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Biomedical subjects

A Guerriero

Publications and source records attributed to A Guerriero.

At least 19 recordsLinked to original sources

Antidisialosyl antibodies in chronic idiopathic ataxic neuropathy.

Antidisialosyl antibodies were found in two out of 13 patients with chronic idiopathic ataxic neuropathy (CIAN) and not in 32 patients with different sensory neuropathies of known cause. This finding confirms the association of antidisialosyl antibodies and CIAN regardless of the absence of the M band. These antibodies may have pathogenic relevance; however, larger series are needed to establish their clinical significance.

Aged↗

PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells.

The ets-family transcription factor PU.1 is required for the proper development of both myeloid and lymphoid progenitors. We used PU. 1-deficient animals to examine the role of PU.1 during dendritic cell development. PU.1(-/-)animals produce lymphoid-derived dendritic cells (DC): low-density class II major histocompatibility complex [MHC-II(+)] CD11c(+) CD8alpha(+) DEC-205(+). But they lack myeloid-derived DC: low-density MHC-II(+) CD11c(+) CD8alpha(-) DEC-205(-). PU.1(-/-) embryos also lack progenitors capable of differentiating into myeloid DC in response to granulocyte-macrophage colony-stimulating factor plus interleukin-4. The appearance of lymphoid DC in developing PU.1(-/-)thymus was initially delayed, but this population recovered to wild type (WT) levels upon organ culture of isolated thymic lobes. PU. 1(-/-)lymphoid DC were functionally equivalent to WT DC for stimulating T-cell proliferation in mixed lymphocyte reactions. These results demonstrate that PU.1 is required for the development of myeloid DC but not lymphoid DC.

Animals↗

T cell development in PU.1-deficient mice.

These studies address the role of PU.1 in T cell development through the analysis of PU.1-/- mice. We show that the majority of PU.1-/- thymocytes are blocked in differentiation prior to T cell commitment, and contain a population of thymocyte progenitors with the cell surface phenotype of CD44+, HSAbright, c-kitint, Thy-1-, CD25-, Sca-1-, CD4-, and CD8-. These cells correspond in both number and cell surface phenotype with uncommitted thymocyte progenitors found in wild-type fetal thymus. RT-PCR analysis demonstrated that PU.1 is normally expressed in this early progenitor population, but is down-regulated during T cell commitment. Rare PU.1-/- thymi, however, contained small numbers of thymocytes expressing markers of T cell commitment. Furthermore, almost 40% of PU.1-/- thymi placed in fetal thymic organ culture are capable of T cell development. Mature PU. 1-/- thymocytes generated during organ culture proliferated and produced IL-2 in response to stimulation through the TCR. These data demonstrate that PU.1 is not absolutely required for T cell development, but does play a role in efficient commitment and/or early differentiation of most T progenitors.

Animals↗

Chronic cigarette smoking is associated with increased plasma circulating intercellular adhesion molecule 1 levels in young type 1 diabetic patients.

OBJECTIVE: The purposes of this study were to compare plasma concentrations of circulating intercellular adhesion molecule 1 (cICAM-1), a marker of endothelial dysfunction, in nondiabetic subjects and type 1 diabetic patients and to evaluate whether chronic cigarette smoking had a deleterious effect on plasma cICAM-1 levels in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Plasma cICAM-1 concentrations were measured in 54 young type 1 diabetic patients without clinical macroangiopathy and in 20 healthy control subjects who were matched for age, sex, BMI, and smoking habit. RESULTS: Type 1 diabetic patients had significantly higher plasma levels of cICAM-1 than control subjects (280.4 +/- 59 vs. 224 +/- 53.6 ng/ml, respectively) (P < 0.001). After stratification by smoking status, diabetic smokers had values for age, sex, BMI, lipids, blood pressure, glycemic control, diabetes duration, and chronic complications of diabetes that were super-imposable on their nonsmoking counterparts. Nevertheless, plasma cICAM-1 levels were markedly elevated in type 1 diabetic smokers (321.4 +/- 64.2 vs. 257.3 +/- 41.5 ng/ml, respectively) (P < 0.001) in a dose-dependent fashion (P < 0.001 by analysis of variance when subjects were categorized by number of cigarettes smoked per day). CONCLUSIONS: Chronic cigarette smoking has a deleterious effect on plasma cICAM-1 levels in young type 1 diabetic patients, which further supports the clinical importance of discouraging the initiation of smoking and promoting its cessation in people with type 1 diabetes.

Adult↗

AlphaIFN-induced hematologic and cytogenetic remission in chronic eosinophilic leukemia with t(1;5).

Chronic eosinophilic leukemia (CEL) is a myeloproliferative disease characterized by excessive eosinophilic proliferation with clonal cytogenetic abnormalities. The most frequent cytogenetic abnormality is a break in the q 31-35 region of chromosome 5, where genes encoding for IL-3, IL-5 and GM-CSF (all cytokines involved in eosinophilopoiesis) are located. We report the case of a patient with CEL with t(1;5) (q23;q31), who obtained complete hematologic and major cytogenetic response after two years of alpha-interferon (alpha-IFN) therapy. Two other cases of complete response to alpha-IFN are reported in the literature. A trial with alpha-IFN could be considered as front line treatment in this rare disease.

Adult↗

A study on lymphocyte subpopulation in diabetic mothers at delivery and in their newborn.

Despite the importance of immunological aspects in pregnancy, until now few studies have been reported on the cellular immune modifications of diabetic pregnancy and on the newborn of diabetic mothers. Therefore, we thought it of interest to evaluate cell immunity in diabetic pregnant women and in their newborn children. Fourteen pregnant women with Type 1 diabetes (T1DM), mean age (+/-SD) 30-4 yr, mean disease duration (+/-SD) 12+/-5 yr, 15 with gestational diabetes mellitus (GDM) (mean age 33+/-6 yr), and 21 healthy pregnant women (mean age 29+/-4 yr) were studied and their metabolic and immunological parameters were evaluated. Fifty newborn babies were examined for immunological evaluation. Mean fasting plasma glucose and HbA1c values were higher in T1DM and GDM patients than in controls. Total lymphocyte subsets were higher in T1DM and GDM patients, although there were no significant differences between the percentual values. In children of T1DM and GDM mothers absolute lymphocyte values were increased, whereas the natural killer (NK) subset had decreased values in both absolute and percentual terms. Our work shows that, with respect to healthy controls, both GDM and T1DM mothers have a significant increase in total lymphocytes, and newborns have a reduced number of NK lymphocytes. Lower numbers of NK lymphocytes are probably related to altered production of lymphokines during foetal life and may also represent a real immune deficit in monitoring against viral infections.

Adult↗

Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic progenitors.

T-cell and B-cell reconstitution was studied in nine patients who received fluorescence activated cell sorter (FACS)-sorted autologous CD34+ hematopoietic progenitor cells (HPC). The mean numbers of T cells (CD3+), B cells (CD19+) and CD34+ HPC administered to each patient were .004, .002, and 1.8 x 10(6) cells/kg, respectively. After high-dose myeloablative chemotherapy (busulfan, cyclophosphamide, etoposide) CD34+) HPC were infused and lymphoid reconstitution was monitored using flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of VDJ T-cell receptor (TcR) sequences. Restoration of normal numbers of peripheral blood T cells and B cells among recipients of FACS-sorted CD34+ HPC was delayed compared to recipients of non-T-cell-depleted PBSC autografts. In both patient groups, the circulating T cells were primarily CD4-, CD8+, alphabeta TcR+, and CD45RO+, CD45RA- during the first 2 months after transplant. Subsequent increases in the frequency of CD45RA+ CD45RO- T cells occurred at 2 to 3 months after transplant, suggesting maturation of CD34+ hematopoietic progenitors to "naive" T cells. Analysis of the TcR repertoire after hematopoietic reconstitution demonstrated decreased diversity of Vbeta TcR expression associated with global decreases in the absolute number of total peripheral blood T cells and most Vbeta TcR+ subsets. Three of nine recipients of FACS-sorted CD34+ HPC demonstrated significant increases in the percentage of gammadelta+ peripheral T cells and CD5+ B cells at 3 to 9 weeks after transplantation, and all patients had transient oligoclonal expansions of T cells expressing specific Vbeta TcR. Transplantation with highly purified CD34+ HPC results in reduced diversity of the peripheral T-cell repertoire during the early post-transplant period compared with patients receiving unmanipulated or MoAb-depleted transplants.

Adult↗

Thrombopoietin is synthesized by bone marrow stromal cells.

We have previously characterized stromal progenitor cells contained in fetal bone marrow by fluorescence-activated cell sorting (FACS) using the differential expression of CD34, CD38, and HLA-DR, and found that a small number were contained within the CD34(+) cell fraction. In the present study, the frequency of stromal progenitors in both the CD34+ and CD34- subpopulations from samples of fetal and adult bone marrow was approximately one in 5,000 of the mononuclear cell fraction. Using multiparameter single-cell sorting, one in 20 fetal bone marrow cells with the CD34+, CD38-, HLA-DR-, CDw90+ phenotype were clonogenic stromal progenitors, whereas greater than one in five single cells with the CD34-, CD38-, HLA-DR-, CDw90+ phenotype formed stromal cultures. We found that cultures initiated by hematopoietic and stromal progenitors contained within the CD34+ fraction of bone marrow cells formed mixed hematopoietic/stromal cell cultures that maintained the viability of the hematopoietic progenitor cells for 3 weeks in the absence of added hematopoietic cytokines. We characterized some of the hematopoietic cytokines synthesized by stromal cultures derived from either CD34+ or CD34- bone marrow cells using reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of interleukin-3 (IL-3), stem cell factor (SCF), CD34, Flt3/Flk2 ligand (FL), and thrombopoietin (TPO) mRNA sequences. We found ubiquitous expression of TPO mRNA in greater than 90% of stromal cultures initiated by either CD34+ or CD34- cells, and variable expression of SCF, FL, and CD34 mRNA. In particular, SCF and CD34 mRNA were detected only in stromal cultures initiated by CD34+ bone marrow cells, although the differences between CD34+ and CD34- stromal cells were not statistically significant. IL-3 mRNA was not found in any stromal cultures. An enzyme-linked immunosorbent assay (ELISA) of soluble SCF and TPO present in culture supernatants demonstrated that biologically significant amounts of protein were secreted by some cultured stromal cells: eight of 16 samples of conditioned media from stromal cultures initiated by fetal and adult bone marrow contained more than 32 pg/mL SCF (in the linear range of the ELISA), with a median value of 32 pg/mL (range, 9 to 230), while 13 of 24 samples of conditioned media had more than 16 pg/mL TPO (in the linear range of the ELISA), with a median of 37 pg/mL (range, 16 to 106). Our data indicate that stromal cultures initiated by single bone marrow cells can make FL, SCF, and TPO. Local production of early-acting cytokines and TPO by stromal cells may be relevant to the regulation of hematopoietic stem cell self-renewal and megakaryocytopoiesis in the bone marrow microenvironment.

Adult↗

[Diabetic nephropathy and pregnancy].

Diabetes mellitus (or type 1) is a long-lasting disease (even twenty years or more) which causes kidney disease and, in the event of pregnancy, it can make differential diagnostic difficult even fort the most expert clinician. Metabolic changes caused by this type of diabetes (e.g., hypoglycemia, hyperglycemia, ketoacidosis) and their difficult compensation can often lead to the onset of eclampsia or convulsion. The diagnostic suspicion of diabetes is supported by the finding of proteinuria, edema and hypertension that are strictly correlated with the evolution of diabetic disease and sometimes exist prior to pregnancy. This cas report focuses on the diagnostic importance of clotting tests, especially in clarifying diagnostic doubts.

Adult↗