Faculty Bibliography

Introduction: Obsessive-compulsive disorder (OCD), characterized by repetitive anxiety-inducing intrusive thoughts and compulsive behaviors, is associated with higher suicide ideation and suicide attempts than the general population. This study investigates the prevalence and the correlates of current suicide risk in adult outpatients in an international multisite cross-sectional sample of OCD outpatients.
Method(s): Data were derived from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network's cross-sectional data set (N = 409). Current suicide risk (assessed by Item C of the MINI) and diagnoses of psychiatric disorders were based on DSM-IV. Chi-squared test for categorical variables and t-test for continuous variables were used to make statistical inferences about main features associated with current suicide risk. P < .05 was considered as statistically significant.
Result(s): The prevalence of current suicidal risk was 15.9%, with equal likelihood in sociodemographic variables, including age and gender. Increased rates of major depression and generalized anxiety disorder were associated to higher current suicide risk. Current suicide risk was also associated with higher severity of OCD, depressive comorbidity, and higher levels of disability. There were no significant differences in treatment correlates-including type of treatment and psychiatric hospitalizations-between the groups of individuals with and without current suicide risk.
Conclusion(s): Our findings suggest that current suicide risk is common in patients with OCD and associated with various forms of pathology. Our work also provides further empirical data to support what is already known clinically: a worse clinical picture characterized by a high severity of OCD, high distress related to obsessions and compulsions, and the presence of comorbidities such as major depression and generalized anxiety disorder should be considered as relevant risk factors for suicide risk.
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Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML), which is characterized by the reciprocal t (15;17) (q24; q21) translocation, resulting in PML-RARA gene fusion. Therapy-related AML (t-AML) is a serious complication after cytotoxic and/or radiation therapy in many malignant diseases. In this report, MLL/KMT2A-MON2, with balanced chromosomal translocation t (11;12) (q23; q14), was identified as a novel fusion in a child transformed to t-AML after successful treatment of APL. This study emphasized that clinical monitoring with an integrated laboratory approach is essential for the diagnosis and treatment of t-AML.
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The etiology of systemic lupus erythematosus (SLE) is determined in part by genetic factors which influence susceptibility to the disease. These factors presumably have a major role in determining the clinical and laboratory manifestations of SLE. Certain newer observations which may pertain to an understanding of the genetic basis of SLE will be critically reviewed in this chapter. These observations are based on advances in the analysis of human SLE and the increased knowledge provided by various murine models of human autoimmune processes. However, the specific genes involved and the mechanisms by which they exert their effect are at present still unknown. Special attention will be given newer insights into the role of genes of the major histocompatibility complex (MHC) and their relationship to the genes encoding the T cell antigen receptor. The role of classic immunoglobulin genes as well as more complex mechanisms involving preferential maternal or paternal genetic effects are also discussed. The contribution of genes encoding complement and complement receptors toward the expression of the disease state are discussed in brief

Among individuals with rheumatoid arthritis the presence of the polymorphic Ia antigen epitope detected by the monoclonal antibody 109d6 is more strongly correlated with disease susceptibility than are other specificities, such as HLA DR4, DRw53 (MT3) or the antigenic determinant, defined by the monoclonal antibody 17-3-3S. The cells of 93% of Caucasian and Hispanic patients react with the 109d6 reagent. As was the case in normal individuals, all DR4-positive patients express the 109d6 determinant; however, 26% of those with rheumatoid arthritis have the epitope recognized by antibody 109d6, but lack the specificity DR4. Of these, one-third expresses only HLA DR1 and DQw1 (MT1, MB1) determinants. Studies of family members reveal that here the determinants 109d6, DR1, and DQw1 are encoded by the same unusual haplotype. In certain other individuals with rheumatoid arthritis who express DR4, DRw53, and the 109d6 determinants, family studies show that the 109d6 epitope is encoded not only by the haplotype specifying DR4 but also by the opposite haplotype that does not bear the genes for DR4. This suggests that homozygosity for certain Ia epitopes is relevant to determining the disease-susceptibility state. These studies emphasize the utility of monoclonal antibodies as reagents for the recognition of Ia epitopes that are more closely involved in the determination of disease susceptibility than are allomorphic molecules detected by conventional typing alloantisera

The induction of most immune responses requires the close cooperation between T cells and antigen-presenting cells (APC), presumably of monocyte/macrophage (M phi) lineage. To characterize human APC further, we used two monoclonal antibodies, OKM1 and OKM5, to isolate and identify M phi subsets. OKM1 has been described and recognizes cell surface antigens on most M phi and granulocytes. OKM5 recognizes cell surface determinants present on the majority of human M phi but does not recognize other hematopoietic cell types. A small subset of peripheral blood M phi is OKM1-OKM5+. Human peripheral blood E- cells were separated into OKM1+ and OKM1- subsets by a rosetting technique utilizing anti-Ig-coated red cells. The capacity to present self antigens in the autologous mixed lymphocyte culture (AMLC) resided predominantly within the E-OKM1- subset, even if surface membrane Ig-positive cells were eliminated. Similar experiments showed that the ability to stimulate in AMLC was contained in the E-OKM5+ population and in fact resided primarily within the E-OKM1-OKM5+ subset. All of these subsets were able to trigger allogeneic T cells to proliferate. The capacity of these APC subsets to present soluble antigens (mumps, tetanus toxoid) was also examined. The data demonstrated that although the majority of these APC are E-OKM1+, E-OKM1-OKM5+ cells can also present foreign antigen. Taken together, these data suggest OKM1 and OKM5 can be used to isolate two functionally distinct human M phi subsets. One subset (E-OKM1+) is capable of presenting soluble antigens but shows minimal ability to trigger AMLC. The other subset (E-OKM1-OKM5+) can also present soluble antigens but is the predominant subset that can trigger AMLC.

In the present report, we characterize a monoclonal antibody directed at a surface differentiation antigen on human T cells. The monoclonal antibody, OKT17, recognizes a cell surface antigen present on the majority of resting normal peripheral T cells. In contrast, OKT17 is unreactive with normal B cells, B cell lines, T cell lines, or SIg+ CLL. Interestingly, after activation, the antigen recognized by OKT17 is lost from a subset of OKT4+ cells. We took advantage of this finding to explore further the functional heterogeneity within activated OKT4+ cells. Evidence was obtained that the PWM-activated OKT4+ subset remaining after depletion of OKT17-reactive T cells (OKT4+ 17-) contains radiosensitive helperr cells but is devoid of suppressor cells. In contrast, the activated OKT4+ 17+ population contains potent radiosensitive suppressor cells as well as radioresistant helpe cells. Taken together, these studies suggest that the OKT17 monoclonal antibody can differentiate two functionally mature, activated OKT4+ human T cells: OKT4+ OKT17+ radiosensitive suppressor cells and OKT4+ 17- radiosensitive helper cells.

Human peripheral blood E+ lymphocytes were alloactivated by E- cells and then purified by repeat E+ selection. As described by others, alloactivated cells (E+d6) but not unactivated E+ cells were capable of stimulating both allogeneic and autologous mixed lymphocyte cultures (MLC). To further characterize the subset of cells responsible for this function, we used a variety of monoclonal antibodies to human T cells and monocytes. Treatment of E+d6 cells with anti-Ia OKI1) plus complement (C) abrogated their stimulating capacity. In contrast, treatment with the anti-T cell antibodies OKT3, OKT11A, OKT4, OKT8 plus C or anti-macrophage antibody (OKM1) plus C failed to eliminate their MLC stimulatory capacintibodies to human T cells and monocytes. Treatment of E+d6 cells with anti-Ia OKI1) plus complement (C) abrogated their stimulating capacity. In contrast, treatment with the anti-T cell antibodies OKT3, OKT11A, OKT4, OKT8 plus C or anti-macrophage antibody (OKM1) plus C failed to eliminate their MLC stimulatory capacintibodies to human T cells and monocytes. Treatment of E+d6 cells with anti-Ia OKI1) plus complement (C) abrogated their stimulating capacity. In contrast, treatment with the anti-T cell antibodies OKT3, OKT11A, OKT4, OKT8 plus C or anti-macrophage antibody (OKM1) plus C failed to eliminate their MLC stimulatory capacity. Because OKT3 recognizes the majority of T cells and OKT11A recognizes virtually all E+ cells, we reasoned that a contaminating non-T cell containing the MLC-stimulating capacity may be present within the alloactivated E+ population. To further address this question, E+d6 cells were positively and negatively selected using a rosetting technique with anti-Ig-coated red cells. The positively selected OKT3, OKT11A, OKT4, or OKT8 E+d6 cells retained minimal ability to stimulate MLC, whereas the corresponding negatively selected populations were highly enriched in this function. Phenotypic analysis of the isolated populations failed to demonstrate greater than 1% surface membrane Ig(SmIg) positive cells. Taken together, these results suggest that the MLC stimulatory capacity of alloactivated E+ cells is contained within an Ia+, OKM1-, SmIg- non-T cell subset.

A monoclonal antibody, PVR-11, was obtained after hybridization of X63Ag8.653 murine myeloma cells with spleen cells from a mouse immunized with human lymphocytes. It recognizes a 175,000- to 185,000-dalton surface antigen present on approximately 80% of normal human peripheral T lymphocytes, 50% of non-T non-B cells, and less than 10% of B cells as determined by complement-dependent microcytotoxicity. It is also present on various leukemia T cells, on some but not all T lymphoblastoid cell lines, and on a small fraction of some B lymphoblastoid cell lines. Some B-cell chronic lymphocytic leukemia cells also express the PVR-11 antigen. Functional analysis of normal human T lymphocytes demonstrated that the PVR-11-depleted T-cell subset contains the precursors of both cytotoxic and suppressor cells but lacks helper cells. On the other hand, cytotoxic effector T cells express the PVR-11 antigen. These results demonstrate that antigenic determinants with relatively wide tissue distribution can dissect functionally distinct human immunoregulatory T-cell subsets.