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Biomedical subjects

G Monti

Publications and source records attributed to G Monti.

At least 19 recordsLinked to original sources

A randomized study comparing filgrastim versus lenograstim versus molgramostim plus chemotherapy for peripheral blood progenitor cell mobilization.

We conducted a prospective randomized clinical trial to assess the mobilizing efficacy of filgrastim, lenograstim and molgramostim following a disease-specific chemotherapy regimen. Mobilization consisted of high-dose cyclophosphamide in 45 cases (44%), and cisplatin/ifosfamide/etoposide or vinblastine in 22 (21%), followed by randomization to either filgrastim or lenograstim or molgramostim at 5 microg/kg/day. One hundred and three patients were randomized, and 82 (79%) performed apheresis. Forty-four (43%) patients were chemonaive, whereas 59 (57%) were pretreated. A median number of one apheresis per patient (range, 1-3) was performed. The median number of CD34+ cells obtained after mobilization was 8.4 x 10(6)/kg in the filgrastim arm versus 5.8 x 10(6)/kg in the lenograstim arm versus 4.0 x 10(6)/kg in the molgramostim arm (P=0.1). A statistically significant difference was observed for the median number of days of growth factor administration in favor of lenograstim (12 days) versus filgrastim (13 days) and molgramostim (14 days) (P<0.0001) and for the subgroup of chemonaive patients (12 days) versus pretreated patients (14 days) (P<0.001). In conclusion, all three growth factors were efficacious in mobilizing peripheral blood progenitor cells with no statistically significant difference between CD34+ cell yield and the different regimens, and the time to apheresis is likely confounded by the different mobilization regimens.

Adjuvants, Immunologic↗

Chemical and biochemical parameters of cultured diatoms and bacteria from the Adriatic Sea as possible biomarkers of mucilage production.

Bacteria and diatom strains from the Adriatic Sea were investigated, under standard and altered environmental conditions, for carbohydrate production and for the presence of specific biomarkers. Algae from P-depleted cultures showed an increase in extracellular carbohydrate production, a significantly lower chlorophyll a content and unchanged total lipid levels. However, the fatty acid composition of algal cultures was severely affected by low P levels, in that, total saturated and monounsaturated fatty acids increased and total polyunsaturated fatty acids decreased. Marine heterotrophic bacteria resulted enriched by 4 to 6 orders of magnitude in mucilage samples respect to surrounding seawater, unlike other groups of bacteria such as the non-halophylic heterotrophs. The major fatty acids detected in bacteria were 16:0 and 18:1n-7; the uneven fatty acids 17:0i, 17:0 and 17:1 also constituted an important component of various strains and, as a result, the total monounsaturated fraction represented the main component of total fatty acids. All the mucilage samples analysed shared the same general fatty acid composition features with a high amount of saturated components, especially 16:0; typical marine polyunsaturated fatty acids, such as 20:5n-3 and 22:6n-3, were found at very low levels. With regard to the sterol composition, the analysed algal species and bacteria showed that different compounds prevailed in the different species, and under P-deprivation sterol distribution resulted differently affected in the various algal species. In mucilage samples an overall prevalence of cholesterol was observed and, among 4alpha-methylsterols, constantly present, dinosterol prevailed in all samples. Vibrational IR spectroscopic analyses confirmed the main results obtained with the GC analysis: a higher unsaturation degree in nutrient replete diatom cultures than in P-depleted ones, a lower amount of P-containing compounds in the latter, bacterial lipid profiles with a high amount of free carboxylic acids and/or ketones and a low unsaturation degree and, finally, mucilage samples with a very low unsaturation degree. All these results allowed some speculations on the involvement of the various microbial and phytoplankton components in mucilage genesis.

Bacteria↗

Misregulation of poly(ADP-ribose) polymerase-1 activity and cell type-specific loss of poly(ADP-ribose) synthesis in the cerebellum of aged rats.

Protein modification by ADP-ribose polymers is a common regulatory mechanism in eukaryotic cells and is involved in several aspects of brain physiology and physiopathology, including neurotransmission, memory formation, neurotoxicity, ageing and age-associated diseases. Here we show age-related misregulation of poly(ADP-ribose) synthesis in rat cerebellum as revealed by: (i) reduced poly(ADP-ribose) polymerase-1 (PARP-1) activation in response to enzymatic DNA cleavage, (ii) altered protein poly(ADP-ribosyl)ation profiles in isolated nuclei, and (iii) cell type-specific loss of poly(ADP-ribosyl)ation capacity in granule cell layer and Purkinje cells in vivo. In particular, although PARP-1 could be detected in virtually all granule cells, only a fraction of them appeared to be actively engaged in poly(ADP-ribose) synthesis and this fraction was reduced in old rat cerebellum. NAD(+), quantified in tissue homogenates, was essentially the same in the cerebellum of young and old rats suggesting that in vivo factors other than PARP-1 content and/or NAD(+) levels may be responsible for the age-associated lowering of poly(ADP-ribose) synthesis. Moreover, PARP-1 expression was substantially down-regulated in Purkinje cells of senescent rats.

Aging↗

Genetic diversity and spread of Bovine leukaemia virus isolates in Argentine dairy cattle.

Effective tools for use in control programmes against bovine leukaemia virus (BLV) infections require insight into the relationship between the variant structure of the bovine leukaemia virus and the spatial-temporal interaction of isolates and hosts. Our study showed the presence of two types of BLV isolates - Australian and Argentine - in dairy herds from various parts of Central Argentina; these isolates were characterised by RFLP on PCR amplicons, and some of them were confirmed by sequencing. One genotype (Argentine) was present in all herds, and the Australian genotype was found in two herds. Phylogenetic analysis indicated four clusters. The first cluster was composed of the Argentine isolates and one from Brazil; the second was composed of several isolates found in European countries and one from Brazil; the third cluster was composed of BLV isolates found in Japan and Germany; the fourth cluster included American and Australian isolates and those from other countries. The comparison of a number of synonymous and non-synonymous nucleotide substitutions using various BLV genes revealed purifying selection, suggesting that molecular evolution occurred under some functional constraint.

Amino Acid Sequence↗

A high neonatal serum eosinophil cationic protein level is a risk factor for atopic symptoms.

AIM: To show whether neonatal eosinophil counts (EC) and eosinophil cationic protein (ECP) can be used in assessing the risk of atopy, alone or in combination with family history of atopy (FHa). PATIENTS AND METHODS: A group of 63 newborns was included: 38 with FHa, 25 without FHa. A blood sample was collected on the 4th day of life for EC and ECP evaluation. Clinical follow-up was conducted after 1, 3, 6, 12, 18, 24 and 36 mo. The chi2 test and the Student's t-test were used to compare dichotomic and continuous variables, respectively. Variables shown to be significant by univariate analysis were evaluated with a multivariate regression model and the relative risks (RR) were estimated. RESULTS: Twenty-six newborns (41%) displayed atopic manifestations during the follow-up. Twenty-one (55%) of 38 newborns with FHa displayed atopic symptoms versus 5/25 (20%) without FHa (p 0.012). Neither EC nor serum ECP levels were significantly different between newborns with FHa and newborns without. ECP levels did not differ between newborns with single heredity and newborns with dual heredity. EC did not differ significantly between newborns who developed atopy and those who did not. Instead, serum ECP levels were significantly higher in newborns who developed atopy (mean 27.9 microU/l vs 16.8 microU/l). Atopic manifestations appeared in 16 (62%) of 26 newborns with ECP > or = 18 microU/l compared with 10 (27%) of 37 with ECP < 18 microU/l (p = 0.006). In the multivariate regression model, with ECP < 18 microU/l and no FHa as reference class, the class 1 (no FHa and ECP > or = 18 microU/l) has a low RR (1.4), class 2 (FHa and ECP < 18 microU/l) an intermediate RR (2.7) and class 3 (FHa and ECP > or = 18 microU/l) a very high RR (16.3). CONCLUSIONS: Neonatal serum ECP levels, in contrast with EC, were significantly higher in newborns who developed atopic manifestations during follow-up. The risk of atopy was about twice as great when ECP was > or = 18 microU/l (and four times as great in multivariate analysis). When serum ECP was combined with FHa, the RR for newborns with FHa and ECP > or = 18 microU/l was 16 times greater than for those without FHa and ECP < 18 microU/l. The identification of newborns at "extremely high atopic risk" (FHa and ECP > or = 18 microU/l) may be expecially useful--in clinical practice--in newborns with only one atopic parent or sibling, for whom it is not universally agreed that dietary and environmental prevention measures should be applied.

Blood Proteins↗

High incidence of adverse reactions to egg challenge on first known exposure in young atopic dermatitis children: predictive value of skin prick test and radioallergosorbent test to egg proteins.

BACKGROUND: Egg skin prick test (SPT) and/or radioallergosorbent test (RAST) positivity has been described in infants and children with a food allergy, or in infants at high risk of atopy who have never eaten eggs. Clinical reactions are also observed when some of these children or infants eat eggs for the first time. OBJECTIVE AND METHOD: A prospective study was made of 107 atopic dermatitis (AD) children (66 boys, 41 girls) aged 1-19 months (median 5 months) who had never ingested egg, to compare the outcome of a first oral egg challenge and the results of albumen and yolk SPTs and RASTs. RESULTS: The egg challenge (conducted at age 12-24 months: mean 16 months, median 15 months) was positive in 72/107 children (67.3%). The reactions were immediate or early (first 6 h) in 56/72 (77.8%). The most severe (all within the first 6 h) were one case of anaphylactic shock (1.4%), three cases of laryngeal oedema (4.1%) and one serious attack of asthma (1.4%). The skin weal diameter at and above which reactions always occurred was 5 mm for both albumen and yolk. They were, however, also observed in the complete absence of a weal. The outcome of the challenge was always positive when the specific IgEs (sIgE) for albumen and yolk were > 99 KU/L and > or = 17.5 KU/L, respectively. Here, too, reactions were noted even when sIgE levels were < 0.35 KU/L. CONCLUSION: AD children who have never eaten eggs may be sensitized and display reactions at the first ingestion. The percentage of reactions in this series was by no means negligible. These findings were observed in children with mild as well as moderate-severe AD when first examined. SPT for albumen and yolk diameter > or = 5 mm, and sIgE for albumen > 99 KU/L and for yolk > or = 17.5 KU/L were 100% specific in predicting the outcome of the challenge. It may thus be concluded that children with AD whose SPT and/or RAST for albumen and/or yolk are equal to or higher than these cut-off values should not be subjected to the oral challenge when consideration is given to the introduction of egg in their diet. Even when these cut-offs are not reached, however, clinical reactions to the challenge cannot be ruled out a priori, and it should be preferably performed in a protected environment, such as a hospital.

Dermatitis, Atopic↗

Is there any difference in PBPC mobilization between cyclophosphamide plus G-CSF and G-CSF alone in patients with non-Hodgkin's Lymphoma?

We attempted to analyze whether the use of high-dose cyclophosphamide (CTX 7g/m2, group A) plus hematopoietic growth factor (G-CSF) or G-CSF alone (10 microg/Kg, group B) as a mobilizing regimen, could result in harvesting different numbers of CD34+ cells, committed progenitors and CD34+ cells subsets. The number of CD34+ cells considered as the target for each high-dose chemotherapy was > or = 2 x 10(6) /Kg/bw. Fifteen leukaphereses procedures were necessary in group A, while 16 procedures were performed in group B. We did not observe any difference between the two groups in terms of CD34+ cells/microl in the peripheral blood (117 vs 78; p = NS), whereas in the aphereses product we found a significant difference between the two groups of patients in terms of CD34+ cells (6.41 vs 2.89 x 10(6) /Kg/bw; p = .009), CFU-GM (82.5 vs 52.3 x 10(4) /Kg/bw; p = .04). Interestingly, we noted a different distribution of CD34+/33- cells between the 2 groups (mean value 39% vs 65%; p < .05), whereas we did not find any differences regarding CD34+/38-, CD34+/Thy1+, CD34+/HLADR-. The higher number of CFU-GM/Kg/bw collected in the former group did not translate into a superior plating efficiency (27.75 vs 30.29). Furthermore, we observed a strong correlation between CD34+ cells/microl in the peripheral blood and the total number of CD34+ cells in the leukaphereses product (r = 0.97), whereas this correlation was not found in group B (r = 0.15). In both groups of patients the number of CD34+ cells collected correlated well with CFU-GM (r = 0.93; r = 0.94), but definitely we did not observe any correlation between CD34+ cells/microl and CFU-GM in patients mobilized with G-CSF alone and this did not allow us to predict the harvest accurately. Finally, we evaluated the engraftment kinetics and we did not observe any statistically significant difference between the two groups of patients.

Adult↗

Relationships between total CD34+ cells reinfused, CD34+ subsets and engraftment kinetics in breast cancer patients.

BACKGROUND AND OBJECTIVE: The aim of the present study was to evaluate the correlation between the number of CD34+ cells transfused and the duration of hypoplasia, and the relationship between various CD34+ subsets (CD34+/33-; CD34+/38-; CD34+/ HLA-DR-; CD34+/Thy-1+) and engraftment kinetics in a series of patients with breast cancer treated with high doses of thiotepa and melphalan. DESIGN AND METHODS: We treated 42 consecutive patients: 19 in an adjuvant context (>= 4 positive axillary nodes) and 23 for metastatic disease. A combination of thiotepa 600 mg/m(2) and melphalan 140-160 mg/m(2) was administered as the conditioning regimen. All patients received peripheral blood progenitor cells (PBPC) and growth factors for hematopoietic rescue. RESULTS: In univariate analysis, we found a significant relationship between the number of CD34+ cells reinfused and the time to hematologic recovery and the duration of hospital stay. We observed an inverse correlation between the number of CD34+ cells reinfused and the units of platelets transfused. Cox multivariate analysis confirmed that the number of CD34+ cells reinfused is the most effective predictor of time to hematologic recovery. CFU-GM resulted to be a better predictor of the duration of hospitalization. INTERPRETATION AND CONCLUSIONS: We found a significant relationship between the number of PBPC reinfused and the time to hematologic recovery after high doses of thiotepa and melphalan. In our experience, the numbers of subsets of CD34+ cells infused did not give compared additional information to that provided by the total number of CD34+ cells infused.

Adult↗

The PEN5 epitope identifies an oligodendrocyte precursor cell population and pilocytic astrocytomas.

PEN5 is a sulfated polylactosamine carbohydrate epitope first described in a subpopulation of mature natural killer cells. Here we report that it is also expressed in a developmentally regulated fashion in human and rat central nervous systems and that its protein carrier is P-selectin glycoprotein ligand-1 (PSGL-1), a ligand for selectins. In rat neural primary cultures, PEN5 is transiently and selectively expressed by oligodendrocyte precursor cells and marks the transition from proliferative to postmitotic stages. In concordance, in human central nervous system tumors, PEN5 is observed in a subset of oligodendrogliomas and in all pilocytic astrocytomas, a class of tumor of uncertain histogenesis. These data suggest that PEN5-PSGL-1 plays a role in the differentiation of oligodendrocytes and that pilocytic astrocytomas are likely to result from a dysregulation occurring in oligodendrocyte precursor cells at the crucial stage of exit from the cell cycle.

Amino Sugars↗

Peripheral blood progenitor cell (PBPC) mobilization in heavily pretreated patients with germ cell tumors: a report of 34 cases.

The aim of the study was to evaluate peripheral blood progenitor cell mobilization by disease-specific chemotherapy in heavily pretreated patients with germ cell tumor (GCT), scheduled for high-dose chemotherapy. Thirty-four consecutive patients, 29 males and five females, with advanced GCT referred to our department for high-dose chemotherapy were evaluated retrospectively. Sixteen patients were mobilized by vinblastine 0.11 mg/kg on days 1 and 2, ifosfamide 1200 mg/m2 days 1-5 and cisplatin 20 mg/m2 days 1-5 (VeIP). In 10 patients, etoposide 75 mg/m2 days 1-5 was used instead of vinblastine (VIP), while in eight patients the mobilization was attempted by administering 7 g/m2 of cyclophosphamide. The choice of either etoposide or vinblastine was predicated upon which of these two drugs was associated with best results during premobilization chemotherapy. Cyclophosphamide was selected in patients refractory to previous cisplatin-based salvage chemotherapy. Twenty-five out of 34 patients underwent a successful PBPC collection. In 17 of them one leukapheresis procedure was sufficient to collect the target number of CD34+ cells, while in eight patients a double procedure was necessary. Altogether 33 aphereses were performed in 25 patients. In nine patients leukapheresis was not attempted. This was due to the fact that the chemotherapy failed to mobilize the target number of CD34+ cells in eight of them, treated with the VeIP mobilizing regimen, while one patient treated with high-dose cyclophosphamide rapidly progressed during therapy and for this reason leukapheresis was not undertaken. In conclusion, in heavily pretreated patients with GCT, PBPC mobilization is feasible by a further course of salvage chemotherapy. The choice of either etoposide (VIP) or vinblastine (VeIP) can be predicated upon which of these two drugs was associated with best results during premobilization chemotherapy. In our hands, VeIP seems to be less satisfactory as mobilizing treatment than VIP, possibly due to a superior number of premobilization courses of chemo therapy in some patients. Moreover, high-dose cyclophosphamide remains a good alternative for mobilizing patients refractory to salvage chemotherapy.

Adolescent↗

Culling policies in dairy herds. A review.

The culling decision is one of the most complex decisions in farm animal management. This article reviews concepts of culling, risk factors for cows to be culled, different culling policies and the present knowledge on how to develop an optimal culling policy. It is pointed out that there are major interactions between other management complexes and culling that influence the result of field research concerning risk factors for culling. The estimated importance of risk factors for culling varies widely in literature. Culling decisions are part of the overall herd management. They cannot be analysed independently. Future research should analyse the interactions between management practices, cow health, economy, and culling in more detail.

Animal Husbandry↗

Paclitaxel and radiotherapy: sequence-dependent efficacy--a preclinical model.

The optimal sequence of a paclitaxel-radiation combination was investigated in vitro in two human colon adenocarcinoma cell lines, HT29 and LoVo. Three schedules of combined treatment were tested by clonogenic and flow cytometric assays. Paclitaxel was given 24 h prior to a single radiation shot (first schedule) or 24 h (second schedule) or 48 h (third schedule) before 3 days of concomitant radiation. Dose-response data were fit to a linear quadratic model, and mean inactivation dose and sensitizer enhanced ratio were calculated. In HT29 cells, the first and second schedule resulted in an additive effect, whereas a supraadditive interaction was observed with the third combination schedule. This effect was obtained with amounts of paclitaxel lower than IC50, which did not result in cell cycle perturbation, and with low radiation dose (2 Gy) that may be given in a clinical setting. LoVo cells were less sensitive to combined treatment than HT29 cells, switching from infraadditive (first and second schedule) to additive interaction (third schedule). Posttreatment recovery studies of third schedule showed a loss of cell survival in HT29 cells but not in LoVo cells. In contrast to LoVo cells, the third schedule in HT29 cells was able to induce perturbation of cell cycle kinetics, an effective impairment of DNA repair, and apoptotic cell death. HT29 and LoVo cells showed constitutional different characteristics: HT29 cells were more sensitive to paclitaxel exposure, less radiosensitive, and had a different cell cycle redistribution after radiation exposure than LoVo cells; moreover, HT29 cells showed a major propensity to undergo apoptosis. These results suggest that the radiosensitizing effect of paclitaxel was strictly schedule dependent, and the inhibition of DNA repair, cell cycle redistribution, and apoptosis could be the mechanisms for the induction of radiosensitization by paclitaxel.

Adenocarcinoma↗

Platelet-derived growth factor expression in primary pulmonary hypertension: comparison of HIV seropositive and HIV seronegative patients.

Primary pulmonary hypertension (PPH) is characterized by intimal fibrosis and cell proliferation (including fibroblasts, smooth muscle and endothelial cells) in the distal pulmonary arterial tree. Considerable interest has been generated by recent reports of PPH in human immunodeficiency virus (HIV)-1-infected individuals. Although the lack of evidence for a pulmonary artery infection has suggested that in such cases HIV may act through mediator release rather than by direct endothelial infection, the mechanisms underlying HIV-associated PPH remain poorly defined. Platelet-derived growth factor (PDGF) has the ability to induce smooth muscle cell and fibroblast proliferation and migration. Given these considerations, we have attempted to document a possible role for PDGF in PPH occurring in HIV seropositive and seronegative patients. Using semiquantitative polymerase chain reaction (PCR), PDGF A-chain messenger ribonucleic acid (mRNA) expression was analysed in surgical lung biopsies from 13 HIV seronegative patients and one HIV seropositive patient, all displaying severe PPH. In parallel, lung samples from two patients with HIV-1-associated PPH were studied by immunohistochemistry and in situ hybridization. Results were compared to those obtained in three HIV-1-infected individuals with no pulmonary complication (as demonstrated by clinical, radiological, bacteriological, and necropsy findings) and five control lung biopsies. As compared to controls, PDGF A-chain mRNA expression is elevated in lung biopsies from patients displaying PPH (p=0.029). In HIV-1-associated PPH, interstitial perivascular cells expressing PDGF A-chain mRNA and protein could be detected by in situ hybridization and immunohistochemistry, respectively. Platelet-derived growth factor expression is elevated in lung biopsies of patients displaying primary pulmonary hypertension. Growth factors such as platelet-derived growth factor may play a part in the initiation and/or progression of primary pulmonary hypertension.

Adult↗

Cytofluorimetric evaluation of DNA ploidy in the diagnosis of bladder cancer.

OBJECTIVE: The aim of the study is to investigate the relationship between urinary cytology, traditional indexes of malignancy of bladder carcinoma and DNA-ploidy (diploid, near-diploid, aneuploid). METHODS: 52 specimens of bladder cancers (transitional cell carcinoma) were obtained from 46 patients at TURB and from 6 patients at radical cystectomy. In every specimen the nuclear content of DNA was investigated using the cytofluorimetric method. Cells were processed in standard fashion for flow cytometry with propidium iodide staining; cellular suspension was obtained mechanically. Peripheral blood lymphocytes were used as diploid standard. Bladder cytology was performed in every patient. RESULTS: A relationship between DNA-ploidy and histological malignancy was observed. The largest portion of near-diploid neoplasm was observed in stage T1, grade G2 malignancies. In some cases negative bladder cytology occurred together with aneuploid DNA content, whilst in other cases positive bladder cytology occurred together with diploid DNA content. In consequence there is not always a relationship between bladder cytology and DNA-ploidy. CONCLUSIONS: Since observed correlations may point out some neoplasms with particular biological behaviour, follow-up of near-diploid malignancies is of great interest.

Carcinoma, Transitional Cell↗