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Biomedical subjects

M T Jennings

Publications and source records attributed to M T Jennings.

29 records · Page 2Linked to original sources
PubMed1989

Antigenic phenotypes of cultured malignant astrocytomas: identification of lineage-consistent, lineage-independent and putative tumor-restricted antigenic expression.

The treatment of CNS neoplasms with monoclonal antibody-mediated immunotherapy optimally requires the identification of tumor restricted cell surface antigens. However, little is known regarding the antigenic phenotype(s) of malignant astrocytomas. The interrelated expression of four neuroectodermal tumor antigens, CNT/11, AJ8, A010 and CNT/2, has been studied in cultured malignant gliomas and correlated with anchorage independent growth, morphology, glial fibrillary acidic protein, and the surface expression of other antigens. Many of these latter antigens have been reported to be expressed by specific fetal and differentiated adult cell lineages or tissues, as well as certain classes of malignant tumors. The tumor-associated expression of these antigens may be broadly classified as lineage-consistent, lineage-independent or putatively tumor-restricted. Malignant glioma tumor antigenic heterogeneity represents the expression of neuroectodermal and non-neuroectodermal cell surface markers. The importance of this observation is 2-fold. Lineage-independent antigen expression may be an indication of altered genome regulatory processes within tumor cells, and thus reflect the degree of anaplasia. The identification of lineage-consistent and lineage-independent tumor associated antigens may contribute to the selection of "target" antigens and the prediction of toxicity for monoclonal antibody mediated immunotherapy.

Antigens, Neoplasm↗
PubMed1989

Immunophenotypic differences between normal glia, astrocytomas and malignant gliomas: correlations with karyotype, natural history and survival.

The karyotypic and antigenic phenotypes of early passage normal and malignant glial cultures were correlated in vitro. Astrocytomas (4) were distinguished from the normal glia (8) by a mixed near-diploid karyotype and anchorage-independent growth. Malignant gliomas (41) demonstrated cytogenetic abnormalities ranging from mixed normal G- and Q-banded and near-diploid cultures, through mixed near-diploid/hyperdiploid to predominantly hyperdiploid stem-lines. This correlated with the differential expression of certain antigens and established qualitative antigenic differences from normal glia. Associations were found between histopathologic grade of glial neoplasm and the expression of antigens 5.1H11 (p = 0.0002), CNT/11 (p = 0.001), CNT/10 (p = 0.004), CAT301 (p = 0.014), M111 (p = 0.024), and L101 (p = 0.044). An ominous association was demonstrated between the duration of clinical survival and the expression of antigens 5.1H11 (p = 0.0007), CNT/10 (p = 0.027) and B2.6 (p = 0.038). Correcting for diagnosis and age, multivariate analysis demonstrated that HLA-DR (p = 0.050) and 5.1H11 (p = 0.069) were unfavorably correlated with patient survival. This suggests the application of the in vitro immunophenotype for its predictive utility, as well as a novel method of selection of tumor-associated antigens for monoclonal antibody-mediated immunotherapy.

Adolescent↗
PubMed1986

Differential expression of cell surface antigens and glial fibrillary acidic protein in human astrocytoma subsets.

We have characterized five distinct cell surface antigens of human astrocytomas and correlated their expression with the expression of glial fibrillary acidic protein (GFAP) and four previously defined cell surface markers of astrocytomas. One of the newly studied antigens, A4, which was originally detected on rat central nervous system (but not peripheral nervous system) neurons, is expressed on GFAP+ human astrocytoma cells, but not on GFAP- astrocytomas or a wide range of other neuroectodermal, epithelial, and hematopoietic cells. Antigens F19 (Mr 140,000/90,000 glycoprotein) and F24 (Mr 90,000 glycoprotein) also show restricted distribution and are expressed on subsets of neuroectodermal and mesenchymal cells. Antigens G253 (Mr 95,000 glycoprotein) and S5 (Mr 120,000 glycoprotein) are more widely distributed on the cultured cell panel. The distribution of these antigens was determined on a series of 22 astrocytoma cell lines and in normal brain tissue and the results were compared with the distribution of 5 additional glial cell markers: GFAP and cell surface antigens A010 (Mr 110,000 glycoprotein); AJ8 (Mr 100,000 glycoprotein); LK26 (Mr 35,000 glycoprotein); and Thy-1. Distinct patterns of expression on cultured astrocytomas and in neural tissues were identified for all antigenic systems studied, and cell surface expression of antigen A4 was found to correlate closely with GFAP phenotype of cultured astrocytomas. The antigens described in this study provide new markers to study normal glial differentiation and to correlate the phenotypes and biological behavior of distinct subsets of astrocytomas.

Animals↗
PubMed1985

Cell surface antigen of human neuroblastomas is related to nuclear antigen of normal cells.

The localization of MC25, an antigen first detected on the surface of human neuroblastoma cells, was determined in cultured cells and tissues. Neuroblastoma cell lines (15/17) express the antigen on the surface and in the cytoplasm (scMC25+), whereas 156/160 cell lines derived from other normal and malignant human cell types are scMC25-. However, MC25 is found in the nucleus of scMC25- cells (nMC25+), presenting a discrete granular pattern. In scMC25+/nMC25- neuroblastoma lines, apparent antigen shifting from the cell surface/cytoplasm to the nucleus accompanies variant formation, which represents a transition in the neuronal differentiation program of these cells. Results of immunohistochemical studies with human tissues parallel the findings with cultured cells. Almost all cell types are scMC25-/nMC25+; basal cells of the epidermis are the only cells constitutively expressing cMC25; and a population of neurons are the only scMC25-/nMC25- cells. Alternative localization of MC25 to different cellular compartments and antigen shifting are reminiscent of the behavior of certain developmentally regulated antigens in Drosophila and Xenopus.

Antibodies, Monoclonal↗
PubMed1985

Intracranial germ-cell tumors: natural history and pathogenesis.

The natural history of primary intracranial germ-cell tumors (GCT's) is defined from 389 previously published cases, of which 65% were germinomas, 18% teratomas, 5% embryonal carcinomas, 7% endodermal sinus tumors, and 5% choriocarcinomas. Intracranial GCT's display specificity in site of origin. Ninety-five percent arise along the midline from the suprasellar cistern (37%) to the pineal gland (48%), and an additional 6% involve both sites. The majority of germinomas (57%) arise in the suprasellar cistern, while most nongerminomatous GCT's (68%) preferentially involve the pineal gland (p less than 0.0001). The age distribution of afflicted patients is unimodal, centering with an abrupt surge in frequency in the early pubertal years; 68% of patients are diagnosed between 10 and 21 years of age. Nongerminomatous GCT's demonstrate an earlier age of onset than do germinomas (p less than 0.0001). Prolonged symptomatic intervals prior to diagnosis are common in germinomas (p = 0.0007), in suprasellar GCT's (p = 0.001), and among females (p = 0.02). Parasellar germinomas commonly present with diabetes insipidus, visual field defects, and hypothalamic-pituitary failure. Nongerminomatous GCT's present as posterior third ventricular masses with hydrocephalus and midbrain compression. Germ-cell tumors may infiltrate the hypothalamus (11%), or disseminate to involve the third ventricle (22%) and spinal cord (10%). Among a subpopulation of 263 conventionally treated patients, two factors were of prognostic significance: 1) histological diagnosis; germinomas were associated with significantly longer survival than nongerminomatous GCT's (p less than 0.0001); and 2) staging of the extent of disease; this emphasizes the ominous character of involvement of the hypothalamus (p = 0.0002), third ventricle (p = 0.02), or spinal cord (p = 0.01). Specific recommendations regarding the necessity of histological diagnosis and staging of the extent of disease are made in light of modern chemotherapeutic advances. The pathogenesis of GCT's may be revealed by their specificity of origin within the positive (suprasellar cistern-suprachiasmatic nucleus) and negative (pineal) regulatory centers for gonadotropin secretion within the diencephalon. The abrupt rise in age distribution at 10 to 12 years suggests that the neuroendocrine events of puberty are an "activating" influence in the malignant expression of these embryonal tumors.

Adolescent↗
PubMed1982

Neuroanatomic examination of spina bifida aperta and the Arnold-Chiari malformation in a 130-day human fetus.

A 130-day human female fetus with the Arnold-Chiari malformation and thoracolumbar myeloschisis revealed evidence of neuroectodermal-mesodermal spatial dyssynchrony. The rhombencephalon and the cervico-medullary junction appear most affected. The phylogenetic and ontogenetic development of the transition zone between brain and spinal cord is reviewed. It is hypothesized that the etiologic event responsible for the Arnold-Chiari malformation is the caudal "displacement" of the site of initial fusion of the neural folds. This is believed to result in the posterior displacement of the cervico-medullary junction and myeloschisis (the Arnold-Chiari malformation, type II).

Arnold-Chiari Malformation↗
PubMed1981

Genetic influences in the epilepsies. Review of the literature with practical implications.

We review hereditary influences in the epilepsies from the perspective of medical genetics. The recurrence risk for epilepsy in close relatives may vary from 2% to 5% up to 50% depending on the etiology of the seizure disorder in the proband. We emphasize the identification of specific disorders with single-gene inheritance that will lead to useful conclusions regarding treatment, prognosis, and family counseling. Also discussed are chromosomal aberrations, polygenic inheritance, gene-environment interactions, animal models of epilepsy, and the pharmacogenetics of anticonvulsants.

Animals↗
PubMed1980

Endocardial fibroelastosis, neurologic dysfunction and unusual facial appearance in two brothers, coincidentally associated with dominantly inherited macrocephaly.

We describe two brothers with endocardial fibroelastosis, unusual facial appearance, and cryptorchidism. The surviving brother has mental retardation, seizures and possible hypothalamic dysfunction. Both brothers have a head size greater than two standard deviations above normal; this appears to be related to superimposed presence of coincidental autosomal dominant macrocephaly in this family.

Cryptorchidism↗
PubMedDate not supplied

Strategies in the treatment of diffuse pontine gliomas: the therapeutic role of hyperfractionated radiotherapy and chemotherapy.

This article will review the current treatment of pediatric patients with diffuse pontine gliomas (DPG) and discuss three potential avenues of therapeutic research including (i) radiotherapy (RT) in combination with radiation sensitizers, (ii) dose-intensive, induction chemotherapy with hematopoietic support followed in sequence with RT applied as a "consolidation' therapy, and (iii) the interleafed application of phase-specific chemotherapeutic agents and hyperfractionated external beam radiotherapy (HFEBRT) referred to as "chemoradiotherapy'.

Antineoplastic Agents↗
PubMedDate not supplied

Pediatric neuro-oncology: controversies in current therapy.

Current Phase III clinical trials for the treatment of malignant central nervous system (CNS) tumors of childhood are reviewed. Combination neurosurgical, radiation treatment and chemotherapy have improved both the quality and duration of life for the affected children. Controversy exists regarding the appropriate adjunctive chemotherapy for newly diagnosed CNS neoplasms but this is being prospectively studied in controlled trials. Major dilemmas persist regarding the management of low-grade gliomas and recurrent CNS neoplasms. Preliminary data on possibly favourable protocols are cited. Future directions for clinical and basic laboratory investigation are also briefly reviewed.

Brain Neoplasms↗