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Biomedical subjects

A Rousseau

Publications and source records attributed to A Rousseau.

At least 19 recordsLinked to original sources
PubMed1995

Distribution of noradrenergic neurons in the female rat pelvic plexus and involvement in the genital tract innervation.

The involvement of the pelvic plexus noradrenergic neurons in the innervation of the genital tract was studied in the female rat. Several small ganglia were observed in addition to the paracervical ganglion and immunocytochemistry for tyrosine hydroxylase was performed to examine the distribution and number of the noradrenergic neurons. 5069 +/- 1525 nerve cell bodies were counted in the paracervical ganglion and 9.0 +/- 0.8% of them were noradrenergic, displaying a clear somatotopic distribution in the ventro-medial part of the ganglion. Some accessory ganglia were located ventral to the main paracervical ganglion. 414 +/- 149 nerve cell bodies were found in the accessory ganglia, of which 20.4 +/- 3.1% were noradrenergic. Ganglia along the vesical branch of the hypogastric nerve, referred to as an hypogastric plexus, contained 233 +/- 83 neurons among which 12.7 +/- 7.2% were noradrenergic. Bilateral removal of the pelvic plexus produced degeneration of all the tyrosine hydroxylase-immunoreactive nerve fibres in the lower part of the uterus and in the cervix. In contrast, excision of the paracervical ganglia and the accessory ganglia caused no significant change in this innervation pattern. Combined retrograde tracing study and immunocytochemistry for tyrosine hydroxylase revealed a very small number of noradrenergic neurons also labelled with fluoro-Gold. Both findings suggest a limited involvement of the pelvic plexus noradrenergic neurons in the innervation of the lower genital tract.

Animals↗
PubMed1995

The hemoregulatory peptide N-acetyl-Ser-Asp-Lys-Pro is a natural and specific substrate of the N-terminal active site of human angiotensin-converting enzyme.

Angiotensin I-converting enzyme (ACE) is a zinc-dipeptidyl carboxypeptidase, which contains two similar domains, each possessing a functional active site. Respective involvement of each active site in the degradation of the circulating peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), a negative regulator of hematopoietic stem cell proliferation, was studied by using wild-type recombinant ACE and two full-length mutants containing a single functional site. Both the N- and C-active sites of ACE exhibit dipeptidyl activity toward AcSDKP, with Km values of 31 and 39 microM, respectively. However, the N-active site hydrolyzes the peptide 50 times faster compared with the C-active site, with kcat/Km values of 0.5 and 0.01 microM-1.s-1, respectively. The predominant role of the N-active site in AcSDKP hydrolysis was confirmed by the inhibition of hydrolysis using a monoclonal antibody specifically directed against the N-active site. The N-domain specificity for AcSDKP will aid the identification of specific inhibitors for this domain. This is the first report of a highly specific substrate for the N-active site of ACE, with kinetic constants in the range of physiological substrates, suggesting that ACE might be involved via its N-terminal active site in the in vivo regulation of the local concentration of this hemoregulatory peptide.

Amino Acid Sequence↗
PubMed1995

The radiosensitivity of uveal melanoma cells and the cell survival curve.

BACKGROUND: No study of the radiosensitivity of uveal melanoma cells and their survival curve has been published. The purpose of this study was to investigate the sensitivity to different single radiation doses of SP6.5, a human uveal melanoma cell line. METHODS: Cells were irradiated with cobalt-60 at doses from 0 to 1200 cGy. Radiosensitivity was measured by three methods: soft-agar bilayer assay, tritiated thymidine incorporation, and bromodeoxyuridine (BrdU) incorporation. RESULTS: The soft-agar bilayer assay, by assessing the colony-forming units, showed that the D1 value was 470 cGy, the Dq value was 400 cGy, and the n value exceeded 10, thus indicating a broad, shoulder and relative radioresistance. The doubling time as estimated by [3H]thymidine incorporation was unaffected at doses below 600 cGy, another indication of radioresistance. BrdU incorporation revealed no significant increase between 0 and 1000 cGy, indicating that the cell cycle was not interrupted. CONCLUSION: Cell survival, doubling time, and cell phases are parameters of growth kinetics, and the results suggest that SP6.5 is radioresistant and virtually unaffected by single radiation doses lower than 600 cGy. Our data parallel published data for cutaneous melanomas.

Aged↗
PubMed1994

Potential strategies for circumventing myeloperoxidase-catalyzed degradation of vinca alkaloids.

Myeloperoxidase (MPO) has recently been shown in an in vitro, cell-free system to catalyze the peroxidative degradation of vincristine (VCR). Oxidation of VCR involves a ring fission between positions 20' and 21', and is thought to be facilitated by the presence of an hydroxyl (-OH) group at position 20'. We report here two different approaches, both with potential clinical application, to decrease MPO-catalyzed vinca degradation. Firstly, we tested the hypothesis that -OH substitution at position 20' increases vinca susceptibility to peroxidation by comparing the relative extent of degradation of vinorelbine (Navelbine or NVB), which lacks a 20' hydroxyl substitution, with that of VCR. As anticipated, NVB was significantly less susceptible to MPO-catalyzed peroxidation than was VCR (p < 0.01). Secondly, we screened an array of compounds that are in current clinical use for their ability to inhibit MPO. Acetaminophen, N-acetylcysteine, propylthiouracil, D-penicillamine, mefenamic acid, dapsone, and methimazole all inhibited MPO at clinically achievable concentrations. Insofar as increased MPO activity has been observed in patients with acute myeloid leukemia, these findings suggest potential strategies for improving the activity of vinca alkaloids in this disease.

Antineoplastic Agents↗
PubMed1993

Synthesis and antithyroid activity of pyridine, pyrimidine and pyrazine derivatives of thiazole-2-thiol and 2-thiazoline-2-thiol.

A series of compounds was synthesized by linking various derivatives of pyridine, pyrimidine or pyrazine to thiazole-2-thiol or to its partially hydrogenated derivative 2-thiazoline-2-thiol. The reactions of the compounds with molecular iodine and lactoperoxidase were examined in vitro. Their antithyroid activity was also examined in vivo in the rat. T4 and TSH levels were determined, and the thyroid gland was examined histologically. 2-(3-Hydroxy-2-pyridyl)-2-thiothiazoline had the highest antithyroid activity of the compounds tested (Kc = 14931.mol(-1),IC(50)0.65 x 10(-4) M, activity of thyroid gland).

Animals↗
PubMed1992

Structure-activity relationship of analogues of endothelin-1: dissociation of hypotensive and pressor actions.

The structural requirements of endothelin-1 to evoke depressor and pressor responses were studied in conscious rats. Formylation of the C-terminal Trp eliminated the depressor but not the pressor activity of endothelin-1. Oxidation of Met7 in this analogue restored the hypotensive activity. Destruction of the Cys1-Cys15 disulphide bridge led to a weak agonist with both depressor and pressor activities. Formylation of Trp21 in this analogue resulted in a complete loss of biological activity. These results indicate that Met7 and the indole moiety of Trp21 are important for the expression of the depressor activity of endothelin-1 whereas the intramolecular loop structure is less important. The results also provide further evidence that the depressor and pressor effects of endothelin-1 are mediated through different receptors.

Animals↗
PubMed1992

Endothelin-1 enhances vascular permeability in the rat heart through the ETA receptor.

Intravenous injection of endothelin-1 (ET-1, 0.1 and 1 nmol/kg) resulted in a dose-dependent increase in vascular permeability in the coronary circulation of conscious rats. The increase was almost completely abolished by the selective ETA receptor antagonist, BQ-123 (1 mg/kg). The ET-1 analogue, [Trp(For)21]ET-1, which is devoid of the depressor but not the pressor activity, evoked changes in protein extravasation similar to those with ET-1. These data indicate that the permeability effect of ET-1 is mediated through the ETA receptor.

Animals↗
PubMed1992

Endothelin-1 enhances vascular permeability in conscious rats: role of thromboxane A2.

The purpose of the present experiments was to study the effects of endothelin-1 (ET-1) on vascular permeability and the involvement of the cyclooxygenase metabolites in the vascular responses to ET-1. Bolus intravenous injection of ET-1 (0.1-1.0 nmol/kg) into conscious rats induced immediate hypotension lasting for 30 s followed by sustained dose-dependent hypertension. A low dose of ET-1 (0.1 nmol/kg) did not modify the hematocrit value but the 1.0-nmol/kg dose increased the hematocrit value from 39.7 to 44.4%. Pretreatment of the animals with BM-13505 (1 mg/kg), a thromboxane A2 (TxA2) receptor antagonist, prolonged the duration of the hypotensive response to ET-1 (1.0 nmol/kg) but had no effect on the pressor response. Pretreatment with OKY-046 (10 mg/kg), a TxA2 synthesis inhibitor, or indomethacin (10 mg/kg), a cyclooxygenase inhibitor, had no significant effect on ET-1-induced changes in blood pressure. Evans blue dye extravasation, a marker of vascular permeability, increased up to 235% over control levels in specific vascular beds including the upper and lower bronchi, stomach, duodenum and kidney of ET-1 (1.0 nmol/kg)-treated animals. Pretreatment of the animals with BM-13505, OKY-046 or indomethacin reduced by 60-100% the Evans blue extravasation in these tissues. These results suggest that the effect of ET-1 on vascular permeability is partly mediated and/or modulated by the secondary release of TxA2, whereas its action on arterial blood pressure appears to be independent from prostanoid release in conscious rats.

Animals↗
PubMed1992

[Metastatic tumors of the soft tissues of the hand. Apropos of a case. Review of the literature].

Soft tissue metastases of the hands are rare tumours, representing 0.1% of all metastases. The authors report a personal case and review the literature concerning another 21 cases. The primary tumour is generally a lung or breast cancer. These metastases appear to be more frequent in men than in women. Their rarity can be explained by the absence of routine investigation of such sites. The development of such metastases always indicates a poor prognosis.

Adenocarcinoma↗
PubMed1991

Characterization of gangliosides in human uveal melanoma cells.

We have evaluated the ganglioside composition of 20 primary uveal melanomas, of 2 cell lines derived from 2 uveal melanomas, of a liver metastasis from an uveal melanoma, and of 8 normal choroids. The results show that normal choroid tissue has a ganglioside content similar to the primary tumors of uveal melanoma except for GD1a, GD1b, and GT1b, which are present only on normal choroid tissues. On the other hand, the uveal melanomas have similarities with cutaneous melanomas, since GM3 (74%) and GD3 (25%) are found in both tissues and are present in about the same amounts. However, GM1 was found in 50%, GM2 in 20% and GD2 in none of the uveal melanomas. According to data published by others, cutaneous melanoma biopsies have no GM1, whereas GM2 is present in 100% and GD2 in 71% of tumor tissues. Transplantation of the 2 cell lines subcutaneously into nude mice resulted in the growth of tumors which had a ganglioside profile larger than that of the primary tumors. GM3 was significantly diminished and GD3 significantly increased in the primary uveal melanoma from patients who had received radiotherapy before enucleation compared with those who did not have radiotherapy. These results show that uveal melanomas contain gangliosides that could be used as targets for monoclonal antibody therapy.

Aged↗
PubMed1991

Effects of endothelin-1 on vascular permeability in the conscious rat: interactions with platelet-activating factor.

1. The objectives of the present experiments were to assess the effects of endothelin-1 on the macrovascular permeability in selected vascular beds, to study the involvement of platelet-activating factor (PAF) in vascular responses to endothelin-1 and to examine the vascular effects of combined administration of endothelin-1 and PAF in conscious rats. 2. Intravenous bolus injection of endothelin-1 (0.1-2 nmol kg-1) resulted in a dose-dependent biphasic change in mean arterial blood pressure (MABP) with initial transient hypotension followed by a prolonged pressor action. These changes were accompanied by a dose-dependent increase in haematocrit values. 3. Endothelin-1 (0.1 and 1 nmol kg-1) increased dose-dependently the vascular permeability of the trachea, upper and lower bronchi, stomach, duodenum, spleen and kidney (up to 240%) as measured by the extravasation of Evans blue dye. The permeability of pulmonary parenchyma, liver and pancreas was not affected significantly by endothelin-1 treatment. 4. Pretreatment of animals with the specific PAF receptor antagonist, WEB 2086 (1 mg kg-1, i.v.) or BN 52021 (10 mg kg-1, i.v.) reduced the endothelin-1 (1 nmol kg-1)-induced rise in haematocrit by about 50 and 30%, respectively. Both antagonists were highly effective at inhibiting protein extravasation in the stomach, duodenum and kidney. On the other hand, BN 52021, but not WEB 2086, significantly attenuated the effect of endothelin-1 on permeability in the lower bronchi and spleen. Neither WEB 2086 nor BN 52021 modified the changes in MABP evoked by endothelin-1.5. When low doses of endothelin-1 (0.1 nmolkg-')and PAF (0.19nmolkg-')were administered simultaneously, enhanced protein extravasation was detected in the upper and lower bronchi, whereas neither endothelin-1 nor PAF by themselves affected vascular permeability in these tissues. These changes occurred in the absence of significant changes in MABP.6. Combined administration of higher doses of endothelin-1 (1nmolkg-') and PAF (1.9nmolkg-') resulted in marked increases (up to 530%) in protein extravasation in the airways, pancreas, stomach and duodenum. The effect of endothelin-1 on permeability was not affected by PAF in the spleen, whereas it was completely inhibited by PAF in the kidney. Combined injection of endothelin-1 and PAF resulted in a slight, but significant increase in MABP.7. The present findings show that endothelin-1 is capable of increasing vascular permeability in selected vascular beds including the airways, gastrointestinal tract and kidney, and suggest that PAF may mediate, in part, its action on permeability, but not its hypotensive action. The present data also suggest that endothelin-1 and PAF can act in concert to increase vascular permeability in rat airways and gastrointestinal tract.

Animals↗
PubMed1990

Uptake and degradation of virus-associated fluorescent sulfatide by skin fibroblasts.

A fluorescent derivative of cerebroside sulfate, pyrene-dodecanoyl sphingosylgalactosylsulfate (P12-CS) was incorporated into the envelope of vesicular stomatitis virus (VSV). When the P12-CS-containing virus was incubated for 24 h with skin fibroblasts, up to 40% of the sulfatide was located in the cells--a value at least 10 fold greater than that observed using sulfatide suspensions without virus. In a similar experiment, in which the 24 h 'pulse' was followed by a 48 h 'chase', about 15-20% of the virus-associated fluorescence was recovered in the skin fibroblasts. Of the latter, about one-third was present as desulfated degradation products of P12-CS. The high uptake and degradation of the virus-associated sulfatide by intact skin fibroblasts suggested that enveloped viruses could be used for introducing other lipids into cells. This could be utilized for studying lipid catabolism and diagnosing lipid storage disorders in intact living cells.

Endocytosis↗
PubMed1989

Canthaxanthin retinopathy. Anatomic and functional reversibility.

Canthaxanthin intake is associated with golden yellow crystalline deposits in the retina around the macula and low static luminance threshold. Our study assesses the anatomic and functional reversibility of canthaxanthin retinopathy. The number of retinal deposits was evaluated in nine patients, two to four times over a mean period of 55 months. There was no significant difference after a nine-month follow-up. A statistically significant decrease in the number of retinal deposits was found after an observation period of 26 months. The deposits disappeared slowly, while some remained even seven years after canthaxanthin therapy was discontinued. Threshold static perimetry performed on eight patients with retinopathy and seven controls did not differ significantly between the two groups at the end of the follow-up period. The results demonstrate that canthaxanthin retinopathy is reversible.

Adult↗
PubMed1989

[Neurodepressive effects of the essential oil of Lavandula angustifolia Mill].

Mice Swiss are orally given essential oil of lavander diluted at 1/60 in olive oil. Sedative effects are observed with some tests (hole board test, four plates test, plus-maze test, potentiation of barbiturate sleeping time). A significant interaction exists with pentobarbital: the sleeping time is increased and the asleeping time shortened.

Animals↗
PubMed1989

[ Neuro-depressive properties of essential oil of lavender].

Toxicity for albino rats is very low. In mice an anxiolytic effect is exhibited and the pentobarbital evokated sleeping time is increased in animals given essential oil, but this effect disappears if they are administrated during five days.

Animals↗
PubMed1988

Static perimetry in canthaxanthin maculopathy.

We performed threshold static perimetry on 19 patients who had ingested canthaxanthin; 11 had maculopathy and eight did not. Patients with no history of canthaxanthin ingestion served as controls. All patients had visual acuity of 6/9 or better. Threshold static perimetry was reevaluated two to three years after cessation of canthaxanthin ingestion. For both testing sessions, patients with maculopathy presented lower retinal sensitivity than controls, while patients without maculopathy did not differ significantly from the control group. These results suggest that canthaxanthin retinopathy can adversely affect the neurosensory retina.

Adult↗