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Biomedical subjects

A Girard

Publications and source records attributed to A Girard.

At least 91 records · Page 5Linked to original sources
PubMed1988

Histamine H1-receptors mediate phosphoinositide and calcium response in cultured smooth muscle cells--interaction with cicletanine (CIC).

Smooth muscle cells were cultured from guinea-pig aorta and labelled with 45Ca++ and 32Pi to investigate the possible effect of cicletanine, a new antihypertensive drug, on the release of intracellular Ca++ and the metabolism of phosphoinositide induced by histamine. In 45Ca++ labelled cells, histamine increased in a dose-dependent manner the 45Ca++ efflux in the first two minutes. Stimulation of 45Ca++ release was observed with H1-agonist [2-pyridylethylamine dihydrochloride (2-PEA)] but not with H2-agonist (dimaprit). In addition, histamine- or 2-PEA- induced 45Ca++ efflux was inhibited by the H1-antagonists (mepyramine and terfenadine) whereas the H2-antagonist (cimetidine) was without effect. Similar results were obtained in 32Pi labelled cells; both H1-agonists (histamine and 2-PEA) increased the labelling of phosphoinositides. This effect was completely blocked by mepyramine. These results demonstrate that the histamine-induced stimulation of 45Ca++ efflux and phosphoinositide metabolism are mediated through H1-receptors. In the above systems, cicletanine was as effective as the H1-antagonist (mepyramine) with an IC50 of 10(-6) M for both 45Ca++ efflux and phosphoinositide metabolism. Blockade of these systems by cicletanine may be part of the mechanism by which this drug produces relaxation of blood vessels and may account for its in vivo antihypertensive action.

Animals↗
PubMed1988

Prognostic significance of endometrial extension in carcinoma of the cervix.

A retrospective analysis of 343 consecutive patients with histologically proven carcinoma of the cervix, treated at the Ottawa General Hospital, was undertaken to evaluate the prognostic significance of endometrial extension. All these patient had a D + C as part of their work-up. Sixty-seven patients had a (+) D + C: 34/150 (23%) in Stage IB, 21/106 (20%) in Stage II, and 12/87 (14%) in Stage III. Survival was closely related to the D + C findings in early stages. In Stage IB, the 5-year survival of D + C (-) patients was 90% vs 50% in D + C (+) patients (P less than 0.003) and in Stage II, the 5-year survival was 77% and 55%, respectively (P = 0.089). There was, however, no difference in survival in Stage III patients (35% vs 29%). Pelvic failures were similar in both groups, stage for stage, but those with a (+) D + C had a higher incidence of distant metastasis. In Stage IB, distant metastases were found in 8.5% (10/116) of D + C (-) patients compared to 38% (13/34) in D + C (+) patients (P less than 0.001) and in Stage II, in 18.5% (16/85 and 33% (7/21) of the patients (P = 0.126), respectively. There was no difference in Stage III patients (28% vs 25%). This study suggests that endometrial extension is a significant prognostic factor in early stages and is associated with a higher risk of distant metastases. Management of these high risk patients is discussed.

Dilatation and Curettage↗
PubMed1988

Phosphoinositides and cicletanine.

In vascular smooth muscle cells, the activation of histaminergic receptors of the H1 subtype induces an increase in cytosolic free calcium. This has been shown to involve the metabolism of inositol-containing lipids. Since according to its pharmalogical characteristics, cicletanine could be considered as an H1 antagonist, it was of interest to check whether the drug behaved as such with regard to phosphoinositide metabolism. Phosphoinositide metabolism was studied by measuring the 32P labelling of phosphatidylinositol (PI) and of its phosphorylated derivatives in cultured smooth muscle cells isolated from guinea-pig aorta and incubated in the presence or absence of various histaminergic agonists and/or antagonists. The results clearly demonstrate that the increase in 32P-PI could be selectively induced by treatment of cells with histamine or 2-pyridylethylamine dihydrochloride (2-PEA) (an H1 agonist) but not with the H2 agonist dimaprit. In addition, histamine- or 2-PEA-induced 32P-PI increase was inhibited by pretreatment of cells with the H1 antagonist mepyramine, whereas the H2 antagonist cimetidine was without effect. These data demonstrate that the histamine-induced 32P-PI increase is mediated through H1 receptors. Under the same experimental conditions, cicletanine was as effective as mepyramine with an IC50 value of 10(-6) M. The development of tension in arterial smooth muscle is under the control of variations of calcium concentration in the intracellular space. Therefore, the blockade by cicletanine of histamine-enhanced phosphoinositide turnover may participate in the mechanism by which the drug exerts its antihypertensive action.

Angiotensin II↗
PubMed1988

[Heterogeneity of large granular lymphocyte leukemia. 2 cases].

Large cell granulocytic leukemia (LCGL) or proliferative lymphocyte T gamma disease, characterized cytologically by the presence of lymphocytes with intracytoplasmic azurophil granules, raises the problem of whether or not it is monoclonal in character. However, although it may resemble a chronic lymphoid T leukemia or Felty's syndrome, it differs by the constant finding of infiltration of the splenic red pulp by large granular lymphocytes. Studies of their immunologic phenotype and functional activity produce heterogeneous results. The disease course varies considerably: the serious nature of the infections, knowledge of the physiopathologic mechanism of the neutropenia and the importance of the tumoral syndrome could represent therapeutic indications the modalities of which have still to be defined.

Adult↗
PubMed1987

Combined intraommaya methotrexate, cytosine arabinoside, hydrocortisone and thio-TEPA for meningeal involvement by malignancies.

Twenty-three adult patients with meningeal involvement by a variety of malignancies were treated with the intra-Ommaya combination of methotrexate, hydrocortisone, cytosine arabinoside, and thio-TEPA. Whole brain irradiation was also administered to most patients who had not previously received it. Most patients demonstrated improvement of cerebrospinal fluid parameters, but only 50% of the patients experienced neurological improvement. Patients who did not receive cranial irradiation and performance status 4 patients were less likely to respond than were patients who did receive cranial irradiation as part of their treatment and patients who were performance status 0-3. Four patients developed possible and 2 patients developed probable or definite serious neurological complications. Another 4 patients developed less severe, reversible neurological toxicity. It is possible (but still uncertain) that this regimen is more toxic than other less intensive regimens, and further studies should be undertaken cautiously.

Adult↗
PubMed1987

Stage III carcinoma of the endometrium: a review of 41 cases.

Forty-one patients with clinical-pathological stage III carcinoma of the endometrium treated between January 1958 and December 1983 at the Ottawa General Hospital were analyzed. Twenty-three patients (56%) presented with clinical stage III and 18 (44%) with pathological stage III. The 5-year survival of all stage III patients was 35%. Patients with clinical stage III had a 5-year survival of 8% compared to 70% for patients with pathological stage III (P less than 0.01). Twenty-nine patients (71%) failed. The site of first recurrence was limited to the abdominal cavity in all but 6 patients (79%). The role of whole abdominal radiation is discussed.

Adenocarcinoma↗
PubMed1987

Aminoglycoside-induced alterations of phosphoinositide metabolism.

There exists a strong interaction between aminoglycosides and phosphoinositides, and these membrane lipids are even considered as the drug receptors. To shed some light on the role of such an interaction in the drug nephrotoxicity, we have investigated the influence of aminoglycosides on phosphoinositide metabolism in kidney proximal tubules where these compounds accumulate. Experiments were carried out by measuring 32P labelling of phosphatidylinositol 4-phosphate (PI-P) and of phosphatidylinositol 4,5-bisphosphate (PI-P2) after incubation of homogenates of isolated proximal tubules with [gamma-32P] ATP. The treatment of rabbits with neomycin, gentamicin and amikacin (50, 50 and 300 mg/kg/day, respectively for seven days) promoted a decrease in 32P-PI-P2 and an increase in 32P-PI-P, when compared to the respective values observed in tubules from untreated rabbits. Under these conditions, the extent of modifications in lipid labelling was similar with the three drugs tested. In in vitro experiments, the exogenous addition of the above aminoglycosides to the incubation medium containing tubule homogenates from untreated rabbits also produced, in a dose dependent manner, a decrease in 32P-PI-P2 and an increase in 32P-PI-P. In the in vitro experiments, however, amikacin and gentamicin appeared to be less potent than neomycin. The results indicated moreover that phosphoinositide metabolism was more sensitive to the in vivo (vs. in vitro) action of the drugs. Phosphoinositides are involved in Ca2+ transport and/or mobilization processes, and aminoglycosides are known to interfere with the Ca2+ binding to membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amikacin↗
PubMed1987

Prognostic factors in early carcinoma of the endometrium.

Two hundred forty-one patients with clinical-pathological Stage I and 58 patients with clinical-pathological Stage II carcinoma of the endometrium treated between January 1959 and December 1983 at the Ottawa General Hospital were analyzed. The adjusted survival rate at 5 years was 92% in patients with Stage I and 66% in patients with Stage II. In patients with Stage I, the most important prognostic factors were the histological grade of the tumor and the depth of myometrial invasion. In patients with Stage II, the single most important prognostic factor was the clinical extent of the disease. Grade and depth of myometrial invasion were also significant prognostic factors, particularly in patients with pathological Stage II. Combined surgery and radiation therapy was clearly superior to surgery alone in patients with Stage II but not in patients with Stage I, although, with long-term follow-up, our results may suggest improved survival in these patients as well.

Adult↗
PubMed1987

Spectrum and mode of action of azithromycin (CP-62,993), a new 15-membered-ring macrolide with improved potency against gram-negative organisms.

The macrolide antibiotic azithromycin (CP-62,993; 9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A; also designated XZ-450 [Pliva Pharmaceuticals, Zagreb, Yugoslavia]) showed a significant improvement in potency against gram-negative organisms compared with erythromycin while retaining the classic erythromycin spectrum. It was up to four times more potent than erythromycin against Haemophilus influenzae and Neisseria gonorrhoeae and twofold more potent against Branhamella catarrhalis, Campylobacter species, and Legionella species. It had activity similar to that of erythromycin against Chlamydia spp. Azithromycin was significantly more potent versus many genera of the family Enterobacteriaceae; its MIC for 90% of strains of Escherichia, Salmonella, Shigella, and Yersinia was less than or equal to 4 micrograms/ml, compared with 16 to 128 micrograms/ml for erythromycin. Azithromycin inhibited the majority of gram-positive organisms at less than or equal to 1 micrograms/ml. It displayed cross-resistance to erythromycin-resistant Staphylococcus and Streptococcus isolates. It had moderate activity against Bacteroides fragilis and was comparable to erythromycin against other anaerobic species. Azithromycin also demonstrated improved bactericidal activity in comparison with erythromycin. The mechanism of action of azithromycin was similar to that of erythromycin since azithromycin competed effectively for [14C]erythromycin ribosomebinding sites.

Anti-Bacterial Agents↗
PubMed1987

[Phospholipase C control of the hyperreactivity of platelets of the spontaneously hypertensive rat].

With respect to their biological responses the platelets of essentially hypertensive patients and of spontaneously hypertensive rats (SHR) are hyper-reactive to a variety of agonists. Platelet responses are mainly controlled by Ca2+ influx and/or mobilization and most of the platelet-activating substances act by stimulating the metabolism of phosphoinositides. Thus it is the hydrolysis of phosphatidylinositol 4,5-bisphosphate by phospholipase C that initiates platelet activation by thrombin. Assuming that an altered metabolism of phosphoinositides might participate in the hyper-reactivity of platelets from hypertensives, we studied phosphoinositide metabolism in washed platelets from SHR in relationship with the physiological cellular responses. This was carried out by measuring the variations in 32P-labeled lipids following incubation of platelets with 32P-orthophosphate. The results were compared with those obtained from washed platelets isolated from normotensive control rats of the Wistar-Kyoto strain (WKY). In unstimulated cells, both the rate and extent of 32P-incorporation into individual phospholipids were identical in SHR and WKY. This suggests that the pool size and basal turnover of phosphoinositides did not differ between the two strains. In contrast, early thrombin-induced lipid metabolism, when monitored as changes in 32P-phosphatidic acid (PA), was significantly higher in SHR than WKY and the extent of the difference was independent of the extracellular calcium concentration. Since following thrombin stimulation, 32P-PA formation likely reflects phospholipase C activity, our results suggest that this enzyme activity is enhanced in SHR platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Enzymatically induced alterations in the structure of rat serum lipoproteins.

Incubation of freshly isolated rat serum induces a large number of changes in the properties of the serum lipoproteins, especially the high density lipoproteins (HDL). The particle diameter of the HDL increases from about 10.4 nm to 12.3 nm and the protein content appears to increase by about 60,000 Daltons. Reactions catalyzed by lecithin:cholesterol acyltransferase (LCAT) lead to a marked decrease in cholesterol and phospholipid content, and an even greater increase in cholesteryl ester content. Especially noteworthy are the marked increases in apoE and apoA-IV which are found associated with HDL as a result of this process. Data indicate that the affinity of apoE and apoA-IV for the HDL particles may be influenced by the proportion of surface to core lipid and by the presence of products of the LCAT reaction. Changes in the apoprotein content of very low density lipoproteins are also observed, with A-I and A-IV appearing in this density interval. All of the above changes can be prevented by the inclusion of 5,5'dithiobis(2-nitrobenzoate) or p-chloromercuriphenylsulfonate during the incubation, or by heat treatment of serum at 56 degrees C for 30 min; these treatments are known to inhibit LCAT activity. It is concluded that LCAT action is the major cause of the various changes in HDL structure that are observed and that alterations in apoprotein content occur to correct the resultant imbalance between core lipid and coverage of this core by amphiphilic components. Increased apoE association with cholesteryl ester-rich HDL may provide an efficient means for receptor-mediated removal of cholesterol from the circulation.

Animals↗
PubMed1986

[Cancers of the left colon with occlusion. Treatment by subtotal colectomy with immediate ileo-sigmoid anastomosis].

The technique of subtotal colectomy with immediate ileo-sigmoid anastomosis in the treatment of the carcinoma of the left colon revealed by obstruction is described. This operation treats, in one stage, both the obstruction and the cancer. The mortality, morbidity and duration of stay in hospital are less than with the usual sequential treatment. Social rehabilitation is quicker, which is particularly valuable since the expected survival of these patients is short due to old age, poor general condition or spreading of the malignancy.

Aged↗
PubMed1986

Comparison of the lipoprotein profiles obtained from rat, bovine, horse, dog, rabbit and pig serum by a new two-step ultracentrifugal gradient procedure.

A new two-step gradient technique has been used in the separation of the different classes of lipoproteins from the serum of cows, horses, dogs, pigs, rabbits and rats. Total lipoproteins were first isolated at d 1.21 then floated through a d 1.006 to d 1.21 gradient. Collection by mean of a gradient fractionator provided directly comparable lipoprotein profiles, allowed the determination of the exact density range of each lipoprotein class and the fraction by fraction analysis of composition. Cholesterol and apo AI recoveries were high. Horse, dog, rabbit and pig exhibited three distinct lipoprotein classes: VLDL, LDL and HDL. LDL were polydisperse in the pig (three components), light in the rabbit and scarce in the horse. In the Sprague-Dawley rat, LDL could not be individualized from HDL. In the bovine, LDL overlapped with a light form of HDL. Although AI was the main apoprotein in the HDL of all species, it ranged in proportion from 35% in the rat to 75% in the bovine. Apo AII was dimeric in the dog, as already known, but also in the horse, rabbit and bovine (MW:17,000) and in the pig MW:13,000). Apo AIV was present in the heavier HDL of all species. Rabbit, horse and pig HDL contained only one species of apo C which, in the pig was identified as apo CII.

Animals↗
PubMed1986

Multivolumetric analysis of CT scans on patients with glioma.

Brain tumor volumes in patients having multimodal therapy for cerebral gliomas were calculated using graphic methods and Simpsonian integration. Volume assessment calculations differed from the clinical assessment of the patient significantly in some cases. These calculations may be useful in on-going tumor therapy and should be used as a true scientific end point in brain tumor treatment protocols.

Brain Neoplasms↗
PubMed1985

Quail neural crest cells transformed by Rous sarcoma virus can be established into differentiating permanent cell cultures.

Quail neural crest cells derived from the truncal neural primordium, infected in vitro by Rous sarcoma virus (RSV) in January 1978, were induced to multiply and have been established into permanent cultures. These cultures contain cells that differentiate into melanocytes, neuron-like cells and flat cells. About 50% of these different cell types are tetanus-toxin positive. Electrophysiological studies have shown that some cells can generate action potentials similar to those reported in quail neural crest primary cultures. Taken together these data show that the RSV-transformed quail neural crest permanent cultures are composed of stem cells which can differentiate into cell types specific for neural crest.

Animals↗
PubMed1985

Phosphoinositide turnover in erythrocyte membranes in human and experimental hypertension.

The metabolism of phosphoinositides, a class of membrane lipids involved in Ca2+ -transport and/or mobilization systems was investigated in patients with moderate essential hypertension and in Sabra rats. Experiments were performed in vitro on isolated erythrocyte membranes by measuring the 32P-labelling of phosphatidylinositol 4,5-bisphosphate (PI-P2) and of phosphatidylinositol 4-phosphate (PI-P) following the incubation of membranes with [gamma-32P] ATP. In untreated essential hypertensives (n = 31) or in hypertensive patients whose blood pressure was controlled by beta-blocker therapy (n = 20), 32P-PI-P2 was significantly higher than in normotensive controls (n = 30); no significant difference was observed between the two groups of hypertensive patients. In Sabra rats fed on a low Na diet, 32P-PI-P2 levels were significantly higher in hypertensive-prone animals (SBH) than in hypertensive-resistant animals (SBN). When the animals were fed a high Na diet or were DOCA/salt treated, 32P-PI-P2 did not change in either substrain, although such conditions differentially affected the blood pressure of SBH and SBN. Our data indicate that the modification of phosphoinositide metabolism is not a consequence of the blood pressure elevation, but can be considered as an intrinsic membrane defect which may be associated with functional alterations of Ca2+ fluxes which in hypertensives result in an enhanced intracellular Ca2+ level.

Adrenergic beta-Antagonists↗
PubMed1985

Serotonin release and phosphoinositide breakdown in thrombin-induced activation of human platelets.

The release reaction and the metabolism of inositol lipids were studied in parallel in washed human platelets following the activation by low doses of thrombin. The breakdown of phosphatidylinositol 4,5-bisphosphate (PI-P2) was accompanied by the release of serotonin. These events preceded the breakdown of the other phosphoinositides and the release of alpha-granules and lysosome constituents, respectively. The secretion of serotonin probably is triggered by products of thrombin-induced activation of the phospholipase C directed against PI-P2.

Blood Platelets↗