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A Giangrande

Publications and source records attributed to A Giangrande.

At least 19 recordsLinked to original sources
PubMed2001

Glide2, a second glial promoting factor in Drosophila melanogaster.

The fly glial cell deficient/glial cell missing (glide/gcm) gene codes for a transcription factor that induces gliogenesis. Lack of its product eliminates lateral glial cells in the embryonic nervous system. Here we identify a second gene, glide2, that is homologous to glide/gcm in the binding domain and that is also necessary and sufficient to promote glial differentiation. glide2 codes for a transcription factor that displays a weaker and delayed expression compared with glide/gcm. The two genes, which are located 27 kb apart and share cis-regulatory elements, are able to auto- and cross-regulate, indicating that they form a gene complex. Finally, we show that lack of both products eliminates all lateral glial cells, which means that the two genes contain all the fly lateral glial promoting activity.

Amino Acid Sequence↗
PubMed2001

Human medulloblastoma cell line DEV is a potent tool to screen for factors influencing differentiation of neural stem cells.

The aim of our study was to investigate whether a human neural cell line could be used as a reliable screening tool to examine the functional conservation, in humans, of transcription factors involved in neuronal or glial specification in other species. Gain-of-function experiments were performed on DEV cells, a cell line derived from a human medulloblastoma. Genes encoding nine different transcription factors were tested for their influence on the process of specification of human DEV cells towards a neuronal or glial fate. In a first series of experiments, DEV cells were transfected with murine genes encoding transcription factors known to be involved in the neuronal differentiation cascade. Neurogenins-1, -2, and -3; Mash-1; and NeuroD increased the differentiation of DEV cells towards a neuronal phenotype by a factor of 2-3.5. In a second series of experiments, we tested transcription factors involved in invertebrate glial specification. In the embryonic Drosophila CNS, the development of most glial cells depends on the master regulatory gene glial cell missing (gcm). Expression of gcm in DEV cells induced a twofold increase of astrocytic and a sixfold increase of oligodendroglial cell types. Interestingly, expression of tramtrack69, which is required in all Drosophila glial cells, resulted in a fourfold increase of only the oligodendrocyte phenotype. Expression of the related tramtrack88 protein, which is not expressed in the fly glia, or the C. elegans lin26 protein showed no effect. These results show that the Drosophila transcription factor genes tested can conserve their function upon transfection into the human DEV cells, qualifying this cell line as a screening tool to analyze the mechanisms of neuronal and glial specification.

Animals↗
PubMed2001

A novel mode of asymmetric division identifies the fly neuroglioblast 6-4T.

Asymmetric cell divisions and segregation of fate determinants are crucial events in the generation of cell diversity. Fly neuroblasts, the precursors that self-reproduce and generate neurons, represent a clear example of asymmetrically dividing cells. Less is known about how neurons and glial cells are generated by multipotent precursors. Flies provide the ideal model system to study this process. Indeed, neuroglioblasts (NGBs) can be specifically identified and have been shown to require the glide/gcm fate determinant to produce glial cells, which otherwise would become neurons. Here, we follow the division of a specific NGB (NGB6-4T), which produces a neuroblast (NB) and a glioblast (GB). We show that, to generate the glioblast, glide/gcm RNA becomes progressively unequally distributed during NGB division and preferentially segregates. Subsequently, a GB-specific factor is required to maintain glide/gcm expression. Both processes are necessary for gliogenesis, showing that the glial vs. neuronal fate choice is a two-step process. This feature, together with glide/gcm subcellular RNA distribution and the behavior of the NGB mitotic apparatus identify a novel type of division generating cell diversity.

Animals↗
PubMed2001

Notch signaling represses the glial fate in fly PNS.

By using gain-of-function mutations it has been proposed that vertebrate Notch promotes the glial fate. We show in vivo that glial cells are produced at the expense of neurons in the peripheral nervous system of flies lacking Notch and that constitutively activated Notch produces the opposite phenotype. Notch acts as a genetic switch between neuronal and glial fates by negatively regulating glial cell deficient/glial cells missing, the gene required in the glial precursor to induce gliogenesis. Moreover, Notch represses neurogenesis or gliogenesis, depending on the sensory organ type. Numb, which is asymmetrically localized in the multipotent cell that produces the glial precursor, induces glial cells at the expense of neurons. Thus, a cell-autonomous mechanism inhibits Notch signaling.

Animals↗
PubMed2000

Some fly sensory organs are gliogenic and require glide/gcm in a precursor that divides symmetrically and produces glial cells.

In flies, the choice between neuronal and glial fates depends on the asymmetric division of multipotent precursors, the neuroglioblast of the central nervous system and the IIb precursor of the sensory organ lineage. In the central nervous system, the choice between the two fates requires asymmetric distribution of the glial cell deficient/glial cell missing (glide/gcm) RNA in the neuroglioblast. Preferential accumulation of the transcript in one of the daughter cells results in the activation of the glial fate in that cell, which becomes a glial precursor. Here we show that glide/gcm is necessary to induce glial differentiation in the peripheral nervous system. We also present evidence that glide/gcm RNA is not necessary to induce the fate choice in the peripheral multipotent precursor. Indeed, glide/gcm RNA and protein are first detected in one daughter of IIb but not in IIb itself. Thus, glide/gcm is required in both central and peripheral glial cells, but its regulation is context dependent. Strikingly, we have found that only subsets of sensory organs are gliogenic and express glide/gcm. The ability to produce glial cells depends on fixed, lineage related, cues and not on stochastic decisions. Finally, we show that after glide/gcm expression has ceased, the IIb daughter migrates and divides symmetrically to produce several mature glial cells. Thus, the glide/gcm-expressing cell, also called the fifth cell of the sensory organ, is indeed a glial precursor. This is the first reported case of symmetric division in the sensory organ lineage. These data indicate that the organization of the fly peripheral nervous system is more complex than previously thought.

Animals↗
PubMed1999

Gliogenesis depends on glide/gcm through asymmetric division of neuroglioblasts.

Some neurons and glial cells originate from neuroblasts and glioblasts, stem cells that delaminate from the ectoderm of developing fly embryos. A second class of glial cells and neurons differentiates from multipotent precursors, the neuroglioblasts. The differentiation of both glial cell types depends on glial cell deficient/glial cell missing (glide/gcm). Although it has been shown that this transcription factor promotes gliogenesis at the expense of neurogenesis, the cellular mechanisms underlying this fate choice are poorly understood. Using loss and gain of function glide/gcm mutations here we show that the cell fate choice takes place in the neuroglioblast, which divides and produces a glioblast and a neuroblast. Such choice requires the asymmetric distribution of glide/gcm RNA, which accumulates preferentially on one side of the neuroglioblast and is inherited by one cell, the presumptive glioblast. Interestingly, glial cells can differentiate from cells that delaminate as neuroglioblasts or they can arise from cells that start expressing glide/gcm several hours after delamination of a neuroblast. Altogether, these findings identify a novel type of asymmetric cell division and disclose the lineage relationships between glia and neurons. They also reveal the mode of action of the glide/gcm promoting factor.

Animals↗
PubMed1999

Prevalence of hypertension in patients on peritoneal dialysis: results of an Italian multicentre study.

BACKGROUND: The tenet that peritoneal dialysis is capable of either normalizing or improving blood pressure control in uraemic patients is based on outdated or monocentric experiences. Therefore, we assessed the prevalence of hypertension and the efficacy of antihypertensive therapy in a large, multicentric cohort of patients on peritoneal dialysis. METHODS: Twenty seven out of the 50 centres belonging to the Italian Co-operative Peritoneal Dialysis Study Group took part in the study. The main patient selection criteria were: peritoneal dialysis therapy for at least 3 months and no peritonitis or changes in dialysis technique for at least 1 month. Clinical blood pressure was measured according to WHO/ISH guidelines. Ambulatory blood pressure monitoring was carried out using a SpaceLabs 90207 recorder. Hypertension was defined according to WHO/ISH criteria and staged according to the criteria of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC), 5th Report. Ambulatory blood pressure monitoring recordings were used to evaluate white-coat hypertension, blood pressure load and the dipping phenomenon. RESULTS: Five hundred and four subjects were evaluated. Hypertension was prevalent in 88.1% of the population, and 362 out of 444 hypertensive patients were on antihypertensive therapy. JNC staging revealed that 188 patients had moderate to severe hypertension. Blood pressure load was pathological in 77.3% of the patients receiving antihypertensive treatment. White-coat hypertension was identified in 9.1% of the hypertensive patients not on antihypertensive therapy, and 53.1% of the patients were non-dippers. CONCLUSIONS: The study demonstrates that hypertension is a dramatic, unsolved problem in uraemic patients treated with peritoneal dialysis, and casts doubts on the effectiveness of our current peritoneal dialysis strategies and pharmacological management of hypertension.

Adult↗
PubMed1999

GCMB, a second human homolog of the fly glide/gcm gene.

Glial cells play fundamental roles in neurogenesis. In addition, defective or abnormal gliogenesis is associated with severe diseases. To understand the molecular basis of such diseases, it is crucial to identify the genes promoting normal gliogenesis. Here we identify GCMB, which encodes a human protein homologous to the fly glial promoting factor glial cell deficient/glial cell missing (glide/gcm).

Amino Acid Sequence↗
PubMed1998

Positive autoregulation of the glial promoting factor glide/gcm.

Fly gliogenesis depends on the glial-cell-deficient/glial-cell-missing (glide/gcm) transcription factor. glide/gcm expression is necessary and sufficient to induce the glial fate within and outside the nervous system, indicating that the activity of this gene must be tightly regulated. The current model is that glide/gcm activates the glial fate by inducing the expression of glial-specific genes that are required to maintain such a fate. Previous observations on the null glide/gcmN7-4 allele evoked the possibility that another role of glide/gcm might be to maintain and/or amplify its own expression. Here we show that glide/gcm does positively autoregulate in vitro and in vivo, and that the glide/gcmN7-4 protein is not able to do so. We thereby provide the first direct evidence of both a target and a regulator of glide/gcm. Our data also demonstrate that glide/gcm transcription is regulated at two distinct steps: initiation, which is glide/gcm-independent, and maintenance, which requires glide/gcm. Interestingly, we have found that autoregulation requires the activity of additional cell-specific cofactors. The present results suggest transcriptional autoregulation is a mechanism for glial fate induction.

Amino Acid Sequence↗
PubMed1998

Glial differentiation does not require a neural ground state.

Glial cells differentiate from the neuroepithelium. In flies, gliogenesis depends on the expression of glial cell deficient/glial cell missing (glide/gcm). The phenotype of glide/gcm loss- and gain-of-function mutations suggested that gliogenesis occurs in cells that, by default, would differentiate into neurons. Here we show that glide/gcm is able to induce cells even from a distinct germ layer, the mesoderm, to activate the glial developmental program, which demonstrates that gliogenesis does not require a ground neural state. These findings challenge the common view on the establishment of cell diversity in the nervous system. Strikingly, ectopic glide/gcm overrides positional information by repressing the endogenous developmental program. These findings also indicate that glial differentiation tightly depends on glide/gcm transcriptional regulation. It is likely that glide/gcm homologs act similarly during vertebrate gliogenesis.

Animals↗
PubMed1998

Myths and reality concerning hypertension in peritoneal dialysis patients: results of a multicenter study.

OBJECTIVES: To evaluate the prevalence of hypertension, the average blood pressure level, the 24 h blood pressure profile, and the efficacy of antihypertensive therapy for a large population of peritoneal dialysis patients.DESIGN: A cross-sectional, observational multicenter study. METHODS: From 504 peritoneal dialysis patients (18% of the Italian peritoneal dialysis population) involved in a multicenter observational study, we selected 414 who had undergone successful ambulatory blood pressure monitoring (i.e. no hours with data absent, >/= 75% successful readings and monitoring duration >/= 24 h). Office blood pressure measurements and ambulatory blood pressure monitoring were performed for each patient on the same day with a standard mercury sphygmomanometer and a SpaceLabs 90207 device, respectively.RESULTS: According to World Health Organization/International Society of Hypertension criteria, 44 peritoneal dialysis patients (10.6%) were normotensive and 370 patients (89.4%) were hypertensive, 304 (82.1%) of whom were being administered antihypertensive therapy. Daytime systolic and diastolic blood pressures were both significantly lower than office systolic and diastolic blood pressures (140.7 +/- 19.7/72.1 +/-11.1 versus 148.3 +/- 23.6/85.6 +/- 12 mmHg; P < 0.001). The difference between office blood pressure and daytime blood pressure was significantly correlated to office blood pressure (P < 0.001 for systolic and P < 0.001 for diastolic). The diurnal blood pressure rhythm evaluated by visual inspection of hourly mean plots was not influenced by sex, age, antihypertensive treatment, and peritoneal dialysis modality. Systolic and diastolic blood pressures exhibited a day-night mean decreases of 8.6 +/- 11.7 and 7.7 +/- 6.9 mmHg, respectively, and daytime blood pressure values were significantly higher than night-time ones (P < 0.001). Two hundred and twenty patients (53.1%) were nondippers according to O'Brien's criteria, 247 patients (59.7%) were nondippers according to Verdecchia's criteria, and 269 patients (65.0%) were nondippers according to Staessen's criteria. Only 39 patients (9.4%) had a reversed circadian rhythm. The day-night differences of systolic and diastolic blood pressures were in a unimodal distribution. Among hypertensive patients not being administered antihypertensive therapy, only six patients ( five women and one man) had white-coat hypertension. Among hypertensive patients being administered antihypertensive therapy, 235 patients (77.3%) had 24 h blood pressure loads > 30%.CONCLUSION: There is a high prevalence of hypertension among peritoneal dialysis patients. White-coat hypertension is very rare in this population. Despite the extensive use of antihypertensive therapy, control of blood pressure is maintained in a large number of our peritoneal dialysis patients. Any classification of patients into dipers and nondippers must be interpreted cautiously.

Journal Article↗
PubMed1998

Quality of health care: the responsibility of health care professionals in delivering high quality services.

According to a recent definition, quality of care consists of the degree to which health services increase the likelihood of desired health outcomes and are consistent with current professional knowledge; a definition that introduces both requirements of outcomes and the appropriateness of the process used. Clearly many different figures are interested in quality assessment initiatives in the health care field and these include patients, administrators and doctors each having different perspective. Doctors obviously pay greater attention to technical quality and results, giving greater emphasis to the health of the individual patient, tending to give priority to technical excellence and interaction between patient and doctor. Although the perspective of health care professionals is widely acknowledged to be important and useful, other perspectives on quality have been emphasised in recent years. The most important of these is the recognition that care must be responsive to the preferences and values of the consumers of health care services. In complete harmony with one's own professional commitment, the attention to the perspectives of patients must give physician the chance to identify methods of measuring and verifying quality which take account of the expectations of the many groups with an interest in improving the functioning of the health system. A global approach in the health field is needed the more specialization advances. The quality of medicine lies in its capacity to integrate what science says is appropriate and to be recommended, what can be reconciled with human rights and the self determination of the patient and what can be achieved by optimising available resources. In this complex context, the doctor could take on both the role of the person who decides on the use of resources and the one of social mediator.

Humans↗
PubMed1997

glide/gcm is expressed and required in the scavenger cell lineage.

Glial cell differentiation in Drosophila melanogaster requires the activity of glide/gcm (glial cell deficient/glial cell missing). The role of this gene is to direct the cell fate switch between neurons and glial cells by activating the glial developmental program in multipotent precursor cells of the nervous system. In this paper, we show that glide/gcm is also expressed and required in the lineage of hemocytes/macrophages, scavenger cells that phagocytose cells undergoing programmed cell death. In addition, we show that, as for glial cells, glide/gcm plays an instructive role in hemocyte differentiation. Interestingly, it has been shown that in the development of the fly adult nervous system the role of scavenger cells is played by glial cells. These data and our findings on the dual role of glide/gcm indicate that glial cells and hemocytes/macrophages are functionally and molecularly related.

Animals↗
PubMed1996

Proteinuria and blood pressure as causal components of progression to end-stage renal failure. Northern Italian Cooperative Study Group.

AIMS: To identify the prognostic factors possibly related to end-stage renal failure development. SUBJECTS AND METHODS: The prognostic factors affecting chronic renal failure progression were analysed in 456 patients who had participated in a formal, multicentre, prospective randomized trial aimed at verifying the role of protein restriction in slowing down or halting the progression of chronic renal failure. The 24-month follow-up foreseen by the protocol was completed by 311 patients and 69 reached an end-point. An inductive analysis on patient survival was made by using the Cox proportional hazard regression model, using a stepwise procedure in order to select only those factors which are significantly associated with survival. For each individual risk factor, a univariate descriptive analysis of survival was performed using the Kaplan-Meier technique. RESULTS: Underlying nephropathy, baseline plasma creatinine, proteinuria, and plasma calcium were all shown to be related to end-stage renal failure onset. Hypertensive patients (mean blood pressure > 107 mmHg) had a worst cumulative renal survival but the degree of proteinuria was even more important as a prognostic factor of renal death than hypertension. The cumulative renal survival of patients whose proteinuria decreased during the trial follow-up was better than those of patients without changes. However, the interaction between baseline lying mean blood pressure and proteinuria was not significant. CONCLUSIONS: Only primary renal disease and proteinuria were related to renal survival, being baseline plasma creatinine confounding factor. By blocking the possible causal role of proteinuria and hypertension, end-stage renal failure could be prevented in a significant percentage of patients.

Adolescent↗
PubMed1996

The PTH-calcium relationship curve in secondary hyperparathyroidism, an index of sensitivity and suppressibility of parathyroid glands.

A sigmoidal relationship, fitting a four-parameter model, has been demonstrated in in vivo and in vitro studies to link the parathyroid hormone (PTH) secretion rate and calcium concentration changes. In uraemic patients different patterns of calcium-mediated PTH secretion were reported in different types of renal bone diseases and a shift to the right and a steeper slope has been observed in secondary hyperparathyroidism. To gain more information that could predict indexes for successful medical therapy we investigated the calcium-PTH sigmoidal relationship in 42 hyperparathyroid patients with different degrees of secondary hyperparathyroidism; we classified as moderate those patients presenting basal PTH (PTHbas) < 600 pg/ml and bone alkaline phosphatase (AP) < 500 U/l, and severe those with a PTHbas > or = 600 pg/ml and bone AP > or = 500 U/l. Changes in ionized calcium (iCa) were induced by calcium-free dialysis on the first day, to induce hypocalcaemia up to serum iCa 3.5 mEq/l, and calcium 8 mEq/l dialysis on the third day, to induce hypercalcaemia. The moderate hyperparathyroidism patients had PTHmax, PTHmin and slope, calculated in absolute values and relative values, lower than severe hyperparathyroidism patients but they did not differ in the minimal to maximal PTH ratio. In the moderate group the PTHbas correlated with all the curve parameters except PTHmin, calculated both in absolute and percentage values, while in the severe group PTHmin was the only parameter correlating to the PTHbas. In conclusion, by performing the dynamic test, we found that some glands were not suppressible among moderate hyperparathyroidism patients.

Adult↗
PubMed1996

Glide directs glial fate commitment and cell fate switch between neurones and glia.

Glial cells constitute the second component of the nervous system and are important during neuronal development. In this paper we describe a gene, glial cell deficient, (glide), that is necessary for glial cell fate commitment in Drosophila melanogaster. Mutations at the glide locus prevent glial cell determination in the embryonic central and peripheral nervous system. Moreover, we show that the absence of glial cells is the consequence of a cell fate switch from glia to neurones. This suggests the existence of a multipotent precursor cells in the nervous system. glide mutants also display defects in axonal navigation, which confirms and extends previous results indicating a role for glial cells in these processes.

Animals↗
PubMed1996

Prevalence of hyperlipidemia in a cohort of CAPD patients. Italian Cooperative Peritoneal Dialysis Study Group (ICPDSG).

An association between hyperlipidemia and cardiovascular disease is well described in the literature. We conducted an observational study in order to evaluate the lipid profile, the prevalence of hyperlipidemia and its relationship with age, sex, duration of CAPD, peritoneal glucose load (PGL), serum albumin (ALB), serum glucose (GLU), and BMI in a large cohort of uremics undergoing long-term treatment with CAPD. 457 nondiabetic patients (245 males, 212 females; mean age 63.8 +/- 11.9 years; mean duration of CAPD: 41.8 +/- 26.9 months) treated during 1992 in 25 centers participating in the Italian Cooperative Peritoneal Dialysis Study Group (ICPDSG) were studied. The serum lipid parameters evaluated were triglycerides (TG), total cholesterol (CHO), HDL-cholesterol (HDL). Indications given in the New England Journal of Medicine, SI Unit Conversion Guide, 1992, were adopted for normal ranges. In the whole population the evaluation of lipid parameters showed: TG 227.4 +/- 123.3 mg/dl, CHO 232.8 +/- 56.0 mg/dl, HDL 40.7 +/- 12.0 mg/dl. No differences were found between the two sexes with regard to age, BMI, duration of CAPD, distribution of renal diseases, TG, ALB, and GLU; whereas CHO and HDL were significantly lower in males than in females (CHO: 222.2 +/- 53.5 vs. 245.0 +/- 56.5 mg/dl, p < 0.001; HDL: 39.3 +/- 11.4 vs. 42.6 +/- 12.6 mg/dl, p < 0.05). The prevalence of hypercholesterolemia was significantly lower in males than in females (19.7 vs. 35.4%; p < 0.001). The multiple regression analysis indicated that TG were directly correlated to PGL (p < 0.05), and HDL was inversely correlated with TG (p < 0.001). The coexistence of the two variables (TG and HDL) may increase the risk of cardiovascular events. Further strategies should therefore be developed to select and manage CAPD patients to reduce the incidence of hyperlipidemia.

Blood Glucose↗