Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

Carcinoid tumors of the gastrointestinal tract. Analysis of 21 cases

Twenty-one patients with carcinoid tumors have been analysed. Out of 18 patients the diagnostic was made at operation and out of 3 by autopsy. The most frequent sites of the primary tumors were the appendix (38.1%), ileum (23.8%) and colon (19.9%). Asymptomatic tumors were found incidentally in 10 patients (55.5%). The symptomatic neoplasms were more common in the ileum. No one patients in this series obtained the diagnostic of carcinoid tumors before operation or autopsy. It was not observed the malignant carcinoid syndrome. Sixteen patients (88.8%) were submitted to resection and the mean survival was 10.7 years. Two patients (11.1%) were submitted to palliative operations and the mean survival was 3.5 months. The incidence of metastases in cases with carcinoid greater than 2.0 cm in diameter was 71.4%; on the other hand, the patients with carcinoids 2.0 cm in diameter or smaller than this size disclosed metastases in 7.6%. No patients with appendix carcinoid showed metastases and all patients with metastases presented ileum or colon carcinoids. In this series, the prognostic was related with the lesion's size, the localization of the tumor in the gastrointestinal tract and with the resection or not of the primary neoplasm.     

In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease

The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28 present on the latter cells. In this study, benign lymphoid tissues, lymphomas, and extralymphoid inflammatory sites were examined immunohistochemically using anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign transformed germinal center B cells, as it was by B cells of follicular lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of macrophages and dendritic cells in a variety of lymphoid tissues. It was present in abundance on all macrophages constituting sarcoid granulomas in lymph nodes. In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that potentially contributes to the lymphocytic accumulation that is a feature of this condition. CD28+ T cells were seen in all areas where T cells were present. B7+ and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a potential for cellular interaction via these molecules at these sites.     

Phenotypes of sickle cell intensive care admissions: an unsupervised machine learning approach in a single-center retrospective cohort

Annals of Hematology - Sickle cell disease (SCD) is associated with multiple known complications and increased mortality. This study aims to further understand the profile of intensive care unit...