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Biomedical subjects

J Michaud

Publications and source records attributed to J Michaud.

At least 55 records · Page 3Linked to original sources
PubMed1995

Pyridoxine-responsive gyrate atrophy of the choroid and retina: clinical and biochemical correlates of the mutation A226V.

We discovered the missense mutation, A226V, in the ornithine-delta-aminotransferase (OAT) genes of two unrelated patients with gyrate atrophy of the choroid and retina (GA). One patient, who was a compound for A226V and for the premature termination allele R398ter, showed a significant (P < .01) decrease in mean plasma ornithine levels, following pyridoxine supplementation with a constant protein intake: 826 +/- 128 microM (n = 5; no pyridoxine supplementation) versus 504 +/- 112 microM (n = 6; 500 mg pyridoxine/d) and 546 +/- 19 microM (n = 6; 1,000 mg pyridoxine/d). In extracts of fibroblasts from a second GA patient homozygous for A226V and from Chinese hamster ovary cells expressing an OAT-cDNA-containing A226V, we found that OAT activity increased from undetectable levels to approximately 10% of normal when the concentration of pyridoxal phosphate was increased from 50 to 600 microM. A226V is the fourth disease-causing pyridoxine-responsive human mutation to be reported.

Amino Acid Sequence↗
PubMed1994

Selective growth inhibition of Porphyromonas gingivalis by bestatin.

Recent work in our laboratory indicates that selected protease/peptidase inhibitors interfere with the growth of Porphyromonas gingivalis. The aim of the present study was to further investigate the inhibitory effect of bestatin on the growth of P. gingivalis. Complete growth inhibition of P. gingivalis (11 strains) was observed when bestatin was incorporated at 2.5 micrograms ml-1 in a complex broth medium. Fifty percent inhibition was still obtained with bestatin at a final concentration of 0.5 microgram ml-1. The inhibitory effect of bestatin was highly specific as the growth of 20 different oral bacterial species, including Gram-positive and Gram-negative as well as saccharolytic and asaccharoltic bacteria, was not affected even at bestatin concentrations up to 50 micrograms ml-1. Bestatin did not significantly affect the viability of P. gingivalis indicating that it has a bacteriostatic rather than a bactericidal effect. Growth assays using other specific inhibitors suggested that the effect of bestatin on the growth of P. gingivalis was unlikely to be related to its aminopeptidase inhibitor activity. Cultivation of P. gingivalis with a subinhibitory concentration of bestatin did not modify the cell envelope protein profile, as determined by SDS-PAGE analysis, but significantly decreased the number of extracellular vesicles produced. The present study indicated that bestatin is a highly effective inhibitor of cell growth of P. gingivalis. Additional studies will indicate whether bestatin should be considered as a potential drug in the control of P. gingivalis, a suspected pathogen in adult chronic periodontitis.

Anti-Bacterial Agents↗
PubMed1994

Autosomal dominant polycystic kidney disease in the fetus.

We report on 3 cases with a fetal presentation of autosomal dominant polycystic kidney disease (ADPKD), which illustrate the variable expression of ADPKD during fetal life. Fetus 1 was diagnosed at 20 weeks of gestation by ultrasonography; a molecular prenatal diagnosis was performed at 10 weeks on fetus 2, a sib of fetus 1; and ADPKD was an incidental finding in fetus 3 who was aborted at 16 weeks for anencephaly. All pregnancies were terminated and pathologic studies of the fetal kidneys were performed. From these cases and a review of the literature, we draw the following conclusions: (1) so far, all fetal ADPKD kidneys that have been histologically studied have shown cystic dilatations; 28/32 of these fetuses had ultrasonographic manifestations of the disease and/or had sibs with an early-onset form of it; (2) these cysts can be found in newly formed nephrons (fetus 2), predominantly in the more mature nephrons of the deep cortex (fetus 1) or more sparsely distributed in the cortex (fetus 3); these different patterns may reflect different rates of progression of the disease; (3) in contrast to the histologic findings in adult kidneys, glomeruli seem to be predominantly affected in fetal ADPKD; (4) severe fetal expression of ADPKD seems to cluster in some families; and (5) so far, all DNA analyses performed in families with subjects presenting during the fetal or neonatal period have been consistent with linkage to the PKD1 locus.

Adult↗
PubMed1994

Demonstration of human immunoglobulin G Fc-binding activity in oral bacteria.

Nonimmune binding of immunoglobulins via the Fc fragment may reduce opsonization and phagocytosis of bacteria and is thus considered a virulence factor. The aim of this study was to investigate a wide range of oral bacterial strains for the presence of human immunoglobulin G (IgG) Fc-binding activity. A total of 132 strains representing 40 different gram-positive and gram negative bacterial species were tested for IgG Fc-binding activity by using a fast and simple dot blot procedure with horseradish peroxidase-conjugated Fc fragments from human IgG. Neither the human nor animal biotype of Porphyromonas gingivalis possessed IgG Fc-binding activity. The strongest positive reaction of gram-negative species with the IgG Fc fragments were obtained with strains of Prevotella intermedia and Fusobacterium nucleatum. Among the gram-positive bacteria tested, Peptostreptococcus micros, Lactobacillus spp., and several species of streptococci possessed IgG Fc-binding activity. In the present investigation, the ability of several oral bacterial species to bind IgG Fc fragments was demonstrated. This factor represents a potential virulence determinant as it may help pathogenic oral bacteria escape host defense mechanisms.

Binding Sites, Antibody↗
PubMed1993

Maturation of the external urinary sphincter: a comparative histotopographic study in humans.

The developmental anatomy of the striated urinary sphincter remains controversial and is scantly documented in children. We compared its structure and configuration in the fetus, infant and adult to determine anatomical differences among these groups. We removed 25 postmortem specimens from fetuses, infants and children, which were fixed and stained for histological study. Ages ranged from 14 weeks of gestation to 12 years postpartum. Transverse and mid sagittal sections were obtained from the bladder neck to the membranous urethra in male and the whole urethra in female subjects. At the level of the membranous urethra in male and mid urethra in female subjects the striated muscle fibers completely encircle the urethra and join behind it to form a tail-like structure that runs posteriorly towards the perineal body. This structure is mid sagittal in male and mediolateral in female subjects. At 3 to 4 months of life, at the level of the bulbourethral glands the tail disappears; the striated sphincter becomes horseshoe-shaped and its 2 branches bifurcate posteriorly to envelop these glands. The urethral striated sphincter consists of scantly dispersed muscle fibers in the fetus. In young infants it becomes well defined in both sexes with the presence of a tail-like structure that characterizes this age group. In older subjects this tail disappears and the sphincter assumes a horseshoe or omega-shaped configuration as splitting of the sphincter progresses caudo-cranially with development. We attempt to determine whether the ring configuration of the voluntary sphincter contributes to high voiding pressures that are reported to occur in some newborns and infants.

Child↗
PubMed1993

Evidence for the absence of hyaluronidase activity in Porphyromonas gingivalis.

The aim of the present study was to evaluate the ability of Porphyromonas gingivalis to degrade hyaluronic acid. No hyaluronidase activity was detected using a turbidimetric method, whereas a standard plate assay showed a positive reaction for P. gingivalis. We postulated that the high proteolytic activity of P. gingivalis may account for this observation. A modified plate assay was designed to avoid false-positive reactions caused by proteolytic bacteria. The new assay, based on the formation of a water-insoluble salt between hyaluronic acid and the polyanion cetylpyridinium chloride, indicated that P. gingivalis does not have hyaluronidase activity. By this modified plate method, it was found that among 24 different oral bacterial species tested, Propionibacterium acnes and Prevotella oris were the only species that possess hyaluronidase activity.

Bacteriological Techniques↗
PubMed1992

Ornithine delta-aminotransferase mutations in gyrate atrophy. Allelic heterogeneity and functional consequences.

Ornithine delta-aminotransferase is a nuclear-encoded mitochondrial matrix enzyme which catalyzes the reversible interconversion of ornithine and alpha-ketoglutarate to glutamate semialdehyde and glutamate. Inherited deficiency of ornithine delta-aminotransferase results in ornithine accumulation and a characteristic chorioretinal degeneration, gyrate atrophy of the choroid and retina. We have surveyed the ornithine delta-aminotransferase genes of gyrate atrophy patients for mutations. Using a variety of techniques, we discovered and molecularly characterized 21 newly recognized ornithine delta-aminotransferase alleles. We determined the consequences of these and three previously described mutations on ornithine delta-aminotransferase mRNA, antigen, and enzyme activity in cultured fibroblasts. The majority (20/24) of these alleles produce normal amounts of normally sized ornithine delta-aminotransferase mRNA. By contrast, only 2/24 had normal amounts of ornithine delta-aminotransferase antigen. Reproducing these mutations by site-directed mutagenesis and expressing the mutant ornithine delta-aminotransferase in Chinese hamster ovary cells confirms that several of these mutations inactivate ornithine delta-aminotransferase and cause gyrate atrophy in these patients.

Alleles↗
PubMed1992

Strand-separating conformational polymorphism analysis: efficacy of detection of point mutations in the human ornithine delta-aminotransferase gene.

We tested the use of a modified method of single-strand conformational polymorphism (SSCP) analysis for the detection of point mutations in the human ornithine-delta-aminotransferase gene. Using a combination of three different electrophoretic conditions, we detected 20/20 known mutations. In a prospective study of 24 previously uncharacterized mutant OAT genes, we found 13 different mutations accounting for 19 (79%) of the 24. We conclude that SSCP is an efficient technique with high sensitivity and specificity.

Base Sequence↗
PubMed1992

Neurological findings in HIV-infected children: a review of 49 cases.

Many HIV-infected children have neurological involvement. We present our observations in 49 cases, 58% of which had some form of clinical neurological impairment. Most of the patients affected (71%) presented with progressive encephalopathy, characterized by developmental delay with loss of acquisitions and cognitive decline, an impaired growth curve, microcephaly and corticospinal dysfunction. CT-scan imaging shows cerebral atrophy in all cases and basal ganglia calcifications in 29%. Non-specific abnormalities are found on the EEG in two-thirds of cases and in the CSF in slightly less than half the cases. Pathological studies sometime revealed HIV encephalitis or lateral corticospinal tracts degeneration. Neurological impairment secondary to vascular events, neoplasms or opportunistic infections were rare, especially when compared with the adult HIV population.

AIDS Dementia Complex↗
PubMed1992

Development of the fetal brain in the second trimester: an anatomic and ultrasonographic demonstration.

The authors provide an anatomic and ultrasonographic description of the fetal brain from the 16th to the 27th week of development. During the second trimester the primitive brain is smooth and homogeneous and has few sulci and relatively large lateral ventricles. The cerebral hemispheres consist largely of cells migrating from the periventricular germinal matrix to the primitive cortex. The "featureless" hemispheres yield homogeneous ultrasonographic images very different from the more complex and familiar cerebral anatomy of fetuses and premature babies in the third trimester.

Brain↗
PubMed1991

Prenatal diagnosis of fetal anomalies during the second trimester of pregnancy: their characterization and delineation of defects in pregnancies at risk.

During a follow-up study of 19,790 pregnancies at risk for a genetic disease, from 1968 to 1989, 1083 fetuses were found to have an anomaly during the second trimester, leading to 977 terminations of pregnancy. Neural tube defects (31.4 per cent), chromosomal disorders (27.1 per cent), and Mendelian or multifactorial diseases (10.6 per cent) were the main causes of fetal anomaly. More than half (52.9 per cent) of the fetal anomalies were detected by routine ultrasound examination. Forty-two per cent of cystic hygromas were secondary to a chromosomal defect. We stress the importance of a comprehensive fetal and newborn examination to ensure an accurate diagnosis so that subsequently accurate counselling can be provided.

Abdominal Muscles↗
PubMed1991

The cycling pool of cells within human brain tumors: in situ cytokinetics using the monoclonal antibody Ki-67.

Brain tumor growth results from the relative proportion of cells contained in three populations: a) cycling/proliferative; b) quiescent (GO)/static, and c) terminally differentiated/dying. The cycling compartment can be detected by the mouse monoclonal Ki-67 antibody, an available, rapid, safe, sensitive, and specific method for immunostaining of proliferative cells. We report the Ki-67 labeling index (LI) in 48 brain tumors. Malignant brain tumors have elevated LIs, ranging from 6.0% to 56.9%: anaplastic astrocytoma, 8.0 +/- 7.3; glioblastoma multiforme, 10.1 +/- 4.2; germinoma, 11.7; medulloblastoma, 13.1 +/- 6.6; metastases, 40.3 +/- 13.1. By contrast, slow-growing tumors showed lower values (P less than .001), approaching 1%: acoustic schwannoma, 0.4 +/- 0.6; pituitary adenoma, 1.3 +/- 1.9; meningioma, 1.2 +/- 1.2; low-grade astrocytoma, less than 1; pilocytic astrocytoma, 5.6. Human brain tumors can therefore be ranked according to the percentage of cycling cells with the acoustic schwannoma among the least proliferative and the metastatic carcinoma among the most proliferative. Within a given histotype, the Ki-67 LI may have prognostic and therapeutic implications for the individual patient. Already important for neuro-oncology research, the Ki-67 labeling index should be added to the armamentarium of the clinical neuropathologist to complement the standard histopathologic diagnosis with a cytokinetic analysis of cellular proliferation.

Antibodies, Monoclonal↗
PubMed1991

Studies on in vitro proteolytic sensitivity of peptides inhibiting herpes simplex virus ribonucleotide reductases lead to discovery of a stable and potent inhibitor.

The nonapeptide, HSV R2-(329-337), corresponding to the subunit 2 (R2) carboxyl terminus of herpes simplex virus (HSV) ribonucleotide reductases, specifically inhibits this enzyme activity. We report here that under standard reductase assay conditions, this peptide was rapidly degraded by proteases present in the partially purified enzyme extract. The main process of proteolysis involves the successive removal of Tyr329 and Ala330, which corresponds to an aminopeptidase activity. Determination of the proteolytic susceptibility of HSV R2-(329-337) analogs showed that natural modifications which are present in the homologous varicella zoster virus (VZV) nonapeptide decreased its susceptibility to protease action 1.5-fold. Nx-acetylation, a modification known to protect peptides against aminopeptidase attacks, greatly improved the proteolytic resistance of HSV and VZV nonapeptides. Moreover, Ac-VZV R2-(298-306) exhibited a 15-fold higher potency on reductase inhibition than HSV R2-(329-337). The degradation process of HSV R2-(329-337) was partially inhibited by amastatin, bestatin, and leupeptin whereas it was completely abolished by bacitracin, suggesting a combined action of more than one aminopeptidase activity. Moreover, bacitracin protected most of these nonapeptide analogs from proteolysis, although it was less effective in preventing HSV R2-(332-337) degradation. Our results indicate that it is possible to determine, in the presence of bacitracin, the relative inhibitory potencies of HSV R2-(329-337) analogs with minimal error due to proteolytic susceptibility. Moreover, HSV R2-(329-337) modifications that were found to protect the peptide against degradation might be useful to increase its efficacy in vivo.

Amino Acid Sequence↗
PubMed1991

Cognitive and physiological feedback on cold pain tolerance.

Results supported the relevancy of cognitive information effects on pain tolerance, in that subjects who were given a rational and accurate explanation of what to expect showed greater tolerance than those who received irrelevant information. Accurate monitoring of hand temperature did not seem necessarily advantagous as an influence on pain tolerance. It appears merely watching a monitor, regardless of the specific contents of the screen, resulted in longer hand immersion times when compared to no monitor. The monitors seem to serve as distractors and specificity of physiological information was not particularly useful. However, neither information nor physiological monitoring emerged as the primary influence on pain tolerance in this study. Instead, the strongest predictors found were motivation and self-efficacy. The subject's own self prediction of anticipated performance with cold induced pain was closely consistent with actual performance. Although these results alone may not generalize to extended field situations, this study does reinforce the general findings of previous research: namely Bandura's (10) evidence on self-efficacy. While it is obvious cold temperatures have measurable physiological consequences, the experience of pain is also psychologically mediated. Pain associated with cold injury and frostbite in hospital studies show personality correlates are significantly related to the frequency, severity and tragedy of subsequent results (15). A replication of this study will include male subjects even though it is anticipated that findings will be consistent, with perhaps longer immersion times. Future research may want to develop training strategies aimed at teaching self-efficacy and realistic expectations of potential consequences in cold environments rather than scare tactics regarding physiological and psychological cold pain tolerance.

Biofeedback, Psychology↗
PubMed1990

Neurologic crises in hereditary tyrosinemia.

Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. The disease is known to cause acute and chronic liver failure, renal Fanconi's syndrome, and hepatocellular carcinoma. Neurologic manifestations have been reported but not emphasized as a common problem. In this paper, we describe neurologic crises that occurred among children identified as having tyrosinemia on neonatal screening since 1970. Of the 48 children with tyrosinemia, 20 (42 percent) had neurologic crises that began at a mean age of one year and led to 104 hospital admissions. These abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (in 75 percent), vomiting or paralytic ileus (69 percent), muscle weakness (29 percent), and self-mutilation (8 percent). Eight children required mechanical ventilation because of paralysis, and 14 of the 20 children have died. Between crises, most survivors regained normal function. We found no reliable biochemical marker for the crises (those we evaluated included blood levels of tyrosine, succinylacetone, and hepatic aminotransferases). Urinary excretion of delta-aminolevulinic acid, a neurotoxic intermediate of porphyrin biosynthesis, was elevated during crises but also during the asymptomatic periods. Electrophysiologic studies in seven patients and neuromuscular biopsies in three patients showed axonal degeneration and secondary demyelination. We conclude that episodes of acute, severe peripheral neuropathy are common in hereditary tyrosinemia and resemble the crises of the neuropathic porphyrias.

Acute Disease↗
PubMed1990

Preferential mitogenic activity for myoblast-like cells can be extracted from uterine leiomyoma tissues.

The presence of mitogen(s) in leiomyoma extracts stimulating cells with the fibroblast, myoblast, and osteoblast phenotype was documented. Mitogenic activity in leiomyoma extracts was acid stable and sensitive to tryptic digestion. Reverse-phase high-performance liquid chromatography successfully separated mitogen(s) with preferential activity for myoblast cells from mitogens with a broad type of cell specificity and from inhibitors. This leiomyoma-derived preferential activity for myoblasts was absent in identically treated myometrial and endometrial extracts. This suggests that leiomyoma-derived substances with preferential growth factor activity for myoblast-like cells may play a role in the pathophysiologic characteristics of uterine leiomyomas.

Adult↗