Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.     

Rapid changes in the gut microbiome during human evolution

Humans are ecosystems containing trillions of microorganisms, but the evolutionary history of this microbiome is obscured by a lack of knowledge about microbiomes of African apes. We sequenced the gut communities of hundreds of chimpanzees, bonobos, and gorillas and developed a phylogenetic approach to reconstruct how present-day human microbiomes have diverged from those of ancestral populations. Compositional change in the microbiome was slow and clock-like during African ape diversification, but human microbiomes have deviated from the ancestral state at an accelerated rate. Relative to the microbiomes of wild apes, human microbiomes have lost ancestral microbial diversity while becoming specialized for animal-based diets. Individual wild apes cultivate more phyla, classes, orders, families, genera, and species of bacteria than do individual humans across a range of societies. These results indicate that humanity has experienced a depletion of the gut flora since diverging from Pan.The human microbiome is shaped by host genetics, environment, and lifestyle (1–3); thus, humanity''s unique evolutionary and cultural histories must have altered our associations with microorganisms (4). Despite intensive investigation of the microbiomes of humans spanning a range of geographic locations and cultures (5–7), how the composition of the microbiome has changed since humans diverged from other species, and since human populations diverged from one another, remains unclear, owing to a lack of knowledge about the microbiomes of ancestral hominid populations.Understanding how the composition of the human microbiome has changed over evolutionary time requires the inclusion of the microbiomes of phylogenetic outgroups (i.e., the African apes) into analyses of human microbiomes. Previous comparisons of the gut microbiomes of humans and the African apes have been restricted to just a few individuals per host species (8), precluding detection of the precise compositional differences that distinguish the microbiomes of the host species. Comparing the microbiomes of populations of chimpanzees, bonobos, gorillas, and humans while considering the phylogenetic relatedness among the hosts can reveal how the composition of the microbiome has changed since the host species diversified.Here we used a phylogenetic approach to identify the shifts in the composition of the microbiome that occurred along the lineages leading to the extant species of Homo and Pan. This analysis shows that humans across a range of cultures and geographies harbor microbiomes that are disproportionately divergent from those within wild apes. In particular, among the living hominid species, humans harbor uncharacteristically low levels of microbial diversity within their gut microbiomes.     

Idiopathic CD4 Lymphocytopenia: Clinical and Immunologic Characteristics and Follow-Up of 40 Patients

Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria.We recruited 40 patients (24 female) of mean age 44.2 ± 12.2 (19–70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-γ release by natural killer (NK) cell were performed. Mean follow-up was 6.9 ± 6.7 (0.14–24.3) years. Infectious, autoimmune, and neoplastic events were recorded, as were outcomes of interleukin 2 therapy.In all, 25 patients had opportunistic infections (12 with human papillomavirus infection), 14 had autoimmune symptoms, 5 had malignancies, and 8 had mild or no symptoms. At the time of diagnosis, the mean cell counts were as follows: mean CD4 cell count: 127/mm³ (range, 4–294); mean CD8: 236/mm³ (range, 1–1293); mean CD19: 113/mm³ (range, 3–547); and mean NK cell count: 122/mm³ (range, 5–416). Most patients had deficiency in CD8, CD19, and/or NK cells. Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01). Patients with autoimmune manifestations had increased CD8 T-cell count. Proliferation of thymic precursors, as assessed by T-cell rearrangement excision circles, was increased. Six patients died (15%). CD4 T-cell count <150/mm³ and NK cell count <100/mm³ were predictors of death.In conclusion, ICL is a heterogeneous disorder often associated with deficiencies in CD8, CD19, and/or NK cells. Long-term prognosis may be related to initial CD4 and NK cell deficiency.Abbreviations: AIHA = autoimmune hemolytic anemia, CDC = Centers for Disease Control, CMV = cytomegalovirus, cpm = count per minute, CVID = common variable immunodeficiency, CXCR4 = C-X-C chemokine receptor type 4, HIV = human immunodeficiency virus, HLA = human leukocyte antigen, HPV = human papillomavirus, HTLV-1/2 = human T-cell lymphotropic 1/2, ICL = idiopathic CD4 T lymphocytopenia, IFN-γ = interferon-γ, IL = interleukin, JC virus = John Cunningham virus, LPA = lymphocyte proliferation assay, NK = natural killer, P = patient, PBMC = peripheral blood mononuclear cell, Pwd = pokeweed, SI = stimulation index, sj = signal joint, TREC = T-cell rearrangement excision circle     

二甲双胍和瑞格列奈对非肥胖的2型糖尿病患者非血糖性心血管危险标志的影响比较

在2型糖尿病患者中，反映炎症和内皮功能障碍的生物标志已经与心血管疾病和代谢调节联系起来。二甲双胍和促胰岛素分泌剂被证明有相同的抗高血糖作用。此研究比较了二甲双胍和促胰岛素分泌剂瑞格列奈在非肥胖的2型糖尿病患者的心血管疾病生物标志上的效能。