence. Conventional treatment is usually effective but no prophylactic regime has been identified. Until such a regime is found the incidence of atrial fibrillation following myocardial revascularization may only be reduced by continuing treatment in patients on beta-blockers in the preoperative period and re-establishing this therapy after surgery.

Aged↗
PubMed1993

Brefeldin A reversibly blocks early but not late protein transport steps in the yeast secretory pathway.

We have found that brefeldin A (BFA) inhibited the growth of an ise1 mutant of Saccharomyces cerevisiae. Genetic complementation and mapping studies demonstrated that ise1 was allelic to erg6, a gene required for the biosynthesis of the principal membrane sterol of yeast, ergosterol. Treatment of ise1 cells with BFA resulted in an immediate block in protein transport through the secretory pathway. Vacuolar carboxypeptidase Y (CPY) and the secreted pheromone alpha-factor accumulated as both the core glycosylated (ER) and alpha 1,6 mannosylated (early Golgi) forms in drug-treated cells. The modification of alpha-factor with alpha 1,6 mannose in BFA-treated cells did not appear to result from retrograde transport of the alpha 1,6 mannosyl-transferase into the ER. We found that transport of CPY from medial and late Golgi compartments to the vacuole was unaffected by BFA, nor was secretion of alpha 1,3 mannosylated alpha-factor or invertase blocked by BFA. The effects of BFA on the secretory pathway were also reversible after brief exposure (< 40 min) to the drug. We suggest that the primary effect of BFA in S. cerevisiae is restricted to the ER and the alpha 1,6 mannosyltransferase compartment of the Golgi complex.

Biological Transport↗
PubMed1993

Effect of vascular clamp on endothelial integrity of the internal mammary artery.

The preservation of endothelial integrity is essential for maintaining patency of vascular grafts. The internal mammary artery flow is often interrupted with the application of a soft vascular clamp to achieve a bloodless field during the anastomosis. We investigated the effect of the vascular clamp on the internal mammary artery endothelium using the scanning electron and light microscope. The endothelium was examined before and at 15 and 30 minutes after clamping in both the pedicled and the skeletonized arteries. Endothelial integrity was breached by clamping with early evidence of platelet adhesion to the damaged areas. The severity of the endothelial damage was related to the clamp time, but there was no difference in the degree of damage between the pedicled and the skeletonized arteries. We conclude that the vascular clamp causes injury to the internal mammary artery endothelium and may be implicated in early postoperative graft failure.

Constriction↗
PubMed1993

Intrahepatic leiomyosarcoma of the inferior vena cava with extension into the right atrium.

We present a case of leiomyosarcoma of the intrahepatic inferior vena cava extending into the right atrium, that has been successfully palliated by removal of the obstructing tumour under conditions of full cardiopulmonary bypass and circulatory arrest. Lesions of this kind have previously thought not to be amenable to surgery. Although resection was incomplete, successful palliation may be achieved facilitating this technique.

Heart Atria↗
PubMed1993

Pathological sequelae of implantation of intracorporeal left ventricular assist devices in the calf.

Thromboembolic complications have previously been a major pathological complication of left ventricular assist device (LVAD) insertion and appear to be a consequence of the use of smooth polyurethane linings. Textured biomaterial surfaces are designed to attract a stable coagulum which becomes organized to form a neointima. We describe the pathological changes following experimental implantation of textured-surface LVADs in calves. The incidence of systemic embolization from such linings appears to be low. Surface modifications with cell seeding offer the possibility of further reduction in incidence of this problem. However, degradation of prosthetic valves may be a potential source of emboli and infection. With these complications minimized, the most significant pathological changes observed appear to relate to the device haemodynamics. At present renovascular changes associated with systemic hypertension appear to be the greatest potential problem for the long-term use of these devices.

Animals↗
PubMed1993

The lining of textured surfaces in implantable left ventricular assist devices. An immunocytochemical and electronmicroscopic study.

OBJECTIVE: The aim was to examine and identify some components of biological linings developed upon the textured surfaces of a circulatory assist device. The development of biological linings upon a textured surface circulatory assist device was evaluated in patients implanted for periods ranging from 84 to 132 days. METHODS: Explanted devices were examined macroscopically. Light microscopy, transmission electron microscopy and immunocytochemistry techniques were employed to evaluate the histogenesis of the tissue deposits upon the device surfaces. Visible material was essentially limited to focal areas upon the static housing and the periphery of the pusher-plate diaphragm (Biomer). RESULTS: Microscopy of the linings showed fibrin-rich areas with platelets, monocytes and few spindle-shaped surface cells. Central areas were composed of multiple layers of spindle-shaped cells separated, mainly, by collagen. Giant-cell foreign-body reaction to Biomer fibrils was seen. CONCLUSION: Transmission electron microscopy and immunocytochemistry indicated the presence of at least two cell populations: fibroblasts and smooth muscle-like cells, or 'myofibroblasts'. There was no evidence of endothelial cell presence.

Adult↗