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P Maldague

Publications and source records attributed to P Maldague.

At least 55 records · Page 3Linked to original sources
PubMed1984

Gentamicin-induced stimulation of DNA synthesis in rat kidney. Comparison between in vivo and in vitro models.

We have performed combined in vivo and in vitro measurements of thymidine uptake into kidney cortex DNA of animals treated with gentamicin for 7 days at 10 or 20 mg/kg daily (BID). Labelled thymidine is taken up by cortex fragments in vitro (90 min incubation) and incorporated into DNA; treatment of the animals with gentamicin results in a significant dose-dependent enhancement of this in vitro thymidine incorporation; labelled cells are found primarily in the proximal tubules and interstitium; there is an excellent correlation (r : 0.983, n = 15) between the changes of incorporation measured in vivo and in vitro as demonstrated by the sequential use of [3H]thymidine (in vivo) and [14C]thymidine (in vitro) within the same animals.

Animals↗
PubMed1984

Recovery of cortical phospholipidosis and necrosis after acute gentamicin loading in rats.

The recovery from gentamicin-induced phospholipidosis in the rat kidney cortex was characterized both morphologically and biochemically after a single 12-hr drug infusion. Total dosages administered were 10, 60, or 140 mg/kg, achieving constant serum concentrations of 3, 11, and 27 micrograms/ml, respectively. At the end of the 12-hr infusion, the cortical drug concentrations corresponding to the three dosages were 124, 450, and 993 micrograms/g of wet tissue. At the low dose (10 mg/kg), myeloid bodies were seen inside lysosomes of proximal tubular cells, along with a modest decrease of lysosomal sphingomyelinase activity. The cortical drug level declined steadily following first-order kinetics along with a disappearance of myeloid bodies and return of sphingomyelinase activity to control levels. At the high dose (140 mg/kg), we observed a sustained loss of sphingomyelinase activity (37% of controls), a subsequent increase of phospholipid concentration in the kidney cortex (up to 117% of controls 2 days after) and a prominent accumulation of myeloid bodies inside the lysosomes of proximal tubular cells (up to 4% of cell volume). Tubular regeneration and interstitial infiltration became detectable by histology and the increase of DNA synthesis as from day 1, along with an apparent reduction of the phospholipidosis at days 3 and 4. Drug cortical concentrations showed a sharp decline 2 days after infusion. An intermediate behavior was observed at 60 mg/kg. It is concluded that the proximal tubular cells behave in a fundamentally different way after gentamicin loading with low and high doses. At the low dose there is a regression of the drug-induced changes in the absence of any sign of necrosis-regeneration. Above a threshold in cortical drug concentration there is further development of the alterations leading to cell death-regeneration.

Animals↗
PubMed1983

Gentamicin nephrotoxicity in cadmium, lead and mercury pretreated rats.

The effect of a previous chronic exposure to cadmium, lead or inorganic mercury on the nephrotoxic potential of gentamicin was investigated in female Sprague-Dawley rats. A daily dose of 10 mg gentamicin/kg body weight/day was administered for 21 days to rats having a renal load of 168 micrograms Cd, 35 micrograms Pb or 129 micrograms Hg/g whole kidney. Urine analysis suggests an attenuation of the nephrotoxic potential of gentamicin while a microscopical examination of kidneys indicates a superimposition of the effects of the metals and the antibiotics. The only clear interaction observed consists in a reduction of gentamicin accumulation in the cortex of cadmium-treated animals. It is concluded that none of the metal pretreatments potentiates the nephrotoxic effects of gentamicin.

Amino Acids↗
PubMed1983

Adaptive response of growing rat small intestine to acute Adriamycin injury.

The response of the intestinal mucosa to Adriamycin (ADR) was studied in the duodenum, jejunum, and ileum of 25-day-old rats. A single injection of ADR resulted in decreases in mucosal DNA per centimeter of length and in sucrase activity, which were proportional to the doses given (2, 5, and 8 mg/kg). ADR at 2 mg/kg had no significant effect on body weight, gut length, epithelial structure, or mucosal protein content per unit length. The morphological modifications occurred mostly in the proximal intestine and consisted of villous atrophy and degenerative changes of villus and crypt cells. A single dose of 5 mg ADR/kg acutely affected the gut. At 48 and 96 h the changes were characterized by marked decreases in mucosal weight, DNA per centimeter, sucrase activity, and villous shortening. At 144 h, the ADR-treated intestine entered a highly proliferative state and showed increased villous height, mucosal weight, and DNA per centimeter. Although villous hyperplasia was observed at 144 and 192 h, the mucosal weight and DNA concentrations did not exceed the corresponding levels in the control. During the period of active epithelial proliferation, sucrase activity remained depressed. We conclude that in the growing rat: (a) the acute intestinal injury of ADR is short-lived, dose dependent, and predominates in the proximal small intestine; (b) the enteric mucosa reacts to cytotoxic injury by excessive proliferation of immature enterocytes; and (c) the hyperplastic response to ADR is confined to the mucosal epithelium.

Animals↗
PubMed1983

Increased renal DNA synthesis in vivo after administration of low doses of gentamicin to rats.

Kidney cortex DNA synthesis was studied in female rats treated with a low dose of gentamicin (10 mg/kg) up to 14 days. Synthesis was measured by incorporation of [3H]thymidine into DNA 1 h after intraperitoneal injection of the labeled precursor (200 muCi per animal). Gentamicin given in one injection per day resulted in a greater incorporation of [3H]thymidine into DNA after both 7 and 14 days of treatment as compared with control animals. When the daily dose was divided into three equal injections given at 8-h intervals, a statistically significant increase in thymidine incorporation was observed as early as 4 days after starting gentamicin administration. Excellent agreement was found between DNA specific radioactivity and kidney cortex nuclear labeling, as measured by histoautoradiography. The greatest amount of [3H]thymidine incorporation occurred within proximal tubular cells and interstitial cells. We conclude that a finite duration of gentamicin treatment at low dosage induces an increased DNA synthesis in vivo in rat kidney cortex. We suggest that this reaction results from cellular proliferation and could reflect a regenerative process after focal necrosis induced by gentamicin at low doses. The demonstrated early increase in DNA synthesis could be a useful tool to measure kidney cortex alterations caused by various aminoglycosides at low, therapeutic doses.

Animals↗
PubMed1982

Early toxic events in kidney of rat and man following administration of gentamicin at low doses.

Kidney cortex of rats and humans treated with low doses of Gentamicin have been examined both morphologically and biochemically. Specific alterations of the lysosomes (loss of activity of phospholipases; accumulation of phospholipid-like material) was detected as early as from 2-4 days of treatment. This finding is consistent with the concept that Gentamicin exerts its toxic action on kidney through lysosomal dysfunction.

Animals↗
PubMed1980

Infiltrating lobular carcinoma of the female breast. Deviations from the usual histopathologic appearance.

Twenty-two cases of breast tumor with infiltrating lobular carcinoma were studied. Thirteen showed the classic single-file pattern as a sole component, and 6 as a predominant pattern; the less common confluent pattern was found in 3 instances as a predominant component. Mucin secretion was evidenced in 59% of the primary tumors; it was a prominent feature in only 1 case. Nine tumors were associated with in situ lobular carcinoma. In 14, nodal metastases had occurred at the moment of diagnosis. In 50% of the metastases, intracellular mucin secretion was present. It appears that the diagnosis of infiltrating lobular carcinoma relies on the convergence of multiple histocytologic hallmarks, as much in the primary tumors as in the metastases. Deviations from the classic appearance need to be recognized as true lobular carcinomas, and even in these cases it is suggested that the well established term lobular carcinoma be maintained.

Adult↗
PubMed1980

Prognostic implications of mean nuclear diameter in breast cancer.

The mean nuclear diameter of 100 breast cancers was measured on tissue sections, to evaluate its importance for early prognosis. The cases were subdivided into 3 subgroups: small (25.5% of cases), medium (63.3%) and large (11.2%) nuclei. Early recurrence and mortality rates were investigated in each of the categories. Increasing nuclear size was shown to be related to mortality from metastatic disease. However, large-nucleus tumours had an inverse relationship with lymphnode involvement and possibly with recurrence rate. Hence, in our material nuclear size as a sole criterion was not a good indicator of the early behaviour of operable breast cancer.

Adult↗
PubMed1979

A modified levanol fast cyanine 5RN staining method for myoepithelial cells.

The specificity of the tannic acid--phosphomolybdic acid--Levanol Fast Cyanine 5RN procedure for myosin-like proteins in myoepithelial cells is hampered by the affinity of the dye for other structures. The selectivity of myoepithelial cell staining is enhanced by oxidation of sections, nuclear staining by Safranin-O, and differentiation with Tartrazine.

Breast↗
PubMed1979

Granulocytes in the endometrium of post-partum women.

Endometrial samples of women at various stages of gonadal activity after parturition were examined for the presence and numbers of endometrial granulocytes. Although samples at all the stages contained significant numbers of the granulocytes (i.e. greater than 7/high-power field), the 100% values for late-proliferative and adaptation hyperplasia were significantly higher than the values for the resting (81.8%), early (82.4%) and mid- (87.9%) proliferative and secretory (83.3%) phases. We suggest that this correlates with the suggestion that the granulocytes constitute a receptor system for oestrogens.

Cell Count↗
PubMed1978

Morphological changes in the amniotic epithelium in relation to placental weight and fetal maturity.

A series of 52 placentas from the 36th week of gestation up to post-maturity was studied. The amniotic epithelium was studied with special regard to the morphological signs of maturation known to occur during this period. The results of the dating were compared with the presumed clinical age of the pregnancy and with the placental weight. A good correlation was found in 42.3% of the cases; the clinical age was overscored in 17.3% and underestimated in 40.4% of the subjects. No clear correlation was found between placental weight and histologic dating of the amniotic epithelium. The significance of the lipid laden amnios cells is discussed.

Amnion↗