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Biomedical subjects

J Andre

Publications and source records attributed to J Andre.

At least 55 records · Page 3Linked to original sources

Response to measles vaccine in Haitian infants 6 to 12 months old. Influence of maternal antibodies, malnutrition, and concurrent illnesses.

To study the factors affecting the serologic response to measles vaccination, we evaluated 595 Haitian infants from 6 through 12 months of age, and their mothers, at the beginning of an immunization program. Thirty-four per cent of the infants had preexisting serologic evidence of measles infections by 11 months of age. Among infants more than nine months of age, those who had had measles had a significantly lower nutritional status than those who had not (P less than 0.01). After vaccination, seroconversion rates increased from 45 per cent at 6 months to 100 per cent at 12 months. The lowest rate of vaccine failure compatible with acceptably low rates of natural infections could be achieved by vaccination after eight months of age. Infants born to mothers with low levels of antibody to measles (hemagglutination-inhibition antibody titers less than 1:40) were significantly more likely to have had natural measles (P less than 0.01) or to have seroconversion after vaccination (P less than 0.001) at 6 to 10 months of age than were infants born to mothers with higher of age than were infants born to mothers with higher titers. Malnutrition and acute infections did not affect seroconversion rates. These data support the World Health Organization recommendation to administer measles vaccine in under-developed countries as soon after nine months of age as possible, regardless of nutritional status or the presence of minor illnesses.

Age Factors↗

The plasmin system in human colonic tumors: an immunofluorescence study.

We studied the plasmin system with specific antisera to plasminogen, its 2 activators (urokinase-type and tissue-type) and the 2 plasmin inhibitors, alpha 2 anti-plasmin and alpha 2 macroglobulin on sections of 34 human colonic tumors by immunofluorescence. Anti-plasminogen serum showed a clear-cut reactivity at the surface of tumor cells, as it stained the contour of tumor glandular structures, foci, and isolated tumor cells. Intratumoral deposits and necrotic areas were stained as well, often strongly. Localization of plasminogen was quite different from that of fibrinogen, which was found only in peritumoral stroma, and never on tumor cells. Traces of both types of plasminogen activator were found, mainly on invasive tumor cells for urokinase type and on large tumor foci for tissue type. Images were weak and inconstant. Large amounts of both plasmin inhibitors were characterized in tumor stroma. Alpha-2 anti-plasmin was also found in intratumoral deposits and necrotic areas. It seems likely that plasminogen exudes from blood capillaries (since anti-plasminogen serum often stained the whole capillary wall), diffuses in the stroma and binds to tumor cells. Once formed, plasmin is likely to play a role in the invasion of surrounding tissues by tumor cells, in the dissociation of tumor cells from tumor glands and in the production of necrosis inside tumor areas.

Adenocarcinoma↗

Importance of specific IgM antibodies in 116 patients with various stages of syphilis.

We tested 222 serum samples obtained from 51 patients presenting with syphilis, before and after treatment; 117 from 65 patients with a history of syphilis (114) or yaws (3); 77 from 71 patients with no evidence of syphilis; and 1117 serologically negative serum samples. Our tests included the IgM fluorescent treponemal antibody absorbed (IgM-FTA-ABS) and solid phase haemadsorption assay (SPHA) techniques. According to the stage of development of syphilis, IgM antibodies were found in 83-100% of the serum samples. This permitted a precise diagnosis to be made and cure assessed. As IgM antibodies were absent in serum from patients with healed syphilis, resolved syphilis could be distinguished from developing syphilis. The sensitivity (92%) of the IgM-FTA-ABS test was comparable with that of the SPHA (96%), but the SPHA was more specific (97.4%) than the IgM-FTA-ABS test (89.61%).

Adolescent↗

Studies on kidney sialidase in normal and diabetic rats.

Rat kidney cortex sialidase was studied using alpha-sialyl-(2----3)-[3H]lactitol and alpha-sialyl-(2----6)-[3H]lactitol as substrates. The enzyme was found mainly in the lysosomal fraction. Only 23% of the sialidase activity of this fraction could be solubilized by a combination of freezing-thawing, sonication and Triton X-100 treatment. The optimal pH for the lysosomal enzyme activity was 4.2 and the enzyme's Km values for alpha-sialyl-(2----3)-lactitol and alpha-sialyl-(2----6)-lactitol were 0.28 and 0.41 mM, respectively. The specific activity was twice as high with the former substrate than with the latter. Sialidase activities in dialyzed kidney cortex homogenates of streptozotocin-diabetic rats and of age-matched control rats were compared. The specific activity was found to be significantly increased in the diabetic animals when using both substrates 5950 +/- 720 (S.E.) dpm/h per mg protein (n = 7) vs. 3970 +/- 370 in the controls (n = 8) with alpha-sialyl-(2----3)-lactitol (P less than 0.025) and 2870 +/- 300 vs. 1820 +/- 170 with alpha-sialyl-(2----6)-lactitol (P less than 0.02). The activities were also found to be increased when expressed per whole kidney cortex (P less than 0.005 and P less than 0.001, respectively). The elevated sialidase activity in diabetic kidney cortex may be related to the reported decrease in sialic acid content of the glomerular basement membrane, which lowers its negative charges and which may contribute to an increased permeability to proteins.

Animals↗

Dual effects of estradiol on normal and tumor pituitary cell multiplication.

We have compared the effects of estradiol on the [3H]thymidine (TdR) incorporation into the DNA of 2 rat tissues whose growth is controlled by estradiol in vivo in 2 opposite directions: the normal anterior pituitary and the MtF4 pituitary tumor transplanted under the kidney capsule. Small pieces of pituitary or tumor from Fischer rats, treated or not by estradiol in silastic tubing, were incubated in vitro with [3H]TdR. The [3H]TdR incorporated per microgram DNA was decreased in tumor after 2 to 8 day-estradiol treatment while simultaneously, in the same rats, it was increased in the pituitary. In addition, we studied the effect of estradiol in vitro on the F4C1 cell line obtained from the MtF4 tumor. A dose-dependent decrease of both the [3H]TdR incorporated into DNA and the DNA amount was observed between 10(-6) and 10(-5) M estradiol. These results suggest that the control of the pituitary or MtF4 tumor growth by estradiol in vivo is in part due to an inhibition of cell multiplication. Although estradiol inhibits the growth of a clone of MtF4 tumor cells in vitro we cannot decide whether or not the in vivo effect of estradiol is direct.

Animals↗

Down-regulation by 17 beta-estradiol of D2 dopamine receptors in the MtTF4 pituitary tumor.

We have recently reported that 17 beta-estradiol (E2) paradoxically inhibits the growth of the rat MtTF4 pituitary tumor which has been induced by estrogen administration. While looking for a molecular explanation for these divergent effects, we observed that E2 treatment resulted in a marked decrease of D2 dopamine receptors (RDA) in the tumor but not in normal pituitary glands. Herein, we characterize further the effect of E2 on RDA concentration in the tumor. Three weeks after a sc injection of a MtTF4 -cell suspension, adult male Fischer rats were treated, or not, either with E2 or with various other steroids. The number of dopamine-binding sites (Bmax) was determined on crude membranes by Scatchard analyses with the dopamine antagonist [3H]spiroperidol. Only one kind of binding site was observed, and the affinity constant for [3H]spiroperidol was not significantly modified by any of the various treatments used. The decrease of Bmax after 8 days of treatment was dose dependent and was maximal with 5-micrograms daily doses of E2. With 10 micrograms E, daily, Bmax decreased exponentially with the duration of the treatment; t 1/2 was approximately 5 days. Treatment for 8 days with progesterone (50 micrograms/day), dihydrotestosterone (50 micrograms/day) or 17 alpha-estradiol (10 micrograms/day), known to be inactive on tumor growth, did not alter Bmax, whereas diethylstilbestrol (10 micrograms/day) or dexamethasone (50 micrograms/day), which inhibit tumor growth, were as efficient as E2 in decreasing Bmax. In conclusion, the number of dopamine-binding sites in the membranes of MtTF4 tumor is decreased by E2 in a time- and dose-dependent fashion. Circumstantial evidence suggests that this decrease is due to a loss of RDA per cell rather than the loss of RDA-bearing cells. The relationship between the control of dopamine-binding sites and cell growth is not clear; however, this model may be useful for the elucidation of the mechanism by which E2 modulates cell membrane properties.

Animals↗

Morphofunctional modifications associated with the inhibition by estradiol of MtTF4 rat pituitary tumor growth.

The MtTF4 pituitary tumor has been induced in Fischer rats by chronic estrogen administration. Recently, we reported that sustained pharmacological treatment of Fischer rats with 17 beta-estradiol inhibited the growth of the MtTF4 tumor transplanted s.c. The present work describes the associated morphofunctional changes occurring in the tumor during 17 beta-estradiol inhibition. It is shown that a 7-day 17 beta-estradiol treatment resulted in an increase of the surface area of cells, nuclei, nucleoli, Golgi complexes, and rough endoplasmic reticulum and an increase in the number of euchromatin-rich nuclei. Flow cytometry analysis of DNA distribution suggested that estradiol affects the cell progression through the early S phase. The ratio of RNA to DNA increased significantly, reflecting cell hypertrophy. Moreover, there was a significant increase in tumor prolactin concentration and a marked enhancement in the intensity of the immunocyto-chemical reaction with rat prolactin antiserum. On the other hand, cell mitoses were dramatically decreased. These morphofunctional changes indicate that the inhibition of the tumor growth by estradiol is accompanied by an evolution of the tumor cell population towards a more differentiated state. However, it cannot be decided whether 17 beta-estradiol induces a shift from a proliferative state to a differentiated state or whether 17 beta-estradiol treatment results in a selection of a subpopulation of tumor cells that are slow growing and more differentiated.

Animals↗

Inhibition of the alpha-glucosidase specific for collagen disaccharide units in diabetic rat kidney by in vivo glucose levels: possible contribution to basement membrane thickening.

The activity of the alpha-glucosidase specific for collagen disaccharide units has been measured in kidney cortex homogenates of streptozotocin-diabetic rats under three different conditions: (1) in dialyzed homogenates; (2) in non-dialyzed homogenates; (3) in non-dialyzed homogenates to which glucose was added to compensate for dilution due to homogenization and to reach the glucose concentration determined in kidney cortex (37.5 +/- 2.8 mmol/kg diabetic cortex versus 6.8 +/- 0.3 mmol/kg normal cortex). Under the latter condition, the enzyme activity was markedly decreased in diabetic kidney cortex when compared with that of normal age-matched controls: 4.03 +/- 0.25 versus 6.82 +/- 0.29 units/mg protein (p less than 0.001). Inhibition of enzyme activity was also significant in non-dialyzed diabetic homogenates without additional glucose. In the absence of glucose (in the dialyzed homogenates), it is confirmed that the enzyme activity is elevated in diabetic kidney. The glucose inhibition of the enzyme activity has been shown to be important under in vivo conditions. It may therefore contribute to kidney basement membrane thickening.

Animals↗

Effects of chloramphenicol on the mitochondrial respiratory chain in the wild strain and in a cytoplasmic chloramphenicol-resistant mutant of Tetrahymena pyriformis.

The effects of chloramphenicol (CAP) on mitochondrial respiratory activity in the wild strain (ST) and in a cytoplasmic CAP-resistant mutant (STR1) of Tetrahymena pyriformis were studied by determining oxygen consumption, by spectrophotometry, and by cytochemistry. In the absence of CAP both strains had the same respiration capacity, and the low-temperature spectra of their isolated mitochondria were similar. Furthermore, the mitochondria of both strains showed a positive reaction with diaminobenzidine, denoting a similar cytochrome oxidase activity. However, when cells were grown in CAP for 24 or 48 h, the peaks of cytochrome oxidase and cytochromb b were almost absent in the wild type. In this type the oxygen consumption was greatly decreased, and the mitochondria were no longer stained by diaminobenzidine. In the mutant, the peaks of cytochrome oxidase and cytochrome b were decreased only; respiration was less affected than in the wild type, and cytochrome oxidase activity was still disclosed by the diaminobenzidine reaction. These results show that CAP inhibits the synthesis of two cytochromes (b and oxidase) which are partially translated into the mitochrondria of T. pyriformis. In the mutant, CAP reduces only the mitochondrial translation, resulting in reduced mitochondrial activity and reduced growth rate of the cell. These results are compared with the nucleo-mitochondrial regulation mechanisms discussed in our previous works.

Animals↗

Induction (or stimulation) of prolactin and growth hormone production in a rat pituitary tumor cell line by bromodeoxyuridine.

Under basal conditions, a rat pituitary tumor cell line (C8 11RAP) does not secrete any detectable PrL, FSH, and LH, and secretes only minute amounts of GH (27.1 +/- 0.5 ng/10(6) cells.24 h), as evaluated by RIA. Bromodeoxyuridine (BrdUrd) added to the culture medium induced the accumulation of PRL into cells and medium, increased that of GH, but did not induce that of LH or FSH. The amount of radioimmunoassayable PRL and GH accumulated in the medium increased after a lag period of 15 days and was drug concentration dependent. Maximal accumulation was 232.9 +/- 36.8 and 493.6 +/- 41.5 ng/10(6) cells.24 h for PRL and GH, respectively, at 50 micrograms/ml BrdUrd. In the presence of BrdUrd (greater than or equal to 20 micrograms/ml), the cells grew more slowly and were more strongly attached to the flasks. All of the effects induced by BrdUrd were reversible. PRL and GH were characterized by three methods; 1) radiocompetition with increasing dilution of samples; 2) Sephadex chromatography, followed by RIAs; and 3) sodium dodecyl sulfate-polyacrylamide gel electrophoresis done on the immunoprecipitate of the proteins secreted by cells incubated with [3H]leucine. Chronic treatment with TRH (3 X 10(-6) M) of cells grown without BrdUrd was unable to increase the production of GH or to induce that of PRL. On the other hand, after the same treatment of cells cultured in the presence of BrdUrd, the amounts of PRL accumulated in the culture medium or cells were increased 2- to 7-fold over unstimulated levels; under the same conditions, GH accumulation in the medium was also increased, but this augmentation was less than that of PRL. These results indicate that BrdUrd simultaneously induces or stimulates the production of PRL and GH in C8 11RAP cells, and that TRH increases the production of both hormones only in BrdUrd-treated cells.

Animals↗

A new antimitochondria antibody (anti-M6) in iproniazid-induced hepatitis.

A new immunofluorescence pattern of non-organ- and non-species-specific antibody has been observed in occasional sera. Variations of the fluorescence were found in different species. Recognition of the new pattern was particularly characteristic in rat organs (liver: the hepatocytes showed intense roughly granular fluorescence evenly distributed in the cytoplasm; kidney: the bright fluorescence of the first portion of the proximal tubules contrasted with the negative aspect of the other portions of the tubules; stomach: only some cells probably corresponding to the APUD system were positive; pancreas: fluorescence was limited to the islets of Langherhans). The positivity in the ellipsoid region of the rods and cones of the eye and the absorption on different liver organelles showed that this aspect corresponded to the mitochondria. We propose to name this pattern 'antimitochondria antibody number 6' or 'anti-M6'. High titres of anti-M6 were found in four patients suffering from iproniazid-induced hepatitis. A decrease in the titre was obtained after stopping the treatment. The now exceptional use of iproniazid and the rare occurrence of anti-M6 suggest a link between these two phenomena.

Adult↗