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Biomedical subjects

C Morin

Publications and source records attributed to C Morin.

At least 73 records · Page 4Linked to original sources

Biological evaluation of two anomeric glucose analogues iodinated in position 6.

Two anomeric analogues of glucose labelled with 123 iodine in position 6, proposed as tracers of glucose transport in vivo, have been synthesized: alpha- and beta-methyl-6-deoxy-6-iodo-D-glucopyranoside (alpha MDIG and beta MDIG). The aim of this study was to determine whether these molecules interact with the glucose transporter and whether they could be used as tracers of glucose transport in vivo. The biodistribution of alpha MDIG and beta MDIG was studied in the mouse in vivo. To determine if these two anomers enter the cell via the glucose transporter, their uptake was measured in isolated perfused rat hearts, in human erythrocytes in suspension, and in cardiomyocytes of neonatal rat in culture. Both alpha MDIG and beta MDIG had similar repartitions in the mouse: myocardial uptake averaged 7% of the injected dose/g of organ at 2 min postinjection and alpha MDIG competed with D-glucose to enter the cells. Insulin produced a 123% increase of its uptake in isolated perfused rat hearts and a 100% increase in cardiomyocytes of neonatal rat in culture. alpha MDIG uptake was lowered in the presence of glucose transport inhibitors in each experimental model. An interaction between beta MDIG and glucose transporters was observed only in human erythrocytes in suspension. Only alpha MDIG interacts with the glucose transporter, and thus could be used to estimate glucose transport in vivo.

Animals↗

[123I]-6-deoxy-6-iodo-D-glucose (6DIG): a potential tracer of glucose transport.

A glucose analogue labelled with iodine-123 in position 6 has been synthesized: [123I]-6-deoxy-6-iodo-D-glucose (6DIG). The aim of this study was to examine its biological behaviour in order to assess whether it could be used to evaluate glucose transport with SPECT. To establish whether 6DIG enters the cells using the glucose transporter, four biological models have been used: human erythrocytes in suspension, neonatal rat cardiomyocytes in culture, isolated perfused rat hearts, and biodistribution in mice. 6DIG competed with D-glucose to enter the cells and its entry was increased by insulin and inhibited in the presence of cytochalasin B. The biological behaviour of 6DIG was similar to that of 3-O-methyl-D-glucose. 6DIG is a tracer of glucose transport which is very promising for clinical studies.

Animals↗

Desipramine treatment differently down-regulates beta-adrenoceptors of freshly isolated neurons and astrocytes.

Eight days' desipramine administration (16 mg/kg per day i.p.) to rats resulted in a significant decrease in the density of beta-adrenoceptors in neuronal and astroglial cells from rat forebrain and cerebellum without modification of their corresponding affinity. beta-Adrenoceptor subtypes, beta 1 and beta 2, which coexist in neurons and astrocytes, are differently distributed in the brain and differently modified by desipramine administration which down-regulates beta 1-adrenoceptor in forebrain neurons and astrocytes and beta 2-adrenoceptor in cerebellum neurons. This down-regulation affects the predominant subtype, beta 1 or beta 2, of the relevant structure. Astroglial and neuronal beta-adrenoceptors are differently coupled to G-proteins. Only neuronal cells contain the high-affinity conformational state of the beta-adrenoceptors which is sensitive to GTP. The percentage of neuronal receptors in the high-affinity state differs according to brain area. Desipramine treatment decreases the neuronal density of both cerebellar high- and low-affinity sites and only the forebrain high-affinity site. The desipramine effects are thus subtype-dependent and differ between the two brain areas selected.

Adrenergic Uptake Inhibitors↗

Docetaxel serum protein binding with high affinity to alpha 1-acid glycoprotein.

The binding of docetaxel to human plasma proteins was studied by ultrafiltration at 37 degrees C and pH 7.4. Docetaxel was extensively (> 98%) plasma protein bound. At clinically relevant concentrations (1-5 micrograms/ml), the plasma binding was concentration-independent. Lipoproteins, alpha1-acid glycoprotein and albumin were the main carriers of docetaxel in plasma, and owing to the high interindividual variability of alpha1-acid glycoprotein plasma concentration, particularly in cancer, it was concluded that alpha1-acid glycoprotein should be the main determinant of docetaxel plasma binding variability. Drugs potentially coadministered with docetaxel (cisplatin, dexamethasone, doxorubicin, etoposide, vinblastine) did not modify the plasma binding of docetaxel. In blood, docetaxel was found to be mainly located in the plasma compartment (less than 15% associated to erythrocytes).

Antineoplastic Agents, Phytogenic↗

[Congenital tarsal synostosis].

Tarsal coalition results from the fusion of at least two tarsal bones. The clinical and radiological pictures depend on the anatomic location of the coalition. Calcaneonavicular and talonavicular coalitions are the most frequent features which may result in peroneal spastic flat foot; however they are symptomless in most cases. Tarsal coalitions are usually evident on plain X-ray films using appropriate incidences. In selected cases, partial talocalcaneal coalition requires CT scan or MRI. No treatment is needed for asymptomatic conditions. Painful spastic flat foot must be treated conservatively by limiting sport activity as a first step treatment. In case of persistent symptoms, cast with correction of deformities under general anesthaesia is recommended. Surgery is needed only in case of failure of previous treatment, requiring resection of the bony bridge and sometimes triple foot arthrodesis.

Child↗

Biological studies of analogues of glucose iodinated in positions 1, 2, or 3.

Analogues of glucose labeled with 123 iodine in positions 1, 2 or 3 have been synthesized. The aim of this study was to examine their biological behavior in four experimental models in order to assess whether they could be used to evaluate the uptake of glucose with single photon emission computed tomography (SPECT). The results obtained have shown that none of these molecules enters the cell using the glucose transporter. Therefore, they cannot be used as tracers of glucose uptake.

Animals↗

Determinants of persistent detection of human papillomavirus DNA in the uterine cervix.

To identify factors associated with persistence of human papillomavirus (HPV) DNA in the uterine cervix, 179 women who were 18-49 years old and who had normal cytologies and positive cervical HPV DNA test at a routine periodic examination were analyzed. Among them, 91 (50.8%) remained HPV-positive a few months (mean, 11 weeks) later. Persistence was higher in women who had used oral contraceptives for > or = 2 years (odds ratio, 3.9; 95% confidence interval, 1.5-10.3) compared with those who never used oral contraceptives or used them for <2 years. HPV types 16, 18, and 31/33/35 appeared more persistent (odds ratio, 2.5; 95% confidence interval, 1.0-6.2) than other types. Persistence seemed to increase with virus load and decrease with increasing interval between examinations.

Chronic Disease↗

Factors influencing Cryptosporidium testing in Connecticut.

To describe patterns of testing for Cryptosporidium oocysts in stool samples, Connecticut laboratories were surveyed. Different detection methods were used. Most laboratories examined stools specifically for Cryptosporidium only on physician request. The rate of positive tests varted widely (0 to 28%). Higher rates of positivity were associated with the use of monoclonal antibody methods, the use of two or more staining procedures, and testing of stool specimens in addition to those requested by physicians.

Animals↗

Measurement of hypoxia in human tumours by non-invasive spect imaging of iodoazomycin arabinoside.

Tumour oxygenation status in individual patients may be assessed using the bioreduction and linkage of 2-nitroimidazole markers to viable hypoxic cells in vivo with subsequent detection by conventional nuclear medicine techniques. Iodoazomycin arabinoside (IAZA) was radiolabelled with Iodine-123 and administered i.v. to 51 patients with newly diagnosed malignancies whose tumours were subsequently imaged by planar and single-photon emission computed tomographic (SPECT) procedures. Quantitative analyses of radiotracer avidity were performed at 24 h post-injection and tumour-normal tissue ratios of greater than 1.10 were deemed positive for tumour hypoxia. By this criterion, the frequencies of hypoxia in small-cell lung cancer, squamous cell carcinomas of head and neck and malignant gliomas were 60% (9/15), 40% (6/15) and 0% (0/11) respectively. The correlation of positive IAZA scans with tumour control and survival in patients with lung cancer and head and neck tumours is currently under study. Preliminary observations in neck metastases from squamous cell carcinoma of head and neck tumours indicates decreased local control at 3 months post-treatment in tumours with IAZA avidity. This study concludes that: (1) 123I-IAZA can be administered safely and repeatedly as an outpatient routine imaging procedure in cancer patients during initial work-up and follow-up; (2) that retained drug can be detected by conventional nuclear medicine procedures in inaccessible deep-seated tumours; and (3) that this technique could prove useful for identifying those patients for whom hypoxia-directed therapy is indicated.

Cell Hypoxia↗

[Latex allergy and orthopedic surgery].

PURPOSE OF THE STUDY: Latex allergy is becoming a subject of extreme concern, especially in patients who have undergone multiple operations and/or have after effects of myelodysplasia. Presenting their data, the authors wish to make it aware to orthopaedic surgeons focusing on different risk groups, and at the same time advising on medical examinations, of the various measures to take. MATERIAL AND METHODS: Twenty patients were tested (17 with spina bifida and 3 with cerebral palsy) for latex and ethylene oxide allergy, and with certain fruits known for their cross-reactivity. Atopic history has also been researched. The immunologic examination had been carried out by means of skin-tests with evidence of specific IgE antibodies being found. RESULTS: Out of the twenty patients tested, eight had clinical signs of a latex allergy while the twelve others were classified as being at risk. The results show that 11 out of 20 are allergic to latex, 4 of them have an allergy to ethylene oxide, and 7 have food allergies: banana (2), kiwi (1), chestnut (1), hazelnut (3). DISCUSSION: We confirm: 1) the increased risk of a latex allergy among patients with spina bifida: 47 per cent in our study; 2) the association of an ethylene oxide allergy, practically the only product used in the sterilisation of medical equipment; 3) a more and more frequent association to food allergies, in particular to fruits: 7 out of 11 patients in our study compared to 50 per cent in other published studies. The classical subject of atopy is not found here. CONCLUSION: Against the increase of latex allergy, it is necessary to propose a strategy: firstly to determine the groups at risk: patients who have undergone multiple operations, atopic persons, isolated cases of food allergies, spina bifida cases. Then, to test them and if necessary, taking draconian measures concerning their medical environment; to identify them; to provide them with auto-injectable epinephrine; to give premedication, though with no success guarantee in case of anticipated surgical procedure. Finally, we recommend to manufacturers that all equipment and products should be free of latex.

Adolescent↗

Inhibition of rat cerebral mitochondrial respiration by cyclosporins A, D, and G and restoration with trimetazidine.

The aim of this work was to investigate possible inhibitory effects of Ca+ and different cyclosporins (Cs) on the rat brain mitochondrial respiratory control ratio (RCR) and whether or not these effects could be antagonized by trimetazidine (TMZ). The RCR was evaluated as the state 3/state 4 ratio of oxidative phosphorylation. CsA, D, and G inhibited about 10% of RCR in a concentration-dependent manner with EC50 of 57, 19 and 7 nM, respectively, whereas CsH did not modify RCR. TMZ was able to fully antagonize this inhibitory effect in a concentration-dependent manner with EC50 of 5,200, 180, and 1 nM, respectively. The Ca2+ added to the mitochondrial preparation decreased RCR in a concentration-dependent manner with a maximal effect of 46% obtained with 100 microM Ca2+. In the presence of TMZ (100 microM), the inhibitory effect of Ca2+ was partly reversed (9%). TMZ alone showed no inhibitory or stimulant effect on RCR. These results show that restoration of RCR by TMZ is due to a Ca(2+)-dependent mechanism, promoting Ca2+ efflux from the mitochondrial matrix. However, Ca2+ efflux is only partial in case of Ca2+ overload. These data suggest that TMZ may restore ATP synthesis in circumstances where neither Ca2+ overload, nor a prooxidant have generated a RCR decrease.

Analysis of Variance↗

[Histopathologic features of cytomegalovirus lymphadenitis in the "immunocompetent" patient. Report of 7 cases].

The authors report seven cases of cytomegalovirus lymphadenitis in apparently immunocompetent patients. One patient presented with an infectious mononucleosis-like illness. The main presentation of the others was isolated cervical lymphadenopathies. The lymph node pathology showed aspecific lymphoid hyperplasia, resembling the human immunodeficiency virus related lymphadenopathy, associated with diagnostic inclusion cells. Infected cells were confined to areas of monocytoid B cell hyperplasia in all cases whereas exceptionally observed in germinal centers. Because of their variable appearance, serial sectioning was frequently necessary to disclose their characteristic features. In all cases, immunohistochemistry using an anti-cytomegalovirus antibody was positive and revealed more infected cells than detected by morphology alone. Except for the endothelial cell, the nature of infected cells remained undetermined. An alteration of the antigenic expression as a consequence of cell infection might be responsible for immunohistochemistry failure in the cell characterization.

Adult↗

Inhibition of glycolysis in boar spermatozoa by 1,6-dichloro-1,6-dideoxy-D-fructose.

The dichloro-analogue of D-fructose 1,6-bisphosphate, 1,6-dichloro-1,6-dideoxy-D-fructose, is a weak substrate for boar sperm aldolase which converts it to (S)-3-chlorolactaldehyde and 3-chloro-1-hydroxypropanone in vitro. Production of these chloro-trioses leads to the strong inhibition of glyceraldehyde-3-phosphate dehydrogenase, the weak inhibition of triosephosphate isomerase and the transient inhibition of aldolase.

Animals↗

Characterizing allelic proteins for genome mapping in maize.

Mapping cDNA probes in order to construct genetic linkage maps is becoming a widespread strategy for genome analysis and gene isolation, particularly in cultivated plant species. Nevertheless, almost all cDNAs reveal two or more unlinked loci, making it difficult to identify the gene(s) actually expressed. In a highly polymorphic species, such as maize, two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) of proteins may circumvent this limitation. With the analysis of various segregating populations, we previously showed that the apparent position shifts of proteins on the 2-D gels are monogenic and codominant. In this paper we compared allelic proteins on the basis of their high performance liquid chromatography (HPLC) profile and partial amino acid sequences. In a sample of 20 position shifts, the allelic proteins appeared to be similar in all but one case, strongly suggesting that polymorphism of structural genes is involved. Thus 2-D PAGE could prove to be a useful tool for genome mapping: when a cDNA probe detects several loci, a position shift of the encoded protein will allow the identification of the gene translated in the organ considered.

Alleles↗

Factors influencing macrophage activation by muramyl peptides: inhibition of NO synthase activity by high levels of NO.

Treatment with muramyldipeptide (MDP) or a lipophilic derivative (MTP-Chol) included in nanocapsules renders macrophages cytostatic towards tumor cells. At the same time, nitric oxide (NO) synthase (EC 1.14.23) activity is induced, as determined by measurement of the two end products of the reaction (nitrite and L-citrulline). The objective of this study was to investigate some factors which might influence this activation and explain the decreased response observed at high nanocapsule concentrations. The glucose content of the medium did not seem to be limiting. Addition of indomethacin decreased nitrite production in the effector phase, suggesting a role for prostaglandins in the maintenance of the activated state. We also tested the hypothesis that NO itself might regulate inducible nitric oxide synthase activity. The addition of NO donors (SIN-1 and nitrosoglutathione) or superoxide dismutase to cultures of activated macrophages inhibited the NO synthase activity. Since these NO donors were non toxic towards macrophages, these observations indicate clearly that the addition of exogenous NO to that formed by the enzymatic reaction can cause inhibition of the inducible NO synthase.

Acetylmuramyl-Alanyl-Isoglutamine↗

Risk factors for cervical intraepithelial neoplasia: differences between low- and high-grade lesions.

This case-control study assesses relations of human papillomavirus (HPV) type 16 infection, sexual history, cigarette smoking, and oral contraceptive use to low- and high-grade cervical intraepithelial neoplasia (CIN). A total of 548 high-grade and 338 low-grade CIN cases and 612 controls were identified among women seen at a colposcopy clinic in Quebec, Quebec, Canada, in 1988-1989. Interviews, colposcopy, cervical scrapings, and colposcopically directed biopsies were performed. One pathologist reviewed all histologic slides. Southern blot techniques were used to assay specimens for HPV 16 DNA. Lifetime number of sexual partners was related to low- and high-grade CIN. Presence of HPV 16 DNA was associated with a 8.7-fold (95% confidence interval 5.1-15.0) elevation in estimated relative risk of high-grade CIN. Relative risk of high-grade CIN increased with amount of HPV 16 DNA (p < 0.0001). Estimated relative risk of high-grade CIN in current cigarette smokers was 2.4 (95% confidence interval 1.8-3.2) compared with never smokers and increased with number of pack-years of exposure (p < 0.0001). Long-term (6 years or more) users of oral contraceptives had an estimated relative risk of high-grade CIN of 1.9 (95% confidence interval 1.1-3.3) compared with those who never used such contraceptives. In contrast, presence of HPV 16 DNA, cigarette smoking, and oral contraceptive use showed little or no relation to low-grade CIN. Risk factors for low- and high-grade CIN may differ substantially.

Adult↗

Influences of horizontal connections on visual responses in rabbit striate cortex.

The goal of this study was to examine the role of horizontal connections in rabbit striate neurons. Anaesthetized rabbits were prepared in the usual fashion for single-cell recordings in area 17 of the visual cortex. We compared responses evoked by moving and stationary stimuli prior to, during and after recovery from lateral microinjection of either lidocaine (n = 61), gamma-aminobutyric acid (GABA, n = 18) or bicuculline (n = 8) 2 mm from the recording site. This procedure allows evaluation of the contribution of neighbouring neurons in visual responses. Results showed that striate neurons are dependent on the adjacent cells' excitability. Modification of responses to stationary targets suggests that lateral interactions play a role in the generation of discharges to fixed stimuli. Lateral inactivation preferentially influenced non-directional over direction-selective units. This influence usually resulted in the non-directional neuron becoming directional by attenuation of the visually driven response in one direction. Simple and complex cells tended to be influenced differently by lateral inactivation. Simple cells became less responsive, whereas complex cells became more responsive. This dichotomy among cellular types suggests that simple cells receive mainly excitatory horizontal influences, while complex cells are contacted mostly by lateral inhibitory inputs.

Action Potentials↗