Tumor regression responses in melanoma patients treated with a peptide encoded by gene MAGE-3.
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Antigens, Neoplasm↗
Biomedical subjects
M Marchand
Publications and source records attributed to M Marchand.
[Surgery of valve replacement with pericardial prosthesis].
The ideal artificial heart valve still does not exist among the various cardiac valves available to the clinician. Morbidity and mortality are directly related to the valve itself. Despite the promising hemodynamic results obtained in the 70s with pericardial prosthesis, these valves were progressively abandoned due to their poor long-term resistance. Based on an analysis of the causes of failures, modifications were made in the manufacturing method and current results with pericardial valves has greatly improved, inciting new interest in their clinical use. Today, the pericardium is recognized as a valid substitution material for bioprostheses. Results of long-term series should confirm current studies. Research is under way to determine how to improve pericardium longevity since tissue deterioration remains the limiting factor.
Bioprosthesis↗
Expression of MAGE genes in transitional-cell carcinomas of the urinary bladder.
Human genes MAGE-1 and MAGE-3 code for distinct antigens, which are recognized on melanoma cells by autologous cytolytic T lymphocytes (CTL). These antigens may constitute useful targets for anti-cancer immunotherapy, since no expression of MAGE genes has been observed in normal tissues other than testis. Out of 57 samples of primary transitional-cell carcinomas of the bladder, 12 (21%) expressed MAGE-1 and 20 (35%) expressed MAGE-3. All but one of the tumors expressing MAGE-1 also expressed MAGE-3. Genes MAGE-2 and MAGE-4, which are closely related to MAGE-1 and MAGE-3, were expressed by 30% and 33% of the tumors respectively. MAGE expression was more frequent in advanced tumor stages: 61% of the invasive tumors (stage > or = T2) were positive for expression of at least one of the four genes, whereas only 28% of the superficial tumors (stages Ta and T1) expressed these genes.
Antigens, Neoplasm↗
[Rapid determination of C-reactive protein in whole blood in pediatrics].
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Adolescent↗
Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection.
We have studied the patterns of antigens recognized by autologous cytolytic T lymphocytes (CTL) on two melanoma cell lines derived from metastases that were removed from patient LB33 at several years distance. Cell line LB33-MEL.A was obtained after surgery in 1988. A large number of CTL clones directed against LB33-MEL.A was obtained with blood lymphocytes collected from the patient in 1990. In vitro selection of melanoma cells that were resistant to these CTL clones indicated that at least five different antigens were recognized on LB33-MEL.A by autologous CTL. Four of these antigens were found to be presented by HLA-A28, B13, B44 and Cw6, respectively. The patient remained disease-free until 1993 when a metastasis was detected and was used to obtain cell line LB33-MEL.B. This cell line proved resistant to lysis by all the CTL clones directed against the LB33-MEL.A cells and showed no expression of HLA class I molecules except for HLA-A24. Using LB33-MEL.B cells to stimulate blood lymphocytes collected from the patient in 1994 we derived CTL clones that lysed these cells. All these CTL clones recognized a new antigen presented by HLA-A24. These results suggest that in patient LB33 the melanoma cells may have lost the expression of several HLA molecules under the selective pressure of an anti-tumor CTL response.
Adult↗
The autologous tissue cardiac valve: a new paradigm for heart valve replacement.
This is a report of early clinical experience with an autologous tissue cardiac valve, which demonstrates the feasibility of making a bioprosthesis in the operating room in 10 minutes at the time of the valve replacement operation. There were 30 implant patients (18 men, 12 women), with ages ranging from 32 to 83 years. Diagnoses included calcified aortic stenosis (n = 16), pure aortic insufficiency (n = 9), and mixed aortic stenosis and insufficiency (n = 5). Associated diagnoses have included chronic renal failure treated with dialysis (n = 1), coronary artery disease requiring concomitant coronary bypass (n = 1), ascending aortic aneurysm requiring resection (n = 3), and mitral insufficiency requiring concomitant mitral valvuloplasty (n = 2). All of the valve replacements were in the aortic position. These implanted patients are being followed up carefully according to the protocol that requires examination every 6 months for the first year and every 12 months subsequently. No patient has been lost to follow-up. Twenty-seven patients are alive and well from 1 to 22 months postoperatively. There were three deaths: two perioperative deaths (one perivalvular leak and one hemorrhage) and one infective endocarditis 1.3 years after valve replacement. All surviving patients were followed up by echocardiographic examination (mean gradient, 15.5 +/- 6.8 mm Hg at 1 year). In conclusion, the feasibility of this method and concept has been demonstrated with implants in 30 patients. The validity of the technique will be judged by clinical results and experiences in children.
Adult↗
Induction of Plasmodium falciparum sporozoite-neutralizing antibodies upon vaccination with recombinant Pfs16 vaccinia virus and/or recombinant Pfs16 protein produced in yeast.
Pfs16 is a sexual stage/sporozoite-specific antigen of Plasmodium falciparum and is a potential candidate for a sporozoite-neutralizing vaccine. To obtain more information on the function of Pfs16 and to investigate its role during transmission and hepatocyte invasion, immunization experiments were performed with both a Pfs16-specific recombinant vaccinia virus and virus-like particles produced in yeast composed of the hepatitis B surface antigen (HBsAg) and antigen Pfs16 fused to HBsAg. Upon transformation of yeast cells, harbouring a genomic copy of the HBsAg gene, with a plasmid carrying the fusion gene Pfs16-HBsAg (Pfs16-S) virus-like hybrid particles composed of HBsAg and Pfs16-S were formed of a size similar to those present in human sera after infection with the hepatitis B virus. Cells infected with recombinant Pfs16 vaccinia virus synthesized a polypeptide of approx. 16 kDa that reacted with a Pfs16-specific polyclonal antibody. Animals vaccinated with the yeast hybrid particles and/or recombinant vaccinia virus both produced Pfs16-specific antibodies. These antibodies showed no transmission-blocking activity, but they efficiently diminished or abolished in vitro invasion of sporozoites into human hepatoma cells (HepG2-A16) and primary human hepatocytes.
Amino Acid Sequence↗
Analysis of low-frequency lung impedance in rabbits with nonlinear models.
Lung mechanics was studied in six paralyzed tracheotomized rabbits ventilated with a specially devised computer-controlled ventilator. The target flow waveform contained noninteger multiple frequencies ranging from 0.83 to 6-10 Hz and met a neither-sum-nor-difference criterion to minimize the effects of nonlinearity (B. Suki and K. Lutchen. IEEE Trans. Biomed. Eng. 39: 1142-1151, 1992). The actual flow, however, contained harmonics of the two lowest frequencies. Measurements were performed at mean airway pressure (Paw) levels of 8 and 12 hPa and during histamine-induced bronchoconstriction. Smooth impedance curves were observed in unchallenged rabbits at low mean Paw levels. In contrast, unrealistic impedance fluctuations, suggestive of cross talk from the unwanted frequency components in the flow input, were seen at high mean Paw levels and during acute bronchoconstriction. Model analysis was performed by using the actual flow signal as an input to various nonlinear models. The impedance fluctuations observed at high mean Paw levels were well simulated by a model featuring a volume-dependent elastance, and those observed after histamine were almost perfectly reproduced by a model where resistance increased with the reciprocal of lung volume. We conclude that impedance data biased by cross talk may provide useful information on the presence and nature of respiratory system nonlinearities.
Airway Resistance↗
[Influence of the valve position on the complications related to pericardial Carpentier-Edwards valve after 8 years].
Between July 1984 and December 1991, 541 Carpentier-Edwards pericardial prostheses were implanted in 536 patients (420 aortic and 121 mitral prostheses). The operative mortality was 2.9% for aortic and 3.3% for mitral valve replacement. All but 8 patients were followed up for an average of 3.9 years, making a total follow-up of 1930 patient-years. There were 61 deaths during follow-up (41 AVR, 20 MVR). The actuarial 8 year survival was 80 +/- 6% for AVR and 74 +/- 10% for MVR. There were 15 deaths related to the prostheses. The probability of absence of valve-related mortality was 97 +/- 3% for AVR and 92 +/- 6% for MVR (NS). The valve-related complications included 15 thromboembolic events (AVR: 12; MVR: 3), 10 endocarditis (AVR: 7; MVR: 3), 8 anticoagulant-related haemorrhages (AVR: 4; MVR: 4), 4 degeneration (AVR: 2; MVR: 2). There were no cases of cusp tear. The probability of absence of thromboembolic events at 8 years was 96 +/- 3% for AVR and 96 +/- 4% for MVR (NS), of absence of endocarditis 97 +/- 2% for AVR and 97 +/- 3% for MVR (NS) and of absence of valve degeneration 99 +/- 1% for AVR and 99 +/- 2% for MVR (NS). These results show that the position of the bioprosthesis had no influence on valve-related morbidity and that pericardium is a satisfactory tissue for the manufacture of mitral bioprostheses.
Actuarial Analysis↗
[Systemic pulmonary shunts in the neonatal period. Short and medium-term results].
Systemic pulmonary shunts were performed in 41 consecutive neonates with congenital cyanotic heart disease between 1981 and 1992. The lesions comprised pulmonary atresia with intact interventricular septum (16 cases), pulmonary atresia with ventricular septal defect (9 cases), tetralogy of Fallot (5 cases), transposition of the great arteries (3 cases) and different complex cardiac lesions (8 cases). A polytetrafluoroethylene tube was used in 40 neonates, 5 mm in diameter in 39 cases, anastomosed to be subclavian artery in 21 patients (group A) and on the ascending aorta or innominate artery in 19 patients (group B). A retrospective analysis of the results was undertaken in all patients with a mean follow-up period of 6.5 years (range: 19 months-12.5 years). There were 4 early deaths (9.7%) and 8 late deaths (19.5%) giving a total mortality of 29.2%. Of the late deaths, 4 occurred in the first year, 3 suddenly at home and 4 in relation with the surgical correction. Occlusion of the shunt was suspected in only one case. The actuarial survival rate was 78% at one year, 75.5% at 7 years and 66% at 10 years. Eleven of the 12 deaths were in children with pulmonary atresia with intact interventricular septum (8 cases) and complex cardiac malformations (3 cases). Early complications were observed in 15 of the 37 survivors of the initial procedure. Cardiac failure occurred in 83% of group B and 22% of group A (p < 0.01). The probability of shunt efficacy was 89% at 1 year, 63% at 2 years and 45% at 3 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Anastomosis, Surgical↗
Expression of mage genes by non-small-cell lung carcinomas.
Human gene MAGE-I codes for an antigen that is recognized on melanoma cells by autologous cytolytic T lymphocytes (CTL). This antigen is potentially useful as a target for cancer immunotherapy because gene MAGE-I is not expressed in any normal tissues except the testis. We tested 46 surgical samples of non-small-cell lung carcinomas and observed MAGE-I expression in 16 of them (35%). Genes MAGE-2 and 3, which are closely related to MAGE-I, were expressed by a similar proportion of these tumors. Some small-cell lung tumors also express MAGE genes. The proportion of tumors expressing MAGE-I suggests that lung tumor patients may constitute the largest group of patients potentially eligible for pilot studies involving MAGE-I immunization.
Base Sequence↗
New procedure to replace the aortic valve with autologous pericardium: a clinical case.
Primary tissue failure is a major problem with pericardial or porcine heterografts, and the causes of calcification of the tissue are not yet known. The deterioration of bioprostheses may be due in part to immunologic response. Using autologous tissue is a current approach of research. We present a case of replacement of the aortic valve using an original procedure with autologous pericardium.
Aortic Valve↗
The Carpentier-Edwards pericardial aortic valve: intermediate results in 420 patients.
From July 1984 to December 1991, 420 patients underwent isolated aortic valve replacement with a Carpentier-Edwards pericardial bioprosthesis in our Institution. Of the patients 71.5% were male, the mean age was 66.9 +/- 11.9 years and 48% were in NYHA clinical stage III or IV. The operative mortality rate was 2.9% (12/420). All patients but six were followed up for an average of 3.9 years after their operation and total follow-up was 1444 patient-years. At this time of the study, over 80% of the patients are in NYHA class I or II, 6% are in atrial fibrillation and 7% receive anticoagulation treatment. There were 41 late deaths. After 8 years the actuarial survival rate is 80% +/- 6%. Nine patients died of valve-related causes (three endocarditis, three thromboembolic complication, one structural failure, and two sudden deaths). The actuarial rate of freedom from valve-related death was 97% +/- 3% at 8 years. Valve-related complications included 12 thromboembolic episodes (0.8% patient-year), 7 endocarditis (0.5% patient-year), 4 anticoagulant-related complications (0.2% patient-year), 6 reoperations (0.4% patient-year) and 2 structural valve failures (0.1% patient-year). After 8 years, freedom from thromboembolic complication was 96% +/- 3%, from endocarditis 97% +/- 2%, from reoperation 98% +/- 2% and from valve failure 99% +/- 1%. There were only two structural deteriorations (calcification and stenosis) and one explanation. No leaflet tear was observed. We conclude that these intermediate results are better than those obtained with previous pericardial bioprostheses.
Actuarial Analysis↗
Electrocardiographic and electrophysiologic properties of cardiac allografts.
The increasing number of heart transplant patients requires that physicians be able to recognize the electrocardiographic (ECG) and electrophysiologic properties of cardiac allografts. Cardiac allografts are characterized by modifications of resting ECGs and frequent arrhythmias in the postoperative period, and the loss of autonomic nervous control illustrated by permanent tachycardia and loss of heart rate variability during 24-hour ambulatory ECG recording. Some clinical and experimental observations suggest a mid-term reinnervation of the cardiac allograft, but this requires histologic confirmation. The electrophysiologic characteristics of the denervated myocardium are similar to those of the innervated myocardium at rest. However, supersensitivity to circulating catecholamines has been observed in cardiac allografts as in experimentally denervated hearts, which is responsible for a progressive increase in heart rate during exercise and a slow decrease during recovery. Supersensitivity of the denervated heart to acetylcholine may explain the high prevalence of donor sinus dysfunction due to impairment of its automaticity. More often, the sinus node dysfunction is transient and can be treated with an adenosine antagonist, such as theophylline, before permanent implantation of a pacemaker. In the case of pacemaker implantation, synchronization of the donor atria with the recipient atria is desirable, and an endocardial lead implantation is preferred. Several electrophysiologic changes have been observed during acute cardiac allograft rejection. From experimental studies, the most important of these are the disturbance of conduction in the atria and the atrioventricular node and a decrease in the amplitude of the ventricular potential. Initial studies on isolated myocytes show profound changes in membrane conductance during experimental cardiac rejection. The development of new noninvasive detection methods of cardiac allograft rejection, such as intramyocardial voltage electrogram monitoring and high-resolution ECG, could help early diagnosis.
Animals↗
[Partial pulmonary embolectomy without extracorporeal circulation. Apropos of a case].
The authors report a case of massive pulmonary embolism compromising the haemodynamic status of a 52 year old man with a formal contraindication to thrombolytic therapy. Unilateral pulmonary embolectomy was performed without cardiac pulmonary bypass, preceded by partial interruption of the inferior vena cava. Postoperative controls confirmed the success of the surgical procedure. Although the indications of surgical embolectomy are limited, especially without cardiopulmonary bypass, it may be considered for the treatment of certain cases of massive pulmonary embolism.
Cerebral Hemorrhage↗
[Estimation of static lung volumes by nitrogen washout method. Single breath of oxygen].
Total lung capacity (TLC) and residual volume (RV) estimations were obtained from single-breath nitrogen washouts in 96 male and 77 female healthy never-smokers with normal spirometry from a non-polluted rural area in north-east France. TLC depended on height (both sexes) and diminished slightly with age in males, with the body-mass index (kg/m2) in females. RV increased with age in both sexes and with weight in males. The RV/TLC ratio was related only to age. When compared with values obtained using multiple-breath helium dilution, our results yielded lower predicted values. The test depends heavily on the subject's co-operation, and errors are frequent if a standard procedure is not observed. This method cannot thus be recommended for routine use in patients with respiratory diseases.
Adult↗
Genes coding for tumor rejection antigens: perspectives for specific immunotherapy.
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Amino Acid Sequence↗
Perspectives for immunization of HLA-A1 patients carrying a malignant melanoma expressing gene MAGE-1.
Many human melanoma tumors express antigens that are recognized in vitro by cytolytic T lymphocytes derived from the tumor-bearing patient. A gene has been identified that directs the expression of antigen MZ2-E on a human melanoma cell line. This gene, which has been named MAGE-1, shows no similarity to known sequences and belongs to a family of at least 3 closely related genes. Gene MAGE-1 is expressed in approximately 40% of melanoma tumor samples and by some tumors of other histological types. No expression has been observed in a panel of normal tissues. Antigen MZ2-E appears to be presented by HLA-A1, a HLA type found in approximately 25% of the population. Thus, precisely targeted experimental immunotherapy directed against antigen MZ2-E could be provided to individuals identified as HLA-A1 and MAGE-1 positive by HLA typing and analysis of the RNA of a small tumor sample.
Antigens, Neoplasm↗