Reactive fibrohistiocytic proliferation simulating fibrous histiocytoma

A pelvic nodule was excised at the time of reexploration of the abdomen in a 32-year-old women who had previously had a malignant germ cell tumor with a mixed histologic pattern of the right ovary. The 3-cm firm lesion from the right vaginal apex was composed predominantly of spindle cells with a prominent storiform pattern. Some findings, such as the presence of foamy histiocytes and a focal foreign body reaction with polarizable material, were atypical for a lesion otherwise quite acceptable histologically as a fibrous histiocytoma. Ultrastructural findings also tended to support the reactive rather than neoplastic nature of this mass. There is a similarity to the silica reaction described by Weiss and co-workers (Cancer 42:2738-2743, 1978).     

Genomic screen for loci associated with alcohol dependence in Mission Indians.

Alcohol dependence is a leading cause of morbidity and mortality in Native Americans, yet biological factors underlying the disorder in this ethnic group remain elusive. This study's aims were to map susceptibility loci for DSM-III-R alcohol dependence and two narrower alcohol-related phenotypes in Mission Indian families. Each participant gave a blood sample and completed an interview using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) that was used to make alcohol dependence diagnoses and the narrower phenotypes of withdrawal, and drinking severity. Genotypes were determined for a panel 791 microsatellite polymorphisms. Analyses of multipoint variance component LOD scores for the dichotomous DSM-III-R phenotype revealed no peak LOD scores that exceeded 2.0 at any chromosome location. Two chromosomes, 4 and 12, had peak LOD scores that exceeded 2 for the alcohol use severity phenotype and three chromosomes 6, 15, 16 were found to have peaks with LOD scores that exceeded 2 for the withdrawal phenotype. Evidence for linkage to chromosomes 4 and 15, and 16 have been reported previously for alcohol related phenotypes whereas no evidence has as yet been reported for chromosomes 6 and 12. Combined linkage and association analysis suggest that alcohol dehydrogenase 1B gene polymorphisms are partially responsible for the linkage result on chromosome 4 in this population. These results corroborate the importance of several chromosomal regions highlighted in prior segregation studies in alcoholism and further identify new regions of the genome that may be unique to either the restricted phenotypes evaluated or this population of Mission Indians.     

2B4-mediated activation of human natural killer cells

2B4 is a member of the CD2 subset of the immunoglobulin superfamily of cell surface receptors. Other members of this family include CD2, CD48, CD58, CD84, signaling lymphocytic activation molecule and Ly-9. Some of these molecules are activating structures expressed by natural killer cells and T cells. We have recently cloned and characterised the human homologue of 2B4 and found that the cytoplasmic domain of 2B4 can interact with SAP, a signaling adaptor protein that is mutated in the immunodeficiency X-linked lymphoproliferative disease (XLP). Additionally, the natural ligand of 2B4 has been identified as CD48. These findings have facilitated the investigation of the functional role of this receptor-ligand pair, and associated signal transduction pathways, on immune cells. In this study, it was found that the interaction between 2B4 on effector cells and CD48 on target cells induced NK-cell activation, as evidenced by increased cytotoxicity and secretion of IFN-gamma. The responses induced by ligation of 2B4 could be reduced by the co-ligation of inhibitory receptors expressed by NK cells, demonstrating that activation signals delivered via 2B4 can be regulated by the action of certain inhibitory receptors. Because the signalling pathway of 2B4 involves SAP, it is possible that 2B4-mediated NK-cell activation may be compromised in patients with XLP due to mutations in SAP. This may contribute to the phenotype and progression of this disease.     

Carcinoma of the lung and coexistent active pulmonary tuberculosis: diverse morphologic and radiographic presentations

Five patients with coexistent carcinoma of the lung and active tuberculosis within the same pulmonary lesion were studied. These cases represent five distinctly varying radiographic presentations and point out the extreme diversity of the morphological pictures of this particular disease combination. Physicians who regularly deal with patients who might present with either entity alone are cautioned to be alert to the possibility that these two diseases may be present simultaneously within single, specific pulmonary lesions.     

Recombinant congenic strains of mice from B10.D2 and DBA/2: Their contribution to behavior genetic research and application to audiogenic seizures

Recombinant congenic strains (RCS) represent a series of related strains, each of which carries a small fraction of the genome of one strain (donor strain) on the genetic background of another strain (background strain). Recombinant inbred strains (RIS) are commonly used to identify major gene segregation and linkage and associations between behavior and quantitative trait loci, whereas recombinant congenic strains (RCS) open other complementary leads. The variability in the reactivity of RCS to a trait is thus the expression of few minor-effect genes originating from the donor strain, because the probability that major genes are present in any one RCS is low. Unlike RIS in which minor-effect genes are often masked by major genes, RCS enable the effects of minor genes to be studied. With our method, for a given trait, an estimate can be made of the gene strength distribution as well as an estimate of the minimal number of genes involved having a certain strength.This study was supported by the Centre National de la Recherche Scientifique (URA 1924 and CSEAL-UPS 44, CNRS), Université René-Descartes, Paris V UFR Biomédicale, and the Fondation pour la Recherche Médicale.     

Congenital anomalies and genetic disorders in families of children with central nervous system tumours.

Medical genetic histories of 165 children with primary central nervous system (CNS) tumours and 4599 relatives of these probands were examined to identify birth defects or genetic disorders that may be associated with the aetiology of CNS tumours. Twelve primary malignancies were found in 329 (4%) of the parents of probands. Two of 99 half sibs but no full sibs had malignancies. Twenty-four percent of families had histories warranting consultation for an inherited disorder or birth defect. Single instances of malformations or genetic disorders were reported in 36 families and several disorders were reported in more than one family, including familial hypercholesterolaemia (4), olivopontocerebellar atrophy (2), and familial abdominal aortic aneurysm (2). Although recurring abnormalities were not identified in probands, it is possible that one or more of the birth defects or genetic disorders observed in probands or relatives may be associated with CNS tumourigenesis.     

Decreased intraocular pressure and aqueous humor turnover rate during longitudinal ocular studies in the rabbit

One group of 5 pigmented rabbits, during a period of 10 weeks, and two groups of 8 albino rabbits, during 16 weeks, showed a fall in aqueous turnover rate and outflow facility of about 30%. A fall in intraocular pressure also occurred of about 10 mm Hg. The biochemical correlative mechanism, systemic and/or local, is conjectural (reduction of "stress"; homeostasis). Empirically a parallel completely untreated control group should accompany any longitudinal study group in order to differentiate these temporal trends from experimental effects.     

High density lipoprotein cholesterol is not a major risk factor for ischaemic heart disease in British men

The concentration of high density lipoprotein cholesterol (HDL cholesterol) in serum was measured at initial examination in a large prospective study of men aged 40-59 drawn from general practices in 24 British towns. After an average follow up of 4.2 years 193 cases of major ischaemic heart disease had been registered in 7415 men in whom both HDL cholesterol and total cholesterol values had been measured. The mean HDL cholesterol concentration was lower in the men with ischaemic heart disease ("cases") compared with other men, but the difference became small and non-significant after adjustment for age, body mass index, blood pressure, cigarette smoking, and concentration of non-HDL cholesterol. The higher mean concentration of non-HDL cholesterol in "cases" remained highly significant after adjustment for other factors. Men in the highest fifth of non-HDL cholesterol values had over three times the risk of major ischaemic heart disease compared with men in the lowest fifth. Multivariate analysis showed that non-HDL cholesterol was a more powerful predictor of risk than the HDL to total cholesterol ratio. These British findings were compared with six other prospective studies. All the larger studies showed similar results, suggesting that HDL cholesterol is not a major risk factor in the aetiology of ischaemic heart disease.