Tumour growth and resistance to gemcitabine of pancreatic cancer cells are decreased by AP-2alpha overexpression.

BACKGROUND: Activator protein-2alpha (AP-2alpha) is a transcription factor that belongs to the family of AP-2 proteins that have essential roles in tumorigenesis. Indeed, AP-2alpha is considered as a tumour-suppressor gene in different tissues such as colonic, prostatic or breast epithelial cells. Moreover, AP-2alpha also participates in the control of colon and breast cancer cells sensitivity towards chemotherapeutic drugs. Despite its potential interest, very few data are available regarding the roles of AP-2alpha in pancreatic cancer. METHODS: We have developed a stable pancreatic CAPAN-1 cell line overexpressing AP-2alpha. Consequences of overexpression were studied in terms of in vivo cell growth, gene expression, migration capacity and chemosensitivity. RESULTS: In vivo tumour growth of CAPAN-1 cells overexpressing AP-2alpha was significantly decreased by comparison to control cells. An altered expression pattern of cell cycle-controlling factors (CDK-4, CDK-6, cyclin-G1, p27(kip1) and p57(kip2)) was observed in AP-2alpha-overexpressing clones by microarrays and western blot analysis. Promoter activity and ChIP analysis indicated that AP-2alpha induces p27(kip1) protein levels by direct binding to and transactivation of its promoter. Moreover, AP-2alpha overexpression increased the chemosensitivity of CAPAN-1 cells to low doses of gemcitabine and reduced their in vitro migration capacity. CONCLUSION: Our data suggested that AP-2alpha overexpression could be exploited to decrease in vivo tumour growth of pancreatic cancer cells and to increase their sensitivity to gemcitabine.

Ultrastructural and biochemical characterization of autophagy in higher plant cells subjected to carbon deprivation: control by the supply of mitochondria with respiratory substrates.

Autophagy triggered by carbohydrate starvation was characterized at both biochemical and structural levels, with the aim to identify reliable and easily detectable marker(s) and to investigate the factors controlling this process. Incubation of suspension cells in sucrose-free culture medium triggered a marked degradation of the membrane polar lipids, including phospholipids and galactolipids. In contrast, the total amounts of sterols, which are mainly associated with plasmalemma and tonoplast membranes, remained constant. In particular, phosphatidylcholine decreased, whereas phosphodiesters including glycerylphosphorylcholine transiently increased, and phosphorylcholine (P-Cho) steadily accumulated. P-Cho exhibits a remarkable metabolic inertness and therefore can be used as a reliable biochemical marker reflecting the extent of plant cell autophagy. Indeed, whenever P-Cho accumulated, a massive regression of cytoplasm was noticed using EM. Double membrane-bounded vacuoles were formed in the peripheral cytoplasm during sucrose starvation and were eventually expelled into the central vacuole, which increased in volume and squeezed the thin layer of cytoplasm spared by autophagy. The biochemical marker P-Cho was used to investigate the factors controlling autophagy. P-Cho did not accumulate when sucrose was replaced by glycerol or by pyruvate as carbon sources. Both compounds entered the cells and sustained normal rates of respiration. No recycling back to the hexose phosphates was observed, and cells were rapidly depleted in sugars and hexose phosphates, without any sign of autophagy. On the contrary, when pyruvate (or glycerol) was removed from the culture medium, P-Cho accumulated without a lag phase, in correlation with the formation of autophagic vacuoles. These results strongly suggest that the supply of mitochondria with respiratory substrates, and not the decrease of sucrose and hexose phosphates, controls the induction of autophagy in plant cells starved in carbohydrates.

[Seronegative myasthenia and myasthenia gravis with anti-MuSK antibody: a retrospective study of 20 cases]. / Myasthénie séronégative et myasthénie avec anticorps anti-MuSK : une série rétrospective de 20 cas.

INTRODUCTION: Despite the fact that anti-muscle specific tyrosine kinase (MuSK) antibodies have been discovered for seven years, only a few studies have, until now, focused on myasthenia without acetylcholine-receptors antibodies (ab) (formerly known as "seronegative myasthenia"), and among them, anti-MuSK-antibody-positive and -negative patients. METHOD: We retrospectively studied 20 patients with "seronegative" myasthenia gravis, eight of them being anti-MuSK-ab positive, the remaining twelve being negative. We searched for clinical, neurophysiological, and therapeutic differences between the two groups (anti-MuSK-ab positive: anti-MuSK+ versus anti-MuSK-ab negative: anti-MuSK-). RESULTS: Anti-MuSK+ patients had more predominantly bulbar involvement and had more severe disease (these patients required referral to intensive care more frequently). There was no difference between the two groups concerning treatment efficiency and tolerance. Most of our patients were treated with acetylcholinesterase-inhibitors, and immunomodulatory or immunosuppressive drugs that could indirectly reflect greater severity. However, there was no difference in treatments for anti-MuSK+ versus anti-MuSK- patients. CONCLUSION: These results both confirm and complete the preexisting data on RACh-negative myasthenia, and especially on myasthenia associated with MuSK antibodies.

Tei index to assess perioperative left ventricular systolic function in patients undergoing mitral valve repair.

BACKGROUND: Using echocardiography, perioperative assessment of systolic function by fractional area change (FAC) is questionable in patients suffering from mitral regurgitation (MR). Tei index, an index expressing global cardiac function, has been reported to be unchanged after mitral valve surgery. We tested the hypothesis where the Tei index could be useful in assessing the perioperative cardiac function in patients undergoing mitral valve repair (MVR). METHODS: Twenty-five patients were enrolled. Transoesophageal echocardiography was performed perioperatively before and after the correction of MR. We compared the impact of the MVR on the left ventricular FAC and the Tei index. FAC was calculated from the transgastric short-axis view and Tei index was determined from the four chambers and deep transgastric views. RESULTS: Two patients were excluded because of poor acoustic windows. FAC significantly decreased after MVR from 53 (9)% to 42 (10)% (P<0.001), while Tei index was unaffected [0.46 (0.16) vs 0.47 (0.17), NS]. A significant relationship was found between the preoperative Tei index and the postoperative FAC (R=-0.64, P<0.001). Moreover, a significant and clinically relevant relationship was determined between the predicted (using preoperative Tei index) and the measured postoperative FAC (R=0.64, P<0.001). CONCLUSIONS: FAC but not the Tei index is influenced by MVR. The preoperative determination of the Tei index allows predicting postoperative FAC and offers the opportunity to identify patients in whom a severe unsuspected systolic dysfunction could render difficult the weaning from cardiopulmonary bypass.

Perfusion MR imaging at 3-Tesla: Can it predict tumor grade and histologic necrosis rate of musculoskeletal sarcoma?

PURPOSE: To identify quantitative perfusion parameters that are best associated with tumor grade and tumor necrosis at magnetic resonance (MR) imaging at 3-Tesla. METHODS: MR perfusion studies of 31 patients with a musculoskeletal sarcoma were retrospectively evaluated by two readers. There were 18 men and 13 women with a mean age of 34.9±24.4 (standard deviation [SD] years) (range: 6-87 years). All patients underwent carcinologic tumor resection less than 3 months after MR imaging. For all patients six perfusion parameters (three semi-quantitative and three permeability parameters) were analyzed. The percentage of tumor necrosis was estimated using MR imaging. Perfusion data were compared between groups of tumors with different grades and necrosis ratios. Interobserver variability was calculated using intraclass correlation coefficient (ICC). RESULTS: Interobserver variability among the perfusion parameters was good to excellent (ICC: 0.72-0.9). The area under the curve and maximum slope values showed a significant association with the degree of tumor necrosis (P=0.02-0.04). When tumors with low necrosis ratios were compared to those with high ratios the former parameter was 80% lower. In the same groups, the imaging necrosis index was 56.9-59.8% higher in patients with grade 2 necrosis (P=0.01). Extracellular space volume (Ve) was 31.4% to 55.8% lower in tumors with high grade while the backflow constant (Kep) was 33.6% to 40.1%% higher in tumors with high grade. CONCLUSION: Semi-quantitative MR perfusion parameters have an excellent reproducibility and are associated with the degree of histologic tumor necrosis in musculoskeletal sarcomas. The utility of permeability parameters for determining tumor grade needs further investigations.

Results after orthotopic heart transplantation accepting donor hearts >50 years: experience at La Pitie Salpetriere, Paris.

INTRODUCTION: We sought to examine the results of orthotopic heart transplantation accepting hearts from donors >50 years of age with special regard to the usefulness of peripheral extracorporeal membrane oxygenation for posttransplant graft dysfunction. PATIENTS: Between January 2000 and December 2004, a total of 247 patients underwent orthotopic heart transplantation. In 143 patients (58%) the heart donor was <50 years (group I, mean age of donor hearts 36 +/- 11 years; range, 8-49 years). In 104 recipients (42%) the heart donor was >50 years (group II, mean age of donor hearts 56 +/- 15 years; range, 50-67 years). Pretransplant characteristics of the two groups showed no significant differences. RESULTS: The in-hospital mortality was slightly increased in group II (24% vs 20% in group I, NS) and the 5-year survival rate significantly increased in group I (75% vs 63% in group II). Freedom from transplant vasculopathy after 3 years was similar in both groups (86% in group I vs 87% in group II). A total of 25 patients (17%) in group I and 27 patients (26%) in group II developed graft dysfunction. Eleven patients in group I and 10 patients in group II were treated using peripheral extracorporeal membrane oxygenation, whereas 3 of the 11 patients in group I and 5 of the 10 patients in group II were discharged following a complete recovery. Two patients in group I and 4 patients in group II were survivors beyond year. CONCLUSION: In our experience it was possible to increase the cardiac donor pool by accepting allografts from donors >50 years of age in selected cases. The incidence of transplant vasculopathy was not increased, whereas in-hospital mortality was slightly higher. In our limited cohort, patients with older donor hearts was developed graft dysfunction profited from primary extracorporeal membrane oxygenation implantation, an indication that should be examined further without delay.

[Reperfusion syndrome with cerebral vasogenic edema after carotid artery endarterectomy]. / Oedème cérébral vasogénique par syndrome de reperfusion post-endartérectomie carotidienne.

INTRODUCTION: Reperfusion (or hyperperfusion) syndrome may be a possible complication of carotid artery endarterectomy or angioplasty. OBSERVATION: We report the case of a 54-year-old man who underwent a right carotid endarterectomy for an asymptomatic carotid stenosis and developed reperfusion syndrome a few days after surgery. The symptoms were marked by a prolonged partial epileptic status and then left hemiplegia lasting several days. Brain MRI with Diffusion sequences was normal, whereas there was a right frontoparietal hypersignal in FLAIR sequences, suggesting the presence of brain vasogenic oedema. Clinical and neuroradiological outcomes were good, confirming the relative good prognosis attributed to vasogenic brain oedema in previous similar publications. This condition may be misdiagnosed as cytotoxic brain oedema, another possible complication of carotid endarterectomy, whose management and prognosis are different. CONCLUSION: When a focal neurological deficit or epileptic seizures follow carotid artery endarterectomy, it is important to consider reperfusion syndrome. MRI (with FLAIR and Diffusion sequences) will show a vasogenic brain oedema, with a better prognosis than what can be expected with cytotoxic oedema.

Cell-to-cell heterogeneity of EWSR1-FLI1 activity determines proliferation/migration choices in Ewing sarcoma cells.

Ewing sarcoma is characterized by the expression of the chimeric EWSR1-FLI1 transcription factor. Proteomic analyses indicate that the decrease of EWSR1-FLI1 expression leads to major changes in effectors of the dynamics of the actin cytoskeleton and the adhesion processes with a shift from cell-to-cell to cell-matrix adhesion. These changes are associated with a dramatic increase of in vivo cell migration and invasion potential. Importantly, EWSR1-FLI1 expression, evaluated by single-cell RT-ddPCR/immunofluorescence analyses, and activity, assessed by expression of EWSR1-FLI1 downstream targets, are heterogeneous in cell lines and in tumours and can fluctuate along time in a fully reversible process between EWSR1-FLI1high states, characterized by highly active cell proliferation, and EWSR1-FLI1low states where cells have a strong propensity to migrate, invade and metastasize. This new model of phenotypic plasticity proposes that the dynamic fluctuation of the expression level of a dominant oncogene is an intrinsic characteristic of its oncogenic potential.

Post-traumatic fibro-osseous lesion of the ribs: a relatively under-recognised entity.

AIM: To report the description of a rare benign osseous lesion affecting the ribs entitled post-traumatic fibro-osseous lesion (PTFOL). METHODS: Seven cases of PTFOLs were retrieved from the archives of the University Hospital of Lille. Histological slides were reviewed and lesions were classified according to the histological patterns described by McDermott et al. Clinical and follow-up data were obtained from the patients' charts. RESULTS: PTFOLs occurred principally in men (mean age 31.8 years) with a known or suspected previous chest injury for four of them. No previous cancer was noted. Radiologically, PTFOLs readily presented as an isolated expansive lucency with a sclerotic rim located on the last five ribs. A constant increased uptake of radionucleotide was noted on bone scan. Microscopically, two fibro-osseous, four xanthomatous and one mixed pattern were individualised. Lesions were characterised by a network of anastomosing bone trabeculae without osteoblast lining within a fibrous stroma. A zonal maturation from woven to peripheral lamellar bone was characterised. Central sheets of lipid-laden histiocytes were conspicuous in the xanthomatous type. For each patient, clinical follow-up was excellent, without any recurrence. CONCLUSIONS: This is the second largest series of PTFOLs, which is considered to be a dysplastic healing process after trauma. It may be symptomatic or shown by imaging studies realised for unrelated reason. PTFOL is regularly misdiagnosed with other more common lesions of the ribs, such as fibro-osseous dysplasia, osteoma osteoid and benign fibrous histiocytoma. Its recognition is of importance because no follow-up is needed after resection.

[Results of video-assisted mitral surgery in a non-selected population]. / Résultats de la chirurgie mitrale vidéo-assistée dans une population non sélectionnée.

A prospective 'analysis of operative risk and results in video-assisted mitral valve surgery performed in a non selected population is reported. Seventy two consecutive patients (1997-2004) with mean age 60 +/- 12 years underwent a video-assisted mitral valve procedure using a femoral CPB. A transthoracic direct aortic clamping was done in 28 patients (TT) and an endo-aortic occlusion balloon was used in 44 patients (Endo). The surgical approach was a right lateral minithoracotomy in all cases; 16 patients had a previous cardiac surgery. The expected mitral operation (39 repairs, 33 replacements) was done in all cases, without conversion. There were 4 early deaths (1 st month), all in Endo group: 1 aortic dissection, 1 heart failure and 2 sudden deaths. Postoperative complication occurred in 17 patients with 5 reoperations for hemostasis of the thoracic wall. Cumulative rate of mortality and morbidity was 29% in Endo and 28% in TT (ns). Hospital stay was 8 +/- 2 days. At discharge, 4 patients had a residual grade 2 echocardiographic mitral regurgitation after valve repair. In January 2005, with a 1.8 years follow-up, there were 4 late deaths, 3 patients underwent a valve reoperation, 2 patients were still in NYHA class 3 and 5 patients had a residual grade 1 or 2 mitral regurgitation. The 3-year actuarial survival was 86 +/- 10% and the 3-year probability to be free of reoperation was 95 +/- 6%. In mitral valve surgery, video-assisted approach is reliable, the operative risk is controlled and midterm results are not compromised. Video-assisted mitral valve surgery is a new less invasive standard; it is the procedure of choice in valve replacement, in reoperation and in non complex valve repair with good cosmetic results.

Glycine and serine catabolism in non-photosynthetic higher plant cells: their role in C1 metabolism.

Glycine and serine are two interconvertible amino acids that play an important role in C1 metabolism. Using 13C NMR and various 13C-labelled substrates, we studied the catabolism of each of these amino acids in non-photosynthetic sycamore cambial cells. On one hand, we observed a rapid glycine catabolism that involved glycine oxidation by the mitochondrial glycine decarboxylase (GDC) system. The methylenetetra- hydrofolate (CH2-THF) produced during this reaction did not equilibrate with the overall CH2-THF pool, but was almost totally recycled by the mitochondrial serine hydroxymethyltransferase (SHMT) for the synthesis of one serine from a second molecule of glycine. Glycine, in contrast to serine, was a poor source of C1 units for the synthesis of methionine. On the other hand, catabolism of serine was about three times lower than catabolism of glycine. Part of this catabolism presumably involved the glycolytic pathway. However, the largest part (about two-thirds) involved serine-to-glycine conversion by cytosolic SHMT, then glycine oxidation by GDC. The availability of cytosolic THF for the initial SHMT reaction is possibly the limiting factor of this catabolic pathway. These data support the view that serine catabolism in plants is essentially connected to C1 metabolism. The glycine formed during this process is rapidly oxidized by the mitochondrial GDC-SHMT enzymatic system, which is therefore required in all plant tissues.

Cooperation and Competition between Adenylate Kinase, Nucleoside Diphosphokinase, Electron Transport, and ATP Synthase in Plant Mitochondria Studied by 31P-Nuclear Magnetic Resonance.

Nucleotide metabolism in potato (Solanum tuberosum) mitochondria was studied using 31P-nuclear magnetic resonance spectroscopy and the O2 electrode. Immediately following the addition of ADP, ATP synthesis exceeded the rate of oxidative phosphorylation, fueled by succinate oxidation, due to mitochondrial adenylate kinase (AK) activity two to four times the maximum activity of ATP synthase. Only when the AK reaction approached equilibrium was oxidative phosphorylation the primary mechanism for net ATP synthesis. A pool of sequestered ATP in mitochondria enabled AK and ATP synthase to convert AMP to ATP in the presence of exogenous inorganic phosphate. During this conversion, AK activity can indirectly influence rates of oxidation of both succinate and NADH via changes in mitochondrial ATP. Mitochondrial nucleoside diphosphokinase, in cooperation with ATP synthase, was found to facilitate phosphorylation of nucleoside diphosphates other than ADP at rates similar to the maximum rate of oxidative phosphorylation. These results demonstrate that plant mitochondria contain all of the machinery necessary to rapidly regenerate nucleoside triphosphates from AMP and nucleoside diphosphates made during cellular biosynthesis and that AK activity can affect both the amount of ADP available to ATP synthase and the level of ATP regulating electron transport.

Transport, Compartmentation, and Metabolism of Homoserine in Higher Plant Cells. Carbon-13- and phosphorus-31-nuclear magnetic resonance studies Carbon-13- and Phosphorus-31-Nuclear Magnetic Resonance Studies

The transport, compartmentation, and metabolism of homoserine was characterized in two strains of meristematic higher plant cells, the dicotyledonous sycamore (Acer pseudoplatanus) and the monocotyledonous weed Echinochloa colonum. Homoserine is an intermediate in the synthesis of the aspartate-derived amino acids methionine, threonine (Thr), and isoleucine. Using 13C-nuclear magnetic resonance, we showed that homoserine actively entered the cells via a high-affinity proton-symport carrier (Km approximately 50-60 mum) at the maximum rate of 8 +/- 0.5 mumol h-1 g-1 cell wet weight, and in competition with serine or Thr. We could visualize the compartmentation of homoserine, and observed that it accumulated at a concentration 4 to 5 times higher in the cytoplasm than in the large vacuolar compartment. 31P-nuclear magnetic resonance permitted us to analyze the phosphorylation of homoserine. When sycamore cells were incubated with 100 mum homoserine, phosphohomoserine steadily accumulated in the cytoplasmic compartment over 24 h at the constant rate of 0.7 mumol h-1 g-1 cell wet weight, indicating that homoserine kinase was not inhibited in vivo by its product, phosphohomoserine. The rate of metabolism of phosphohomoserine was much lower (0.06 mumol h-1 g-1 cell wet weight) and essentially sustained Thr accumulation. Similarly, homoserine was actively incorporated by E. colonum cells. However, in contrast to what was seen in sycamore cells, large accumulations of Thr were observed, whereas the intracellular concentration of homoserine remained low, and phosphohomoserine did not accumulate. These differences with sycamore cells were attributed to the presence of a higher Thr synthase activity in this strain of monocot cells.

Peripheral extracorporeal membrane oxygenation (ECMO) in patients with posttransplant cardiac graft failure.

INTRODUCTION: We sought to report the usefulness of extracorporeal membrane oxygenation (ECMO) in heart transplant patients. PATIENTS: Between March 2002 and August 2004, 14 heart transplant patients (11 men and three women, 36 +/- 15 years old, range = 12 to 50) with primary graft failure underwent peripheral ECMO implantation. Three patients had pulmonary hypertension and three had been transplanted with hearts from marginal donors. At the time of implantation, all were in severe cardiogenic shock despite maximal inotropic support. In six patients, the ECMO was implanted in the operating room since cardiopulmonary bypass could not be weaned. In the eight remaining patients, ECMO was implanted in the intensive care unit, during the first 48 hours in seven cases. In one patient, implantation was performed during external resuscitation. In all cases, femoral vessels were canulated using the Seldinger technique after anterior wall exposure. Distal arterial perfusion of the lower limb was systematically used. RESULTS: Pump outflow was high enough in all the cases (mean: 2.6 +/- 0.2 L/min/m(2)). Three patients died on circulatory support. One patient was implanted with a total artificial heart after a few hours and another one underwent unsuccessful emergent retransplantation. Nine patients were weaned from ECMO after a mean duration of 5 +/- 2.5 days. Among them, one died of infection at 10 days after weaning and seven others were discharged to rehabilitation centers. CONCLUSION: Fast operating room or bedside implantation of a peripheral ECMO allows the physician to stabilize the hemodynamic status of patients with cardiac graft failure, potentially leading toward myocardial recovery.

[Evolution of the Fontan operation and results in patients with single ventricles or mixed congenital malformations]. / Evolution et résultats des opérations de Fontan dans les cardiopathies congénitales univentriculaires ou assimilées.

STUDY OBJECTIVES: To examine the results of right heart derivations and clinical outcomes according to preoperative characteristics and operative strategy implemented. METHODS: Fontan operations were performed in 65 patients (mean age = 10.3 years, 41 males). The majority of cardiopathies were single ventricles (SV) with (49% of patients) or without (26%) tricuspid atresia. A palliative bidirectional cavo-pulmonary (BCP) anastomosis was performed prior to Fontan in 15 patients. Intra-atrial Fontan tunnelling was performed in 43 patients, Kreutzer-type operations in 10, and extracardiac tubes were used in 8 patients. The mean duration of follow-up was 6.1 +/- 0.3 years. RESULT: The 30-day mortality was 13.8%. Early mortality was higher among patients with SV with than without tricuspid atresia (P < 0.01), and among patients < 4 years old. Early reoperations were required in 5 patients, including dismounting in 1, BCP anastomosis after Kreutzer procedure in 1, and tube thrombosis in 1 patient. A single death occurred past 30 days, and late adverse events included protein-losing enteropathy in 1 patient, complete atrioventricular block in 1, and tube thrombosis treated with heparin in 2 patients. At the end of follow-up, 75% were in New York Heart Association functional class I. CONCLUSION: Our intermediate-term results of Fontan-type operations were satisfactory, and steadily improving. The prognosis was better in patients operated at age 4 or older. A prior BCP anastomosis improved the results. A higher morbidity was observed with intra- than with extra-atrial Fontan procedures. The merit of fenestration procedures with respect to morbidity remains the be evaluated.

Chronic endocarditis due to Legionella anisa: a first case difficult to diagnose.

Endocarditis due to Legionella spp. is uncommon but presumably underestimated given the prevalence of Legionellae in the environment. We report a first and unusual case of chronic native valve endocarditis due to L. anisa and advocate that the diagnosis of endocarditis be made collaboratively between the cardiologist, surgeon, microbiologist and pathologist.

[Coronary stent evaluation with cardiac CT: Literature review]. / Évaluation des stents coronaires en scanner cardiaque: revue de la littérature.

Since the introduction of the 64-generation scanners, the accuracy and robustness of the diagnosis of coronary artery disease has progressed. The main advantage of cardiac CT is the exclusion of coronary artery disease by its excellent negative predictive value. Currently, cardiac CT applications extend thanks to innovations both in terms of technological development systems scanner or stents implanted. This is a literature review of stent evaluation with cardiac CT.

Induction of beta-methylcrotonyl-coenzyme A carboxylase in higher plant cells during carbohydrate starvation: evidence for a role of MCCase in leucine catabolism.

Induction of beta-methylcrotonyl-coenzyme A carboxylase (MCCase) activity was observed during carbohydrate starvation in sycamore cells. In mitochondria isolated from starved cells, we noticed a marked accumulation of the biotinylated subunit of MCCase, of which the apparent molecular weight of 74000 was similar to that of the polypeptide from mitochondria of potato tubers. Our results provide evidence for a role of MCCase in the catabolic pathway of leucine, a branched-chain amino acid which transiently accumulates in carbon-starved cells in relation to a massive breakdown of proteins. Furthermore, when control sycamore cells were incubated in the presence of exogenous leucine, this amino acid accumulated in the cells and no induction or accumulation of MCCase was observed, indicating that leucine is not responsible for the induction of its catabolic machinery. Finally, MCCase is proposed as a new biochemical marker of the autophagic process triggered by carbohydrate starvation.

Arrest of mitochondrial biogenesis in copper-treated sycamore cells.

Sycamore suspension cells (Acer pseudoplatanus L.) were grown in the presence of sublethal concentrations of copper (50 microM). During the first 5-6 days of treatment, growth was not affected, but cell respiration (coupled and uncoupled) declined to approximately 60% of its normal value. This decline of respiration was attributed to a progressive diminution of the number of mitochondria in copper-treated cells, based on the demonstration of the concomitant decline of (1) cardiolipin (diphosphatidylglycerol) and cytochrome aa3 (cytochrome oxidase), two specific markers of mitochondrial inner membrane, and (2) fumarase activity, a specific marker of mitochondrial matrix space. In addition, the mitochondria extracted from copper-treated cells presented the same properties as those from control cells, concerning substrate oxidation, cardiolipin and cytochrome aa3 contents, and fumarase activity. These results strongly suggest that copper triggered an arrest of mitochondrial biogenesis, which preceded cell division arrest.

Minimal focus of adenocarcinoma on prostate biopsy: clinicopathological correlations.

AIMS: To establish the clinicopathological features of minimal volume prostate adenocarcinoma on prostate biopsy. METHODS: Twenty four cases of minimal adenocarcinoma diagnosed on prostate biopsy and treated by radical prostatectomy were reviewed. RESULTS: The major microscopic criteria were nuclear enlargement (22 of 24), infiltrative pattern (19 of 24), prominent nucleoli (19 of 24), intraluminal eosinophilic secretions (15 of 24), and high grade intraepithelial neoplasia associated (11 of 24). Sixteen of 24 cases were assigned a Gleason score 6 on biopsy. When the whole gland was assessed, 22 of these tumours were localised to the prostate (stage pT2), and only two cases were stage pT3. CONCLUSIONS: Minimal focus of adenocarcinoma on prostate biopsy is not an uncommon finding. It is usually an intermediate grade and localised stage neoplasm.