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Biomedical subjects

J Michaud

Publications and source records attributed to J Michaud.

At least 73 records · Page 4Linked to original sources

Neuronal and photoreceptor differentiation of retinoblastoma in culture.

This study describes an in vitro system, which favors attachment and differentiation of primary retinoblastoma cells. Indeed, tumor cells from primary retinoblastomas were successfully grown as long-term monolayer cultures, using collagen type-1 coated flasks, preincubation of tumor cells in fetal calf serum and a medium richly supplemented with serum. This reliable system allowed growth and attachment and induced differentiation towards neuronal and photoreceptor morphology. Each of the nine tumors studied showed substantial cell proliferation and differentiation. Cells with glial characteristics were observed in lower numbers. Furthermore, in five cell-lines, some cell clusters showed pigmentation characteristic of pigment epithelial cells (PE). By electron microscopy, a significant proportion of cells showed conventional neuronal differentiation; others formed typical Flexner-Wintersteiner rosettes with individual photoreceptor cells showing a more highly differentiated pattern quite similar to fleurette inner segments. Immunohistochemical studies did not reveal evidence of transition between undifferentiated retinoblastoma cells and glial cells, although foci of multipolar cells were found resembling glial elements and containing glial fibrillary acidic protein. Thus no definite sign of glial differentiation was observed. These results show that most primary retinoblastoma cells can grow in attachment culture and differentiate into at least two distinct morphological cell types. This study also offers a potentially rewarding system to analyse the factors controlling growth and differentiation of human tumor cells in vitro.

Cell Adhesion↗

First cytogenetic evidence of homozygosity for the retinoblastoma deletion in chromosome 13.

Retinoblastoma (Rb) provided the first model in which both normal alleles of a recessive gene had to be lost as a prerequisite for tumorigenicity. However, region q14 of chromosome 13 appears cytogenetically normal in the majority of Rb tumors, and no homozygotic deletion had previously been observed. High-resolution cytogenetics of an Rb tumor revealed a homozygotic deletion in bands q13.3-14.2 of chromosomes 13 in 35% of the cells and a heterozygotic deletion, involving the same region, in 17%. In one third of the cells, although random chromosome loss occasionally occurred, no specific anomaly was detected. The remaining cells showed either monosomy 13, tetraploidy, or an i(1p). Revealing a homozygotic deletion in subbands 14.1 and 14.2 of chromosomes 13 provides the first cytogenetic evidence of the two somatic mutations considered essential to inactivate the Rb gene. These results allow insight into the succession of events necessary for tumor development.

Chromosome Banding↗

Paraneoplastic optic neuritis and encephalomyelitis. Report of a case.

A 63-year-old man developed bilateral paresis of horizontal and upward eye movements. He was found to have a small oat cell carcinoma of the lung. Four months later he experienced acute visual blurring on the right side. Examination of the right eye at that time revealed a visual acuity of 3/200 and a central scotoma. There was swelling of the right optic disc. Three weeks after the onset of the visual loss, the acuity of the right eye spontaneously improved to 20/60, the field deficit lessened, and there was a decrease in the swelling of the optic disc. Subsequently, his neuro-ophthalmologic condition remained unchanged but his general health deteriorated, and he died nine months after the onset of the disease. Neuropathologic examination showed mild perivascular lymphocytic infiltration and fibrosis of the meninges throughout the central nervous system, loss of neurons and gliosis in the third and fourth cranial nerve nuclei, perivascular inflammation and gliosis of the optic nerves, and chiasm and central demyelination of the right optic nerve. No tumor cells were seen. These findings were consistent with a diagnosis of paraneoplastic optic neuritis and paraneoplastic encephalomyelitis. The present case confirms the existence of paraneoplastic optic neuritis and illustrates the clinical course of the disease.

Encephalomyelitis↗

Encephalitis among Cree children in northern Quebec.

We report a neurological disease among Cree Indian children in a northern Quebec village. The disease manifests as severe mental retardation, cerebral atrophy with white matter changes and calcifications, and systemic immunological abnormalities. Eleven cases are known in five families. The familial incidence of cases and the high degree of parental consanguinity suggest a genetic contribution. We propose that this entity may be caused by an unusual viral infection in a genetically vulnerable host.

Adolescent↗

Structure-activity studies on synthetic peptides inhibiting herpes simplex virus ribonucleotide reductase.

Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) ribonucleotide reductase is formed by the association of two nonidentical subunits. A peptide corresponding to the COOH terminus of the subunit 2, Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu (H2-(7-15)), has been shown to completely inhibit the reductase activity (IC50 = 36 microM) without affecting the host isoenzyme. In order to study the relationship between chemical requirements and inhibitory potencies, a series of peptides, including fragments and analogs of H2-(7-15), were synthesized. The minimum active core can be assigned to the Val-Val-Asn-Asp-Leu sequence (IC50 = 760 microM). N alpha-Extended peptides, such as Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu (H2-(4-15)) and Glu-Cys-Arg-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu (H2-(1-15) ), respectively, have inhibitory potencies 2.1- and 1.4-fold greater than the nonapeptide H2-(7-15). N alpha-Deamination or acetylation of H2-(7-15) increases its potency by 1.8- and 3.0-fold, respectively, whereas amidation of the alpha-carboxylic function diminishes its activity by 3.2-fold. These results indicate that the alpha-amino group is not essential for maximum potency but suggest that a free carboxylic function is required. Substitution of Tyr7 or Ala8 by their respective D-isomer leads to a decrease of potency, suggesting that a specific conformation of the NH2-terminal portion is required to have a maximum activity. Monosubstitution in positions 11, 13, 14, and 15, by L-alanine completely abolishes activity stressing the importance of each amino acid residue contained in the minimum active core. Finally, nonapeptides corresponding to the COOH-terminal portion of the subunit 2 of Epstein-Barr and varicella-zoster virus ribonucleotide reductases also inhibit the HSV-1 reductase activity. The varicella-zoster virus nonapeptide is 4.0 times more potent than H2-(7-15), whereas the Epstein-Barr virus nonapeptide is 3.1 times less potent. These results should help us to design a new generation of potent inhibitors of herpes virus ribonucleotide reductases.

Amino Acid Sequence↗

Pathogenicity of HIV in lymphatic organs of patients with AIDS.

HIV antigens were searched for in the thymus, lymph nodes, bone marrow, and spleen of AIDS patients, by means of immunofluorescence technique. Human IgG against HIV and monoclonal antibodies against viral gag P24 protein yielded strong cytoplasmic fluorescence of cells in sections of the thymus, lymph nodes and spleen. Some cells containing HIV antigens were morphologically multinucleated giant cells. They reacted with monoclonal antibodies against helper/inducer T-cells (OKT4+), and were complexed with antibody or with complement as demonstrated by double-staining immunofluorescence technique. A large number of inflammatory cells infiltrated the thymus in areas containing cells expressing HIV antigens. These studies demonstrated an association of HIV virus with cytopathic and immunopathogenic reactions in lymphatic organs of AIDS patients, and are consistent with previous results, as well as indicative of a primary aetiologic role for the virus.

Acquired Immunodeficiency Syndrome↗

[Myxoma of the jaws].

Findings in two cases of mandibular myxoma confirmed the benign but recurring nature of these relatively rare mesenchymatous tumors.

Adult↗

Pathogens in children with severe combined immune deficiency disease or AIDS.

We evaluated the frequency and severity of illnesses caused by various microbial pathogens in 15 children with severe combined immune deficiency disease (SCID) and 8 with acquired immune deficiency syndrome (AIDS). There were 35 viral, 23 bacterial, 19 mycotic and 13 parasitic infections. Nineteen of the 23 patients died of infection; Pneumocystis carinii pneumonia, giant-cell pneumonia due to paramyxoviruses and various disseminated viral infections were responsible for most deaths in both groups. The emerging role of paramyxoviruses was illustrated by the fact that they were responsible for giant-cell pneumonia in seven patients. Viral enteric infections were frequent in both groups. The variety of infectious microorganisms and the severity of resulting illnesses in the patients with AIDS were similar to those in the patients with SCID.

Acquired Immunodeficiency Syndrome↗

Detection of HTLV-III/LAV antigens in peripheral blood lymphocytes from patients with AIDS.

HTLV-III was searched for in frozen sections of peripheral blood lymphocytes obtained from AIDS patients by an immunofluorescence technique. Human IgG against HTLV-III/LAV and monoclonal antibodies against HTLV-III/LAV P 24 antigen, yielded a strong cytoplasmic fluorescence in frozen sections of the lymphocytes. Some cells containing HTLV-III antigens displayed multinucleated giant forms. They also reacted with monoclonal antibodies against helper/inducer T-cells (OKT4+), as demonstrated by direct double staining immunofluorescence. Similarly, complexes of immunoglobulins and C3 component of complement were also detected on HTLV-III/LAV Ag expressing lymphocytes. Immunofluorescence study of frozen sections of peripheral blood lymphocytes appeared to be a simple, fast and reliable method for detection of HTLV-III/LAV Ag in AIDS patients.

Acquired Immunodeficiency Syndrome↗

Intrarenal epidermoid cyst.

Epidermoid cyst is a very unusual cause of renal mass. Only two cases have been reported in the English or French literature. We have encountered this entity in a 4-year-old Haitian boy investigated for urinary frequency. This diagnosis must be included in the differential of coarse calcified intrarenal masses.

Child, Preschool↗

[Giant-cell lesions of the maxilla. The diagnostic difficulties].

A 30 year old woman with a giant cell tumor of maxilla developed recurrence of tumor two years after initial surgical resection. The place of this benign but relapsing tumor among giant cell lesions (called "myeloplaxic tumors" in the past) is discussed and the differential diagnosis of these lesions outlined.

Adult↗

Microcystic meningioma of the falx cerebri with numerous palisaded structures: an unusual histological pattern mimicking schwannoma.

We report a microcystic meningioma of the falx cerebri which had an unusual histological pattern. It contained numerous palisaded structures in loose areas, giving the appearance of the loose and dense areas of a schwannoma. There were minimal meningeal whorls. Ultrastructural study confirmed the totally meningiomatous nature of this tumor.

Diagnosis, Differential↗