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Biomedical subjects

E L Khoury

Publications and source records attributed to E L Khoury.

At least 19 recordsLinked to original sources

The impact of Hurricane Andrew on deviant behavior among a multi-racial/ethnic sample of adolescents in Dade County, Florida: a longitudinal analysis.

Findings from a longitudinal study are presented on the relationships between the problems and stresses resulting from Hurricane Andrew and posthurricane minor deviant behavior. The sample (N = 4,978) included Hispanic, African-American, and White non-Hispanic middle school students enrolled in Dade County, Florida public schools. Two waves of data were collected prior to the hurricane; a third was obtained approximately 6 months following the storm. Results indicated that females were likely to report higher levels of hurricane-related stress symptoms than males. After controlling for prehurricane levels of minor deviance, family support, and race/ethnicity, hurricane stress symptom level remained a significant predictor of posthurricane minor deviant behavior. The findings lend support to stress theories of social deviance.

Adolescent↗

Disaster related stresses, depressive signs and symptoms, and suicidal ideation among a multi-racial/ethnic sample of adolescents: a longitudinal analysis.

Longitudinal findings are presented on the relationships between disaster related stresses, depression scores, and suicidal ideation among a multi-racial/ethnic sample of adolescents (N = 4,978) all of whom have been exposed to Hurricane Andrew. Regression analysis showed that being female, hurricane generated stresses, low levels of family support, pre-hurricane suicidal ideation, and post-hurricane depression scores were significant predictors of post-hurricane suicidal ideation. Path analysis revealed that being female, low socioeconomic status, pre- and post-hurricane depression, high stress scores, low family support, and pre-hurricane suicidal ideation had significant direct/indirect effects on post-hurricane suicidal ideation.

Adaptation, Psychological↗

Gender and ethnic differences in the prevalence of alcohol, cigarette, and illicit drug use over time in a cohort of young Hispanic adolescents in south Florida.

The purpose of this study was to describe patterns of substance use among young Hispanic adolescents of Cuban and Central/South American heritage, many of whom are recent immigrants to the U.S. At present there are very little epidemiologic data on these Hispanic ethnic subgroups, particularly for girls. A cohort of 848 middle school boys and girls in Miami, Florida completed questionnaires in 7th, 8th, and 9th grades concerning their use of alcohol, cigarettes, marijuana, and other illicit drugs. African Americans and White non-Hispanics were used as comparison groups. In general, White non-Hispanics and U.S.-born Hispanics had the highest lifetime and past year prevalence rates of substance use. While no statistically significant gender differences were found for any of the racial/ethnic groups, the use of substances among Hispanic girls often exceeded that of their male counterparts. A progressive increase in use of alcohol, cigarettes, marijuana, and other illicit drugs was evident over the two and one-half year duration of the study for both gender groups.

Adolescent↗

Teacher and parent perceptions of behavior problems among a sample of African American, Hispanic, and non-Hispanic white students.

A multiracial/multiethnic sample of middle school adolescents and their teachers was used to assess whether teacher ratings of student behavior problems varied according to teacher-student racial/ethnic differences and students' perception of teachers' attitudes toward them. No significant mean score differences were found for Hispanic or non-Hispanic white students according to the race/ethnicity of the teachers doing the ratings. However, African American students rated by Hispanic and non-Hispanic white teachers had significantly higher mean total behavior problem scores than African American students rated by African American teachers. Teacher ratings were also compared to those made by parents. The percentage of students rated as cases by teachers but not by parents differed significantly by race/ethnicity of student. Other findings indicated highly significant relationships between student-perceived teacher disparagement and the assignment of high behavior problem scores to students by teachers.

Adolescent↗

HLA class II antigen associations help to define two types of alopecia areata.

BACKGROUND: Multiple HLA class I and class II antigen associations have been described for alopecia areata (AA). As in other immune-mediated diseases, the HLA antigens associated with AA could influence the patient's ability to respond to immune challenge from both self- and non-self-antigens and may offer clues to the cause and prognosis of and potential therapy for the disease. OBJECTIVE: Our purpose was to determine which HLA class II antigens are associated with two forms of long-standing AA, which we define to be long-standing patchy AA and long-standing alopecia totalis (AT) and alopecia universalis (AU). We also examined other factors such as age at onset of disease and familial and patient histories of autoimmune disease for correlation with the two groupings. METHODS: Patients were typed for HLA class I and class II antigens by serologic methods and were typed by molecular methods for the subtypes of the HLA class II antigens. RESULTS: HLA-DR11 (DRB1*1104) and HLA-DQ7 (DQB1*0301) were found to be highly significantly increased in frequency in patients with long-standing AT/AU (group III) but not in patients with long-standing patchy AA (group II); both patient groups showed increased frequencies of HLA-DQ3 (DQB1*03). Group III patients were unique in their early age at onset of disease. Familial incidence of AA was 37% in patients who had their first patch by 30 years of age and 7.1% with the first patch after 30 years of age. CONCLUSION: The data support the differential association of two well-defined clinical forms of AA, namely long-standing AT/AU and long-standing patchy AA, with specific HLA antigens and age at onset; they also suggest that the broad antigen HLA-DQ3, DQB1*03, is a likely candidate for general susceptibility to AA. Our findings also suggest a bimodal pattern of disease with an early-onset form associated with greater severity, long duration, and family history of the disease and a late-onset form characterized by milder severity, shorter duration, and low family incidence.

Alleles↗

Topical minoxidil in alopecia areata: no effect on the perifollicular lymphoid infiltration.

The therapeutic value of topical minoxidil in alopecia areata (AA) has been investigated in recent years, with variable results. Although the mechanism whereby minoxidil may stimulate hair regrowth in some cases of AA has not yet been elucidated, there have been reports of a decrease in the perifollicular infiltrates of mononuclear leukocytes (MNC)--particularly T lymphocytes--that characterize this condition, in patients "responding" to topical minoxidil. In a randomized and double-blind study, we have investigated the effect of 5% topical minoxidil versus placebo (vehicle alone) on the extent and composition of the perifollicular MNC infiltration in 20 patients having extensive AA (26-99% scalp hair loss). The proportions of hair follicles showing perifollicular infiltration by MNC and their main subsets were determined with histologic and immunohistochemical stainings of scalp biopsies obtained before treatment, after 12 weeks of randomized double-blind minoxidil versus placebo treatment, and after 12 additional weeks during which all patients received minoxidil. Six of the patients showed cosmetically acceptable hair regrowth (CAHR) at the end of the 24 weeks and this was associated with a significant decrease in the proportions of follicles infiltrated by total T and B lymphocytes, macrophages, and Langerhans cells at week 12, and by total T lymphocytes at week 24. However, no significant differences in the extent or composition of the perifollicular infiltrates were detected at week 12 between patients receiving minoxidil and placebo, or between the week-12 and week-24 biopsies of those patients who first received placebo and then minoxidil. These findings indicate that in AA the reduction in perifollicular T-cell infiltration associated with CAHR is not attributable to an effect of topical minoxidil.

Adolescent↗

Increasing the cancer screening of the medically underserved in south Florida.

Diagnosis and treatment of cancers at advanced stages have contributed to a significantly lower survival rate among individuals of low socioeconomic status compared with those in higher brackets. In an effort to increase the accessibility and acceptability of cancer screening among such individuals in Dade County, Florida, the Cancer Control Division of the Sylvester Comprehensive Cancer Center at the University of Miami School of Medicine initiated a pilot early detection program in 1987. The program initially provided breast cancer screening for women, aged 40 and older, who attended ten community health care centers located in low-income neighborhoods. With the selection of Miami by the American Cancer Society as one of three sites for conducting a screening demonstration project for the socioeconomically disadvantaged, this program has recently been expanded to include pelvic screening for women, aged 40 and older, and prostate screening for men, aged 65 and older.

Adult↗

Human cytomegalovirus ie2 negatively regulates alpha gene expression via a short target sequence near the transcription start site.

Repression of human cytomegalovirus alpha (immediate-early) gene expression is under the control of the viral ie2 gene. Here we show that ie2 negatively regulates gene expression directed by the strong cytomegalovirus enhancer via a specific 15-bp target sequence (which we term cis repression signal [crs]). This crs is located between -14 and +1 relative to the transcription start site and will function in an orientation-independent fashion, consistent with repression occurring at the transcriptional level. Repression is dominant over transactivation by ie1 gene products. The crs (5'-CGTTTAGTGAACCGT-3') does not contain previously recognized binding sites for cellular transcription factors, and a precise copy is not found elsewhere in the human cytomegalovirus genome. The position of the signal near the transcription start site appears to be important in function; addition of the crs near the transcription start site of a heterologous promoter, from the thymidine kinase gene of herpes simplex virus type 1, conferred cytomegalovirus ie2-dependent repression upon this promoter. Thus, we propose that an ie2 gene product or an induced cellular protein mediates repression by binding to crs. Negative regulation of alpha gene expression may be important during viral replication or latency.

Animals↗

Induction of HLA-DR expression on thyroid follicular cells by cytomegalovirus infection in vitro. Evidence for a dual mechanism of induction.

Cytomegalovirus (CMV) infection of primary cultures established from human thyroid nodular and normal (paranodular) tissues resulted in induction of human leukocyte antigen (HLA) DR expression on thyroid follicular cells (TFC), as detected by cell-surface immunofluorescence staining with monoclonal antibodies (MAb). Two distinct modalities of induction were observed. The first type occurred in cultures of normal tissue obtained from CMV-seropositive but not seronegative donors, was detected on 30% to 50% of the TFCs, even though the vast majority of these cells failed to show any morphologic or antigenic evidence of individual CMV infection, and was associated with production of gamma-interferon (gamma-IFN) in vitro. The induced molecules displayed the characteristic DR polypeptide profile on immunoprecipitation and electrophoretic analysis. These results demonstrate that CMV infection of normal thyroid cultures may induce DR expression on TFCs in the absence of pre-existing lymphoid infiltrates and suggest that the induction is the result of an in vitro response to CMV by previously sensitized immunocompetent cells present in these primary cultures. Such a response, associated with the release of gamma-IFN, would induce DR expression on neighboring uninfected cells. The second mode of induction occurred in all CMV-infected cultures, regardless of their tissue origin (nodular or normal) or the serologic status of the donors. Up to 50% of infected TFCs at a late stage of infection, having fully developed CMV antigen-positive intranuclear inclusions, also displayed the cell-surface DR-related determinant recognized by one of the four anti-DR MAbs used. This induction was restricted to TFCs, while CMV-infected fibroblastoid cells present in the monolayers were invariably negative. Induction by CMV of major histocompatibility class II antigens on human epithelial cells may have significant implications in the development of normal immune responses against local viral infection, the enhancement of alloimmune rejection of grafted organs, and the generation of organ-specific autoimmune responses.

Adult↗

Luteinization of human granulosa cells in vivo is associated with expression of MHC class II antigens.

We previously described the presence of MHC class II (HLA-DR) antigens, structurally similar to those on lymphoid cells and bearing the genetically-appropriate allotypic determinants, on human adrenocortical cells in the zona reticularis of normal glands. We now report a similar expression by granulosa-lutein cells (GLC) in corpora lutea (CL) of normal ovaries, as detected by indirect immunofluorescence techniques with the use of mouse monoclonal antibodies (MAb). In some cases, GLC were also positive for HLA-DQ and -DP antigen expression. Neither granulosa nor theca interna cells in large antral follicles of the same ovaries showed any detectable expression of MHC class II antigens. Moreover, theca-lutein (paralutein) cells, identified by their reactivity with specific human autoantibodies in 5 of the 7 human CL examined, were also negative. Similarly, GLC, but not paralutein cells, in rhesus monkey CL showed significant cross-reactivity with anti-HLA-DR MAb. In contrast, lutein cells in ovaries from either cycling or 7-day-pregnant rats were negative for MHC class II (Ia) antigen expression. Expression of MHC class II antigens by human granulosa cells after their luteal transformation confirms the normal inducibility of certain human steroidogenic cells at the time of their further functional differentiation and enhanced biosynthetic activity, and suggests that these molecules may have additional functions beyond serving as restriction elements in the immune response.

Adult↗

HLA-DR expression by hair follicle keratinocytes in alopecia areata: evidence that it is secondary to the lymphoid infiltration.

There is evidence suggesting that alopecia areata (AA) may have an autoimmune pathogenesis, and it was recently reported that keratinocytes in the bulb of some hair follicles affected by this condition express class II HLA (HLA-DR) antigens, which are not present on the same cells in normal tissue. Since it has been proposed that an analogous ectopic HLA-DR expression by epithelial cells in other organs might be an early event leading to organ-specific autoimmunity, we have investigated the sequence in which perifollicular mononuclear cell (MNC) infiltration and ectopic HLA-DR expression on keratinocytes appear in recent-onset and long-standing cases of AA by immunostainings of affected and unaffected areas with monoclonal antibodies against leukocyte and HLA-DR antigens. In recent-onset AA lesions, ectopic HLA-DR expression on hair follicle keratinocytes was found only occasionally (in 3 out of 247 follicles examined) and was restricted to biopsies from the affected areas. This prevalence was significantly lower than the prevalence of hair follicles showing perifollicular MNC infiltrates in the same biopsies, and was also significantly lower than the prevalence of hair follicles showing ectopic HLA-DR expression on keratinocytes in the affected areas of longstanding cases. These findings suggest that in AA lesions the perifollicular MNC infiltration precedes the ectopic HLA-DR expression on hair follicle keratinocytes, and therefore argue against the notion of a primary role for that ectopic HLA-DR expression on epithelial cells in triggering the putative autoimmune response in AA.

Adolescent↗

HLA-DR expression by adrenocortical cells of the zona reticularis: structural and allotypic characterization.

We previously reported that human adrenocortical cells in the zona reticularis of normal glands express antigenic determinants recognized by HLA-DR monoclonal antibodies (MoAbs). In the present study, it is shown that these adrenocortical HLA-DR determinants are present on glycoproteins having similar structural characteristics, regarding subunit composition and molecular weight, to those of HLA-DR molecules present on immunocomponent cells. Furthermore, adrenocortical HLA-DR molecules include serologically-defined genetically-appropriate allotypic specificities, detectable by immunostainings with both HLA-DR human alloantisera and MoAbs against polymorphic HLA-DR determinants. The finding of a normal expression of HLA-DR antigens by these highly differentiated and biosynthetically active endocrine cells gives support to the notion that MHC class II molecules may perform biological functions in addition to those related to the immune response.

Adrenal Cortex↗

Ectopic expression of HLA class II antigens on thyroid follicular cells: induction and transfer in vitro by autologous mononuclear leukocytes.

Ectopic expression of HLA class II antigens by thyroid follicular cells (TFC) might trigger the immune recognition of TFC-specific surface constituents by self-reactive T helper/inducer lymphocytes, with the consequent generation of organ-specific autoimmunity. To explore the alternative possibilities underlying this ectopic expression, i.e. that it either reflects a primary abnormality of the TFC or is secondarily induced by the autoimmune attack itself, we employed immunofluorescence staining of monolayers cultured from thyroid tissue of patients with autoimmune thyroid disease as well as neoplastic, nodular, and normal thyroid tissues to assess the role that autologous mononuclear leukocytes (MNC) and serum factors play in HLA class II induction and modulation in vitro. In all Graves' disease (GD) tissues that initially displayed HLA-DR (DR) antigens, this expression was transient. Primary TFC cultures from tissues with tumor-associated chronic thyroiditis (CT) showed more widespread and persistent DR expression than did cultures from GD tissues. However, in contrast with the findings in GD, there was no correlation between ectopic DR expression on TFC from the CT areas and the presence of organ-specific autoimmune markers. DR expression by TFC was detected in only one of the five nontoxic nodules studied, and involved a small proportion (approximately 20%) of the TFC. A similarly low proportion of DR-positive TFC was found in cultures from two papillary carcinomas, while much stronger DR expression was seen on TFC cultured from the contralateral lobes affected with CT. Only one of four follicular adenomas expressed DR on about 35% of the cultured TFC. In contrast with the rapid extinction of DR expression on TFC cultured from GD tissues after depletion of infiltrated MNC, DR antigen loss did not occur or was significantly delayed when parallel TFC monolayers were cocultured in the presence of autologous MNC from the intrathyroidal infiltrates. Coculture of DR-negative TFC from normal tissues with autologous peripheral blood MNC in individuals without detectable thyroid autosensitization also resulted in pronounced induction of DR expression on the TFC. Purified T lymphocytes from the same peripheral blood MNC preparations, however, did not induce DR expression on these normal TFC. Similarly, MNC obtained from two follicular adenomas, mostly macrophages, did not induce DR expression when cultured with autologous TFC from the same lesions. Addition of 15% autologous serum did not prevent progressive extinction of DR expression on TFC cultured from GD or tumor-associated CT tissues after depletion of infiltrated MNC.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Aberrant expression of class II HLA antigens by the target cell: cause or consequence of the autoimmune aggression?

Since the aberrant HLA-DR expression on thyroid follicular cells (TFC) has been found in glands already having an ongoing immune response, the possibility exists that this ectopic expression is not the primary event leading to the infiltration by autoreactive lymphocytes, but rather a consequence of that infiltration. We have explored that possibility in studies on the behaviour of TFC from normal and autoimmune glands with respect to their expression of HLA-DR antigens when they are cultured with or without autologous mononuclear cells from the intrathyroidal infiltrates or peripheral blood. Our findings suggest that 1) the ectopic expression of class II HLA antigens by TFC in autoimmune conditions is not the result of a primary or intrinsic defect of those cells but a consequence of their response to an environmental stimulus operating in situ; 2) this stimulus appears to be the lymphoid infiltration itself; 3) there are no significant differences in the responses given by TFC from autoimmune and normal glands. In alopecia areata, another presumably autoimmune condition characterized by the presence of lymphoid infiltration precedes that ectopic HLA-DR expression in vivo. In addition, we have found that human adrenocortical cells in the zona reticularis of adult glands normally express HLA-DR antigenic determinants. Therefore, the co-existence of both HLA-DR and potentially autoantigenic cell-surface constituents does not seem to be a sufficient stimulus to trigger an organ-specific autoimmune response.

Cells, Cultured↗

Adrenocortical cells of the zona reticularis normally express HLA-DR antigenic determinants.

A distinct population of normal human adrenocortical cells from adult glands spontaneously express HLA-DR, and occasionally also HLA-DQ, antigenic determinants in vivo and in vitro, as detected by immunofluorescence techniques using monoclonal antibodies on frozen tissue sections, primary cultures, and viable cell suspensions. In vivo, these antigenic determinants were found to be confined to the compact-type cells in the zona reticularis. In vitro, the adrenocortical identity of these HLA-DR+ cells was conclusively established by the characteristic change in their morphologic features induced by ACTH1-24 and by the simultaneous detection of tissue-specific adrenal autoantigens in double-label immunofluorescence staining. The cell surface expression of HLA-DR determinants by compact cells persisted in culture for several weeks and was not significantly affected by treatment with ACTH1-24. On the other hand, fetal adrenocortical cells of both transient and definitive zones were invariably negative for the expression of these HLA Class II antigenic determinants. Because normal human adrenocortical cells also express on their surface the molecules which constitute specific autoantigens in autoimmune adrenalitis, these findings argue against the notion that an ectopic HLA-DR expression associated with an otherwise "silent" autoantigen might trigger an organ-specific autoimmune response against endocrine cells. In addition, the expression of HLA-DR determinants by viable normal reticularis cells provides a readily detectable surface marker which may allow the physical separation of this population for studies in vitro.

Adrenal Cortex↗