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Biomedical subjects

M Marchand

Publications and source records attributed to M Marchand.

At least 109 records · Page 6Linked to original sources

A limiting dilution assay for quantifying Leishmania major in tissues of infected mice.

A limiting dilution assay for the quantification of Leishmania major in infected mouse tissue was developed. The assay was found to be both sensitive and reliable, and, due to its design, could be scored either visually or following the incorporation of 3H-thymidine by the growing parasites. Results are presented in which the assay was employed to enumerate L. major in the tissues of susceptible (BALB/c) and resistant (CBA) mice at intervals after infection with L. major. It was found that parasites could be detected at the site of injection with L. major as early as 3 days after infection. By day 8, a substantial increase in the number of parasites at the lesion site had occurred in both strains of mice. Subsequently, whereas the number of parasites decreased in the lesions of CBA mice, their number steadily increased in the lesions of BALB/c mice. Parasites were detected in lymph nodes draining the lesion site in both BALB/c and CBA mice by 28 days after infection. Interestingly, a low number of L. major was found in the lymph nodes of CBA mice at 100 days after infection, a time when no parasites could be detected at the lesion site. Previous results from this laboratory have demonstrated that the adoptive transfer of L. major-specific L3T4-positive T-cell populations exacerbated cutaneous lesions induced by L. major in BALB/c mice. Experiments presented here indicate that the adoptive transfer of L. major-specific T-cells also exacerbated cutaneous leishmaniasis in CBA mice. Using the sensitive limiting dilution assay presently described, it was found that this unexpected exacerbative effect of L. major-specific T-cells on lesion development was accompanied by a substantial increase in the number of parasites in the lesions of the adoptively transferred mice.

Animals↗

[Computerizing the single-breath nitrogen washout test].

The classical assembly used for the single breath nitrogen washout implies the manipulation of valves by the operator, a perfect coordination of respiratory maneuvers by the subject and a rigid standardization of the interpretation of the tracings by the technicians doing the calculations. We present a computerized analysis of the single breath nitrogen test, based on a microcomputer (Apple II 48K) solving most of the problems above. The opening of the valves is operated by the computer program recorded on disk; the tidal volume and expiratory flow are displayed on the screen on line allowing the subject to comply with the requested limits; the nitrogram is displayed at the end of the test, allowing the technician to explain the errors (if any). The program then goes on computing the slope of phase III, the closing volume, total lung capacity and its subdivisions for each trial, and the average values for two or three trials accepted by the operator. The system worked satisfactorily during a pilot study in healthy adults (variability and reproducibility) and was particularly useful in a field survey of children and adolescents.

Closing Volume↗

[Effects of incomplete inspiration and previous pulmonary volume history on the nitrogen test].

The effect of incomplete inspiration and of preceding lung volume history on the different parameters of the expired nitrogen curve after inhaling pure oxygen were studied in 12 healthy non-smokers, aged 21 to 35. The equipment used was attached to a mini-computer enabling the regulation of the measurements and the performance of the tests with immediate calculations on the different indices derived from the curve (VC, RV, TLC, delta N2, CV-closing volume, CV/VC). With each subject three measurements were made: measurements in the normal way (N) after incomplete inspiration (I) and finally after 5 forced inspirations and expirations (previous history - P). The procedure (I) gave values of VC and TLC which were lower than those observed with the other methods and the slope of delta N2 and the CV/VC were higher. After the previous lung volume history (P) VC and TLC were significantly higher, the CV/VC ratio was lower (due to the increase of CV). The measurement technique was not influenced either within sessions or between sessions a week apart.

Adult↗

Trypanosoma cruzi variants with reduced virulence obtained by mutagenesis.

Previous reports have indicated that by mutagen treatment of mouse tumour cells in vitro it is possible to obtain at high frequency stable tumour cell variants that fail to form tumours in syngeneic mice because of increased immunogenicity. By analogy with these tumour cell variants, we examined whether variants with reduced virulence could be obtained by mutagen treatment of trypomastigotes derived from a Trypanosoma cruzi strain that was adapted to culture and produced lethal infections in DBA/2 mice at a dose of 5 X 10(4) parasites. A very large frequency of T. cruzi clones were obtained that failed to provoke an acute lethal infection after injection of 5 X 10(5) parasites. Most of these variants with reduced virulence (vir-) multiplied actively in normal mice until day 8 after injection. After that time the parasitaemia decreased gradually. For most variants a low level of residual parasitaemia persisted for more than 100 days. Unlike the situation encountered with mouse tumour cell variants it was not possible to demonstrate the presence of new antigens on the T. cruzi vir- variants. However, these variants seemed to have acquired an increased immunogenicity since they provoked the rejection of virulent parasites injected concomitantly. Mice that had been immunized with living vir- clones were protected against a challenge with a virulent clone derived from the original parasite population.

Animals↗

Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. VI. Occasional escape from host rejection due to antigen-loss secondary variants.

After mutagenesis of mouse mastocytoma P815, it is possible to obtain variant (tum-) clones that are almost always rejected by syngeneic DBA/2 mice. Most tum- clones express new variant-specific antigens that can be detected by cytolytic T cells (CTL). Occasionally, mice injected with tum- variants eventually develop progressive tumors. Cells from these tumors were analyzed for antigen expression with variant-specific and P815-specific CTL clones. Out of 13 tumors examined, 11 were composed of cells that had clearly lost a variant-specific antigenic determinant. These results indicate that tum- variants induce a specific host rejection response which usually results in complete elimination of the variant cells, but that occasional antigen-loss constitutes an important mechanism of escape. The loss of a variant-specific antigenic determinant from one tum- clone that had escaped rejection allowed the detection of a residual variant-specific determinant. This was demonstrated by isolating a new CTL clone that lysed both the original tum- clone and its antigen-loss variant, but not other P815 targets. Thus, some complex transplantation antigens can be separated into independent determinants by using antigen-loss variants.

Animals↗

Increased frequency of immunogenic variants obtained by repeated mutagen treatment of mouse mastocytoma P815.

A previous report from this laboratory demonstrated that treatment of mouse mastocytoma P815 with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) produces tumor cell variants that are unable to form tumors in syngeneic animals. We examined whether repeated mutagen treatment could increase the frequency of tum- variants above that obtained after a single treatment. This was found to occur with frequencies increasing from a few percent after 1 treatment to more than 90% after 8 treatments. Moreover, uncloned survivor populations obtained after 8 or more MNNG cycles that contained such a high proportion of tum- variants had a markedly decreased tumorigenicity for syngeneic mice. As reported for tum- variants obtained after 1 mutagen treatment, several tum- variants obtained after repeated treatments carried new variant-specific antigens that elicited a specific cytolytic T cell response. Some of these tum- antigens were found to consist of multiple determinants that could be lost independently. We observed that the resistance of the mutagenized populations to MNNG increased gradually with the number of mutagen treatments. In addition, some tum- variants obtained after 8 mutagen treatments showed a reduced sensitivity to mitomycin C.

Animals↗

[Surgical treatment of congenital aortic valve constriction with associated obstructive cardiomyopathy. Perioperative left intraventricular gradient treated with beta blockers. Apropos of a case].

The authors report a case of congenital valvular aortic stenosis associated with echocardiographic and angiographic appearances of hypertrophic obstructive cardiomyopathy. After valvular replacement and partial myotomy a high intraventricular pressure gradient (125 mmHg) with low intra aortic pressure was recorded. High dose intravenous propranolol (25 mg in 2 hours) reduced this gradient to 50 mmHg allowing cardiopulmonary bypass to be discontinued. This clinical combination is associated with a risk of aggravation of the intra-ventricular obstructive phenomenon when the obstacle to left ventricular ejection is relieved: surgical myotomy was performed in similar, previously published cases. High doses betablocker therapy can be performed in similar, previously published cases. High dose betablocker therapy can be useful in this association and it may also be instituted when right intraventricular pressure gradient increase after relief of pulmonary valvular stenosis.

Adolescent↗

Tricuspid atresia. Results of treatment in 115 children.

We present our experience in the management of tricuspid atresia in 115 children. The anatomic data are categorized as follows: type I, 83.5%, type II, 16.5%. Type IB is the most frequent, representing 63.5% of all the cases. Each patient was operated upon one to four times. The age at first operation ranged from 10 days to 20 years. The first operation was a shunt in 94 children, a Fontan operation in four, and banding of the pulmonary artery in 17. Hospital mortality for the first operation was 12.2%, significantly higher in children under 6 months and in those having Waterston shunts. Potts and Blalock-Taussig operations give low long-term mortality; although few (six) have been done, Potts shunts also seem to give good long-term palliation in this series. The Glenn anastomosis is a good operation when performed after a systemic-pulmonary arterial shunt. The Fontan operation was performed in 24 children (hospital mortality 16.6%). There have been no late deaths after the third month postoperatively. Mean follow-up for this operation is only 2 years, but 88% of the survivors lead a normal life, two thirds of them receiving no treatment. There has been one reoperation for stenosis of a Dacron conduit with a good result. Late arrhythmias are well tolerated. In conclusion, the Fontan procedure is a good operation, but palliative procedures still allow good long-term survival.

Actuarial Analysis↗

[Results of the repair of isolated coarctation of the aorta during the 1st 6 months of life, Apropos of 46 cases].

Between 1972 and 1978, forty-six infants under six months of age underwent surgery for isolated coarctation of the aorta. These forty-six patients represent 32% of the total number of infants aged less than six months who had surgery for coarctation of the aorta during the same period. At the time of operation, 41% were aged less than one month and the youngest was five days old. The main cause for surgery was heart failure in infants under one month (14/19) and severe systemic hypertension (150 to 300 mm Hg) in the one to six month age group (18/27). Overall mortality rate in our series was 17%. Six of the eight infants who died were under one month of age. Recoarctation occurred in 31,5% of infants; in eight cases the first surgical procedure had been done before one month of age. A second procedure was necessary in four cases. Early surgical repair of severe coarctation diagnosed during the first six months of life leads to functional improvement and avoids residual hypertension. After repair, the main risk is recoarctation.

Aortic Coarctation↗

[Right coronary artery arising from the pulmonary artery. Surgical treatment].

The authors report the case of an anomalous right coronary artery arising from the pulmonary artery. The patient was an active 18 years old boy who had a continuous murmur with diastolic accentuation, the cause of which was determined at angiography. There were electrical and echocardiographic signs of moderate left ventricular dilatation and thallium scintigraphy showed a myocardial perfusion defect. These were the only detectable consequences of this rare malformation. Normal coronary circulation was reestablished surgically, the indication being the risk of sudden death which has been previously reported rather than acute myocardial ischemia.

Adolescent↗