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Biomedical subjects

C Santoro

Publications and source records attributed to C Santoro.

At least 19 recordsLinked to original sources
PubMed2006

Idiopathic thrombocytopenic purpura (ITP) in the elderly: clinical course in 178 patients.

Idiopathic thrombocytopenic purpura (ITP) is often diagnosed in the elderly (age >or=65 yr), where it generally presents as a chronic disease. The objective of the present study was to describe the natural history of ITP in the elderly and to evaluate the risk of bleeding and the possible occurrence of other pathologies. We retrospectively evaluated 178 ITP patients (82 men, 96 women; mean age: 72 yr) diagnosed between 1981 and 1998. Therapy was started at diagnosis or during follow-up, depending on the platelet count and/or bleeding events. Sixty-six out of one hundred and seventy-eight patients (37%) initiated therapy at diagnosis; whereas in 11 of the 112 untreated patients (9.8%) therapy was necessary during the follow-up. Low-dose of prednisone was the first-line treatment in all patients (mean daily dose of 0.43 mg/kg). Forty-nine (63.6%) of the seventy-seven treated patients showed a response, 14 of these (28.6%) suffered a relapse. Another pathology occurred in 19 of the 178 patients (10.7%). We conclude that low-dose prednisone is an appropriate initial treatment for elderly persons. We also stress that an adequate follow-up is advisable, given that isolated thrombocytopenia could in some cases be the first sign of another underlying pathology.

Aged↗
PubMed2004

Respiratory changes during defecation in patients with chronic respiratory failure.

Oxygen (O2) desaturation may occur in patients affected by respiratory diseases during daily activities, although most of these activities, e.g. walking, washing and cooking, can be avoided or eventually performed with an external aid. In this prospective study, the respiratory changes induced by the mandatory effort of defecation were assessed in patients with chronic respiratory insufficiency. Twenty-four consecutive patients with chronic respiratory failure due to obstructive or restrictive pulmonary disorders, showing a marked O2 desaturation during the 6-min walk test, were enrolled. Thirteen of them were already established on long-term O2 therapy (LTOT), while 11 were not. O2 saturation (Sa,O2), respiratory rate (RR), cardiac frequency (fC) and dyspnoea were measured at rest, and during and after defecation. Sa,O2 decreased significantly during defecation, while RR, fC and dyspnoea increased, both in the subgroup of patients without significant resting hypoxaemia and in the subgroup of patients receiving their usual resting flow of LTOT, as compared to resting values. In conclusion, the respiratory system of patients with chronic respiratory failure may be significantly strained by defecation.

Activities of Daily Living↗
PubMed2004

[Dietetic indications for obesity treatment in childhood].

A growing organism needs to have a steady availability of nutrients, in suitable quantities and in correct ratios, in order to achieve its genetic potential. Overweight and obesity in growing individuals may conceal lack of one or more nutrients. Obesity in childhood is the consequence of an excess of calories compared with the energetic waste because of the interlacing of genetic factors, metabolic factors (cellularity of the adipose tissue, deficit of thermogenesis), excessive food intake, alteration of some neuro-endocrine mechanisms which regulate bodily weight (set point theory), lack of suitable physical exercise; therefore a complicity of endogenous, exogenous, biological, psychological and social factors to which we cannot ascribe singularly a primary role. It is however necessary to start, since the first year of a child's life, a food education program as the latest acquisition shows that degenerative pathologies of metabolism start in a very precocious age and unbalanced nutrition starts since childhood. The most suitable therapeutic approach is that which takes in consideration all the aspects of obesity. This requires an intervention on several aspects: food, psychological mechanisms which sometimes are the cause of hypernutrition, attitude towards physical exercise, and also family and social behaviors concerning the patient. The traditional diet approach towards childhood obesity is based on balanced hypochaloric diets which provide about 1200-1800 kcal per day, distributed in 4 or 5 daily meals. The correct meal division educates the child to self-control and it is advantageous from a metabolic point of view because it avoids both high instability of glyco-insulin, caused by an excess of food, and because improving thermogenesis, induced by the diet, the result will consist in an increase of energetic waste. For the main meals it is advantageous to apply to a main course.

Child↗
PubMed2003

Germ-line origin of intron 1 inversion in two haemophilia A families.

Factor VIII gene inversion of intron 1 has recently been reported to be the mutation responsible for haemophilia A in about 5% of severe cases. In our series of patients, which is made up of 77 Italian cases negative for intron 22 inversion, the mutation was found in three sporadic and in one familial patients, with an overall frequency of 5.2%. The carrier status of the patients' female relatives was assessed by mutation analysis and showed that only two-thirds of cases could be considered truly sporadic. The germ-line origin of the mutation was investigated in the two sporadic families by haplotype analysis on genomic DNA of the patients' maternal grandparents. These studies indicated that both mutation events had occurred in the germ cell lines of the patients' healthy grandfather, suggesting that, as already demonstrated for the inversion of intron 22, the male germ cell line is more susceptible to the intrachromosome recombination which leads to the inversion of intron 1.

Chromosome Inversion↗
PubMed2002

Activity of GH/IGF-I axis in trauma and septic patients during artificial nutrition: different behavior patterns?

The aim of this study was to compare several parameters of GH/IGF-I axis activity in septic and trauma patients during Intensive Care Unit (ICU) stay. To this goal, 13 patients with sepsis (SEP) and 16 with trauma (TRA) were studied. Thirty-three adult subjects (AS) were studied as controls. Serum IGF-I and -II, IGFBP-1, -2 and -3, GH and GHBP levels were studied on day 1, 3, 5 and 7 after ICU admission, during comparable artificial nutrition in SEP and TRA and basally in AS. In 5 patients with SEP and 6 with TRA, the GH response to GHRH was evaluated on day 3. On ICU day 1, IGF-I and -II and IGFBP-3 in SEP were lower (p<0.05) than in TRA which, in turn, were lower (p<0.01) than in AS. IGF-I increased (p<0.05) both in SEP and TRA, but, on ICU day 7, those in SEP persisted lower than in TRA, which became similar to those in AS. IGF-II levels increased (p<0.05) in SEP only, persisting lower (p<0.05) than in TRA. On ICU day 1, GH in SEP and TRA were similar and did not vary until day 7, overlapping those in AS. The GH response to GHRH in SEP and TRA was similar and lower (p<0.01) than in AS. These findings indicate that IGF-I activity is impaired more in septic than in trauma patients. Reduced IGF-I activity probably reflects peripheral GH resistance though basal and GHRH-induced GH levels were not increased in these conditions.

Adult↗
PubMed2001

Cooperation and competition between the binding of COUP-TFII and NF-Y on human epsilon- and gamma-globin gene promoters.

The nuclear receptor COUP-TFII was recently shown to bind to the promoter of the epsilon- and gamma-globin genes and was identified as the nuclear factor NF-E3. Transgenic experiments and genetic evidence from humans affected with hereditary persistence of fetal hemoglobin suggest that NF-E3 may be a repressor of adult epsilon and gamma expression. We show that, on the epsilon-promoter, recombinant COUP-TFII binds to two sites, the more downstream of which overlaps with an NF-Y binding CCAAT box. Binding occurs efficiently to either the 5' or the 3' COUP-TFII site but not to both sites simultaneously. However, adding recombinant NF-Y induces the formation of a stable COUP-TFII.NF-Y-promoter complex at concentrations of COUP-TFII that would not give significant binding in the absence of NF-Y. Mutations of the promoter indicate that COUP-TFII cooperates with NF-Y when bound to the 5' site, whereas binding at the 3' site is mutually exclusive. Likewise, in the gamma-promoter, COUP-TFII binds to a site overlapping the distal member of a duplicated CCAAT box, competing with NF-Y binding. Transfections in K562 cells show that both the mutation of the 5' COUP-TFII or of the NF-Y site on the epsilon-promoter decrease the activity of a luciferase reporter; the mutation of the 3' COUP-TFII site has little effect. These results, together with transgenic experiments suggesting a repressive activity of COUP-TFII on the epsilon-promoter and the observation that, on the 3' site, COUP-TFII and NF-Y binding is mutually exclusive, suggest that COUP-TFII may exert different effects on epsilon transcription depending on whether it binds to the 5' or to the 3' site. At the 5' site, COUP-TFII might cooperate with NF-Y, forming a stable complex, and stimulate transcription; at the 3' site, COUP-TFII might compete for binding with NF-Y and, directly or indirectly, decrease gene activity.

Animals↗
PubMed2001

Macrophage stimulating protein (MSP) evokes superoxide anion production by human macrophages of different origin.

1. Macrophage Stimulating Protein (MSP), a serum factor related to Hepatocyte Growth Factor, was originally discovered to stimulate chemotaxis of murine resident peritoneal macrophages. MSP is the ligand for Ron, a member of the Met subfamily of tyrosine kinase receptors. The effects of MSP on human macrophages and the role played in human pathophysiology have long been elusive. 2. We show here that human recombinant MSP (hrMSP) evokes a dose-dependent superoxide anion production in human alveolar and peritoneal macrophages as well as in monocyte-derived macrophages, but not in circulating human monocytes. Consistently, the mature Ron protein is expressed by the MSP responsive cells but not by the unresponsive monocytes. The respiratory burst evoked by hrMSP is quantitatively higher than the one induced by N-formylmethionyl-leucyl-phenylalanine and similar to phorbol myristate acetate-evoked one. 3. To investigate the mechanisms involved in NADPH oxidase activation, leading to superoxide anion production, different signal transduction inhibitors were used. By using the non selective tyrosine kinase inhibitor genistein, the selective c-Src inhibitor PP1, the tyrosine phosphatase inhibitor sodium orthovanadate, the phosphatidylinositol 3-kinase inhibitor wortmannin, the p38 inhibitor SB203580, the MEK inhibitor PD098059, we demonstrate that hrMSP-evoked superoxide production is mediated by tyrosine kinase activity, requires the activation of Src but not of PI 3-kinase. We also show that MAP kinase and p38 signalling pathways are involved. 4. These results clearly indicate that hrMSP induces the respiratory burst in human macrophages but not in monocytes, suggesting for the MSP/Ron complex a role of activator as well as of possible marker for human mature macrophages.

Adult↗
PubMed1998

Evaluation of a new automated instrument for pretransfusion testing.

BACKGROUND: A number of automated devices for pretransfusion testing have recently become available. This study evaluated a fully automated device based on column agglutination technology (AutoVue System, Ortho, Raritan, NJ). STUDY DESIGN AND METHODS: Some 6747 tests including forward and reverse ABO group, Rh type and phenotype, antibody screen, autocontrol, and crossmatch were performed on random samples from 1069 blood donors, 2063 patients, and 98 newborns and cord blood. Also tested were samples from 168 immunized patients and 53 donors expressing weak or variant A and D antigens. Test results and technician times required for their performance were compared with those obtained by standard methods (manual column agglutination technology, slide, semiautomatic handler). RESULTS: No erroneous conclusions were found in regard to the 5028 ABO group and Rh type or phenotype determinations carried out with the device. The device rejected 1.53 percent of tests for sample inadequacy. Of the remaining 18 tests with discrepant results found with the device and not confirmed with the standard methods, 6 gave such results because of mixed-field reactions, 10 gave negative results with A2 RBCs in reverse ABO grouping, and 2 gave very weak positive reactions in antibody screening and crossmatching. In the samples from immunized patients, the device missed one weak anti-K, whereas standard methods missed five weak antibodies. In addition, 48, 34, and 31 of the 53 weak or variant antigens were detected by the device, the slide method, and the semiautomated handler, respectively. Technician time with the standard methods was 1.6 to 7 times higher than that with the device. CONCLUSION: The technical performance of the device compared favorably with that of standard methods, with a number of advantages, including in particular the saving of technician time. Sample inadequacy was the most common cause of discrepancy, which suggests that standardization of sample collection can further improve the performance of the device.

ABO Blood-Group System↗
PubMed1995

Alternative translation initiation site usage results in two functionally distinct forms of the GATA-1 transcription factor.

GATA-1 is a zinc-finger transcription factor that plays a critical role in the normal development of hematopoietic cell lineages. In human and murine erythroid cells a previously undescribed 40-kDa protein is detected with GATA-1-specific antibodies. We show that the 40-kDa GATA-1 (GATA-1s) is produced by the use of an internal AUG initiation codon in the GATA-1 transcript. The GATA-1 proteins share identical binding activity and form heterodimers in erythroleukemic cells but differ in their transactivation potential and in their expression in developing mouse embryos.

Animals↗
PubMed1995

CTF/NF-1 binds the stage selector element of the human gamma-globin gene promoter.

The human gamma-globin gene undergoes to a transcriptional switch during development, being expressed in the fetus and silenced at birth. It has been proposed that the sequence centered at -50 of the gamma-globin promoter contains a stage selector element (SSE) involved in the gamma- to beta-globin switching. The presence of the SSE confers preferential functional interactions of the promoter with the locus control region (LCR) in the fetal liver. It has been shown that two factors bind the gamma-globin SSE: Sp1 and the stage selector protein (SSP). Here we show that also the ubiquitous transcription factor CTF/NF-1 binds to the -53 to -35 element of the human gamma-globin promoter and its specificity is not influenced by flanking sequences.

Animals↗
PubMed1995

Differential binding of the NFE3 and CP1/NFY transcription factors to the human gamma- and epsilon-globin CCAAT boxes.

Naturally occurring nondeletional mutations affecting the distal CCAAT box of the human gamma-globin gene promoter result in hereditary persistence of fetal hemoglobin in adult life. Although the distal CCAAT box is the target of several factors, including CP1/NFY, CDP, GATA-1 and NFE3, only NFE3 binding activity is consistently sensitive to well characterized mutations in this region such as G-117-->A, C-114-->T, and delta 13 hereditary persistence of fetal hemoglobin. We extensively characterized the binding specificities of NFE3 and demonstrated that NFE3 has unique properties with respect to other CCAAT box-binding proteins. Affinity-purified NFE3 from erythroid K562 cells binds the distal but not the proximal human gamma-globin CCAAT box, the single CCAAT box of the human epsilon-globin promoter, and the proximal CCAAT box of the evolutionarily related Galago crassicaudatus gamma-globin gene. Within the epsilon-globin CCAAT box, NFE3 represents the major and almost exclusive binding activity. Disruption of such a binding site essentially inactivates the epsilon-globin promoter, suggesting that NFE3 plays an important role in the embryonic expression of this gene.

Adult↗
PubMed1995

In vitro and ex vivo activities of antimicrobial agents used in combination with clarithromycin, with or without amikacin, against Mycobacterium avium.

MICs of clarithromycin, amikacin, isoniazid, rifabutin, ciprofloxacin, sparfloxacin, ethambutol, and clofazimine were determined for six isolates of Mycobacterium avium complex (MAC) from AIDS patients both by the radiometric method and by an ex vivo model of infection in human macrophages. The median MICs in macrophages were similar or slightly lower than values found in broth, except for amikacin, which had slightly higher MICs inside the cells. Combinations of clarithromycin with other antimicrobial agents showed that clarithromycin-clofazimine and clarithromycin-rifabutin were synergistic on five of six strains while clarithromycin-amikacin and clarithromycin-isoniazid were antagonistic on one and two strains, respectively. The addition of amikacin made the combinations of clarithromycin-clofazimine and clarithromycin-ethambutol synergistic against all the MAC strains. In the macrophage model, the combination of clarithromycin-clofazimine (mean survival, 21%) and clarithromycin-rifabutin (mean survival, 29%) showed a strong reduction in viable counts compared with single drugs, while clarithromycin-amikacin was less active than single drugs alone. In general, the addition of amikacin did not improve the activity of the combinations, except for clarithromycin-isoniazid-amikacin (mean survival, 19%), which was significantly more active than either clarithromycin-isoniazid or clarithromycin-amikacin. The use of the macrophage model can suggest new combinations of antimicrobial agents with anti-MAC activity which, on the basis of their in vitro effectiveness, would probably be disregarded for assay in animal models.

Amikacin↗
PubMed1994

Structure and inducible regulation of the human MET promoter.

The MET oncogene, encoding the tyrosine kinase receptor for the hepatocyte growth factor/scatter factor, is expressed in epithelial cells and overexpressed in a significant proportion of human epithelial cancers, suggesting the occurrence of transcriptional alteration(s). To identify the MET promoter, we isolated recombinant cDNA clones encompassing the entire 5'-noncoding sequence of MET messenger RNAs. Using probes derived from this region, we cloned the entire genomic region spanning the first MET exon and the flanking regulatory sequences. The first exon, containing the entire untranslated sequence, is present in the MET mRNAs of 7.1, 5.9, and 4.6 kilobases, showing that the expression of the multiple transcripts is regulated by a single promoter. The start site of transcription was determined by primer extension and by rapid amplification of cDNA ends. We show that a 300-base pair fragment, containing sequences upstream from the start site, efficiently drives the expression of a reporter gene in transfected epithelial cells. This promoter fragment also contains the cis-acting elements responsible for phorbol-ester induction.

Base Sequence↗
PubMed1994

Expression, purification, and functional characterization of the two zinc-finger domain of the human GATA-1.

The DNA-binding domain of the erythroid transcription factor GATA-1 consists of two closely related, but distinct zinc-fingers which are highly conserved among the members of the growing family of GATA-like factors. The DNA-binding domain of the human GATA-1 (F1F2) was expressed as a histidine-tagged fusion protein in Escherichia coli. The denaturated protein was purified by Ni(2+)-chelate affinity chromatography and renaturated in situ. The active recombinant protein was purified by DNA affinity chromatography. F1F2 displayed GATA-1 specific binding activity toward its DNA recognition sequences within the hypersensitive site 3 of the human locus control region and the human gamma-globin promoter. In contrast to GATA-1 protein purified from K562 nuclei, the recombinant F1F2 bound also the CCAAT-box region of the human gamma-globin promoter.

Base Sequence↗
PubMed1994

Induction of IL-1 beta, IL-6, TNF-alpha, GM-CSF and G-CSF in human macrophages by smooth transparent and smooth opaque colonial variants of Mycobacterium avium.

Both smooth transparent (SmT) and smooth domed-opaque (SmD) colonial variants were obtained from a strain of Mycobacterium avium isolated from a patient with AIDS. The two variants showed similar biochemical characteristics but SmT bacteria proliferated better than SmD bacteria inside human macrophages and were much less capable than the SmD variant of inducing the release of IL-1 beta, IL-6, TNF-alpha, GM-CSF and G-CSF, after incubation for either 3 or 6 days. As cytokines are important extracellular signals for immune cells, the lack of induction observed in SmT-infected macrophages may be one of the pathogenic mechanisms of M. avium.

AIDS-Related Opportunistic Infections↗
PubMed1992

Promoter for the human ferritin heavy chain-encoding gene (FERH): structural and functional characterization.

We conducted a functional analysis of the promoter for the human ferritin heavy chain-encoding gene (pFERH) in HepG2 and HeLa cells. The activity of pFERH is equivalent in both cell types, despite their different ferritin (Fer) isotypes. Transfections of a series of 5'-deletion mutants indicate that pFERH activity is essentially dependent on two motifs. One of them, accounting for about 50% of the total transcriptional activity, is recognized by the RNA polymerase II transcription factor, Sp1, and the other by a low-affinity factor present in both the cell types analyzed.

Base Sequence↗
PubMed1992

Activity of antimicrobial agents against Mycobacterium avium-intracellulare complex (MAC) strains isolated in Italy from AIDS-patients.

Twenty-five strains of Mycobacterium avium-intracellulare (MAC) isolated from acquired immunodeficiency syndrome (AIDS) patients in three medical centres in Italy have been studied. Serotyping performed on eighteen strains showed various serovars within either M. avium or M. intracellulare serotypes and with serovars 1 and 21 being the most prevalent (four strains for each serovar). Among fourteen drugs used for testing the antibiotic sensitivity, rifapentine, rifabutin and clofazimine showed to have the best in vitro activity. In an ex vivo model of infection using peritoneal resting macrophages from the C57BL/6 mouse, the intracellular viability of a strain of M. avium (strain 489, serovar 3) was reduced by clofazimine, amikacin, ciprofloxacin, rifabutin and clarithromycin (99, 98, 93, 89 and 69%, respectively), thus indicating for clofazimine a good correlation between in vitro and ex vivo activity.

Acquired Immunodeficiency Syndrome↗