Biomedical subjects

A Di Marco

Publications and source records attributed to A Di Marco.

At least 19 recordsLinked to original sources

PubMed2006

Development of humanized mice for the study of hepatitis C virus infection.

The development of a small animal model for hepatitis C virus (HCV) infection is a critical issue for the development of novel anti-HCV drugs. To this aim, we have tried many different approaches for generating mice carrying humanized liver. Main efforts were focused on the transplantation of human hepatocytes into immunocompromised mice (SCID-/-, Bg-/-) carrying a genetic lethal liver disease (Alb-uPA). Survival of homozygotic animals should largely depend on early transplantation with healthy hepatocytes. In parallel to establishing a colony of Alb-uPA/SCID/Bg mice, we developed a microsurgical procedure for intrasplenic xenotransplantation of healthy hepatocytes in 1-week-old mice. So far, we generated several chimeras by xenotransplanting human hepatocytes in Alb-uPA+/+/SCID-/-/Bg-/- mice at 1 week after birth. In a first step, identification of successfully engrafted animals is possible by quantification of human serum albumin and human alpha 1 antitrypsin in mouse sera. Additional preliminary histomorphological analysis of liver sections from chimeric animals was also carried out. One of the mice was transiently infected with HCV, reaching viremia levels of approximately 10(5) genomes/mL. However, the efficiency of this system to generate chimeric mice is still very limited. We are currently exploring the use of more robust models of hepatic disease. Moreover, we have been also exploring novel strategies for the generation of chimeric mice by xenotransplanting human adult stem cells, instead of human hepatocytes, at preimmune stages of development.

Animals↗

PubMed2005

[Not Available].

Explore the source record for details and available documents.

Journal Article↗

PubMed2003

Effect of different sports on body cell mass in highly trained athletes.

The objective of this study was to verify the impact of various sports on body cell mass (BCM). Ninety-eight male subjects, 17-33 years of age, participated in the study. The sample included athletes from three professional Italian football (soccer) teams, representing three different divisions (A, n=16; B, n=14; and C, n=18), judo athletes (J, n=10), and water polo athletes (W, n=14) who all competed at the national level. Twenty-six age-matched individuals served as the control group (CG). Fat-free mass (FFM), fat mass (FM), percent body fat (%BF), and BCM were assessed using bioimpedance spectroscopy (BIS). There were no significant differences in body weight and FFM among the groups. A and B were significantly taller than J and CG. B had a significantly lower body mass index (BMI; kg/m(2)) than CG, while C had a significantly lower BMI than J and CG. CG had a significantly greater FM and %BF than A, B, and C. C had a significantly lower BCM than Aand B. CG had a significantly lower BCM than A, B, J, and W. In conclusion, differences in BCM exist among athletes of different sports, and among athletes within the same sport who compete at different levels.

Adipose Tissue↗

PubMed2002

Can losartan improve cardiac performance during the treadmill exercise test in hypertensive subjects?

Systolic blood pressure (SBP) normally increases during exercise. This increase is frequently exaggerated in hypertensive individuals. The aim of our study was to evaluate the antihypertensive effects of losartan at peak exercise and on cardiac performance during the treadmill test in individuals with essential hypertension. Forty subjects with a mean age of 44.2 +/- 12.4 years and with mild-to-moderate essential hypertension were enrolled. After a 14-day washout period, all selected subjects were given a treadmill exercise test using the modified Bruce protocol for exercise. The test was performed at the end of the washout period (step 0), again after 1 month (step 1), after 3 months (step 2) and after 6 months (step 3) of losartan administration (50 mg/daily per oral). Heart rate, SBP and diastolic blood pressure (DBP) were measured at rest and at maximal exercise. Exercise duration and double product were also recorded. In all patients who completed the study, a significant reduction from baseline in SBP at rest was found at 3 and 6 months (p < 0.05). No significant reduction from baseline in SBP at peak exercise was observed. No significant changes from baseline were found in double product, DBP, heart rate or exercise time. The results of our study suggest that losartan is effective in reducing blood pressure only at rest but is unable to improve exercise BP response or cardiac performance in subjects with mild-to-moderate essential hypertension.

Adult↗

PubMed2001

Blockade of endogenous neurotrophic factors prevents the androgenic rescue of rat spinal motoneurons.

Target-derived neurotrophic factors are assumed to regulate motoneuron cell death during development but remain unspecified. Motoneuron cell death in the spinal nucleus of the bulbocavernosus (SNB) of rats extends postnatally and is controlled by androgens. We exploited these features of the SNB system to identify endogenously produced trophic factors regulating motoneuron survival. Newborn female rat pups were treated with the androgen, testosterone propionate, or the oil vehicle alone. In addition, females received trophic factor antagonists delivered either into the perineum (the site of SNB target muscles) or systemically. Fusion molecules that bind and sequester the neurotrophins (trkA-IgG, trkB-IgG, and trkC-IgG) were used to block activation of neurotrophin receptors, and AADH-CNTF was used to antagonize signaling through the ciliary neurotrophic factor receptor-alpha (CNTFRalpha). An acute blockade of trkB, trkC, or CNTFRalpha prevented the androgenic sparing of SNB motoneurons when antagonists were delivered to the perineum. Trophic factor antagonists did not significantly reduce SNB motoneuron number when higher doses were injected systemically. These findings demonstrate a requirement for specific, endogenously produced trophic factors in the androgenic rescue of SNB motoneurons and further suggest that trophic factor interactions at the perineum play a crucial role in masculinization of this neural system.

Androgens↗

PubMed2000

In vivo localization and characterization of functional ciliary neurotrophic factor receptors which utilize JAK-STAT signaling.

The ciliary neurotrophic factor receptor is critically involved in embryonic motor neuron development. Postnatally, it may contribute to neuronal maintenance and regeneration. In addition, pharmacological stimulation of the receptor may slow the progression of several neurodegenerative disorders. The widespread nervous system expression of ciliary neurotrophic factor receptor components and the effects of low ciliary neurotrophic factor concentrations on a wide variety of cells in culture combine to suggest that functional ciliary neurotrophic factor receptors are expressed by many classes of neurons in vivo. However, the in vivo signaling properties and distribution of functional ciliary neurotrophic factor receptors have not been directly determined. We developed a novel in vivo assay of functional ciliary neurotrophic factor receptors which revealed that, in the adult nervous system, cranial and spinal motor neurons are very sensitive to ciliary neurotrophic factor and display a rapid, robust increase in phospho-STAT3 in their dendrites, cell bodies and nuclei, which is specifically blocked by the ciliary neurotrophic factor receptor antagonist, AADH-CNTF. In distinct contrast, several other classes of ciliary neurotrophic factor receptor expressing neurons fail to increase phospho-STAT3 levels following ciliary neurotrophic factor treatment, even when ciliary neurotrophic factor is applied at high concentrations. Leukemia inhibitory factor and epidermal growth factor elicit the same cell-type-dependent pattern of phospho-STAT3 increases. Responsive and non-responsive neurons express comparable levels of STAT3.Therefore, in vivo ciliary neurotrophic factor receptor-initiated STAT3 signal transduction is regulated in a very cell-type-dependent manner. The present data suggest that at least some of this regulation occurs at the STAT3 tyrosine phosphorylation step. These unexpected results also suggest that other forms of receptor-initiated STAT3 signal transduction may be similarly regulated.

Amino Acid Sequence↗

PubMed2000

Leptin receptor-mediated regulation of cholinergic neurotransmitter phenotype in cells of central nervous system origin.

Leptin is an adipocyte-secreted hormone that regulates body weight and exerts effects on hematopoiesis, reproduction, and immunity. The leptin receptor (OBR) shares sequence similarity and signaling capabilities with receptors for cytokines of the ciliary neurotrophic factor (CNTF) family. Our previous finding that CNTF and leptin exert similar anti-obesity effects and activate common neuronal signaling pathways, prompted us to investigate whether leptin may share with CNTF the ability to regulate the expression of specific neuronal genes. To this end, we established a cell line, derived from the murine septal cholinergic neuronal cell line SN-56, which stably expresses OBR. In this cell line, termed SN-56/OBR, leptin induces STAT transcription factor activation and STAT-dependent reporter gene expression in a manner similar to that of CNTF. Furthermore, in SN-56/OBR cells both CNTF and leptin produce changes in neurotransmitter and neuropeptide phenotype characteristic of cholinergic neurons, such as an increase in choline acetyltransferase and vasoactive intestinal polypeptide, and a decrease in neuropeptide Y expression. SN-56/OBR cells thus constitute an interesting new model system to investigate leptin action in cells of central nervous system origin. Possible physiological implications of OBR's intrinsic ability to regulate cholinergic phenotypic markers are discussed.

Alternative Splicing↗

PubMed2000

Enhancing B- and T-cell immune response to a hepatitis C virus E2 DNA vaccine by intramuscular electrical gene transfer.

We describe an improved genetic immunization strategy for eliciting a full spectrum of anti-hepatitis C virus (HCV) envelope 2 (E2) glycoprotein responses in mammals through electrical gene transfer (EGT) of plasmid DNA into muscle fibers. Intramuscular injection of a plasmid encoding a cross-reactive hypervariable region 1 (HVR1) peptide mimic fused at the N terminus of the E2 ectodomain, followed by electrical stimulation treatment in the form of high-frequency, low-voltage electric pulses, induced more than 10-fold-higher expression levels in the transfected mouse tissue. As a result of this substantial increment of in vivo antigen production, the humoral response induced in mice, rats, and rabbits ranged from 10- to 30-fold higher than that induced by conventional naked DNA immunization. Consequently, immune sera from EGT-treated mice displayed a broader cross-reactivity against HVR1 variants from natural isolates than sera from injected animals that were not subjected to electrical stimulation. Cellular response against E2 epitopes specific for helper and cytotoxic T cells was significantly improved by EGT. The EGT-mediated enhancement of humoral and cellular immunity is antigen independent, since comparable increases in antibody response against ciliary neurotrophic factor or in specific anti-human immunodeficiency virus type 1 gag CD8(+) T cells were obtained in rats and mice. Thus, the method described potentially provides a safe, low-cost treatment that may be scaled up to humans and may hold the key for future development of prophylactic or therapeutic vaccines against HCV and other infectious diseases.

Adenovirus E2 Proteins↗

PubMed1998

Lack of in vitro anti-gp160 antibody production is a correlate of nonprogression among HIV type 1-infected individuals.

The aim of our study was to investigate the possible correlation of in vitro antibody production (IVAP) directed to the gp160 protein of HIV-1 with CD4+ slopes, plasma viremia, and disease progression in long-term nonprogressors (LTNPs). Nineteen subjects with a long-term nonprogressive HIV-1 infection were studied and followed for 2 years. During the follow-up, in vitro anti-gp160 producers showed negative CD4+ slopes in the majority of cases (9 of 12), whereas 5 of 7 nonproducers showed positive CD4+ slopes. Plasma viremia values, which were not significantly different in the two groups at baseline, became significantly higher in anti-gp160 producers when compared with nonproducers during the follow-up (p = 0.012). Finally, a trend toward progression was observed in the group of producers but not in nonproducers. These findings suggest that the in vitro production of anti-gp160 antibodies by peripheral B cells is not a correlate of protection, and may represent an early predictor of progression in LTNPs.

CD4 Lymphocyte Count↗

PubMed1998

[Case report of a double ano-rectal neoplasia (adenocarcinoma and melanoma)].

The association in a single organ of two neoplasms with different, histogenensis is uncommon. A dual ano-rectal neoplasms, pigmented malignant melanoma in collision with adenocarcinoma is reported, along with a discussion concerning the problems related with primary origin of the melanocytic component.

Adenocarcinoma↗

PubMed1997

Agonistic and antagonistic variants of ciliary neurotrophic factor (CNTF) reveal functional differences between membrane-bound and soluble CNTF alpha-receptor.

Ciliary neurotrophic factor (CNTF) drives the sequential assembly of a receptor complex containing the ligand-specific alpha-receptor subunit (CNTFR) and the signal-transducing beta-subunits gp130 and leukemia inhibitory factor receptor-beta (LIFR). CNTFR can function in either membrane-bound or soluble forms. The membrane-bound form mediates the neuronal actions of CNTF, whereas the soluble form serves to confer cytokine responsiveness to non-neuronal cells expressing gp130 and LIFR. The objective of this work was to analyze whether the two receptor isoforms differ in their ability to interact functionally with CNTF and related proteins. Two new types of CNTF variants, characterized by weakened interactions with either CNTFR or both LIFR and gp130, were developed, and the biological activities of these and other mutants were determined in non-neuronal versus neuronal cells, as well as in non-neuronal cells transfected with an expression vector for CNTFR. Membrane anchoring of CNTFR was found to render the CNTF receptor complex relatively insensitive to changes in agonist affinity for either alpha- or beta-receptor subunits and to promote a more efficient interaction with a gp130-depleting antagonistic variant of CNTF. As a result of this phenomenon, which can be rationalized in terms of the multivalent nature of CNTF receptor interaction, CNTF variants display striking changes in receptor selectivity.

Antigens, CD↗

PubMed1997

Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance.

Receptor subunits for the neurocytokine ciliary neurotrophic factor (CNTF) share sequence similarity with the receptor for leptin, an adipocyte-derived cytokine involved in body weight homeostasis. We report here that CNTF and leptin activate a similar pattern of STAT factors in neuronal cells, and that mRNAs for CNTF receptor subunits, similarly to the mRNA of leptin receptor, are localized in mouse hypothalamic nuclei involved in the regulation of energy balance. Systemic administration of CNTF or leptin led to rapid induction of the tis-11 primary response gene in the arcuate nucleus, suggesting that both cytokines can signal to hypothalamic satiety centers. Consistent with this idea, CNTF treatment of ob/ob mice, which lack functional leptin, was found to reduce the adiposity, hyperphagia, and hyperinsulinemia associated with leptin deficiency. Unlike leptin, CNTF also reduced obesity-related phenotypes in db/db mice, which lack functional leptin receptor, and in mice with diet-induced obesity, which are partially resistant to the actions of leptin. The identification of a cytokine-mediated anti-obesity mechanism that acts independently of the leptin system may help to develop strategies for the treatment of obesity associated with leptin resistance.

Animals↗

PubMed1997

Ten-year results of treatment of ductal carcinoma in situ (DCIS) of the breast with conservative surgery and radiotherapy.

The optimal treatment of ductal carcinoma in situ (DCIS) of the breast has not yet been established. The effectiveness of adjuvant postoperative radiotherapy after conservative surgery is debated. Few data are available in Italy on the combined treatment. A collaborative multi-institutional study on this issue in 10 radiation oncology departments of the north-east of Italy was conducted. One hundred and thirty nine women with DCIS of the breast were treated between 1980 and 1990. Age ranged between 28 and 88 years (median 50 years). Surgical procedures were: quadrantectomy in 108, lumpectomy in 22 and wide excision in 9 cases. The axilla was surgically staged in 97 cases: all the patients were node-negative. Radiation therapy was delivered with 60Co units (78%) or 6 MV linear accelerators (22%) for a median total dose to the entire breast of 50 Gy (mean 49.48 Gy; range 45-60 Gy). The tumour bed was boosted in 109 cases (78%) at a dose of 4-30 Gy (median 10 Gy) for a minimum tumour dose of 58 Gy. Median follow-up was 81 months. Thirteen local recurrences were recorded, 7 intraductal and 6 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease. Actuarial overall, cause-specific and recurrence-free survival at 10 years are of 93%, 100% and 86%, respectively. The results of this retrospective multicentric study substantiate the favourable data reported in the literature and confirm the efficacy of the breast-conserving treatment of DCIS employing conservative surgery and adjuvant radiation therapy.

Adult↗

PubMed1997

[Cardiovascular "risk" and diabetes mellitus. Results of a retrospective study].

BACKGROUND: To examine the relationship of non-insulin dependent diabetes mellitus (NIDDM) with the prevalence of coronary heart disease (CHD) in a hospitalized population. METHODS AND RESULTS: Diabetes was associated with a markedly increased risk of developing CHD, whose prevalence was of 48.3% in NIDDM subjects (528 males and 661 females). Between the two groups (with and without CHD) of diabetic patients, the mean age was higher in the CHD-group, but no differences were noted with regard to gender distribution, BMI, history of cigarette smoking, alcohol consumption, glycemic control, hypoglycemic treatment, lipid pattern (although a slight increase in mean level of serum total triglycerides was observed in NIDDM subjects with CHD). On the contrary, CHD was significantly associated with a higher prevalence of periferal vascular disease (49.3% vs 32.5%) and with hypertension and renal dysfunction. CONCLUSIONS: These observations support the evidence that diabetes exerts a deleterious effect on general risk factors of atherosclerosis and increases the susceptibility to cardiovascular disease, although the prevalent mechanism of this susceptibility is only partly explained. Because the adverse "independent" effect of diabetes on the risk of cardiovascular disease is amplified in the presence of other cardiovascular risk factors, these data underscore the importance of prevention of diabetes and, once diabetes is clinically established, the need for standard risk factors management (hypertension, obesity, elevated lipid levels) as well as the development of new therapeutic strategies, in order to reduce the progress of macrovascular disease and the hemostatic derangements which may predispose to thrombosis and endothelial cell injury.

Aged↗

PubMed1997

[Lipoleiomyoma of the uterus].

The presence of fatty tissue in the myometrium is anomalous; this alteration has been interpreted either as a lipomatous degeneration or as a metaplasia of smooth muscle cells or, still, as a real neoplasm, frequently associated with a leiomyoma, the so-called lipoleiomyoma. The observation of a case of lipoleiomyoma stimulated us to ascertain the real incidence of this lesion which is commonly considered to be rare. We examined 620 single or multiple uterine leiomyomas with extensive sampling of all the areas suspected to contain fatty tissue islands. Five times out of seven the presence of fat cells in a leiomyoma resulted to be a true lipoleiomyoma. It has thus been possible to ascertain the incidence of lipoleiomyoma versus uterine leiomyomatosis (0.8%). Futhermore we observed a prevalence in menopause, an association with multiple leiomyoma and a preferential onset in the subserosa. The pathogenesis of this lesion, which can be fully ascribed to a mixed, benign, heterologous, mesenchymal neoplasm, is briefly discussed.

Adipose Tissue↗

PubMed1996

Identification of ciliary neurotrophic factor (CNTF) residues essential for leukemia inhibitory factor receptor binding and generation of CNTF receptor antagonists.

Ciliary neurotrophic factor (CNTF) drives the sequential assembly of a receptor complex containing the ligand-specific alpha-receptor subunit (CNTFR alpha) and the signal transducers gp130 and leukemia inhibitory factor receptor-beta (LIFR). The D1 structural motif, located at the beginning of the D-helix of human CNTF, contains two amino acid residues, F152 and K155, which are conserved among all cytokines that signal through LIFR. The functional importance of these residues was assessed by alanine mutagenesis. Substitution of either F152 or K155 with alanine was found to specifically inhibit cytokine interaction with LIFR without affecting binding to CNTFR alpha or gp130. The resulting variants behaved as partial agonists with varying degrees of residual bioactivity in different cell-based assays. Simultaneous alanine substitution of both F152 and K155 totally abolished biological activity. Combining these mutations with amino acid substitutions in the D-helix, which enhance binding affinity for the CNTFR alpha, gave rise to a potent competitive CNTF receptor antagonist. This protein constitutes a new tool for studies of CNTF function in normal physiology and disease.

Amino Acid Sequence↗

PubMed1995

[Wolfram syndrome. Peculiar urologic aspects].

The 6-year follow-up of a patient affected by Wolfram's syndrome, a rare disease characterized by diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), neurosensory deafness (D), atony of the urinary tract and other abnormalities (DIDMOAD or Wolfram's syndrome), is described. Our patient has diabetes insipidus, diabetes mellitus, abnormal audiograms, without subjective evidence of hearing loss, and dilatation of the urinary tract. Diagnosis was suspected at the age of 8 years. Diabetes mellitus was the first manifestation and treatment with insulin was necessary. Desmopressin therapy decreased dramatically the daily urinary output. In view of the significant morbidity and mortality from renal failure associated with recurrent urinary infections, we have drawn special attention to the urological manifestations of the syndrome. During the follow-up, the patients underwent some investigations, such as renal ultrasound and echotomography and cystourethroscopy. Outstanding results of these studies are severe bilateral hydronephrosis with dilatated ureters and loss of renal tissue. The particular finding is the presence of posterior urethral valves with obstructed bladder. The anatomical outlet obstruction are variable and may be disastrous. There may be failure to thrive, sepsis, anemia be disanal failure. In such instances corrective surgery could improve bladder and ureteral functions.

Adolescent↗

PubMed1994

[Hypertension at the threshold of the year 2000: classification, treatment, prevention].

Despite the clear benefits of treating established hypertension, this approach alone will not prevent all of the blood pressure-related cardiovascular-renal disease in the community. Primary prevention of hypertension is a natural extension of hypertension treatment which provides opportunity to reduce costly cycle of managing hypertension and its complications. The purpose of this report is to guide practician physicians and health professionals in their care of hypertensive patients. In order to provide specific guidelines, a new classification schema of high blood pressure that includes systolic as well diastolic levels is proposed (source, Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure 1993). Furthermore, recommendations for follow-up based on initial set of blood pressure measurements, life-style modifications and pharmacologic therapy are proposed, suggesting a new treatment algorithm in which diuretics and beta-blockers are preferred as first-choice agents because their confirmed reduction in morbidity and mortality (unless they are contraindicated or unacceptable), but including an expanded list of agents that are suitable for initial monotherapy and guidelines for selecting and individualizing the antihypertensive drug regimen.

Adolescent↗