Recurrence of clonal hematopoiesis after discontinuing pegylated recombinant interferon-alpha 2a in a patient with polycythemia vera.
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Amino Acid Substitution↗
Biomedical subjects
E Bruno
Publications and source records attributed to E Bruno.
Experimental use of a new surface acoustic wave sensor for the rapid identification of bacteria and yeasts.
AIMS: Use of an electronic nose (zNose(TM)) to discriminate between volatile organic molecules delivered during bacterial/fungal growth on agar and in broth media. METHODS AND RESULTS: Cultures of bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli) and yeasts (two Candida albicans strains) were grown on agar and in broth media and incubated for 24 h at 37 degrees C. Headspace samples from microbial cultures were analysed by the zNose(TM), a fast gas chromatography-surface acoustic wave detector. Olfactory images of volatile production patterns were observed to be different for the various species tested after 24 h. Moreover, some strains (two K. pneumoniae, two C. albicans) did not show changes in volatile production patterns within our species. CONCLUSIONS: Our experiments demonstrate that the electronic nose system can recognize volatile production patterns of pathogens at species level. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results, although preliminary, promise exciting challenges for microbial diagnostics.
Acoustics↗
Direct observation of the multisheet Fermi surface in the strongly correlated transition metal compound ZrZn2.
The existence of flat areas of a Fermi surface (FS), predicted by electronic structure calculations and used in models of both magnetically mediated and phonon-mediated Fulde-Ferrell-Larkin-Ovchinnikov superconducting states, is reported in the paramagnetic phase of the ferromagnetic superconductor ZrZn2 using positron annihilation. The strongly mass-renormalized FS sheet, dominating the Fermi level density of states, is seen for the first time. The delocalization of the magnetization is studied using measured and calculated magnetic Compton profiles.
Journal Article↗
Nicergoline in the treatment of dizziness in elderly patients. A review.
In elderly patients, dizziness occurs very frequently with significant effects on the patient's life. Its frequency increases with age, and may arise from a variety of causes. Chronic dysequilibrium in elderly patients is most probably related to disturbances within the central nervous system, due either to altered neuronal functions or to an underlying vascular disease. Nicergoline, a drug used in the treatment of cognitive disturbances in geriatric patients, improves dizziness in elderly demented and non-demented patients. In a double blind,placebo controlled trial the drug improved (i) the severity of symptoms, measured by the dizziness assessment rating scale (DARS), (ii) the overall clinical conditions revealed by global impression scale, and (iii) the perceived quality of life estimated by the dizziness handicap inventory (DHI). These results indicate a possible positive effect also on posturographic measures. Moreover, the improvement occurred at no expense of the established strategy of postural control suggesting that the effect is mediated by a substitute compensatory mechanism allowing the patient to preserve consolidated postural strategies. The results of previous open clinical studies in about 3000 patients are in agreement with those findings. Overall, severity of symptoms decreased by 68 % (57 % in the control study). Globally, the results indicate a beneficial effect of nicergoline on symptoms related to balance disorders of central origin. Animal studies show that the drug displays a broad spectrum of actions on cellular and molecular mechanisms. Moreover, animal research specifically aimed at vestibular pathophysiology has revealed that nicergoline improves vestibular compensation in models of vestibular lesion. Chronic treatment with nicergoline improved the time-course of behavioral recovery in old rats after hemi-labyrinthectomy and counteracted the regulation of cholinergic receptors observed after lesion in old rats. Nicergoline interacts at several levels by various mechanisms, from the molecular level to cognitive function, probably enhancing spontaneous plasticity phenomena underlying the central vestibular compensation. This effect is not dependent from the interaction with a single-transmitter-identified neural pathway, but from anatomical, functional and neurochemical synergistic adjustments in several brain areas.
Aged↗
Functional and structural characterization of two populations of human monocyte-derived dendritic cells.
BACKGROUND: The characterization of human monocyte-derived dendritic cells (HM-DC) subsets have been a very difficult and elusive task because of the lack of appropriate reagents. We, therefore utilized several diverse approaches to evaluate two populations of HM-DC including flow cytometry, ultra-structural evaluation by electron microscopy, and functional assays. In addition, we studied the kinetics of the expression of antigens on HM-DC at diverse intervals of time and identify surface markers and functional differences of these two HM-DC subsets. RESULTS: This study identified that a phenotype of HM-DC as defined by CD11c+, CD86+, and CD40+ could be separated in the presence or absence of TGF-beta1 into two different subsets of DC: (i) HM-DC without Birbeck granuli (Mo-DC) and (ii) HM-DC with Birbeck granuli (Mo-LC). Furthermore, the functional studies showed that the HM-DC treated with TGF-beta1 (Mo-LC) exhibited the presence of Birbeck granuli and could actively divide. In addition, after undergoing more than four cell divisions, these cells split into at least two additional subsets of Mo-LC: (iia) Mo-LC with high forward scatter (FSC) and (iib) Mo-LC with normal FSC. In contrast, the Mo-DC cultured in absence of TGF-beta1 did not exhibit Birbeck granuli, showed reduced ability to divide, and kept the normal FSC when analyzed. CONCLUSIONS: This study enabled us to determine in HM-DC: (i) the existence of antigenic and functional differences between various subpopulations of Mo-DC and Mo-LC; (ii) the existence of differences in the kinetics of antigens expression among the subsets of Mo-DC and Mo-LC; (iii) the existence of specific markers for each of the subpopulations of HM-DC.
Antineoplastic Agents↗
Nose: aesthetics and function. Rhinoplasty and functional problems related to anterior ethmoid.
Aesthetic nasal surgery has progressed in the last years, as concerning both surgical techniques and surgical instruments, which allowed the finding of new and more sophisticated surgical solutions. Clinical practice led to observe sometimes functional surgical failures, due rather than an inaccurate surgical technique, to an incomplete diagnostic approach to the patient. It has been observed that modifying the external conformation of nasal pyramidis inner-nose volumes and spaces will be subsequently reduced, giving as a result a condition which is only aesthetically but not functionally valid. 32 subjects, selected for a rhinoplasty and presenting nasal respiratory obstruction and anterior ethmoid abnormalities, confirmed by nasal endoscopy and nasal CT, were evaluated and subdivided into two groups: the first (A) group underwent only to an aesthetic rhinoplasty, the second group (B) was operated of a rhinoplasty combined with functional endoscopic sinus surgery (FESS) in order to correct the above mentioned anatomical abnormalities. The nasal airflow, and though the nasal cavities patency, was evaluated pre- and post-operatively in the two groups of patients, referring to rhinomanometric conductance values. Patients of group A reported decreased post-operative conductance values, patients of group B reported increased post-operative conductance values, showing though the functional involvement of anterior ethmoid in nasal obstruction and the necessity of correcting its anatomical abnormalities, in order to reach not only a new nasal profile, but also a better respiratory performance.
Adolescent↗
Dual X-ray absorptiometry for estimating the volume of the soft tissue in the human skull.
The aim of this study was to analyze the relationship between soft and hard tissue measurements of the head so as to identify the range of soft tissues parameters that should be applied in forensic facial approximation. The study was performed on 85 healthy female volunteers with an age range of 35-45 years. Total and regional body composition analysis was undertaken with subjects in a recumbent position using dual X-ray absorptiometry. The head was defined from the inferior part of the mandible to the vertex. We found the range of total head soft tissue weight to be between 3.02 and 4.96 kg. The quantity of soft tissue applicable to Caucasian female subjects in good health was estimated by subtracting the weight of the brain (approximately 1.17 kg in a typical adult female) from these values. Thus, the minimum and maximum values of the soft tissue are 1.85 and 3.79 kg, respectively.
Absorptiometry, Photon↗
Malignant degeneration of oral lichen planus: our clinical experience and review of the literature.
Lichen planus of the oral mucosa (OLP) is characterized by lymphocytic infiltrate in the epithelial layer and basal cells lysis. Some studies have suggested a high incidence of oral squamous cell carcinoma in patients with OLP that has been implicated as a premalignant lesion. We describe 19 cases of OLP, and the immunopathologic basis for OLP, its potential association with malignancy and the variable clinical pictures in patients with OLP are reviewed. Also, specific recommendations are given for treatment and follow-up of lesions.
Adult↗
Perilymphatic fistula following trans-tympanic trauma: a clinical case presentation and review of the literature.
The perilymphatic fistula is constituted by an anomalous connection between the perilymphatic space and the middle ear. The principal accuses are to be sought in the intracranial pressure increasement, cranial traumas, barotraumas, congenital anomalies, trans-tympanic traumas, etc. Stapes's dislocation in the vestibule and the fracture of the platina are the most frequent pathogenic mechanisms. In clinical practice, the diagnosis remains a problem rather debated, even if the clinical pattern, the laboratory investigations, the diagnostic images and the tympanic exploration, all together can confirm, in the majority of the cases, the diagnostic suspect. This article presents a clinical case of a transtympanic trauma with perilymphatic fistula caused by a foreign body. The peculiarity of this case must be set in relation with both the aetiopathogenesis of the labyrinthine lesion and the severity of the symptomatology caused by it.
Anti-Inflammatory Agents↗
Fermi surface nesting in disordered Cu1-xPdx alloys.
The concentration-dependent position of the diffuse peaks in electron and x-ray diffraction patterns of Cu1-xPdx alloys in the disordered state is attributed to Fermi surface nesting. We present the first experimentally determined Fermi surfaces of Cu0.72Pd0.28 and Cu0.6Pd0.4, and show that they do indeed possess significant flat areas capable of nesting. Moreover, the magnitudes of the nesting vectors are in excellent agreement with those deduced from electronic structure calculations and diffraction experiments.
Journal Article↗
A case of solitary nasal schwannoma.
A case of solitary neurilemmoma is presented. The patient was a 35-year-old male with progressive nasal obstruction due to a neoformation of the left vestibule. After the surgery the pathological diagnosis was neurilemmoma.
Adult↗
Saccadic eye movement and visual pathways function in diabetic patients.
We assessed saccadic eye movements (SEM) and the visual evoked potentials (VEP) with the aim to evaluate whether a correlation exist between SEM and visual pathways function, in insulin-dependent diabetes mellitus (IDDM) patients. In IDDM patients we observed significantly longer SEM latency, while SEM velocity and accuracy were similar to those of the controls; VEP showed a significant delay of the latencies and significant reduction of the amplitudes in IDDM patients no relationship between SEM and VEP parameters were found. In conclusion SEM latency delay suggest an impairment of the saccadic eye movement system, while impaired VEP may be ascribed to a dysfunction of the visual pathways. The lack of correlation between VEP impairment and SEM latency delay suggests that in our IDDM patients the delay of saccadic latency could be ascribed to a difuse neuronal problem exceeding the visual pathways disfunction.
Adult↗
[Dermoid cysts of the floor of the mouth: case report].
Dermoid cysts are for the most part benign neoformations most likely deriving from ectodermic differentiation of totipotent cells. Although localization on the floor of the mouth has been described for more than a century it is still reported as rare and can give rise to problems in differential diagnosis. This work presents a case of dermoid cyst of the floor of the mouth in a 16-year-old patient and provides considerations on clinical approach, diagnosis and therapy for this type of lesion.
Adolescent↗
Interleukin 10-induced thrombocytopenia in normal healthy adult volunteers: evidence for decreased platelet production.
Recombinant human interleukin 10 (rhuIL-10) inhibits the production of proinflammatory cytokines and has shown promise in the treatment of inflammatory bowel disease. Clinical trials have been accompanied by a reversible decline in platelet counts. We conducted a randomized, double-blinded, placebo-controlled, parallel group trial in 12 healthy volunteers to investigate the aetiology of rhuIL-10-induced thrombocytopenia. Eight volunteers received 8 microg/kg/d of rhuIL-10 subcutaneously, while four subjects received a placebo alone for 10 d. A reversible decline in the platelet counts from a mean of 275 x 10(9)/l to 164 x 10(9)/l was observed in the IL-10-treated cohort (P = 0.012). A fall in the haemoglobin mean levels was also observed in the IL-10-treated cohort from 13.7 to 11.7 g/dl (P = 0.011). No significant change was observed in the bone marrow cellularity or myeloid/erythroid ratio or in the number of megakaryocytes per high-powered field (HPF). A fall was observed in the number of megakaryocyte colony-forming units (CFU-MKs) after the administration of IL-10 compared with those receiving the placebo (P = 0.068). No difference in the change in granulocyte-macrophage CFUs (CFU-GMs), mixed lineage CFUs (CFU-GEMMs) or erythroid burst-forming units (BFU-Es) was observed when comparing the IL-10- vs. placebo-treated groups (P > 0.465). Serum cytokine levels of thrombopoietin (TPO). IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) were not decreased following IL-10 administration. In fact, both TPO and GM-CSF appeared to be slightly increased in the serum. All subjects underwent In111-labelled platelet survival studies with liver/spleen scans to assess splenic sequestration prior to and then on day 7 of treatment. A significant reduction in splenic sequestration of platelets (P =0.012) was observed in the IL-10-treated group, but not in the placebo-treated subjects.
Adult↗
Ex vivo expansion of autologous bone marrow CD34(+) cells with porcine microvascular endothelial cells results in a graft capable of rescuing lethally irradiated baboons.
Hematopoietic stem cell (HSC) self-renewal in vitro has been reported to result in a diminished proliferative capacity or acquisition of a homing defect that might compromise marrow repopulation. Our group has demonstrated that human HSC expanded ex vivo in the presence of porcine microvascular endothelial cells (PMVEC) retain the capacity to competitively repopulate human bone fragments implanted in severe combined immunodeficiency (SCID) mice. To further test the marrow repopulating capacity of expanded stem cells, our laboratory has established a myeloablative, fractionated total body irradiation conditioning protocol for autologous marrow transplantation in baboons. A control animal, which received no transplant, as well as two animals, which received a suboptimal number of marrow mononuclear cells, died 37, 43, and 59 days postirradiation, respectively. Immunomagnetically selected CD34(+) marrow cells from two baboons were placed in PMVEC coculture with exogenous human cytokines. After 10 days of expansion, the grafts represented a 14-fold to 22-fold increase in cell number, a 4-fold to 5-fold expansion of CD34(+) cells, a 3-fold to 4-fold increase of colony-forming unit-granulocyte-macrophage (CFU-GM), and a 12-fold to 17-fold increase of cobblestone area-forming cells (CAFC) over input. Both baboons became transfusion independent by day 23 posttransplant and achieved absolute neutrophil count (ANC) >500/microL by day 25 +/- 1 and platelets >20,000/microL by day 29 +/- 2. This hematopoietic recovery was delayed in comparison to two animals that received either a graft consisting of freshly isolated, unexpanded CD34(+) cells or 175 x 10(6)/kg unfractionated marrow mononuclear cells. Analysis of the proliferative status of cells in PMVEC expansion cultures demonstrated that by 10 days, 99.8% of CD34(+) cells present in the cultures had undergone cycling, and that the population of cells expressing a CD34(+) CD38(-) phenotype in the cultures was also the result of active cell division. These data indicate that isolated bone marrow CD34(+) cells may undergo cell division during ex vivo expansion in the presence of endothelial cells to provide a graft capable of rescuing a myeloablated autologous host.
Animals↗
CrkL and CrkII participate in the generation of the growth inhibitory effects of interferons on primary hematopoietic progenitors.
Interferons are potent regulators of normal and malignant hematopoietic cell proliferation in vitro and in vivo, but the signaling mechanisms by which they exhibit their growth inhibitory effects are unknown. We have recently shown that CrkL is engaged in Type I IFN signaling, as shown by its rapid tyrosine phosphorylation during engagement of the Type I IFN receptor. In the present study, we provide evidence that the related CrkII protein is also rapidly phosphorylated on tyrosine during treatment of U-266 and Daudi cells with IFNalpha or IFNbeta. We also show that both members of the Crk-family, CrkL and CrkII, are phosphorylated in an interferon-dependent manner in primary hematopoietic progenitors. Furthermore, inhibition of CrkL or CrkII protein expression by antisense oligonucleotides, reverses the inhibitory effects of IFNalpha or IFNgamma on the proliferation of normal bone marrow progenitor cells (colony forming units-granulocytic/monocytic [CFU-GM] and burst-forming units-erythroid [BFU-E]). Thus, both CrkL and CrkII are engaged in a signaling pathway (s) that mediates interferon-regulated inhibition of hematopoietic cell proliferation.
Adaptor Proteins, Signal Transducing↗
CD109 is expressed on a subpopulation of CD34+ cells enriched in hematopoietic stem and progenitor cells.
CD109 is a monomeric cell surface glycoprotein of 170 kD that is expressed on endothelial cells, activated but not resting T-lymphocytes, activated but not resting platelets, leukemic megakaryoblasts, and a subpopulation of bone marrow CD34+ cells. Observing an apparent association between CD109 expression and the megakaryocyte lineage (MK), we sought to determine whether CD109 was expressed on MK progenitors. In fetal bone marrow (FBM), a rich source of MK progenitors, CD109 is expressed on a mean of 11% of CD34- cells. Fluorescence activated cell sorting (FACS) of FBM CD34+ cells into CD109+ and CD109- fractions revealed that the CD34+CD109+ subset contained virtually all assayable MK progenitors, including the colony-forming unit-MK (CFU-MK) and the more primitive burst-forming unit-MK (BFU-MK). The CD34+CD109+ subset also contained all the assayable burst-forming units-erythroid (BFU-E), 90% of the colony-forming units-granulocyte/macrophage (CFU-GM), and all of the more primitive mixed lineage colony-forming units (CFU-mix). In contrast, phenotypic analysis of the CD34+CD109- cells in FBM, adult bone marrow (ABM) and cytokine-mobilized peripheral blood (MPB) demonstrated that this subset comprises lymphoid-committed progenitors, predominantly of the B-cell lineage. CD109 was expressed on the brightest CD34 cells identifiable not only in FBM, but also in ABM and MPB indicating that the most primitive, candidate hematopoietic stem cells (HSC) might also be contained in the CD109+ subset. In long-term marrow cultures of FBM CD34+ cells, all assayable cobblestone area forming cell (CAFC) activity was contained within the CD109+ cell subset. Further phenotypic analysis of the CD34+CD109+ fraction in ABM indicated that this subset included candidate HSCs that stain poorly with CD38, but express Thy-1 (CD90) and AC133 antigens, and efflux the mitochondrial dye Rhodamine 123 (Rho123). When selected CD34+ cells were sorted for CD109 expression and Rho123 staining, virtually all CAFC activity was found in the CD109+ fraction that stained most poorly with Rho123. CD34+ cells were also sorted into Thy-1 CD109+ and Thy-1 CD109+ fractions and virtually all the CAFC activity was found in the Thy-1+CD109+ subset. In contrast, the Thy-1-CD109+ fraction contained most of the short-term colony-forming cell (CFC) activity. CD109, therefore, is an antigen expressed on a subset of CD34+ cells that includes pluripotent HSCs as well as all classes of MK and myelo-erythroid progenitors. In combination with Thy-1, CD109 can be used to identify and separate myelo-erythroid and all classes of MK progenitors from candidate HSCs.
Adult↗
Impaired saccadic eye movement in diabetic patients: the relationship with visual pathways function.
The aim of this study was to evaluate whether a correlation existed between saccadic eye movements and visual pathways function in diabetic patients. Saccadic or fast Eye Movement System (EMS) and Visual Evoked Potentials (VEPs) were assessed in 20 insulin-dependent diabetic mellitus (IDDM) patients without long-term complications and in stable metabolic control and in 21 age-matched control subjects. In IDDM patients we observed significantly (p<0.01) longer EMS latency, while EMS velocity and accuracy were similar to those of controls; VEPs showed a significant delay in N75, P100, N145 latencies and significant reduction of N75-P100 and P100-N145 amplitudes. In IDDM patients no relationships between EMS and VEP parameters were found. In conclusion, EMS latency delay suggests an impairment of the saccadic eye movement system, while impaired VEPs may be ascribed to a dysfunction of the visual pathways. The lack of correlation between VEPs impairment and EMS latency delay suggests that in our IDDM patients the delay of saccadic latency cannot be exclusively related to a visual pathways dysfunction and could be ascribed to a diffuse neuronal involvement.
Adult↗