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PubMed1996

Nasal T-cell lymphoma causally associated with Epstein-Barr virus: clinicopathologic, phenotypic, and genotypic studies.

BACKGROUND: The authors have previously demonstrated nasal T-cell lymphoma (NTL) associated with Epstein-Barr virus (EBV). The detailed clinical, phenotypic, and genotypic features and the role of EBV in lymphomagenesis remain to be clarified. METHODS: The study group consisted of 18 patients with NTL. The phenotype was determined by immunoperoxidase staining with various monoclonal antibodies. Genotypic study was done using Southern blot hybridization. The presence of EBV-encoded small nuclear early region (EBER) RNA and EBV DNA were determined by in situ hybridization. The expression of EBV-encoded nuclear antigen (EBNA) and latent membrane protein (LMP1) were identified by immunohistologic methods. Clonotypic analysis of EBV genomes was performed by Southern blot hybridization with EBV termini fragment probe. RESULTS: The clinical features of NTL were characterized as prolonged fever (16 patients), widespread dissemination into distant sites (13 patients), and poor prognosis with a median survival of only 6 months. EBER transcripts were identified in 16 of 18 patients. Monoclonal EBV genomes EBNA1 and LMP1 were also detected in all EBER-positive cases tested. All 18 patients expressed pan-T antigens such as MT1, CD45RO, and/or CD2. The rearrangements of T-cell receptor (TCR)-beta, -gamma, and/or -delta genes were shown in all 11 patients tested. The natural killer (NK) cell phenotype CD56 was expressed in all EBV-positive cases tested, and was not detected in EBV-negative cases. Seven EBV-positive cases expressed a TCR-delta chain with rearranged TCR-gamma or -delta genes whereas both EBV-negative cases corresponded to alpha beta T-cell lymphoma, which expressed a TCR-beta chain with a rearranged TCR-beta gene. CONCLUSIONS: These data suggest that EBV-positive NTL may be derived from the lineage of NK-like T-cells or gamma delta T-cells, and that EBV may play a role in lymphomagenesis. Therefore, we propose that NTL which has peculiar clinical and histologic features could be classified as a new lymphoma entity.

Adult↗
PubMed1996

Coexistence of renal cell carcinoma and malignant lymphoma. A causal relationship or coincidental occurrence?

BACKGROUND: Secondary malignant neoplasms are increasingly being observed in cancer populations and a considerable amount of data have accumulated in the literature. Among the secondary malignant neoplasms that occur with a higher incidence in cancer patients are lymphomas and renal cell carcinoma (RCC), as well as melanoma, lung/bronchus carcinoma. METHODS: The authors analyzed the patient population at the Memorial Sloan-Kettering Cancer Center in New York City between 1985 and 1995 for coexisting carcinomas, and identified 15 patients who had both RCC and malignant lymphoma among a total of 1262 patients with RCC and 1660 patients with malignant lymphoma. The occurrence and time of diagnosis of both malignant neoplasms and their clinical features, types, and stages, as well as short term follow-up, results, are presented. RESULTS: The data show a greater than coincidental coexistence of RCC and malignant lymphoma (P < 0.01). In addition, there was a significant increase in the number of patients with both melanoma and RCC (P < 0.01), as well as melanoma and malignant lymphoma (P < 0.01). No significant increase was found in cases of coexisting RCC or malignant lymphoma with either lung/bronchus carcinoma or colorectal carcinoma (P > 0.05). CONCLUSIONS: Causes of this increased coexistence may include a genetic predisposition to cancer, similar immune mechanisms associated with these neoplasms, closer scrutiny of this group of patients, or a combination of these factors. Studies are underway to elucidate a common genetic component in these patients.

Adult↗
PubMed1996

Familial eating concerns and psychopathological traits: causal implications of transgenerational effects.

OBJECTIVE: This study extends an earlier investigation on the link between familial traits and eating disorders (EDs), and examines the extent to which selected eating attitudes and psychopathological traits are (a) familial in nature and (b) specific to anorexia- and bulimia-spectrum disorders. METHODS: We measured various ED-relevant dimensions (eating and body image attitudes) and psychopathological traits (e.g., affective instability, narcissism, compulsivity, restricted expression) in the mothers, fathers, and sisters of probands displaying an ED (n = 88), another psychiatric disturbance (n = 42), or neither disturbance (n = 59). Total sample, including relatives, was 553. RESULTS: A principal components analysis (PCA), used to reduce variables and to characterize main sources of variation, yielded three interpretable factors: eating concerns and symptoms (grouping all eating-related dimensions), dramatic-erratic traits (grouping affective instability, narcissism, and conceptually related dimensions), and obsessive-compulsive traits (grouping compulsivity and restricted expression). Correlations among subjects' factor scores (derived from the PCA) showed two types of transgenerational effects: correspondences between daughters' and parents' psychopathological traits, and between daughters' and mothers' eating concerns. Despite these, relatives of ED probands were not discriminable on any factor score from relatives of controls. DISCUSSION: These results imply that transgenerational effects exist on eating attitudes and psychopathological traits, but do not uniquely identify families in which clinical ED syndromes occur.

Adolescent↗
PubMed1996

Heterogeneous rates for birth defects in Latin America: hints on causality.

The aim of this work was to disclose risk factors associated with birth defects which were heterogeneously distributed in the different geographic regions sampled by the Latin American Collaborative Study of Congenital Malformations (ECLAMC). The material included 2,159,065 hospital births, delivered in the 1967-1989 period in 24 geographic regions of Latin America. Birth defect types with 50 case-control pairs or more were analyzed. A risk factor was defined as that available variable with differential geographic rates, correlated with those of a given birth defect type. Identified factors were tested by case-control multivariate logistic regression to confirm their role in the occurrence of the defect. Altitude and maternal acute illness during first trimester of pregnancy, named influenza, were risk factors for microtia. Prenatal drug exposure, mainly sex hormones, were connected with the occurrence of hypospadias in low frequency areas, while Native ancestry was a "protective" factor in the same regions. Acute (influenza), and chronic (epilepsy and syphilis) maternal illness during first trimester of pregnancy and gravidity higher than four were risk factors for cleft lip. The independence of these variables from maternal age suggested that low maternal socioeconomic level could explain the high birth defect order and, perhaps, syphilis in mothers. Postaxial polydactyly was associated with parental consanguinity, as well as Afro-American ancestry, suggesting genetic heterogeneity.

Case-Control Studies↗
PubMed1998

Testing causal hypotheses in multivariate linkage analysis of quantitative traits: general formulation and application to sibpair data.

We provide a general framework for the development of model-free methods for the linkage analysis of multivariate phenotypic data. It is possible within this framework to test both for linkage of a set of phenotypes to one or more markers and for the presence of structural relations among the phenotypes themselves. This report presents the general model, paying special attention to the assumptions that enter its formulation, and outlines the estimation procedures that may be used.

Chromosome Mapping↗
PubMed1995

Reported sexual abuse and eating psychopathology: a review of the evidence for a causal link.

It has been claimed that there is no specific link between a reported history of sexual abuse and the eating disorders. In particular, studies and reviews investigating the relationship between reported sexual abuse and the eating disorders have concluded that the prevalence rate of abuse among eating-disordered women is similar to the rates found in other psychiatric groups and in the general population. However, it is argued in this review that such a conclusion is based on an inappropriate level of analysis of the phenomena of sexual abuse and diagnosable eating disorders. When these two relatively blunt constructs are considered in finer detail, there appears to be a complex link between the nature of sexual abuse and specific bulimic symptomatology. This relationship is discussed with particular reference to important mediating factors (including dissociation, self-denigration, borderline personality disorder, and disclosure experiences), the functions of the bulimic behaviors, and the particular cognitive schemata that the victims of abuse may develop. The clinical implications of this relationship are considered, and suggestions are made for further research.

Adolescent↗
PubMed1976

Active power and causal flow in Aristotle's theory of vision.

Aristotle's theory of vision has been characterized as naive, incommensurate with his theory of audition, and of historical interest only. This view is based on an analysis which fails to acknowledge the role of the concepts acting upon and active power in the theory. The meaning of these terms and the role Aristotle assigned them in vision and in sensation generally is demonstrated. It is argued that with the inclusion of these concepts (1) the theory of vision is sufficiently sophisticated and modern to be more than comparable with more recent perceptual theorizing, and (2) theoverall integrity of Aristotle's sensory philosophy is preserved. It is further argued that given the cohesiveness and comprehensiveness of Aristotle's psychological works, more attention should be given them by modern psychologists.

Greece, Ancient↗
PubMed2001

Do studies of wire code and childhood leukemia point towards or away from magnetic fields as the causal agent?

A long-standing point of controversy in the epidemiologic literature concerns the meaning of a wire code-childhood leukemia association for assessing the role of magnetic field exposure. Six studies of wire codes and childhood leukemia in North America were examined, three of which reported positive associations and all of which found some relation between wire codes and measured magnetic fields. Supporting magnetic fields as the basis for the wire code associations are the correspondence between those wire code levels which predict distinct magnetic fields and those which predict leukemia risk in the positive studies. Geographic locations and methods that refine wire codes as magnetic fields predictors also tend to strengthen the association with leukemia. Opposing arguments are based on the failure of the wire code-magnetic field association to predict the strength of association across studies, including the unexplained lack of association between wire codes and leukemia in the Midwest and in Canada. Alternatives to magnetic fields are less supported; residential mobility, social class, and neighborhood characteristics are unlikely to explain a wire code effect. Ambiguity persists because of the modest strength of the wire code-leukemia association, the complexity of the relation between wire codes and magnetic fields, lack of knowledge of risk factors for childhood leukemia, and the limited evaluation of wire code correlates other than magnetic fields.

Canada↗
PubMed2001

Elevated Bcl-2 is not a causal event in the positive selection of T cells.

T cell development is characterized by the induction of apoptosis in most immature thymocytes and the rescue from apoptosis of a small proportion of cells by the process of positive selection.Up-regulation of the anti-apoptotic molecule Bcl-2 is associated with thymocytes undergoing positive selection and a bcl-2 transgene promotes the generation of mature T cells. In contrast,mice transgenic for the pro-apoptotic molecule Bax show impaired T cell maturation. We have used fetal thymic organ culture to determine the action of Bcl-2 and Bax on positive selection of thymocytes. Our data show that Bcl-2 and Bax do not alter the number of thymocytes positively selected by a defined peptide ligand. This implies that Bcl-2 and Bax alter the production of mature T cells in vivo by influencing thymocyte viability rather than by direct action on positive selection. It also presents a solution to the 'chicken-and-egg' scenario relating to Bcl-2 up-regulation and positive selection. The data suggest that the up-regulation of Bcl-2 associated with T cell maturation is a consequence of positive selection rather than a cause of it.

Animals↗
PubMed1984

Myoblast fusion and inositol phospholipid breakdown: causal relationship or coincidence?

The fusion of embryonic chick myoblasts has been examined in culture. Cells were prepared from 12-day-old chick embryonic breast muscle and cultured for 50 h at a Ca2+ concentration in the medium of 10(-7) M. During this period they attain fusion competence. Addition of 1.4 mM-Ca2+ to these cells elicits rapid fusion. Changes in the metabolism of myoblast phospholipids in response to the raised Ca2+ concentration have been examined. Only the inositol phospholipids are affected. Phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate are rapidly broken down and 1,2-diacylglycerol and phosphatidic acid are synthesized. Myoblast fusion has also been found to be stimulated by a factor present in chick embryo extract, probably of neuronal origin. A receptor-mediated mechanism for myoblast fusion is proposed. This envisages the polyphosphoinositides acting as a fusion block, either themselves or by their binding to membrane proteins. The inositol phospholipid breakdown could result in a more fluid membrane and the breakdown products 1,2-diacylglycerol and phosphatidic acid, two known fusogens, could stimulate fusion.

Animals↗
PubMed2002

Platelet satellitism, spurious neutropenia, and cutaneous vasculitis: casual or causal association?

About 90 cases of platelet satellitism (PS) have been published, most of them involving neutrophils, a few comprising monocytes, and one case involving basophils. The case of a 30-year-old female patient with cutaneous vasculitis who developed asymptomatic severe neutropenia is reported. All blood smears (BS) prepared from peripheral blood samples collected with either ethylenediaminetetraacetic acid, trisodium citrate, and heparin showed PS involving neutrophils, eosinophils, and monocytes. Immunohistochemistry analysis of her skin biopsy and BS, employing peroxidase stain for the detection of antibodies directed against IgG, IgA, IgM, and C3, revealed an intense positive reaction only for IgG in the endothelium and leukocyte clumps within the microvasculature, as well as in peripheral blood neutrophils displaying the PS phenomenon. Transfer of the PS phenomenon was demonstrated by incubating the patient's plasma with leukocytes from an ABO-compatible healthy donor. In our patient, PS did not disappear after incubation at 37 degrees C, suggesting that this might be a different or "atypical" PS phenomenon probably mediated by an autoimmune process involving an IgG-class antibody responsible for both conditions, PS, and cutaneous vasculitis.

Adult↗