Biomedical subjects

D E McLoughlin

Publications and source records attributed to D E McLoughlin.

9 recordsLinked to original sources

PubMed2000

The role of mesenchyme in thymus development.

We have reviewed the evidence that thymic mesenchymal cells and their progeny thymic fibroblasts play an important role in early T-cell development. Although it is possible that mesenchyme plays an inductive role in thymic epithelial morphogenesis, we have presented evidence to suggest that there is a direct effect of mesenchyme and fibroblasts on T-cell development. Moreover the association of these cell types with an ECM raises the possibility that the latter might be important in integrin and/or cytokine presentation especially during the CD4(-)8- phase of T-cell development.

Cell Communication↗

PubMed1999

Cellular and matrix interactions during the development of T lymphocytes.

The thymus contains an extensive extracellular matrix. Although thymocytes express integrins capable of binding to matrix molecules, the functional significance of the matrix for T cell development is uncertain. We have shown that the matrix is associated with thymic fibroblasts which are required for the CD44+ CD25+ stage of double negative (CD4-8-) thymocyte development. The survival of cells at this stage is dependent on IL-7 and we propose that the role of fibroblasts is to present, via the matrix, IL-7 to developing T cells.

Epithelial Cells↗

PubMed1995

Endoventricular remodeling of left ventricular aneurysm. Functional, clinical, and electrophysiological results.

BACKGROUND: Recent advances in surgical techniques for the repair of left ventricular aneurysms (LVAs) include the use of an endoventricular patch to exclude the aneurysm cavity. This technique has replaced conventional linear plication of the aneurysm. The endoventricular patch technique remodels the left ventricular cavity to a more physiological geometry that improves function. METHODS AND RESULTS: From December 1989 through November 1993, 45 patients underwent an LVA repair with an endoventricular patch. This procedure was performed in association with coronary artery bypass grafting in 40 patients. Twenty-eight patients (62.2%) also had nonguided encircling subendocardial incisions. Operative procedures included 7 emergency operations, 3 concomitant valve procedures, and a mean of 2.2 bypass grafts per patient. Eight patients had previous cardiac operations. Hospital mortality was 15.6% (7/45) for all patients and 9.1% (3/33) for nonemergent revascularization and LVA repairs. Ejection fraction improved from a mean of 25.8% preoperatively to 37.8% postoperatively; the mean New York Heart Association classification improved from 3.5 to 1.5. Of patients known to have preoperative arrhythmias (inducible or sudden death), 69% were not inducible postoperatively without antiarrhythmic medication. Survival from late cardiac death (including death of unknown origin) was 86.5% at 2 years. Freedom from documented ventricular arrhythmias was 94.3% at 2 years. CONCLUSIONS: These results indicate that the patch endoaneurysmorrhaphy technique can provide an excellent functional and physiological outcome in patients with LVAs and severely impaired ventricular function.

Aged↗

PubMed1995

Effect of cannula length on aortic arch flow: protection of the atheromatous aortic arch.

Atheromatous disease in the transverse aortic arch is associated with an increased incidence of perioperative stroke. In addition, tissue erosion in the aortic arch is caused by the high-velocity jet emerging from an aortic cannula during cardiopulmonary bypass (CPB), termed the "sandblast effect". To quantify this phenomenon, flow in the aortic arch was measured intraoperatively by epiaortic ultrasonography in 18 patients undergoing CPB. All were cannulated in the ascending aorta, 10 with a short (1.5 cm) cannula and 8 with a long (7.0 cm) cannula. The peak forward aortic flow velocities (mean +/- standard deviation) measured on the caudal luminal surface of the aortic arch were 0.80 +/- 0.23 m/s off CPB and 2.42 +/- 0.69 m/s on CPB (p < 0.001) for the short cannula and 0.53 +/- 0.20 m/s off CPB and 0.18 m/s on CPB for the long cannula. Thus, during CPB the peak forward aortic flow velocity with the short cannula was significantly greater (p < 0.001) than before CPB, whereas the long cannula produced a lower peak forward aortic flow velocity during CPB. Furthermore, Doppler examination revealed severe turbulence in the aortic arch in all patients with a short cannula. No arch turbulence, however, was seen in 7 patients with a long cannula, and only mild turbulence appeared in the remaining patient with a long cannula. These results show that use of a long aortic cannula results in a significant decrease in peak forward aortic flow velocity and turbulence in the aortic arch during CPB, which may reduce the risk of erosion or disruption of existing atheroma and ensuing embolic complications.

Aorta, Thoracic↗

PubMed1995

Heparin bonding of bypass circuits reduces cytokine release during cardiopulmonary bypass.

BACKGROUND: Heparin bonding of the cardiopulmonary bypass (CPB) pump circuit decreases complement activation and fibrinolysis. It is not known whether inflammatory cytokines produced during CPB can also be modulated by the more biocompatible heparin-coated circuit. METHODS: This initial study evaluated the impact of heparin-bonded CPB circuits on production of the cytokines interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-a), IL-6, and IL-8 in adults undergoing complex cardiac operations with prolonged CPB. Twenty patients had blood samples drawn immediately before and at hourly intervals after the start of CPB using either a conventional oxygenator and circuit (n = 14) or a covalently bonded heparin oxygenator and circuit (n = 6). Levels of IL-1, TNF-a, IL-6, and IL-8 were measured in all serum samples using a "sandwich" enzyme-linked immunosorbent assay. RESULTS: The levels of IL-6 and IL-8 increased in a time-dependent fashion in both groups, but the response was significantly less over time in the heparin-bonded group (p < 0.05) for both IL-6 and IL-8. Levels of IL-1 and TNF-a were not significantly elevated with lengthening bypass interval in either group. CONCLUSIONS: These data indicate that the use of heparin-coated bypass pump circuits results in lower serum levels of the inflammatory cytokines IL-6 and IL-8 than standard circuits. Biocompatible materials that decrease the inflammatory response to CPB may ultimately reduce the morbidity associated with cardiac operations.

Adult↗

PubMed1994

Differential expression of Mtv loci in MHC class II-positive thymic stromal cells.

Despite the important role played by endogenous superantigen in shaping the T cell repertoire, little is known concerning the expression of the different Mtv loci in cells of the thymic microenvironment involved in repertoire selection. Here we have examined the expression of a panel of Mtv Ags by different MHC class II+ stromal cel types using reverse transcriptase-PCR and monitored the effects of these stromal cells on the development of cells expressing Mtv-reactive TCR V beta elements in closed thymic organ culture systems. Although Mtv-6 and Mtv-8/9 mRNAs are expressed in normal thymus lobe organ cultures, no Mtv expression was detected in MHC class II+ thymic epithelial cells. In contrast a striking pattern of differential expression was observed in dendritic cells of thymic origin that were devoid of Mtv-8/9 but expressed readily detectable levels of Mtv-6. This pattern of Mtv gene expression correlated well with TCR V beta repertoire development. TCRV beta 3+ T cells, normally deleted in response to Mtv-6, were virtually absent from the single positive thymocyte compartment in thymic organ cultures where dendritic cells are present but were present in reaggregate cultures where the only MHC class II-positive cells were thymic epithelial cells. On the other hand, V beta 11+ T-cells were not deleted in organ cultures, possibly reflecting the absence of Mtv-8/9 expression in dendritic cells. Our studies suggest that the influence Mtvs have on shaping the T cell repertoire not only depends on their expression within a particular strain but also on their tissue specific expression in relation to MHC class II, which is necessary for their presentation.

Animals↗

PubMed1994

Wound healing after harvesting of the internal thoracic and the superior and inferior epigastric arteries.

Wound healing of sternal incisions and midline or paramedian abdominal incisions was studied at 2 weeks postoperatively in three groups of dogs. Group 1, 10 dogs, had harvesting of bilateral internal thoracic arteries, superior epigastric arteries, and inferior epigastric arteries. Group 2, 5 dogs, had removal of the same arteries, but the superior and inferior epigastric arteries were harvested through paramedian rather than midline incisions. Group 3, 5 dogs, served as control and had median sternotomies and midline abdominal incisions only. All wounds healed without complication. Wound breaking strength of the skin of the chest incisions was significantly greater (p < 0.05) in the control group (group 3) (52.6 lb) compared with groups 1 (38.0 lb) and 2 (34.8 lb). Wound breaking strength of the skin of the abdominal incisions was significantly greater (p < 0.05) in group 2 (50.4 lb) when paramedian incisions were made compared with group 1 (35.1 lb). Hydroxyproline content was similar for all groups and all incisions. We conclude that abdominal wound breaking strength is significantly greater when paramedian incisions are performed to harvest the inferior epigastric arteries. Harvesting bilateral internal thoracic, superior epigastric, and inferior epigastric arteries may lower sternal wound breaking strength.

Abdomen↗

PubMed1992

Electrophysiological effect of the maze procedure on canine sinoatrial node function.

The maze procedure is an operation that has had great initial success in curing atrial fibrillation. This procedure includes several right atrial incisions that may interrupt the integrity of the sinoatrial node or its arterial supply. To assess the effect of the maze procedure on sinus node function (SNF), the following studies were performed: sinus node recovery times (SNRT), corrected SNRT (CSNRT), CSNRT under autonomic blockade maximal heart rate and intrinsic heart rates. Thirty-four dogs underwent a right thoracotomy with cardiopulmonary bypass (CPB). The dogs were divided into three groups. Group 1 (n = 9), the sham group, underwent CPB without any incisions. Group 2 (n = 8) underwent CPB and one of the right atrial incisions. Group 3 (n = 18) underwent CPB and all three of the right atrial incisions. SNF was determined before and after the procedure. Groups 1 and 2 had no significant difference in measured SNF acutely after the procedure. In Group 3 the mean SNRT increased from 552 msec to 1,984 msec (P = 0.005). Sinus node dysfunction was corroborated by all studies. In the chronic studies, a trend toward recovery of SNF was observed. The maze procedure results in significant acute sinus node dysfunction. This dysfunction may resolve spontaneously over the ensuing months. Modifications of the maze procedure that avoid the sinus node or its blood supply area may reduce procedure related sinus node dysfunction.

Animals↗

PubMedDate not supplied

Studies on thymic epithelial cells in vitro.

Thymic epithelial cells are unique in their ability to support positive selection and are essential throughout thymocyte development. Here, we describe a technique for measuring the proliferation of thymic epithelial cells by flow cytometry using a combination of BrdU and pancytokeratin labelling, and we examine the effects of different in vitro culture strategies on thymic epithelial cell function. We find that at d15 gestation, 74% (+/- 0.4%) of thymic epithelial cells are in cycle, which declines to 63% (+/- 1.3%) by d16, and to 34% (+/- 1.9%) by d18. This decline in proliferation is also found in organ cultures and in cultures depleted of lymphoid cells by 2-dGuo, suggesting that the cell cycle status of thymic epithelial cells is independent of the lymphoid population. When cultured in vitro as 3-dimensional aggregates, purified MHC class II+ thymic epithelial cells retain the ability to support thymocyte maturation. In contrast, 2-dimensional monolayer culture abrogates the ability of these cells to support positive selection, causes a reduction in whn gene expression and reduces their ability to re-form coherent reaggregate structures. Intact lobes and 3-dimensional aggregates are therefore the best way of maintaining thymic epithelial cell function and gene expression in vitro.

Animals↗