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Biomedical subjects

A Luciano

Publications and source records attributed to A Luciano.

At least 37 records · Page 2Linked to original sources

A (15;17) translocation not associated with acute promyelocytic leukaemia.

We report a woman with acute myeloid leukaemia (AML) type M2 according to FAB classification, showing a t(15;17) apparently identical to that of acute promyelocytic leukaemia (APL) on conventional cytogenetic analysis. Fluorescence in situ hybridization (FISH) using cosmidic probes specific for RAR alpha and PML, regions did not show a fusion signal as in APL. The breakpoints were assigned to 15q24.3 and 17q21.1. Detailed molecular analyses did not reveal any involvement of RAR alpha and PML genes. The patient was resistant to several front-line AMI treatments and to all-trans retinoic acid (ATRA). These findings reinforce FISH and RT-PCR as useful tools for the characterization of a t(15;17) as the translocation specifically associated with APL.

Adult↗

Lifespan and lesions in genetically heterogeneous (four-way cross) mice: a new model for aging research.

Genetically heterogeneous animal models provide many advantages for research on aging but have been used infrequently. We present here lifespan and lesion data from a study of mice bred as a cross between (AKR/J x DBA/2J)F1 females and (C57BL/6J x SJL/J)F1 males. In such a four-way cross population, each mouse is genetically unique, but replicate populations of essentially similar genetic structure can be generated quickly, at low cost, and of arbitrary size from commercially available, genetically stable hybrid parents. We employed a protocol in which mice judged to be severely ill were euthanatized to obtain tissue in optimal condition for necropsy, and we were able to infer a likely cause of illness in 42 of 44 animals. Malignant lymphoma, including at least four histopathologically distinct subtypes, was the most common cause and was also a frequent incidental finding in mice dying of other causes. Neoplastic disease, benign or malignant, was the sole or a contributing cause of illness in 90% of the mice for which a cause could plausibly be assigned. A wide range of lethal and nonlethal degenerative lesions was also noted. The coefficient of variation for lifespan in these genetically heterogeneous mice was 26%, similar to that seen in analyses of recombinant inbred mouse lines. Baseline lifespan and pathology data on four-way cross mice is a useful prelude to the exploitation of this rodent model in tests of genetic and mechanistic hypotheses about aging.

Adenocarcinoma↗

Usefulness of 123I-metaiodobenzylguanidine (MIBG) scintiscan in the diagnosis of juxta-adrenal schwannoma.

The adrenal scintiscan with 123I-metaiodobenzylguanidine (MIBG), a reliable morphofunctional technique to evaluate catecholamine turnover in adrenal tumors, can be a useful method to investigate adrenal incidentalomas with arterial hypertension. A male patient, 44 yr old with diabetes, unstable arterial hypertension, and sudden paroxysms of tachycardia is described. The presence of a disomogeneous right juxta-adrenal neoplasm with calcifications was evidenced with ultrasound tomography and confirmed by computerized tomography (CT) scan. Adrenal 123I-MIBG scintiscan revealed a unilateral uptake at level of the right juxta-adrenal region, sized similarly to the neoplasm previously evidence by CT scan. Histological findings of the surgically removed neoplasm were consistent with an ancient schwannoma. Apart from pheochromocytomas, the MIBG uptake is commonly reported in neuroblastomas. In neuroblastoma, a bidirectional process of transdifferentiation has been previously reported in vitro between two coexistent cells: cells with specific uptake system for norepinephrine, with 123I-MIBG uptake capability, and cells oriented toward schwann/melanocytic line. The evidence of in vivo MIBG uptake in our schwannoma may be caused by the same possible phenotypic interconversion of above mentioned cell types. In conclusion, the presence of adrenal tumors with MIBG uptake capability, apart from pheochromocytomas, neuroblastomas, ganglioneuroblastomas, and ganglioneuromas, must be considered in the diagnosis of adrenal tumors.

3-Iodobenzylguanidine↗

Height and weight reference charts for children aged 2-18 years from Verona, Italy.

OBJECTIVE: To compile curves for growth in weight and height for Italian children and adolescents. DESIGN: Cross-sectional. SETTING: All primary and secondary schools in the area of Verona, Italy, between October 1986 and January 1987. SUBJECTS: 20534 female and 20345 male children aged 2-18 years. METHODS: Weight and height were measured using Salus balances, and age in days was calculated between the date of measurement and that of birth: centiles of weight and height by age were calculated by the LMS method of Cole (1990). RESULTS: The height and weight curves were similar for both boys and girls to those obtained in Switzerland by Prader & Budliger (1977). However pre-pubertal Italian boys and girls are taller and heavier than the standards for France (Sempè & Pedron, 1953-1970) or for the UK by Tanner & Whitehouse (1976).

Adolescent↗

Percutaneous computed tomography-guided ethanol injection in aldosterone-producing adrenocortical adenoma.

The feasibility, safety and effectiveness of percutaneous computed tomography-guided ethanol injection (PEI-CT) was investigated in a patient affected by aldosterone-producing adenoma (APA). A 42-year-old male patient with typical features of hyperaldosteronism presented a solitary left adrenal adenoma measuring 2 cm, with a normal contralateral gland, evidenced by both CT scan and adrenal [75Se-19]-nor-cholesterol scintigraphy. After normalization of potassium plasma levels, 4 ml of sterile 95% ethanol with 0.5 ml of 80% iothalamate sodium was injected. The procedure was completed in about 30 min. No severe pain or local complication was noted. Five hours after PEI, a fourfold and a twofold increase in aldosterone and cortisol plasma levels were observed, respectively. After 11 days on a normal sodium and potassium diet, normal potassium plasma levels and reduced aldosterone plasma levels were present, with reappearance of an aldosterone postural response. Plasma renin activity and aldosterone plasma levels normalized 1 month later, with reappearance also of a plasma renin activity postural response and maintenance of normal potassium plasma levels even on a high sodium and normal potassium diet. The patient has remained hypertensive, although lower antihypertensive drug dosages have been employed. After 17 months, normal biochemical, hormonal and morphological findings were still present. Thus, we suggest PEI-CT as a further alternative approach to surgery in the management of carefully selected patients with APA.

Adrenal Cortex Neoplasms↗

CD2 expression in acute promyelocytic leukemia is associated with microgranular morphology (FAB M3v) but not with any PML gene breakpoint.

In the t(15;17) translocation of acute promyelocytic leukemia (APL) at least three regions of the PML gene are involved in the reciprocal translocation between the PML and the RAR-alpha loci. The chimeric PML/RAR-alpha fusion transcripts can be demonstrated in all cases of APL, by a specific reverse-transcription PCR (RT-PCR). Previous studies found a correlation between expression of CD2 and involvement of the PML bcr3. In this study, we assessed this association in 43 children and adults with APL. A blind morphologic review of all smears was performed by four experienced hemopathologists who agreed the diagnosis of M3 vs M3v APL. CD2 expression on APL was detected by using different monoclonal antibodies (MoAbs) directed against specific CD2 epitopes by flow cytometry and in selected cases by Northern blot by the use of a specific CD2 cDNA probe. Nineteen of 43 cases displayed the typical microgranular features consistent with the diagnosis of M3v. Of these, 12 had the bcr3 breakpoint on chromosome 15, while seven had the bcr1 type. In 16 of the 19 patients, leukemic cells expressed both CD2 protein and the corresponding mRNA. Similarly, in the negative cases, Northern blot analysis failed to demonstrate the presence of specific mRNA. The remaining 24 patients, with the classic morphologic features of M3, were CD3 negative. These results point out that CD2 expression correlates with the FAB M3v and not with the PML breakpoints. During the course of all-trans retinoic treatment a down-modulation of CD2 expression was observed in three M3v cases. Overall, our findings might suggest a role of CD2 epitopes in the regulation of adhesion properties of APL blast cells.

Adolescent↗

Involvement of multiple protein kinases in CD3-mediated activation of human T lymphocytes.

The role of different protein kinases in the process of T cell activation has been studied using several inhibitors. The model we adopted was the activation of PBMC by monoclonal antibody OKT3. The results obtained confirm that PKC and PTK are involved. Thus, the inhibitors H-7, staurosporine, and genistein exerted a dose-dependent inhibition of CD2 up-regulation, CD25 expression, IL-2 production, and cellular proliferation. On the other hand, our data indicate that PKA is not involved since the inhibitor HA1004 was ineffective. W-7, an inhibitor of Ca(2+)-CaM protein kinases, inhibited OKT3-induced modulation of cell-surface markers and PBMC proliferation, whereas a slight increase in IL-2 release was detected at the highest dose used (20 microM). Using the MLCK inhibitor ML-9, we extended our studies to the myosin light chain kinase, which influences the organization of the cytoskeleton. ML-9-inhibited PBMC activation in terms of modulation of cell-surface markers and proliferation but stimulated IL-2 production. Similar results were obtained using the cytoskeleton disruptors demecolcine and cytochalasin B. Taken together the data described herein indicate that T cell activation is a complex event in which, aside from classical signal transduction-associated kinases PKC and PTK, at least two other kinases, Ca(2+)-CaM kinases and MLCK, seem to be involved, the latter probably through correct assembly of the cytoskeleton.

Antigenic Modulation↗

Age-sensitive T cell phenotypes covary in genetically heterogeneous mice and predict early death from lymphoma.

We have assessed several age-sensitive indicators of immune status in young (i.e., 6 to 11-month-old) mice of a genetically heterogeneous population to see if these varied in parallel and to determine if one or more of the status indices predicted life span or cancer incidence. We report that the number of memory (i.e., CD44hi) T cells within the CD8 subset is correlated with number of memory cells in the CD4 population, and inversely correlated with the number of naive (i.e., CD45RBhi) CD4 cells at both 6 and 11 months of age, suggesting that the conversion of naive to memory cells may occur at similar rates in both T cell subsets. Mice that ranked high in the proportion of memory T cells (within the CD4 and CD8 pools) at 6 months of age tended to retain their ranking at 11 months, suggesting that the pace or extent of memory cell formation may be a consistent trait that distinguishes mice at least within a genetically heterogeneous population. Mice that at 6 months of age exhibited high levels of CD4 or CD8 memory T cells, low levels of naive CD4 cells, or low levels of T cells able to proliferate in response to Con A and IL-2 were found to be significantly more likely than their littermates to die within the first 18 months of life. Cases of follicular cell lymphoma, lymphocytic and lymphoblastic lymphoma, and hepatic hemangiosarcoma were seen within the group of mice dying at early ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Acute promyelocytic leukemia in children: experience of the Italian Pediatric Hematology and Oncology Group (AIEOP).

Scanty information is available on acute promyelocytic leukemia (APL) in children, and whether differences are present with respect to the adult form. The experience of the Italian Pediatric Hematology and Oncology Group (AIEOP) will be presented with respect to the following aspects: 1. Incidence of APL. The incidence of APL is generally considered to account for 3-9% of acute myelogenous leukemia (AML) in children and approximately 10-15% in adults. Recently a single Italian pediatric institution reported that APL constituted one third of observed acute nonlymphocytic leukemia (AnLL) cases. Data from the AIEOP cooperative study group have confirmed that APL in Italy is more frequently observed in children as compared to other countries. Environmental and/or genetic factors should be considered to explain such differences. 2. Diagnosis of M3v. The clinical and biological features of the largest series of childhood M3v will be presented and the problems encountered in the proper separation of 'classic' M3 and M3v in children will be discussed. 3. Clinical Aspects. The clinical features of the APL patients enrolled in the AIEOP study groups since 1989, will be presented with emphasis on the recent experience with the use of all-trans retinoic acid. 4. Analysis of PML/RAR alpha Fusion Transcripts. An RT-PCR analysis of 32 pediatric APL cases from cryopreserved bone marrow samples has been performed. It is concluded that APL in children did not differ significantly from the adult form, with the exception of a higher incidence of PML bcr3 breakpoint.

Age Factors↗

Hypothalamic-pituitary-adrenal axis and immune system.

Complex and bidirectional relationships operate between the hypothalamic-pituitary-adrenal (HPA) axis and the immune system (IS) and either in vivo or in vitro evidence supports a physiological role of the HPA axis-IS network. A part of the well-known pharmacological effects of glucocorticoid hormones (GC) as immunodepressive agents, the direct effects of many HPA axis hormones on IS functions are actually documented also in physiologic conditions. Conversely, numerous IS soluble mediators are reported to affect the HPA axis functions at various steps of HPA axis regulation, in both physiologic and pathologic conditions. Stress and aging may represent two paradigmatic conditions to show the relevance of the bidirectional network between HPA axis and IS, as in both HPA activation and IS impairment are frequently coexistent. Finally, in the context of the wide spectrum of HIV-related HPA axis abnormalities, a case of a Cushing's syndrome associated to an acquired immunodeficiency syndrome (AIDS-related complex) in a 24-year-old homosexual drug abuser is reported.

AIDS-Related Complex↗

Acute promyelocytic leukemia in children: experience of the Italian Pediatric Hematology and Oncology Group (AIEOP).

Scanty information is available on acute promyelocytic leukemia (APL) in children, and whether differences are present with respect to the adult form. The experience of the Italian Pediatric Hematology and Oncology Group (AIEOP) will be presented with respect to the following aspects: 1. Incidence of APL. The incidence of APL is generally considered to account for 3-9% of acute myelogenous leukemia (AML) in children and approximately 10-15% in adults. Recently a single Italian pediatric institution reported that APL constituted one third of observed acute nonlymphocytic leukemia (AnLL) cases. Data from the AIEOP cooperative study group have confirmed that APL in Italy is more frequently observed in children as compared to other countries. Environmental and/or genetic factors should be considered to explain such differences. 2. Diagnosis of M3v. The clinical and biological features of the largest series of childhood M3v will be presented and the problems encountered in the proper separation of 'classic' M3 and M3v in children will be discussed. 3. Clinical Aspects. The clinical features of the APL patients enrolled in the AIEOP study groups since 1989, will be presented with emphasis on the recent experience with the use of all-trans retinoic acid. 4. Analysis of PML/RAR alpha Fusion Transcripts. An RT-PCR analysis of 32 pediatric APL cases from cryopreserved bone marrow samples has been performed. It is concluded that APL in children did not differ significantly from the adult form, with the exception of a higher incidence of PML bcr3 breakpoint.

Adolescent↗

Basic cardiac arrhythmias: a review for postanesthesia care unit nurses.

Nurses in PACUs care for a variety of patients who may have or who are at risk for arrhythmias. Surgical trauma and anesthesia may exacerbate underlying heart disease and promote arrhythmias. This article reviews the basic cardiac conduction system and gives a brief description and illustration of both normal and ectopic rhythms. Nursing interventions and common pharmacological and nonpharmacological treatments are discussed. Through accurate detection and prompt interventions, nurses may contribute significantly to lower morbidity and mortality in the PACU.

Aged↗

Molecular variants of the 1;19 chromosomal translocation in pediatric acute lymphoblastic leukemia (ALL).

The t(1;19)(q23;p13), a non-random chromosome rearrangement associated with childhood pre-B acute lymphoblastic leukemia (ALL), results at molecular level in the hybrid E2A-PBX1 gene. This gene is expressed in a typical set of fusion transcripts and oncogenic chimeric proteins. However, the occurrence of t(1;19) molecular variants has been recently suggested. In an attempt to identify these variants, we analyzed 25 pediatric cases of pre-B cIg+ cell ALL. We used Southern blot analysis to detect E2A gene rearrangements and RT-PCR to detect chimeric E2A-pbx1 transcripts. In addition to seven cases with the molecular pattern usually associated with the t(1;19), we identified three molecular variants. In one case, a variant E2A-pbx1 transcript showed 27 additional base pairs inserted in frame at the junction site. In two cases, Southern blot evidenced the expected E2A gene rearrangements. However, extensive RT-PCR analysis failed to detect any E2A-pbx1 transcript. These findings led us to hypothesize that a gene other than PBX1 might be involved in these 1;19 variant translocations.

Base Sequence↗

ALL-1 gene at chromosome 11q23 is consistently altered in acute leukemia of early infancy.

Early infancy (< 1 year of age), massive tumor cell burden, and extremely poor prognosis are characteristic features of a particular subset of childhood acute leukemias (AL). In these cases, chromosome aberrations at the 11q23 band are the most frequently reported cytogenetic abnormalities. We have recently cloned a genetic locus named ALL-1, in which DNA breakpoints are clustered in leukemic patients with 11q23 aberrations. Analysis of the ALL-1 genomic configuration in DNA from 15 infants with AL showed specific ALL-1 rearrangements in 12 cases (80%), including 5 with normal karyotypes. These findings indicate that a consistent genetic defect underlies this particular leukemic subset.

Acute Disease↗

Drug utilization research in primary health care as exemplified by physicians' quality assessment groups.

Drugs in primary health care are often prescribed for nonrational reasons. Drug utilization research investigates the prescription of drugs with an eye to medical, social and economic causes and consequences of the prescribed drug's utilization. The results of this research show distinct differences in drug utilization in different age groups and between men and women. Indication and dosage appear irrational from a textbook point of view. This indicates nonpharmacological causes of drug utilization. To advice successfully changes for the better quality assessment groups of primary health care physicians get information about their established behavior by analysis of their prescriptions. The discussion and the comparisons in the group allow them to recognize their irrational prescribing and the social, psychological and economic reasons behind it. Guidelines for treatment are worked out which take into account the primary health care physician's situation. After a year with 6 meetings of the quality assessment groups the education process is evaluated by another drug utilization analysis on the basis of the physicians prescription. The evaluation shows a remarkable improvement of quality and cost effectiveness of the drug therapy of the participating physicians.

Cost-Benefit Analysis↗