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Biomedical subjects

M Richard

Publications and source records attributed to M Richard.

At least 127 records · Page 7Linked to original sources

Study of the fucosyltransferase system in intestinal microsomes.

Fucosyltransferase activity of rat small intestine microsomes is solubilized by 0.5% Triton X-100. The solubilized activity can be purified up to 8,300-fold using DEAE-cellulose and affinity chromatography on GDP-Sepharose. At this step, chromatography on Sephadex G15 separates different specificities: N-acetylglucosaminide-alpha-(1,3)-fucosyltransferase acting on asialoserotransferrin, and galactoside-alpha-(1,2)-fucosyltransferase acting on O-glycans of asialofetuin. The use of small saccharidic acceptors also indicates the presence of a N-acetylglucosaminide-alpha-(1,4)-fucosyltransferase and of a very weak glucose-alpha-(1,3)-fucosyltransferase activity. These activities are tightly bound to concanavalin A-Sepharose, suggesting that they are supported by N-glycosylproteins.

Animals↗

Laser or razor? A novel experimental peripheral nerve repair technique.

An operative repair technique for crushed sciatic nerve in the rat was used to examine whether removal of the damaged tissue could be better achieved with a low wattage CO2 laser or a blade. This approach was compared to results in rats undergoing conventional end-to-end nerve anastomosis using a microsurgical approach. Crushed sciatic nerves were exposed bilaterally 24 hours after injury and treated as follows. A longitudinally split polyethylene catheter was placed under the nerve, which was fixed to the catheter with 9-0 stitches placed away from lesion area; the nerve was bathed in ice-cold polyvinyl alcohol/chlorpromazine (PVA/CPZ) solution. After the nerve was crushed, the lesioned tissue was removed using laser pulses or a thin blade. A collagen matrix was used to fill the gap, and the preparation was covered and allowed to recover for 6 weeks. End-to-end anastomosis was done following same parameters, but with omission of the nerve catheter, PVA/CPZ solution, and collagen matrix; these nerves were reunited using epineurial stitches. High performance liquid chromotography (HPLC) analysis of each group showed that the laser approach reduced the levels of norepinephrine distal to the lesion, least, suggesting better regeneration of proximal axonal growth. Morphological and neuroelectric findings, although suggestive, showed no significant differences between laser and blade repair, a finding that reinforces the idea that such endpoints are not as sensitive as chemical assays of tissue transmitter levels such as HPLC. Laser or blade repair using nerve-catheter fixation and collagen bridge matrix was superior to end-to-end nerve anastomosis when morphological, neuroelectric, and HPLC values were compared in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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↗

Screening of degradative enzymes from articular cartilage in experimental osteoarthritis.

Sixteen rabbits were killed 12 weeks after sectioning of the right knee anterior cruciate ligament. The left unoperated knee served as a control. The surface area of fibrillated cartilage from femoral condyles and tibial plateau was evaluated and expressed as a percentage of articular surfaces area. Cartilage from the femoro-patellar surfaces was homogenized for the quantification of several degradative activities, based on the release of digested products. Acid phosphatase, several glycosidases and neutral protease activity from the operated joint cartilage were significantly elevated, while collagenolytic activity was unmodified. The percentage of fibrillated cartilage correlated positively with arylsulfatase, glucosidase and neutral protease but negatively with mannosidase and fucosidase. The results may be consistent with the hypothesis of a sequential degradative process leading to cartilage destruction.

Animals↗

Presence of somatomedin receptors on primary human breast and colon carcinomas.

Competitive binding techniques were used to study the interaction of insulin-like growth factor I (IGF-I) with a plasma membrane-enriched subcellular fraction purified from primary breast and colon carcinoma specimens obtained at surgery. The presence of specific binding sites for IGF-I was detected in all tumour specimens studied. Scatchard analysis and competition studies with insulin and insulin-like growth factor-II (IGF-II) revealed the presence of specific IGF-I receptors, showing a Kd-value of approximately 2 nM. These results are consistent with the hypothesis that somatomedins play a role in determining the proliferative behaviour of human breast and colon tumors, and suggest that recent laboratory studies showing dependence of neoplastic cells on somatomedins for optimum proliferation may have clinical relevance.

Breast Neoplasms↗

Purification and separation of two soluble fucosyltransferase activities of small intestinal mucosa.

1. Rat small intestinal soluble fucosyltransferase is purified more than 2000-fold using chromatographic procedures with DEAE-cellulose, CM-cellulose, GDP-Sepharose and Concanavalin A-Sepharose. 2. Chromatography on Sephadex G15 of the final enzymatic fraction clearly separates two activities: a first peak incorporates fucose on asialoserotransferrin and a second peak on asialofetuin. 3. The use of small saccharidic acceptors (phenylgalactose, lactose, lacto-N-fucopentaose I) and the analysis of fucosylated asialoglycoproteins indicate that the first activity corresponds to an alpha-(3/4)-fucosyltransferase and the second one to an alpha-(1-2)-fucosyltransferase. 4. Protein analysis by polyacrylamide gel electrophoresis in the presence of SDS for each enzyme shows two bands corresponding to a mol. wt of about 65,000 and 70,000. The two enzymes have the same sensitivity to the action of N-ethylmaleimide.

Animals↗

Acrokeratosis paraneoplastica (Bazex' syndrome).

A 55-year-old white man born in Canada presented with all the clinical features of acrokeratosis paraneoplastica of Bazex. He showed the characteristic violaceous erythema and scaling of the nose and face, the aural helices, and the palmoplantar regions with severe nail dystrophy. Extensive examinations failed to reveal any associated malignancy up to 5 months after the onset of the skin eruption. While the skin was improving, and although the patient was still asymptomatic except for a weight loss of 5 kg, evidence of metastatic squamous cell carcinoma of the cervical region was obtained. Only palliative treatment could be undertaken. The bizarre clinical aspects of the syndrome are reviewed.

Carcinoma, Squamous Cell↗

Developmental changes in intestinal glycosyl-transferase activities.

The carbohydrate composition of some intestinal glycoproteins has been demonstrated previously to be modified during development. To evaluate the role of the enzymatic mechanisms of glycosylation, the activities of three soluble and microsomal glycosyl-transferases were studied during postnatal development in rat intestinal mucosa. Nonexistent as soluble forms in the cell sap from suckling rats, the membrane-bound N-acetylgalactosaminyl-, sialyl-, and fucosyl-transferases showed different activities in microsomal fractions before weaning. The N-acetylgalactosaminyl-transferase activity was constant whereas the sialyl-transferase activity, which was maintained at a rather high level until the age of 2 wk, decreased just before weaning, while the fucosyl-transferase activity declined progressively from birth to weaning. After weaning, the three enzymatic activities progressively enhanced until adult age. Their variable behaviors on several glycoprotein acceptors may suggest the presence of several sialyl--and fucosyl-transferases with differences in specificities, varying in different ways according to age. Such developmental modifications in intestinal glycosylation patterns may be linked with certain transformation observed in the carbohydrate level of mucus or membrane-bound glycoproteins and related to the profound modifications in nutritional status at the weaning period.

Animals↗

Combined intraarterial and systemic chemotherapy for intracerebral tumors.

Twenty-six patients with intracerebral tumors (predominantly gliomas) were treated with intraarterial BCNU, VM-26, and cisplatin combined with the systemic administration of VM-26, methotrexate, vincristine, bleomycin, and procarbazine. Oral glycerol was given before i.v. VM-26. Twelve patients responded (46% of all patients and 63% of the fully evaluable patients). The response rate for gliomas was 50% if all patients were considered and 71% if only fully evaluable patients were considered. The response rate did not seem to be affected by glioma grade, prior chemotherapy, or pretreatment performance status. Median time to tumor progression for responders was 19 weeks. Median survival from initiation of treatment was 21 weeks for evaluable patients and 17 weeks for all patients. Median survival from initial diagnosis was 55 weeks. Myelosuppression was dose-limiting for the systemic chemotherapy. Reversible neurological toxicity was common, but tolerable. One patient developed ipsilateral blindness, and two patients developed prolonged neurological toxicity. Pulmonary toxicity was also seen. Vertebral artery infusions proved feasible, although difficult and more toxic than carotid infusions. Overall, this regimen was not more active than the intraarterial combination of BCNU, VM-26, and cisplatin without the systemic chemotherapy. Further studies of more intensive intracarotid therapy combined with different systemic drugs are being initiated.

Adolescent↗

Pharmacological activity and toxicity of apyramide: comparison with non-steroidal anti-inflammatory agents.

An experimental and comparative study was conducted on 1-(p-chlorobenzoyl)-2-methyl-5-methoxyindole-3-p-acetamidophenol acetate (Apyramide) and known anti-inflammatory agents. Apyramide was far less toxic than indomethacin in rats and mice by the oral or the i.p. route. It exhibited anti-inflammatory activity on carrageenin-induced paw oedema, cotton pellet granuloma and adjuvant arthritis, as well as analgesic and antipyretic activities. The acute ulcerogenic effect of Apyramide was lower than that of indomethacin.

Animals↗

Cytosine arabinoside plus cisplatin and other drugs as chemotherapy for gliomas.

Twenty-five evaluable patients with gliomas were treated with a combination of cytosine arabinoside plus cisplatin administered intravenously (IV). Ten of the 25 patients (40%) responded, including three of 13 patients (23%) with prior cranial radiation, and seven of 12 patients (58%) without prior cranial radiation. In a second study, intramuscular (IM) and oral caffeine were added to IV cytosine arabinoside plus cisplatin. Caffeine-induced seizures prevented escalation of the dose of caffeine to a level that would have been anticipated to potentiate the cytotoxicity of the cytosine arabinoside plus cisplatin. Twelve of 25 treated patients (48%) responded. Most of the patients had not received prior cranial radiation. In a third study, IV cytosine arabinoside was administered in combination with intracarotid and IV cisplatin, plus BCNU and tenoposide (VM-26). This study is continuing to accrue patients. Myelosuppression has been pronounced, but has generally been rapidly reversible. It is too early to comment on efficacy of this combination. Our results to date permit us to conclude that the combination of cytosine arabinoside plus cisplatin is capable of inducing regression of gliomas in some patients. We feel that further studies are warranted.

Antineoplastic Combined Chemotherapy Protocols↗

A rapid and sensitive non-competitive avidin-biotin immuno-enzymatic assay for lysozyme.

A non-competitive avidin-biotin immuno-enzymatic assay (NABA) for lysozyme is described. The assay was found to be more sensitive than a competitive assay with biotinylated lysozyme. The lower detection limit of NABA was 0.1 ng lysozyme/ml compared to 1 ng/ml for the competitive assay. The intra-assay and inter-assay coefficients of variation for NABA were 5.9 and 9.1%, respectively. The total time for NABA can be decreased (to less than 1 h) without influencing the detection limit or the analytical range. Serum lysozyme levels measured by NABA and the enzymatic assay in 32 samples showed a correlation coefficient of r = 0.97.

Avidin↗

Staphylococcal scalded skin syndrome in a homosexual adult.

A homosexual man developed staphylococcal scalded skin syndrome associated with a Staphylococcus aureus septicemia. We discuss the role of prednisone, renal insufficiency, and immunosuppression as predisposing factors to staphylococcal scalded skin syndrome in adults. In particular, our study of the patient's immune function revealed anergy and lymphopenia, with a reduced response to phytohemagglutinin. Studies of T cell subpopulations revealed an elevated percentage of T suppressor cells and a diminished percentage of T helper cells with a depressed T helper/T suppressor ratio. Because of those abnormalities, we suspected acquired immunodeficiency syndrome. A few months after recuperation from the acute disease, the patient has had a normalization of the T helper/T suppressor ratio, but because of persistent polyadenopathy, hypergammaglobulinemia, and a negative sensitization to keyhole-limpet hemocyanin (KLH), we now consider the patient to have an acquired immunodeficiency syndrome-related complex.

Acquired Immunodeficiency Syndrome↗