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Biomedical subjects

P Morin

Publications and source records attributed to P Morin.

At least 55 records · Page 3Linked to original sources

Immunization of HIV-infected adults with a three-dose series of inactivated Mycobacterium vaccae.

Heat-killed Mycobacterium vaccae vaccine was administered in a 3-dose schedule to 12 HIV-infected adults with CD4 cell counts > or = 300/mm3. Local and systemic side effects were monitored. Delayed-type hypersensitivity to purified protein derivative and Mycobacterium avium sensitin was measured at baseline and after the final dose. Antibody to aralipoarabinomannin, man-lipoarabinomannin, and a short-term culture filtrate of Mycobacterium tuberculosis were also measured. Lymphocyte proliferation responses to M avium sensitin and M vaccae sonicate were determined. Vaccine site induration was maximal at 2 days (median, 6 mm) and no systemic side effects were noted. Purified protein derivative skin test conversions did not occur. Changes in CD4 counts and HIV viral load were not significant. Three (27%) of 11 subjects who completed the trial showed either M avium skin test (n = 1) or short-term culture filtrate antibody (n = 2) responses. A three-dose schedule of M vaccae vaccine is safe and well tolerated in adults with early HIV infection and produces detectable immunologic responses in a subset of these subjects.

AIDS-Related Opportunistic Infections↗

APC mutations in colorectal tumors with mismatch repair deficiency.

We have investigated the influence of genetic instability [replication error (RER) phenotype] on APC (adenomatous polyposis coli), a gene thought to initiate colorectal tumorigenesis. The prevalence of APC mutations was similar in RER and non-RER tumors, indicating that both tumor types share this step in neoplastic transformation. However, in a total of 101 sequenced mutations, we noted a substantial excess of APC frameshift mutations in the RER cases (70% in RER tumors versus 47% in non-RER tumors, P < 0.04). These frameshifts were characteristic of mutations arising in cells deficient in DNA mismatch repair, with a predilection for mononucleotide repeats in the RER tumors (P < 0.0002), particularly (A)n tracts (P < 0.00007). These findings suggest that the genetic instability that is reflected by the RER phenotype precedes, and is responsible for, APC mutation in RER large bowel tumors and have important implications for understanding the very earliest stages of neoplasia in patients with tumors deficient in mismatch repair.

Adenomatous Polyposis Coli↗

Capillary electrophoresis analysis of chemical warfare agent breakdown products. I. Counterelectroosmotic separation of alkylphosphonic acids and their monoester derivatives.

An analytical method has been developed for the analysis of chemical warfare agents by capillary zone electrophoresis (CZE). Sorbate anion has been selected as indirect UV-absorbing agent and decamethonium cation reduces the electroosmotic flow. The optimized electrolyte (5 mM sorbic acid, 0.1 mM decamethonium bromide pH 6) allows the simultaneous separation of alkylphosphonic acids and their monoester derivatives in less than 15 min. The measurement of phosphonic solutes has been achieved in spiked soils using calibration curves in the 5-50 mg/l concentration range.

Alkylation↗

New insights into p53 function from structural studies.

Recent structural analysis of p53 has greatly enhanced our understanding of the biochemical activities of this protein by presenting us with a detailed picture of the chemical groups in the protein that are involved in protein stability, conformation and functional interactions. The current structures form the basis for the design of potential therapeutics which could, for example, revert a DNA-binding mutant back to a DNA-binding competent conformation. The structure of the tet domain forms the basis for designing an active therapeutic p53 with an oligomerization domain which would not cross react with a DNA-binding mutant p53. However, as useful as these structures have been in providing insight into the structure/function relationship for p53, a complete understanding of this protein awaits more detailed information on the full-length protein. In this respect, one of the most useful roles for future structural studies will be to help identify the nature of the conformational transition between latent and active p53, and how it can be modulated.

Base Sequence↗

Leishmania major: differential resistance to infection in C57BL/6 (high interferon-alpha/beta) and congenic B6.C-H-28c (low interferon-alpha/beta) mice.

In murine cutaneous leishmaniasis caused by Leishmania major (Lm), resistance often associates with the outgrowth of Lm-specific Th1 cells. Parasites are eliminated by Th1-mediated activation of infected macrophages (M phi) which destroy Lm by producing toxic nitrogen and oxygen radicals. The cytokine IFN-alpha activates microbicidal functions of M phis and facilitates outgrowth of Th1 cells. Therefore, we compared the course of infection with Lm in resistant C57BL/6 mice, bearing the If-1h high expression allele for IFN-alpha/beta, with the congenic B6.C-H-28c mouse, bearing the If-1I low expression allele from the Lm-susceptible BALB/c strain. We observed that B6.C-H-28c animals developed up to 70% larger footpad lesions and harbored up to 1000-fold more parasites than C57BL/6 mice. Furthermore, peak Lm-specific IFN-gamma production in the B6.C-H-28c animals was lower and delayed by approximately 2 weeks, whereas IL-4 production was higher and persisted approximately 2 weeks longer. Since these results suggested that IFN-alpha/beta plays a protective role in mice infected with Lm, we determined whether infusing B6.C-H-28c mice with IFN-alpha would influence the course of infection with Lm. Unfortunately, the mice developed severe peritoneal hemorrhaging in response to injection with IFN-alpha. Therefore, we examined the ability of IFN-alpha to activate M phis to destroy Lm in vitro. We observed that rIFN-alpha could synergize with subactivating doses of LPS to activate both C57BL/6 and BALB/c peritoneal M phis to produce NO and to kill intracellular Lm. Taken as a whole, these results suggest that type I interferons may play a protective role in cutaneous leishmaniasis.

Animals↗

Colonization and disinfection of biofilms hosting coliform-colonized carbon fines.

The documented release of carbon fines from granular activated carbon filters is a concern for drinking water utilities, since these particles may carry coliform and even pathogenic bacteria through the disinfection barrier. Such a breakthrough could have an impact on distribution system biofilms. Using total cell counts, specific monoclonal antibody staining, and computerized image analysis, we monitored the colonization of introduced Klebsiella pneumoniae associated with carbon fines in mixed-population biofilms. The particles transported the coliforms to the biofilms and allowed successful colonization. Chlorine (0.5 mg/liter) was then applied as a disinfectant. Most K. pneumoniae along with the carbon fines left the biofilm under these conditions. The impact of chlorine was greater on the coliform bacteria and carbon fines than on the general fixed bacterial population. However, 10% of the introduced coliforms and 20% of the fines remained in the biofilm. The possibility that this represents a mechanism for bacteria of public health concern to be involved in regrowth events is discussed.

Journal Article↗

A PET study of the functional neuroanatomy of writing impairment in Alzheimer's disease. The role of the left supramarginal and left angular gyri.

A dissociation in the central processes of spelling, with preferentially lexical over phonological impairment, frequently affects patients with early Alzheimer's disease. The aim of this work was to test whether dissociations in the language domain in Alzheimer's disease can be exploited with PET to assess the neural basis of cognition. To this end, we studied the functional neuroanatomy of writing impairment in Alzheimer's disease by means of PET measurements of the local cerebral glucose utilization and neuropsychological tests specially designed to assess the phonological and lexical components of writing. We analysed the performance in written spelling of irregular words and non-words of 11 right-handed patients with mild-to-moderate Alzheimer's disease. For each patient, we calculated a residual phonological score and a residual lexical score, based on a cognitive interpretation of the errors according to the item category. In each of these 11 patients, using PET, we measured the resting-state utilization of glucose in the left supramarginal gyrus and the left angular gyrus, two cortical regions selected a priori because of their presumed role in the central processes for spelling, and identified on CT scans obtained according to stereotaxic references and coregistered with PET. To assess the relationships between the neuropsychological scores and the metabolic data, we used the 'ratio paradigm', the sensitivity of which has been previously documented in cognitive-metabolic correlative PET studies of Alzheimer's disease that were less focused than the present study in both cognitive and anatomical terms. We found a highly significant positive correlation between phonological score:lexical score neuropsychological ratios and corresponding supramarginal gyrus:angular gyrus metabolic ratios. These findings further support the role of these two left-sided temporo-parietal regions in the central processes of writing and show that the neuropsychological dissociations in early Alzheimer's diseases can be exploited to further our understanding of the functional neuroanatomy of cognitive operations. The role of focal, as compared with more diffuse, brain damage in the development of impaired written language of central origin in Alzheimer's disease is also discussed.

Aged↗

[Infarction in the area of the right anterior choroidal artery and minor hemisphere syndrome: clinical and metabolic study using positron-emission tomography].

A 72 year-old right handed woman had a right sided anterior choroidal artery infarction. She presented the triad of hemiplegia, hemianaesthesia, and homonymous hemianopsia, as well as complete non-determinant hemisphere syndrome that combined: disorientation for place and time, anosognosia, hemiasomatognosia, left spatial neglect, constructional apraxia and spatial fabulation concerning both the present time and the weeks that preceded the vascular event. Language and verbal memory were normal. Spatial memory could not be studied because of the severity of the neglect. The clinical course was poor: when tested one and a half year post-onset, the hemiplegia, the hemianaesthesia, and the hemianopsia as well as left spatial neglect remained severe. Vestibular caloric stimulation, carried out with left ear cold water irrigation, resulted in brief but clear-cut alleviation of the spatial neglect. An MRI with both axial and coronal slices showed a right-sided infarct affecting the whole posterior limb of the internal capsule including the genu, the posterior part of the globus pallidus, the anterior third of the cerebral peduncle and the amygdala but sparing the thalamus and the corona radiata. This crescent-shaped lesion transected entirely the thalamo-cortical connection fibers which resulted in a "thalamic exclusion". The measurement of brain glucose utilisation with (18F)-Fluoro-2-Deoxy-D-Glucose and positron emission tomography performed in the chronic phase (3 months post-onset) showed an exceptionally severe and widespread hypometabolism of the right hemisphere, relative to the left hemisphere, which correlated with both the unusual, severe and protracted non-dominant hemisphere syndrome. All the brain regions on the right side were hypometabolic relative to the left including the temporal region (mostly medial temporal), the left cerebellar lobe, the frontal lobe (mostly prefrontal region), the occipital region and the thalamus. The hypometabolism of the basal ganglia, the sensorimotor area and the parietal cortex was less severe. This most uncommon clinical-metabolic presentation presumably reflects a global thalamo-cortical disconnection inducing a diffuse dysfunction of the whole hemisphere.

Aged↗

Evaluation of a recombinant parasite antigen for the diagnosis of lymphatic filariasis.

We evaluated the usefulness of a recombinant parasite antigen (recSXP1) for the serologic diagnosis of lymphatic filariasis. A large proportion of sera from microfilaremic donors living in five different endemic countries (356 of 446 [80%]) contained IgG antibodies to recSXP1, as do sera from approximately 33% of amicrofilaremic patients with acute filarial disease and/or indirect evidence of active filarial infection. Exposure to filarial worms per se does not appear sufficient to elicit an anti-SXP1 antibody response. Thus, this serologic test identifies a large proportion of persons with active lymphatic filariasis among residents of endemic areas.

Animals↗

[Multimodal or multisensorial agnosia?].

A 75 year-old right handed woman had persistent right homonymous hemianopia and alexia without agraphia caused by a haemorrhagic stroke of the left occipito-temporal region. Six months later she suffered sudden onset visual and auditory agnosia, following a second haematoma, contralateral to the first one, in the right occipito-temporal region including the lingual and fusiform gyri. None of the disorders concerned semantic representation, so that an asemantic agnosia was excluded. Her performance in naming and recognition tests, in both visual and auditory modalities, demonstrated a wide range of responses and errors. The pattern of visual symptoms suggested "associative visual agnosia narrow sense" (Farah, 1990); auditory agnosia concerned only the non verbal stimuli. These findings were discussed in terms of anatomical mechanisms subserving perceptual, semantical, visuo and auditory-verbal representation. In this case, visual and auditory, agnosia appears to be independent.

Aged↗

Borate complexation of flavonoid-O-glycosides in capillary electrophoresis. II. Separation of flavonoid-3-O-glycosides differing in their sugar moiety.

Capillary electrophoresis was found to give significantly higher efficiency, selectivity and speed than high-performance liquid chromatography for the separation of a mixture of flavonoid-3-O-glycosides differing in their sugar moiety. Boric acid running buffer (0.2 M, pH 10.5) was used for this electrophoretic separation. The migration order in free solution capillary electrophoresis (CE) and the selectivity of these flavonoid-3-O-glycosides can be mainly explained by in situ borate complexation of both the sugar moiety and the cis-1,2-hydroxyl groups on the flavonoid skeleton and, to a lesser extent, by the ionization of hydroxyl groups on the flavonoid skeleton due to alkaline pH conditions. The correlation of the electrophoretic mobilities with the configuration and conformation of the compounds is discussed.

Anions↗

Gender differences in horizontality and verticality representation in relation to initial position of the stimuli.

Research on gender differences in the ability to represent horizontality in the water-level task has suggested that failure in some women may be connected with responding while envisioning the upright container as shifting to a tilted position and holding liquid in motion, rather than imaging that the container has reached the tilted position and holds still liquid. The present experiment attempted to eliminate such faulty conceptualization by solely presenting containers that had already reached a stable, tilted position. College students of both sexes were submitted either to the modified, static presentation of the water-level task or to the standard, dynamic format using both upright and tilted positions. The subjects were also submitted to corresponding plumb-line tasks requiring verticality representation. In addition, they rated the vividness of their movement imagery. Contrary to prediction, women's proficiency was not higher under the static format of the water-level and plumb-line tasks. However, as expected, men's achievement was independent from presentation format. Men surpassed women under both static and dynamic formats. Finally, performance was not correlated with movement imagery. Lack of a presentation effect on women's performance was attributed to the fact that a number of women presumed an element of motion when responding, even though stationary stimuli were shown.

Adolescent↗