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Biomedical subjects

E Sobel

Publications and source records attributed to E Sobel.

At least 19 recordsLinked to original sources
PubMed1992

Divergent effects of cytokines on human leukocyte antigen-DR antigen expression of neoplastic and non-neoplastic human thyroid cells.

Apparently complex modulatory effects of alpha-interferon (alpha-IFN), tumor necrosis factor (TNF), and epidermal growth factor (EGF) have been found in neoplastic human thyroid cells, which could possibly affect the final outcome in neoplastic disease. This was achieved by examining the influence of alpha-IFN, TNF, and EGF alone and in combination, on human leukocyte antigen-DR (DR) antigen expression and viability of neoplastic and non-neoplastic human thyroid cells in culture. alpha-IFN-induced DR antigen expression on non-neoplastic human thyroid cells, whereas TNF-alpha or EGF alone were ineffective. The addition of the same TNF-alpha concentrations (10 to 100 ng/ml) to alpha-IFN enhanced the expression of DR antigens compared with the effect of alpha-IFN alone. However, EGF inhibited alpha-IFN-induced DR on the same cells and at the same concentrations (10 to 500 ng/ml) at which the growth factor alone was ineffective. In contrast to the common pattern of cytokine effects on DR expression of all nonmalignant thyroid cell lines, neoplastic thyroid cell lines showed divergent responses to alpha-IFN, TNF-alpha, and EGF. In three malignant thyroid cell lines that were DR negative (follicular carcinoma WRO 82-1 and NRO 87-1 cell lines, and anaplastic carcinoma ARO 81-1), DR antigen could be induced by alpha-IFN and enhanced by TNF-alpha, whereas EGF was ineffective. In a fourth cell line (an anaplastic carcinoma SW1736) alpha-IFN, TNF-alpha, and EGF alone were capable of inducing DR, and a combination of either TNF-alpha and EGF with alpha-IFN potentiated DR induction. In a fifth neoplastic cell line (papillary carcinoma, NPA) that constitutively expressed surface DR, its expression was inhibited by both alpha-IFN and TNF-alpha and was not affected by EGF.

Antibodies↗
PubMed1992

Childhood brain tumors that occupy more than one compartment at presentation. Multiple compartment tumors.

Children whose brain tumor involves two or more compartments at presentation differ clinically and pathologically from children whose brain tumor is confined to one compartment. In this study of 3,291 children with a brain tumor, at least 10% had a tumor that occupied two or three compartments at first hospitalization. Infratentorial tumors occupying multiple compartments were 1.7 times more likely to involve the cervicomedullary junction than the mesodiencephalic junction. Younger children (1-3 years) were more likely to have had multiple compartment tumors than older children. Children whose tumor was limited to the infratentorial compartment had a longer survival than children whose tumor also occupied other compartments. Ependymoma, anaplastic ependymoma, and astrocytoma (nos) were over represented among infratentorial multiple compartment tumors. Pilocytic astrocytoma, primitive neuroectodermal tumor (medulloblastoma), and desmoplastic medulloblastoma were less likely to have occupied multiple compartments at the time of the first surgical exploration. The distributions of histologic features in tumors at the cervicomedullary junction differed from those in tumors limited to the posterior fossa or to the spinal canal. Seizures were more likely if the tumor was confined to the supratentorial compartment, whereas nausea or vomiting and headache were more likely if the tumor was confined to the infratentorial compartment. Children whose tumor was confined to the spinal canal were significantly more likely to have bladder symptoms and back and/or abdominal pain than those whose tumor also involved compartments above the foramen magnum. We conclude that brain tumors apparently confined to one compartment at presentation are biologically and structurally different from tumors evident in two or more compartments.

Adolescent↗
PubMed1992

Epidemiology of seizures in children with brain tumors. The Childhood Brain Tumor Consortium.

We examined potential clinical and pathologic correlates of seizures among the 3,291 children in the Childhood Brain Tumor Consortium database. Fourteen percent had seizures prior to their hospitalization for a brain tumor. Among children who had a supratentorial tumor, seizures occurred in 22% of those less than 14 years of age. The prevalence of seizures increased to 68% of older teenagers. Among children with an infratentorial tumor, the prevalence of seizures was relatively constant at 6% over all age groups. The onset of seizures began more than one year prior to surgical tumor removal in over half of the children aged five or more with supratentorial tumors, significantly longer than for those of the same age with infratentorial tumors. Almost all children (98.9%) with an infratentorial tumor and seizures had at least one other symptom and more than three-fourths of them had at least three. Eighty-nine percent of children with a supratentorial tumor and seizures had at least one other symptom and more than one-half had at least three symptoms. Regardless of whether the tumor was above or below the tentorium, confusion or stupor and coma were more common in children with seizures than in children without seizures. Among children with supratentorial tumors, symptoms of a declining academic performance or an abnormality of personality, speech, walking, or sensation were significantly more frequent in children with seizures, while visual symptoms (other than visual loss or diplopia) and nausea or vomiting were less frequent. Among children with supratentorial tumors, those who had seizures were more likely to have paralysis of an arm, hand, or face, confusion or stupor, or coma and less likely to exhibit irritability, papilledema, optic atrophy, decreased visual acuity, pupillary abnormalities, or abducens paresis. Among children with infratentorial tumors, those with seizures were significantly less likely to have truncal ataxia, but more likely to experience confusion, stupor, or coma. In the supratentorial compartment, astrocytoma (nos), protoplasmic astrocytoma, anaplastic astrocytoma, and ependymoma were more frequently associated with seizures than was craniopharyngioma. No infratentorial tumor type was more or less likely to be associated with seizures. All common tumor types that were represented in both the supratentorial and the infratentorial compartment except astrocytoma (nos) were associated with significantly greater rates of seizures when located in the supratentorial compartment. The tumor location with the highest incidence of seizures was, as expected, the superficial cerebrum. More than 40% of the children with such tumors had seizures.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

Ataxia-telangiectasia: linkage analysis of chromosome 11q22-23 markers in Turkish families.

To further pinpoint the location of the genes for ataxia-telangiectasia on the long arm of chromosome 11, we performed linkage analysis and analysis of recombinants of genetic haplotypes on 14 Turkish families with ataxia-telangiectasia, 12 of which were consanguineous. These studies used more than 25 polymorphic genetic markers spanning a region of the long arm of chromosome 11 that is larger than 50 cM. Seven markers gave significant LOD scores to AT: CJ5, DRD2, CJ208, S144, CD3E, PBGD, and S147, as did haplotypes created with pairs of markers DRD2/CJ5 and S144/CJ208, giving recombination fractions (theta) of 0.00, 0.00, 0.05, 0.08, 0.03, 0.09, 0.07, 0.00, and 0.06, respectively. Monte Carlo analysis of these 14 Turkish families indicated the best location for a single AT gene to be within a 6 cM sex-averaged (3 cM male-specific) interval defined by STMY and CJ77; this was three times more likely than the next most likely location (peak III) at the DRD2 locus. The analysis also revealed a peak (peak II) between S147 and S133, which may represent the complementation group D gene. Recombinant analysis of haplotypes also localized an AT locus to the STMY-CJ77 interval. Taken together, these results suggest that at least two distinct AT loci exist (ATA and ATD) at 11q22-23, with perhaps a third locus, ATC, located very near to the ATA gene. This genetic heterogeneity further complicates plans to isolate the major ATA and ATC genes and to begin identifying AT carriers in the general population.

Ataxia Telangiectasia↗
PubMed1992

The agraphia of Alzheimer's disease.

Hypothesizing that agraphia in Alzheimer's disease (AD) reflects disturbances in multiple cognitive domains, we evaluated writing samples from 33 patients meeting strict criteria for probable AD. We found agraphia to be common on a standard narrative writing task. When compared with 41 education- and age-matched normal control subjects, AD patients had significantly lower writing scores, wrote significantly fewer words, mentioned significantly fewer categories of information, and were significantly more likely to make writing errors. On stepwise regression procedures, neuropsychological measures of visuoperceptual impairment and disease severity were the strongest predictors of agraphia, but other analyses indicated that measures of language, praxis, and attention could also contribute significantly to agraphia. On two writing tasks, we failed to confirm the previous contention that agraphia is a marker for familial AD. However, there was a highly significant interaction between family history, oral naming, and writing: patients with nonfamilial AD, but not those with a family history of dementia, showed a strong correlation between naming and writing performance. We conclude that agraphia in AD can be variously determined and that agraphia is not a reliable marker for familial disease.

Aged↗
PubMed1992

Divergent effects of thyroid HLA-antigens on T and natural killer (NK) cell cytotoxicity.

We have used non-autoimmune non-neoplastic human thyroid cells to explore the role of surface class I and DR antigens on these cells' sensitivity towards T and Natural Killer (NK) cell cytotoxicity. Non-treated thyrocytes expressed class I but no DR antigens. Following incubation with gamma-interferon (gamma-IFN) class I antigens were markedly elevated and DR expression was induced. Whereas non-treated thyrocytes were minimally lysed by sensitized T cells, they served as appropriate targets for NK cells. Following incubation with gamma-IFN, the thyroid cells became highly sensitive to T cell lysis, with no significant reduction in their vulnerability to NK cell killing. The addition of monoclonal anti class I or DR antigens, or brief acid treatment which specifically eliminates class I molecules, inhibited T cell cytotoxicity but enhanced the sensitivity to lysis by NK cells. Thus, the presence of HLA antigens on the same thyroid cells have an opposite effect on two major cytotoxi mechanisms. Our findings are relevant within the context of recent suggestions of intervening with target HLA antigens for the management of autoimmune and malignant diseases.

Cytotoxicity, Immunologic↗
PubMed1991

Exposure to residential electric and magnetic fields and risk of childhood leukemia.

The relation between exposure to electric and magnetic fields in the home, as assessed by measurements, wiring configuration, and self-reported appliance use, and risk of leukemia was investigated in a case-control study among children from birth to age 10 years in Los Angeles County, California. Cases were ascertained through a population-based tumor registry from 1980 to 1987. Controls were drawn from friends and by random digit dialing. Interviews were obtained from 232 cases and 232 controls. Available for analysis were measurements of the magnetic field in the child's bedroom over 24 hours or longer (164 cases and 144 controls), spot measurements of magnetic and electric fields (140 cases and 109 controls), and wiring configuration (219 cases and 207 controls). No clear associations between leukemia risk and measured magnetic or electric fields were seen. An association between the Denver Wertheimer-Leeper wiring configuration and childhood leukemia risk was observed (odds ratio for very high relative to very low current and underground configuration combined = 2.15, 95% confidence interval 1.08-4.28; p for trend = 0.008) and was not substantially altered by adjustment for potential confounding factors. Cases were more likely than controls to report use of several appliances that produce high electric and magnetic fields. Our results support an association between childhood leukemia risk and wiring configuration, but not direct measurements of electric and magnetic fields.

Adult↗
PubMed1991

Clinical importance of myeloid-antigen expression in acute lymphoblastic leukemia of childhood.

BACKGROUND: Leukemic cells in 15 to 25 percent of patients with acute lymphoblastic leukemia (ALL) express myeloid antigens as well as lymphoid antigens (the latter reflecting B-cell or T-cell lineage). The relations of myeloid-antigen expression to other features of ALL and to prognosis have been controversial. METHODS: We analyzed clinical and laboratory features present at diagnosis in 236 consecutive cases of ALL in children. Immunophenotyping, including single- and dual-fluorescence analyses, was used to classify leukemic cells as B or T lymphoblasts and also to identify myeloid-antigen expression--the simultaneous expression of lymphoid-associated antigens and at least one of three myeloid-associated antigens (CD33, CD13, and CD14) on cells classified as L1 or L2 according to the French-American-British system. RESULTS: Forty-five of 185 patients with B-lineage ALL had myeloid-antigen expression, as did 8 of 41 patients with T-lineage ALL. In 10 patients, the lineage could not be determined. Myeloid-antigen expression was associated with L2 morphology (P less than 0.05), but it did not correlate with other prognostic features recognized previously. Multivariate analysis showed that myeloid-antigen expression was an important predictor of relapse in childhood ALL and the most significant prognostic factor statistically (P less than 0.0001). A white-cell count greater than or equal to 50 x 10(9) per liter at diagnosis was also an important and highly significant prognostic feature (P less than 0.001). After 40 months, the estimated disease-free survival for patients with ALL was 84 percent for those without myeloid-antigen expression and with a low white-cell count, 57 percent for those without myeloid-antigen expression and with a high white-cell count, 47 percent for those with myeloid-antigen expression and a low white-cell count, and 26 percent for those with myeloid-antigen expression and a high white-cell count (P less than 0.00001). CONCLUSIONS: Myeloid-antigen expression is an important independent predictor of a poor response to chemotherapy in childhood ALL.

Adolescent↗
PubMed1991

Localization of an ataxia-telangiectasia locus to a 3-cM interval on chromosome 11q23: linkage analysis of 111 families by an international consortium.

Linkage of at least two complementation groups of ataxia-telangiectasia (AT) to the chromosomal region 11q23 is now well established. We provide here an 18-point map of the surrounding genomic region, derived from linkage analysis of 40 CEPH families. On the basis of this map, 111 AT families from Turkey, Israel, England, Italy, and the United States were analyzed, localizing the AT gene(s) to an 8-cM sex-averaged interval between the markers STMY and D11S132/NCAM. A new Monte Carlo method for computing approximate location scores estimates this location as being at least 10(8) times more likely than the next most likely interval, with a support interval midway between STMY and D11S132 that is either 5.2 cM (sex-averaged and conservatively based on 3 lod scores from the maximum-location score) or 2.8 cM (male specific, based on a 2.72:1 interval-specific female-to-male distance ratio.

Ataxia Telangiectasia↗
PubMed1991

A random walk method for computing genetic location scores.

Calculation of location scores is one of the most computationally intensive tasks in modern genetics. Since these scores are crucial in placing disease loci on marker maps, there is ample incentive to pursue such calculations with large numbers of markers. However, in contrast to the simple, standardized pedigrees used in making marker maps, disease pedigrees are often graphically complex and sparsely phenotyped. These complications can present insuperable barriers to exact likelihood calculations with more than a few markers simultaneously. To overcome these barriers we introduce in the present paper a random walk method for computing approximate location scores with large numbers of biallelic markers. Sufficient mathematical theory is developed to explain the method. Feasibility is checked by small-scale simulations for two applications permitting exact calculation of location scores.

Chromosome Walking↗
PubMed1990

Concomitant effect of 2'-deoxycoformycin on natural killer cell activity and tumour cell sensitivity to lysis in hairy cell leukaemia--discordant effects of alpha interferon.

The effects of 2'-deoxycoformycin (dCF) and alpha interferon (IFN-alpha) on natural killer (NK) cell-enriched fractions and hairy cell (HC) targets from three patients with HC leukaemia (HCL) were investigated. There was no significant increase in NK activity when either the HC targets or NK-enriched cells were preincubated with dCF. However, preincubation of both HC and NK cells with dCF resulted in increased NK activity. Culture of enriched NK cells with IFN-alpha enhanced their activity. However, preincubation of HC targets with this drug in the presence or absence of dCF resulted in a protective effect. Maximal NK activity towards HCL was obtained when the target tumour cells were separately precultured with dCF and the NK-enriched effectors precultured with dCF + IFN-alpha. The effect of dCF and IFN-alpha was also measured using the standard K562 cells as targets for NK activity. dCF enhanced NK activity following preculture of both effector and target K562 cells, but IFN-alpha did not reduce K562 cell susceptibility to NK lysis as it did for HC cells. Our findings suggest that (a) dCF and IFN-alpha, which are used to treat HC, could function via activation of NK cells, (b) effects on both effector and tumour target cells should be taken into account, and (c) caution should be exercised in extrapolating the effects of NK-cell activity against K562 cells to those on HC targets.

Cytotoxicity, Immunologic↗
PubMed1990

Transient ischemic attacks: their frequency in the Lehigh Valley.

The incidence of transient ischemic attacks (TIAs) in the Lehigh Valley was analyzed using the Lehigh Valley Stroke Register based on data collected between July 1, 1982, and June 30, 1986. The overall average annual incidence rate was 22.9 per 100,000 population, and 23.2 and 22.5 per 100,000 population in men and women, respectively. Men had a statistically significant higher age-specific rate of TIAs than women. Our incidence appears to be lower than that reported in earlier studies but, because of methodologic differences, only continued observations in our population and in similar populations using a standardized methodology will resolve the question of whether TIA frequency is, in fact, declining.

Adult↗
PubMed1990

Thyrotropin, acting at least partially via adenosine 3',5'-monophosphate, exerts both mitogenic and antimitogenic effects in cultured human thyroid cells.

The aim of this study was to examine the role of TSH and cAMP in human thyroid cell proliferation. For this purpose, human thyrocytes were cultured in the absence or presence of TSH, cAMP analogs, or forskolin, and the following parameters were measured during 7 consecutive days: [3H]thymidine incorporation into trichloroacetic acid-precipitable material, cell count (to assess cell proliferation), and cAMP accumulation. Cells proliferated during the first days in culture, reaching a maximum on day 5, followed by a decline in cell growth. TSH dose-dependently enhanced thyrocyte proliferation during the first few days of culture, but attenuated cell growth during the later stages of culture. The TSH mitogenic action was only apparent at a low cell density (10(4) cells/well in 96-well microtiter plates). TSH elicited a dose-dependent elevation of cAMP during all phases of cell culture. Furthermore, the cAMP analogs, 8-bromo-cAMP and dibutyryl cAMP, mimicked the thyrocyte proliferative and antiproliferative actions of TSH. Forskolin also mimicked the TSH mitogenic and antimitogenic effects while concomitantly elevating cAMP levels during both instances. The data, therefore, seem entirely consistent with the premise that the TSH stimulatory and inhibitory actions on human thyroid cell growth are mediated, at least partially, by cAMP. The dual actions of TSH as a mitogenic and antimitogenic factor may, thus, provide an experimental in vitro basis for the well established in vivo goitrogenic effect of TSH observed initially, followed by desensitization on prolonged exposure to the hormone.

Cells, Cultured↗
PubMed1990

Effects of gamma-interferon on DR antigen expression, growth, 3,5,3'-triiodothyronine secretion, iodide uptake, and cyclic adenosine 3',5'-monophosphate accumulation in cultured human thyroid cells.

We have examined, using the same system of human thyroid cells in culture, the effects of the cytokine human gamma-interferon (gamma IFN) on the expression of DR antigen, cell pro-liferation, cAMP accumulation, and the differentiated functions, iodide uptake and T3 secretion. gamma IFN elicited a dose- and time-dependent increase in DR expression, with a maximum effect on day 5 of culture. The cytokine, at the same concentrations and experimental conditions as those found to be effective in inducing DR antigen expression, caused on day 5 of culture a dose-dependent inhibition of [3H]thymidine incorporation, DNA content, cell count, as well as TSH-stimulated (but not basal) iodide uptake and T3 secretion. The gamma IFN suppressive influence on the differentiated functions was not merely due to a reduction in cell number, but was also apparent when results were expressed per micrograms DNA. Since the cytokine did not inhibit TSH- or forskolin-stimulated cAMP accumulation and showed a suppressive influence toward 8-bromo-cAMP- and forskolin-stimulated T3 secretion, its inhibitory effect seems to be exerted at a site located distal to cAMP formation. Although gamma IFN alone was devoid of any effect on cAMP accumulation, it enhanced forskolin-stimulated (as well as TSH-activated) cAMP in the presence of 3-isobutyl-1-methylxanthine, an inhibitor of cAMP degradation. Thus, it would seem that gamma IFN also exerts an influence on cAMP formation (rather than degradation) at a step subsequent to TSH binding to its receptor. The effects we observed seem specific to gamma IFN, since alpha IFN, although capable of inhibiting human thyrocyte multiplication, lacked any influence on DR antigen expression, cAMP accumulation, or T3 secretion by human thyroid cells. In what way, if any, is gamma IFN-induced DR antigen expression on human thyrocytes, an event believed to be critical in the pathophysiology of autoimmune thyroid disease, related to decreased thyroid function and growth is presently unknown.

Cell Count↗