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E Boder

Publications and source records attributed to E Boder.

At least 19 recordsLinked to original sources
PubMed1994

Identification of type-2 phosphatidic acid phosphohydrolase (PAPH-2) in neutrophil plasma membranes.

Plasma membrane phosphatidic acid phosphohydrolase (PAPH) plays an important role in signal transduction by converting phosphatidic acid to diacylglycerol. PAPH-2, a Mg(2+)-independent, detergent-dependent enzyme involved in cellular signal transduction, is reportedly absent from the plasma membranes of neutrophilic leukocytes, a cell that responds to metabolic stimulation with abundant phospholipase D-dependent diacylglycerol generation. The present study was designed to resolve this discrepancy, focusing on the influence of cellular disruption techniques, detergent availability and cation sensitivity on the apparent distribution of PAPH in neutrophil subcellular fractions. The results clearly indicate the presence of two distinct types of PAPH within the particulate and cytosolic fractions of disrupted cells. Unlike the cytosolic enzyme, the particulate enzymes was not potentiated by magnesium and was strongly detergent-dependent. The soluble and particulate enzymes displayed dissimilar pH profiles. Separation of neutrophil particulate material into fractions rich in plasma membranes, specific granules and azurophilic granules by high speed discontinuous density gradient centrifugation revealed that the majority of the particulate activity was confined to plasma membranes. This activity was not inhibited by pretreatment with n-ethyl-maleimide in concentrations as high as 25 mM. PAPH activity recovered in the cytosolic fraction of disrupted neutrophils was almost completely inhibited by 5.0 mM n-ethylmaleimide. We conclude that resting neutrophils possess n-ethylmaleimide-resistant PAPH (type 2) within their plasma membranes. This enzyme may markedly influence the kinetics of cell activation by metabolizing second messengers generated as a result of activation of plasma membrane phospholipase D.

Cell Membrane↗
PubMed1991

Ataxia-telangiectasia: an interdisciplinary approach to pathogenesis.

Ataxia-telangiectasia is a syndrome with many facets, involving a progressive cerebellar ataxia, immunodeficiency, cancer susceptibility, radiosensitivity, defects in DNA repair/processing, chromosomal breakage and rearrangements, elevated serum alphafetoprotein, and premature aging. Ataxia-telangiectasia is an autosomal recessive disorder, rare in outbred populations; carriers of the ataxia-telangiectasia gene may be as common as 1 in 60 and have subclinical radiosensitivity and cancer susceptibility. One estimate suggests that 8.8% of patients with breast cancer could be carriers of ataxia-telangiectasia. These carriers may be responsible for underestimating normal tolerance doses for radiation therapy by 15% to 20%; thus by preselecting and excluding carriers of ataxia-telangiectasia from cohorts of patients with cancer, conventional radiation doses might be increased so as to improve greatly the efficacy of radiotherapy. The genes for the 3 most common ataxia-telangiectasia complementation groups, which include 97% of tested families, have recently been localized to the long arm of chromosome 11.

Ataxia Telangiectasia↗
PubMed1989

Heterogeneity of chromosomal breakage levels in epithelial tissue of ataxia-telangiectasia homozygotes and heterozygotes.

The objective of this study was to obtain an estimate of the frequency distribution of spontaneous chromosomal breakage occurring in vivo in oral epithelia of 20 ataxia-telangiectasia patients (A-T homozygotes) and 26 parents (A-T obligate heterozygotes). Samples of exfoliated cells were obtained from each individual by swabbing the oral cavity and preparing air-dried slides. The percentage of exfoliated cells with micronuclei (MEC frequency) was used as an in vivo indicator for the amount of chromosomal breakage occurring in the tissue. As a population group, MEC frequencies of the A-T patients differed significantly from controls (mean for A-T patients, 1.51; for controls, 0.29; P less than 0.01). However, the values observed in individual patients ranged from MEC frequencies 10- to 12-fold above control values, to frequencies overlapping the upper values observed in the controls. Similarly, MEC frequencies observed among the A-T heterozygotes differed significantly from controls (mean for A-T heterozygotes, 1.02, mean for controls, 0.29; P less than 0.01). However, only 16 of the 26 individuals sampled had MEC frequencies greater than 0.5%, the 90th percentile for controls (compared with 16 of the 20 A-T patients examined). Of the A-T patients 11 had been previously assigned to complementation groups on the basis of sensitivity to x-irradiation. Seven of the patients belonged to group A and had MEC frequencies ranging from 0.3% to 1.9% with the remaining patients belonging to group C with MEC frequencies of 0.2% to 0.9%. The data presented in this paper suggest that although levels of spontaneous breakage in epithelial tissues of A-T patients and A-T obligate heterozygotes are often significantly elevated, this is not the case in all individuals.

Adolescent↗
PubMed1989

Uterine tumors in ataxia-telangiectasia.

Roughly one-third of patients with ataxia-telangiectasia (AT) develop malignant tumors, usually of lymphoid origin. AT patients also exhibit progeric changes. We describe three patients, between the ages of 27 and 32 years, with uterine tumors: one with a frank leiomyosarcoma and chronic T-cell leukemia, one with a multilobulated leiomyoma of uncertain malignant potential, and one with an unremarkable leiomyoma. Thus, the spectrum of tumors in AT patients beyond adolescence includes nonlymphoid malignancies and precocious, benign leiomyomas.

Adult↗
PubMed1988

Localization of an ataxia-telangiectasia gene to chromosome 11q22-23.

Ataxia-telangiectasia (AT) is a human autosomal recessive disorder of childhood characterized by: (1) progressive cerebellar ataxia with degeneration of Purkinje cells; (2) hypersensitivity of fibroblasts and lymphocytes to ionizing radiation; (3) a 61-fold and 184-fold increased cancer incidence in white and black patients, respectively; (4) non-random chromosomal rearrangements in lymphocytes; (5) thymic hypoplasia with cellular and humoral (IgA and IgG2) immunodeficiencies; (6) elevated serum level of alphafetoprotein; (7) premature ageing; and (8) endocrine disorders, such as insulin-resistant diabetes mellitus. A DNA processing or repair protein is the suspected common denominator in this pathology. Heterozygotes are generally healthy; however, the sensitivity of their cultured cells to ionizing radiation is intermediate between normal individuals and that of affected homozygotes. Furthermore, heterozygous females are at an increased risk of breast cancer. These findings, when coupled with an estimated carrier frequency of 0.5-5.0%, suggest that (1) as many as one in five women with breast cancer may carry the AT gene and that (2) the increased radiation sensitivity of AT heterozygotes may be causing radiation therapists to reduce the doses of radiation used for treating cancer in all patients. To identify the genetic defect responsible for this multifaceted disorder, and to provide effective carrier detection, we performed a genetic linkage analysis of 31 families with AT-affected members. This has allowed us to localize a gene for AT to chromosomal region 11q22-23.

Ataxia Telangiectasia↗
PubMed1985

Ataxia-telangiectasia: an overview.

The more subtle clinical findings that facilitate early diagnosis and the most provocative long-term clinical observations in our series of patients are emphasized. The most striking pathological findings in our own series of 11 complete autopsies are reviewed in relation to new findings from 57 autopsy reports in the recent literature. Clinical and pathological findings in our oldest patient, who died at age 32, are systematically compared with those of her sister, who died 20 years earlier at age 10 1/2 and who was the subject of the first autopsy in AT, thus providing a rare comparison of the early and late stages of the disease. The clinical and pathological findings, including the gliovascular malformations in the CNS described recently in autopsies on older patients, reveal that AT is characterized throughout its course by multisystemic progeric changes. It is proposed, therefore, that AT can serve as a model for the study of premature aging. Clinical diagnosis, laboratory markers, and special diagnostic procedures, along with general management, immunotherapy, and rehabilitative measures, are reviewed in Part II.

Adolescent↗
PubMed1982

Fetal proteins in ataxia-telangiectasia.

Ataxia-telangiectasia (AT) is a genetic disorder of unknown pathogenesis, with primary effects on the immune and nervous systems. The presence of a fetal-like thymus and elevated alpha-fetoprotein (alpha FP) levels in patients with AT suggests that suppressed mesodermal development may be a factor in the development of this disease. We investigated this hypothesis by using electrophoretic and quantitative analyses to test for the presence of other fetal proteins in mesodermal tissues. With the exceptions of alpha FP and carcinoembryonic antigen, all other proteins assessed in these patients were present at levels or in isozymic patterns characteristic of a normal, nonfetal state.

Adult↗
PubMed1980

Ataxia-telangiectasia and xeroderma pigmentosum: no evidence of linkage to HLA.

Nine HLA-typed multiplex nuclear families segregating ataxia-telangiectasia (A-T), an autosomal recessive disorder, were studied. Linkage analysis performed by lod scores and by a previously published sib pair method revealed no evidence for linkage between A-T and HLA. An alternative method of linkage detection, previously applied to xeroderma pigmentosum (XP) and HLA, was reexamined and found to contain an error. As a consequence, neither of these "DNA repair disorders" appears to be linked to HLA.

Ataxia Telangiectasia↗
PubMed1979

Ataxia-telangiectasia with a 32 year survival. A clinicopathological report.

The clinicalpathological findings in a 32-year old woman with ataxia-telangiectasia are presented. This is the oldest patient with this disease to be studied thoroughly clinically and at autopsy. Multiple small gliovascular malformations in the brain and spinal cord and telangiectasis of the liver were found. Other advanced lesions of ataxia-telangiectasia are illustrated. The vascular malformations of the central nervous system and liver are unique. The patient died of a malignant lymphoproliferative disorder and had five other malignant and benign neoplasms.

Adult↗
PubMed1978

Eye movements in ataxia-telangiectasia.

The spectrum of eye movement disorders in six patients with ataxia-telangiectasia at different stages of progression was assessed quantitatively by electrooculography. All patients demonstrated abnormalities of voluntary and involuntary saccades. The youngest and least involved patient had significantly increased reaction times of voluntary saccades, but normal accuracy and velocity. The other patients demonstrated increased reaction times and marked hypometria of horizontal and vertical voluntary saccades. Saccade velocity remained normal. Vestibular and optokinetic fast components (involuntary saccades) had normal amplitude and velocity but the eyes deviated tonically in the direction of the slow component. We conclude that patients with ataxia-telangiectasia have a defect in the initiation of voluntary and involuntary saccades in the earliest stages. These findings are distinctly different from those in other familial cerebellar atrophy syndromes.

Adolescent↗
PubMed1975

Ataxia-telangiectasia: some historic, clinical and pathologic observations.

Although an isolated clinical case report was published in 1926 and another in 1941, ataxia-telangiectasia (A-T) was not established as a distinct entity until 1957, when it was first delineated clinicopathologically. Susceptibility to sinopulmonary infection was identified as the main cause of death and as the third major component of the syndrome; its heredofamilial nature was documented, and it was designated "ataxia-telangiectasia." In a later review of 101 published cases, lymphoreticular malignancy emerged as the second most frequent cause of death. Although the thymus was found to be absent in the first reported autopsy in 1957 and the serum IgA deficiency was first recorded in 1961, A-T was not established as an immunodeficiency disease until 1963. Thymic abnormality and dysgammaglobulinemia explain the 2 main causes of death, sinopulmonary and neoplastic, but the immunodeficiency is probably not the central defect. It does not appear to explain either of the 2 main clinical diagnostic keys, the ataxia and the telangiectasia, or any of the other seemingly unrealted multisystemic facets of this complex disorder. Some of our most provocative long-term clinical observations and recent pathologic findings in our series of 9 autopsies are discussed.

Adolescent↗
PubMed1974

Congenital and genetic skin disorders with tumor formation.

There are a great number of genetic and congenital disorders with skin manifestations ("genodermatoses") with tumor formation. Some of these tumors are benign (hamartomas, in part) and others are malignant. There is a large group of heredodegenerative disorders with such complications as lymphosarcoma and leukemia. There are congenital tumors with malignancy developing. Lastly, there are the chromosomal abnormalities with skin manifestations and tumors, usually malignant. This will be an ever increasing field and the use of fibroblast and virus cultures will become more important in ascertaining the cause of malignancy.

Adolescent↗
PubMed1970

Ataxia-telangiectasia. (Clinical and immunological aspects).

This syndrome was defined by the authors in 1947. Earlier publications of similar disease descriptions were by Syllaba and Henner (1926), Louis-Bar (1941). The authors at present have a stock of 253 cases. The cardinal symptoms of this phakomatosis are: Cerebellar ataxia which begin in infancy and take a slowly progressive course. In the late stages free walking and standing are no longer possible. Progressive atactic speech disorders, cerebellar atrophy in the pneumoencephalogram. Slowly progressing symmetrical skin and mucosal telangiectasia in the face and especially on the conjunctivae at the age of 3 to 6 years. Relapsing sinopulmonary infections with a tendency toward the development of bronchiectases. Apraxia of eye movements. Atrophy of facial skin and premature graying of hair. Recessively hereditary disorder with a high familial manifestation. This syndrome combines the spinocerebellar degeneration, phakomatoses, and infantile dementia processes. Such other conditions as abnormity or absence of thymus, reduction in gamma globulins, amino-aciduria, autosomal-recessive inheritance suggest a genetically determined "error of metabolism".

Ataxia Telangiectasia↗