Effects of interleukin-3 on hematopoietic recovery after 5-fluorouracil or cyclophosphamide treatment of cynomolgus primates.

Interleukin-3 (IL-3) is a hematopoietic growth factor that supports the growth of early hematopoietic progenitors in vitro. In vivo administration of recombinant human interleukin-3 (rhIL-3) to normal primates results in a modest and delayed leukocytosis secondary to increases in neutrophils, basophils, and eosinophils. We postulated that the effects of rhIL-3 might be more pronounced in hematologically stressed primates, and therefore administered rhIL-3 to primates after intensive myelosuppressive therapy. Primates received either cyclophosphamide (CPM) at 60 mg/kg or 5-fluorouracil (5-FU) at 75 mg/kg i.v. on two consecutive days. Subsequently, rhIL-3 was administered intravenously or subcutaneously at 20 micrograms/kg per d for 14 d. Compared to controls, all rhIL-3 treated primates experienced higher absolute neutrophil count (ANC) nadirs and dramatic decreases in the period of severe neutropenia (ANC less than 500) after myelosuppressive therapy. RhIL-3 administration resulted in a significant basophilia and eosinophilia, which resolved after discontinuation of the drug. RhIL-3 did not enhance erythroid recovery. Platelet recovery was earlier in rhIL-3-treated animals. However, variations in the platelet recovery observed in control animals, precluded accurate estimation of this effect or its significance. Our results indicate that the administration of rhIL-3 following intensive myelosuppressive therapy dramatically enhances myeloid recovery and ablates the predicted period of prolonged severe neutropenia.     

Guidelines for implementation of population-based newborn screening for severe combined immunodeficiency

Severe combined immunodeficiency (SCID) is a Primary Immune Deficiency that is under consideration for population-based newborn screening (NBS) by many NBS programs, and has recently been recommended for inclusion in the US uniform panel of newborn screening conditions. A marker of SCID, the T cell receptor excision circle (TREC), is detectable in the newborn dried blood spot using a unique molecular assay as a primary screen. The New England Newborn Screening Program developed and validated a multiplex TREC assay in which both the TREC analyte and an internal control are acquired from a single punch and run in the same reaction. Massachusetts then implemented a statewide pilot SCID NBS program. The authors describe the rationale for a pilot SCID NBS program, a comprehensive strategy for successful implementation, the screening test algorithm, the screening follow-up algorithm and preliminary experience based on statewide screening in the first year. The Massachusetts experience demonstrates that SCID NBS is a program that can be implemented on a population basis with reasonable rates of false positives.     

Celiac disease in a patient with systemic lupus erythematosus: a case report and review of literature

Celiac disease (CD) is an inflammatory condition of the gut with a known autoimmune pathogenesis. Many similarities exist between the pathogenesis of CD and systemic lupus erythematosus (SLE); it is still unknown whether there is an association. There are 13 case reports in the literature of both diseases occurring simultaneously. We report another patient who was diagnosed with SLE and 8 years later, developed CD. A review of the literature is also presented.     

Well-being and family support among elderly rural Mexicans in the context of migration to the United States

OBJECTIVE: To explore perceptions of well-being, family support, and economic resources in relation to level of contact with migration to the U.S. among a sample of elderly males from rural Mexico. METHOD: The snowballing technique was used to obtain a sample of 372 participants. Four groups were created according to the level of contact with migration among older adults and their children. RESULTS: Greater level of contact with migration was associated with a higher likelihood that an older adult was literate, married or living with someone, self-employed, and retired or pensioned. In addition, greater level of contact with migration to the U.S. was associated with a higher level of perceived well-being, family support, and economic security. DISCUSSION: Elderly, rural Mexican men with a greater degree of contact with migration to the U.S. seem to have more security and well-being in their old age.     

CCL genes in multiple sclerosis and systemic lupus erythematosus

This follow up study aims to refine the roles of previously suggested candidate genes (CC chemokine ligands or CCLs) in multiple sclerosis (MS), and to test these markers in another autoimmune disorder, systemic lupus erythematosus (SLE). After stringent correction for multiple testing, we reject the importance of previously suggested borderline associations with CCLs in MS. A new finding is the differential distribution of CCL8 marker alleles and a haplotype in extreme severity subgroups of MS. In SLE, this study reveals strong associations with a marker and a haplotype encompassing the CCL14 gene, which suggests that a lupus relevant variant may lie within or in the proximity of this haplotype.     

Arteriovenous fistula for long-term venous access for boys with hemophilia

OBJECTIVES: Hemophilia is a sex-linked condition affecting about 1 of every 5000 males in the United States. The management of children with hemophilia can be improved with regular intravenous infusion of factor VIII or IX, thus preventing crippling and sometimes fatal hemorrhage. Maintaining this vital intravenous access is often hampered by gradual loss of superficial veins or repeated central catheter sepsis and thrombosis. This study reviewed an experience with arteriovenous fistula in selected hemophilia patients with limited venous access. METHODS: Consecutive patients operated on between October 2000 and July 2006 for venous access with the creation of an arteriovenous fistula were reviewed. They were selected because of repeated problems with other venous access. Patency, ease of use, duplex scan derived brachial artery diameter, and arm length were assessed. RESULTS: During a 69-month period, 10 arteriovenous fistulas (five brachial artery-basilic vein fistulas, 5 brachial artery-cephalic vein fistulas) were created for nine patients. The patients were a median age of 5.5 years (range, 1 to 27 years), and all were <13 except the 27-year-old patient. There were no postoperative hematomas requiring evacuation. One arteriovenous fistula failed to mature and was redone in the opposite arm, which subsequently occluded after 13 months. Of the mature fistulas, patency was 100% at 1 year, 80% (4/5) at 3 years, and 75% (3/4) at 4 years, with mean follow-up of 22 months. Brachial artery diameter increased in the involved arm by a ratio of 1.95 (range, 1.51 to 2.5) compared with the opposite arm. Arm length disparity was increased by 0.5 cm (range, 0.8 to 1.5 cm) in the involved arm. All fistulas allowed good access at home by a care provider. CONCLUSIONS: For hemophilia patients with compromised venous access, arteriovenous fistulas provide good early patency. Brachial artery diameter and arm length require continued follow-up.     

Identification of midbrain floor plate radial glia-like cells as dopaminergic progenitors

The floor plate (FP), a signaling center and a structure rich in radial glia-like cells, has been traditionally thought to be devoid of neurons and neuronal progenitors. However, in the midbrain, the FP contains neurons of the dopaminergic (DA) lineage that require contact with radial glia-like cells for their induction. We, therefore, decided to explore the interaction relationship between radial glia and neurons during DA neurogenesis. Taking advantage of a novel FP radial glia-like cell culture system and retroviruses, DA neurons were lineage traced in vitro. In utero BrdU pulse-chases extensively labeled the midbrain FP and traced DA neurons both in vivo and in FP cultures. Moreover, from E9.5 to E13.5 the midbrain FP contained dividing cells only in the most apical part of the neuroepithelium, in cells identified as radial glia-like cells. We, therefore, hypothesized that midbrain FP radial glia-like cells could be DA progenitors and tested our hypothesis in vivo. Lineage tracing of DA progenitors with EGFP in Tis21-EGFP knock-in mice, and genetic fate mapping in GLAST::CreERT2/ZEG mice identified the neuroepithelium of the midbrain FP, and specifically, GLAST+ radial glia-like cells as DA progenitors. Combined, our experiments support the concept that the midbrain FP differs from other FP regions and demonstrate that FP radial glia-like cells in the midbrain are neurogenic and give rise to midbrain DA neurons.     

Clinicopathological characteristics of breast carcinomas with allelic loss in the p73

p73, a new member of the p53 family, has been mapped to chromosome 1p36, a region where loss of heterozygosity (LOH) is frequently observed in primary human tumors. Allelic loss studies involving the 1parm in breast carcinomas offer rates ranging from 13% to 75%, depending on the genetic interval being studied. We investigated LOH in an intragenic microsatellite marker, and those centromerically flanking the p73 gene, at 1p36, and their correlations with patient age and 10 pathologic parameters in a series of 193 breast carcinomas. The LOH analysis was performed by amplifying DNA by PCR, using five markers of the 1p36 region (p73P1, D1S2694, D1S214, D1S2666 and D1S450). LOH was found in at least one of these markers in 27% of tumors. When we established the comparison between tumors with and without LOH and the distribution of the 10 pathologic parameters considered, we observed statistically significant differences in association with higher histologic grade (p=0.02), more advanced pathological stage (p=0.02), peritumoral vessel involvement (p=0.04) and poorly differentiated carcinomas (p=0.01), as well as in tumors that concomitantly exhibited lymph node metastases, peritumoral vessel involvement and absence of steroid receptors (p=0.02). These data suggest that LOH in the p73 region could be pathogenically related to breast cancer and possibly to a poor tumor prognosis.