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Biomedical subjects

A C Thomas

Publications and source records attributed to A C Thomas.

At least 19 recordsLinked to original sources
PubMed2004

Endogenous endothelin increases gallbladder tone and leads to acute cholecystitis in the Australian possum.

Endothelins are bioactive peptides produced by gallbladder epithelial cells. We aimed to determine the role of endothelins in acute cholecystitis. Escherichia coli lipopolysaccharide vs saline (sham) was instilled into the gallbladder lumen of Australian possums. Some animals received the non-selective endothelin antagonist, tezosentan. At 4 or 24 h, plasma and gallbladder endothelins and white blood cell count (WBCC) were determined. Acute cholecystitis was assessed using a histopathology score. In other animals gallbladder tone was determined. At 4h, a dose-dependent 60-fold increase in gallbladder endothelin level occurred (P = 0.001) but other parameters remained comparable with sham animals. Epithelial cells were endothelin-immunoreactive. At 24 h, the WBCC rose (P < 0.007), and severe cholecystitis developed. Gallbladder but not plasma endothelin levels remained elevated. Tezosentan pre-treatment resulted in a histologically normal gallbladder, but the WBCC and gallbladder endothelin levels were elevated. Lipopolysaccharide or saline instillation also caused a time-dependent increase in gallbladder tone over 4 h (P < 0.001), but not in control animals. This increase was reduced by tezosentan treatment. Gallbladder endothelin production is an early event in acute cholecystitis, increases gallbladder tone and plays a crucial role in the inflammatory process.

Animals↗
PubMed2001

Smooth muscle cells of injured rat and rabbit arteries in culture: contractile and cytoskeletal proteins.

The aim of this study is to determine whether subpopulations of smooth muscle cells (SMC), as distinguished by variations in contractile and cytoskeletal proteins, appear in the neointima at different times after vascular injury, and/or whether subpopulations develop during serial passaging of these cells. Rat aortae and rabbit carotid arteries were injured with a 2F Fogarty balloon catheter and cultures established from the resulting neointima and the media 2, 6, 12, 16 and 24 weeks later. Cultures were examined at passages 1-5 and subpopulations of SMC categorised by intensity of staining for each protein by immunohistochemistry. Two populations of SMC with different staining intensities ('++', '+') were observed for each of the following proteins: alpha-SM actin, SM-myosin, desmin and vimentin. Populations without these proteins were also found. Changes in the percentages of cells expressing these proteins were transitory, indicating that the populations were not limited to a particular tissue (neointima or media), time after injury or passage number. One exception was found in rabbit cultures where the number of desmin-expressing cells quickly decreased with both time after injury and time in culture. Subpopulations of SMC were found at all times after injury in the media and neointima of rat and rabbit arteries, and after multiple passage of these cells. There was no pattern of development of one population suggesting that either no subpopulation has a proliferative or migratory advantage over others, or that only one population exists that is capable of diverse phenotypic changes.

Actins↗
PubMed2001

Symptomatic ureteropelvic junction obstruction in children in the era of prenatal sonography-is there a higher incidence of crossing vessels?

OBJECTIVES: To determine whether prenatal sonography and early detection and correction of ureteropelvic junction obstruction (UPJO) has changed the incidence of crossing vessels as the etiology of obstruction in older children presenting with symptomatic UPJO. METHODS: We reviewed the medical records of all children and adolescents who underwent pyeloplasty for symptomatic UPJO between 1986 and 1999, during the era of widespread use of prenatal sonography. Operative notes were used to determine which patients had obstruction due to lower pole crossing vessels. RESULTS: Thirty-eight patients were identified who underwent pyeloplasty for symptomatic UPJO. Lower pole vessels were identified in 22 (58%) of 38 patients (P <0.0001 compared with historical controls). All patients underwent dismembered pyeloplasty and remained asymptomatic after surgery, with renal scans demonstrating excellent drainage and preservation of function. CONCLUSIONS: Prenatal ultrasonography has increased the incidence of crossing vessels as the etiology of UPJO in young children and adolescents presenting with symptomatic UPJO compared with the historical incidence of 11% to 15%. This finding may impact treatment recommendations with respect to endourologic management of the obstruction in this patient population. Currently, we recommend open dismembered pyeloplasty for young children and adolescents presenting with symptomatic UPJO.

Child↗
PubMed2000

Biventricular pacing in end-stage heart failure improves functional capacity and left ventricular function.

BACKGROUND: Asynchronous patterns of contraction and relaxation may contribute to hemodynamic and functional impairment in heart failure. In 1993, we introduced biventricular pacing as a novel method to treat heart failure by synchronous stimulation of the right and left ventricles after an appropriate atrioventricular delay. The objectives of this study were to assess the early and long-term effects of this therapy on functional capacity and left ventricular function in patients with severe heart failure and left bundle branch block. METHODS AND RESULTS: Twelve patients with end-stage congestive heart failure, sinus rhythm and complete left bundle branch block were treated with biventricular stimulation at optimized atrioventricular delay. The NYHA functional class and maximal bicycle exercise capacity were assessed. Systolic and diastolic left ventricular function were studied with echocardiography and radionuclide angiography. Data was collected at various intervals during 1-year follow-up. Cumulative survival [95% CI] was 66.7% [40.0,93.4] at 1 year and 50 % [21.8, 78.2] at 2 and 3 years. Median NYHA class improved from class IV to class II at 1 year (p=0.008). After 6 weeks an increase in exercise capacity occurred, which was sustained. A less restrictive left ventricular filling pattern, an increase in dP/dt and left ventricular ejection fraction, and a decrease in mitral regurgitation were observed early and long-term. CONCLUSIONS: Biventricular pacing at optimized atrioventricular delay results in improvement in functional capacity, which is associated with improved systolic and diastolic left ventricular function, and a decrease in mitral regurgitation during short- and long-term follow-up.

Bundle-Branch Block↗
PubMed2000

Contractile and cytoskeletal proteins of smooth muscle cells in rat, rabbit, and human arteries.

The aim of this study was to determine whether similar populations of smooth muscle cells, in relation to contractile and cytoskeletal proteins, are present in normal and diseased human coronary arteries and normal and injured rat and rabbit arteries. Rat aortae and rabbit carotid arteries were de-endothelialised and the resulting neointimal thickening examined at set time points 2-24 weeks later. Immunohistochemistry revealed that arteries had three distinct populations of cells in respect to alpha-smooth muscle actin, smooth muscle myosin heavy chain and vimentin (staining intensities '-', '+' or '++' for each protein), but only two populations in respect to desmin ('-' and '+'). The different populations of cells were found in the neointima at all times after injury, in human atherosclerotic plaque and in the media of diseased, injured and uninjured vessels, although in different proportions. It was concluded that arteries of the human, rat and rabbit have cells with a wide spectrum of contractile and cytoskeletal proteins. Expression of the different proteins did not reflect the state of the artery after injury or during the disease process, and was not associated with the expansion of a subset of cells within the artery wall.

Adult↗
PubMed1999

Matrix metalloproteinase can facilitate the heparanase-induced promotion of phenotype change in vascular smooth muscle cells.

Previous studies from this laboratory have shown that degradation of heparan sulphate proteoglycan by both living macrophages and macrophage lysosomal heparanase induces phenotypic change of vascular smooth muscle cells (SMC) from a high volume fraction of myofilaments (V(v)myo) to a low V(v)myo [Campbell et al. Exp Cell Res 1992; 200: 156-167]. The aim of this study was to determine whether matrix metalloproteinase (MMP) activity is also involved in the induction of SMC phenotypic change by macrophages. A specific inhibitor of MMPs (BB94) was able to block macrophage-induced SMC phenotypic change and subsequent DNA synthesis in freshly dispersed SMC seeded in primary culture at confluent density. The inhibitor did not block these SMC changes when SMC were seeded at low density without macrophages nor did it block heparanase activity directly. We also determined whether heparanase and MMP activities are upregulated together in vivo. Artery homogenates were analysed in a heparanase enzyme assay and for MMPs using zymograms. Increased heparanase activity was observed 3-14 days following balloon catheter injury of rabbit carotid arteries, and returned to control levels 6 weeks after injury. Active MMP2 was induced with heparanase after injury. MMP9 induction was also apparent 6 h after injury. Immunohistology on sections of these arteries showed the presence of MMPI1, 2, 3 and 9 with these MMPs being strongly induced in the intima 7 days after balloon catheter injury. Both heparanase and MMP activities were also present in human end-stage complex lesions from coronary arteries, carotid endarterectomies and abdominal aortic aneurysms. Because MMPs and heparanase are expressed at the same time, it is possible that MMPs facilitate heparanase activity in promotion of phenotypic modulation of SMC in vivo during neointimal thickening following injury and in atherosclerotic lesions.

Actin Cytoskeleton↗
PubMed1999

Resistance of ovine, caprine and bovine endothelial cells to Clostridium perfringens type D epsilon toxin in vitro.

Ovine, caprine and bovine endothelial cells were grown in vitro and challenged with Clostridium perfringens type D epsilon toxin to compare their susceptibility to this toxin. Madin Darby canine kidney (MDCK) cells, which are known to be susceptible to epsilon toxin, were used as a positive control. No morphological alterations were observed in any of the endothelial cell cultures tested, even after challenging with doses as high as 1200 MLD50/ml of epsilon toxin. MDCK cells showed contour rounding and nuclear condensation as early as 30 min after exposure to 100 MLD50/ml of epsilon toxin and after 60 min of exposure to 12.5 MLD50/ml of the same toxin. All the MDCK cells were dead after 3 h of exposure to all concentrations of epsilon toxin. The results indicate that ovine, caprine and bovine endothelial cells are not morphologically responsive to the action of epsilon toxin in vitro.

Animals↗
PubMed1999

Copper deprivation potentiates oxidative stress in HL-60 cell mitochondria.

Cytochrome-c oxidase is the copper-dependent terminal respiratory complex (complex IV) of the mitochondrial electron transport chain whose activity in a variety of tissues is lowered by copper deficiency. Because inhibition of respiratory complexes increases the production of reactive oxygen species by mitochondria, it is possible that copper deficiency increases oxidative stress in mitochondria as a consequence of suppressed cytochrome-c oxidase activity. In this study, the activities of respiratory complex I + III, assayed as NADH:cytochrome-c reductase, complex II + III, assayed as succinate:cytochrome-c reductase, complex IV, assayed as cytochrome-c oxidase, and fumarase were measured in mitochondria from HL-60 cells that were grown for seven passages in serum-free medium that was either unsupplemented or supplemented with 50 n M CuSO4. Fumarase activity was not affected by copper supplementation, but the complex I + III:fumarase and complex IV:fumarase ratios were reduced 30% and 50%, respectively, in mitochondria from cells grown in the absence of supplemental copper. This indicates that copper deprivation suppressed the electron transfer activity of copper-independent complex I + III as well as copper-dependent complex IV. Manganese superoxide dismutase (MnSOD) content was also increased 49% overall in the cells grown in the absence of supplemental copper. Furthermore, protein carbonyl groups, indicative of oxidative modification, were present in 100-kDa and 90-kDa proteins of mitochondria from copper-deprived cells. These findings indicate that in cells grown under conditions of copper deprivation that suppress cytochrome-c oxidase activity, oxidative stress in mitochondria is increased sufficiently to induce MnSOD, potentiate protein oxidation, and possibly cause the oxidative inactivation of complex I.

Copper↗
PubMed1997

Quinine-induced hemolytic uremic syndrome.

Although quinine use is very common, hemolytic uremic syndrome (HUS) following exposure to quinine is only a recently reported phenomenon, with the first description published in 1991. Previous reports have concentrated on the nature of the hematological process and in particular characterization of the quinine-induced antibodies involved. We present a case of HUS with a clear temporal and immunological relationship to quinine which demonstrates the pathognomonic renal features of HUS. An indirect antiglobulin test with the patient's serum agglutinated red blood cells only in the presence of quinine. Renal biopsy features included glomerular and arteriolar endothelial swelling, capillary loop thrombi, mesangiolysis, segmental sclerosis and segmental ischemia. Early empiric treatment with plasma exchange and corticosteroids was instituted and this resulted in recovery of renal function to normal.

Biopsy↗
PubMed1996

Technological advances in implantable cardioverter-defibrillators before the year 2000 and beyond.

The implantable cardioverter-defibrillator (ICD) has evolved rapidly since its clinical introduction; product life cycles have been exceedingly short. This swift transition from early shock-only devices to small, programmable, tiered-therapy systems has been driven by 2 major factors: minimally invasive implant procedures and technological innovation. Yet, while many new ICD systems have been introduced recently, even more advanced products are on the horizon before the year 2000 and beyond. In general, devices will be smaller and smarter. Certainly, ICD volume will be further reduced without detrimentally affecting longevity. Endocardial lead systems will become smaller and more versatile. Rhythm discrimination algorithms will become more effective. New adaptive-rate pacing systems that limit the maximum paced rate based on hemodynamic indices will become features of tachyarrhythmia products. Pacing schemes for prevention of supraventricular tachyarrhythmias and improvement of hemodynamic function in patients with congestive heart failure will likely be introduced for clinical evaluation.

Cardiac Pacing, Artificial↗
PubMed1995

Expression of growth factor receptors in arterial smooth muscle cells. Dependency on cell phenotype and serum factors.

The effects of modulation of rabbit aortic smooth muscle cells (SMCs) from the 'contractile' phenotype on surface membrane receptors binding epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and platelet-derived growth factor-BB (PDGF-BB), as well as their responsiveness to these growth factors was investigated in cell culture. Cells predominantly of the 'contractile' phenotype expressed low numbers of high affinity EGF and bFGF receptors (EGFr: 1.09 +/- 0.18 fmol/10(6) cells; bFGFr: 0.32 +/- 0.07 fmol/10(6) cells). Upon modulation from the 'contractile' phenotype, the expression of these cell surface receptors increased greatly: 8- and 11-fold with respect to EGF and bFGF receptors. Cell surface receptors binding [125I]-PDGF-BB were largely unaltered. The elevated bFGF receptor number appeared dependent on SMC modulation from the 'contractile' phenotype and serum; the latter factor did not influence EGF receptor numbers. In both instances the increase in receptor numbers was independent of the proliferation status of the cells. Cells expressing high levels of the growth factor receptors also rapidly entered the cell cycle, proliferated, and exhibited growth factor-specific changes in shape in the presence of these growth factors. Because the effects on growth factor receptor numbers were observed in confluent cells, such alterations, are likely to play a significant role in vessel remodelling following balloon catheter angioplasty, in atherosclerotic vessels and the vascular hypertrophy associated with hypertension.

Animals↗
PubMed1995

Infiltration of the kidney by alpha beta and gamma delta T cells: effect on progression in IgA nephropathy.

We have studied renal biopsies from three groups of patients to determine if alpha beta T cells or gamma delta T cells are present, and whether their presence is correlated with disease progression in IgA nephropathy (IgAN). Group one comprised thin basement membrane disease biopsies (non-immunological control, N = 7); group two were patients with IgAN and stable renal function one year following biopsy (stable, N = 7); and group three were IgAN patients with rapidly declining renal function after one year (progressive, N = 7). Immunohistochemical staining using monoclonal antibodies (CD3, TcR beta, TcR delta) and molecular studies utilizing polymerase chain reaction amplification of cDNA transcribed from biopsy RNA, with primers specific for either the alpha beta TcR or gamma delta TcR, were undertaken. On immunohistochemistry a significant increase in CD3 + cells in progressive biopsies was seen (vs. control P = 0.002, vs. stable P = 0.002). The progressive biopsies infiltrate consisted of both alpha beta TcR (vs. control P = 0.001, vs. stable P = 0.003) and gamma delta TcR cells (vs. control P = 0.01). The RNA study demonstrated an increase in TcR C alpha transcription in the progressive (vs. control P = 0.003) biopsies. Increased TcR C delta transcription was seen in the progressive group (vs. control P = 0.01, vs. stable P = 0.02). We confirm that the presence of lymphocytes in IgAN biopsies predicts progressive disease. While alpha beta T cells are found in both stable and progressive disease, the presence of gamma delta T cells is only associated with progressive IgAN.

Adult↗
PubMed1995

Aortitis with dissection complicating systemic lupus erythematosus.

A 31 yr old female under treatment for systemic lupus erythematosus complained of episodes of atypical chest pain radiating to the back. Subsequently she suddenly collapsed and died. Post mortem revealed a well-defined, localized area of non-giant cell aortitis extending from the supra-aortic ridge of the aortic valve to the ligamentum arteriosum. Active arteritis with fibrinoid necrosis and obliterative endarteritis of vasa vasorum had resulted in multiple infarcts of differing ages with associated inflammation and disruption of the aortic wall, culminating in aortic dissection and cardiac tamponade.

Adult↗
PubMed1995

A reproducible model of chronic rejection in rat renal allografts.

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 66% after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.

Animals↗
PubMed1994

Recurrent mesangial IgA nephritis following renal transplantation.

Recurrence of mesangial IgA deposits in renal allografts of patients whose original disease was primary IgA nephropathy (IgAN) has been studied. Forty-six patients with primary IgAN received 51 renal allografts and have been followed for 3-183 months. A prospective study of 11 patients (11 biopsies) and a retrospective analysis of 17 patients (16 biopsies; 2 nephrectomy specimens) have been combined. Seventeen of the 29 allografts had recurrent mesangial IgA deposits and of these three patients have negative urinalysis, normal glomeruli by light microscopy, and stable renal function; six patients have microhaematuria, mesangial proliferative nephritis, but at present stable renal function; and five have mesangial proliferative glomerulonephritis with microhaematuria, heavy proteinuria, hypertension, and progressive allograft failure secondary to IgA disease alone, and one of these is now back on dialysis. Three other grafts with recurrent deposits are failing because of transplant glomerulopathy or rejection. The only predictor identified for recurrence of mesangial IgA deposits was length of time post-transplantation, with allograft tissue being studied at 45.9 +/- 10.0 versus 15.3 +/- 4.8 months (P = 0.008) post-transplantation in patients with and without recurrent deposits respectively. Cyclosporin A did not prevent recurrence. By virtue of a longer follow-up of patients post-transplantation than all other reported series, these results suggest that with increasing time post-transplantation recurrence of mesangial IgA disease will become increasingly important as a cause of progressive allograft dysfunction and failure unless effective treatment is found for the primary disease.

Complement C3↗
PubMed1993

Brain protection via cerebral retrograde perfusion during aortic arch aneurysm repair.

Eleven patients underwent resection and graft replacement of ascending and aortic arch aneurysms. Retrograde cerebral perfusion was used during the procedures to minimize cerebral ischemia. Retrograde cerebral perfusion (15 degrees to 24 degrees C) was administered through the superior vena cava. The mean cerebral ischemic time was .35 minutes (range, 11 to 71 minutes). Throughout retrograde cerebral perfusion, blood samples were drawn from the innominate and left carotid arteries at 1, 5, and every 10 minutes thereafter for analysis of arterial oxygen content, total creatine kinase level, and creatine kinase BB fraction. All patients survived. All except 1 awoke neurologically intact. In this patient, electroencephalogram and transcranial Doppler studies conducted before circulatory arrest were consistent with embolic phenomena. There was no significant difference between the current group's intraoperative electroencephalograms and those of a similar historical group. Postoperative complications included transient renal failure, myasthenia gravis, cholecystitis, premature atrial contractions, atrial fibrillation, and vocal cord paralysis. The creatine kinase BB fraction range was 1.8 to 13.4. The increase of total creatine kinase level was due to MM fraction. Retrograde cerebral perfusion during circulatory arrest is a valuable adjunct for protecting the brain. The creatine kinase BB band was not a good marker to detect brain injury. With continued use of this technique and accumulation of a larger series, we may better define the role of retrograde cerebral perfusion in brain protection.

Adult↗