Biomedical subjects

N Sacchi

Publications and source records attributed to N Sacchi.

At least 19 recordsLinked to original sources

PubMed2006

Progenitor cells trapped in marrow filters can reduce GvHD and transplant mortality.

A bone marrow harvest is filtered either in the operating room, in the laboratory or during infusion to the patient. Filters are usually discarded. Little is known of haemopoietic progenitor cells (HPCs) trapped in the filters. The aim of the study was to evaluate HPC content in the filters and to assess the outcome of transplants with filter-discarded or filter-recovered cells. Haemopoietic progenitors were grown from filters of 19 marrow transplants. We then compared the outcome of 39 filter-recovered transplants from HLA-identical siblings (years 2001-2004) with a matched cohort of 43 filter-discarded marrow grafts (years 1997-2000). Filters contained on average 21% long-term culture-initiating cells (LTC-IC) and 15% fibroblasts colony-forming units (CFU-F) of the total progenitor cell content. Filter-discarded transplants had significantly more grade II-IV graft-versus-host disease (GvHD) (42 vs 15%, P=0.008) as compared to filter-recovered transplants, and more transplant-related mortality (TRM) (20 vs 3%, P=0.04). The actuarial survival at 5 years is 69 vs 87%, respectively (P=0.15). This study suggests that a significant proportion of LTC-IC is lost in the filters together with CFU-F. Recovery and add back of progenitors trapped in the filters may reduce GvHD and TRM.

Adolescent↗

PubMed2006

RAR-mediated epigenetic control of the cytochrome P450 Cyp26a1 in embryocarcinoma cells.

Retinoic acid (RA) is a signaling molecule that plays a pivotal role in major cellular processes and vertebrate development. RA action is mediated by specialized transcription factors, the nuclear RA receptors (RARs), which regulate the transcription of genes containing a RA-responsive element (RARE). Here we demonstrate that the genes for the RA-receptor RARbeta2 and the cytochrome P450 RA-specific hydrolase Cyp26a1 involved in RA catabolism are coordinately regulated by RA. We found that both RARbeta2 and Cyp26a1 genes are epigenetically silenced in the absence of DNA methylation in RAC65, a P19 embryocarcinoma cell line derivative carrying a dominant-negative RARalpha mutant and resistant to the growth-inhibitory and differentiation effects of RA. In response to RA, RARbeta2 transcription is epigenetically regulated by RARalpha. Similarly, we found that Cyp26a1 transcription is epigenetically regulated by RARbeta2. Knocking down RARbeta2 transcription by RNA interference in wild-type P19 cells, with an intact RARalpha, induced Cyp26a1 transcriptional repression in the absence of DNA methylation. Concomitantly, cells developed RA resistance and did not undergo RA-induced neuron differentiation. Apparently, RARalpha, RARbeta2 and Cyp26a1 are components of a RA-regulated gene network. Factors affecting an upstream gene of the network can trigger repressive chromatin changes -- which are propagated in a domino fashion - at downstream genes of the network. This study also shows that chromatin inactivity, and consequent transcriptional silencing, can be achieved in the absence of DNA methylation.

Animals↗

PubMed2003

Impact of marrow unrelated donor search duration on outcome of children with acute lymphoblastic leukemia in second remission.

We analyzed the outcome of 167 consecutive children with second CR acute lymphoblastic leukemia (ALL), for whom an unrelated donor (UD) search was activated between 1989 and 1998 at a median time of 2 months after relapse. A suitable donor was identified for 70 patients at 1 year and 6.5 months before and after 1995 from search activation, respectively; a further leukemia relapse occurred during the search in 94 children at a median of 4 months after search activation, 36 of whom underwent UD (14) or other types of transplant (22), beyond second CR, while 58 died of progressive disease. Of 73 patients not experiencing a second relapse, 64 underwent UD (46) or other types of transplant (18), while nine proceeded with chemotherapy, and only four of them survived. The 3-year disease-free survival (DFS) from second CR for the 167 patients is 15.1%, whereas 3-year DFS after transplant for the 60 UD and 40 alternative donor transplanted children is 31.6 and 25.4%, respectively. In conclusion, a further relapse is the main factor adversely affecting outcome of children with second CR ALL. Thus, for these patients, the search should be activated early after relapse and either a UD or an alternative transplant should be performed as early as possible.

Adolescent↗

PubMed2003

Resveratrol structure and ceramide-associated growth inhibition in prostate cancer cells.

Resveratrol (3,4',5-trans-trihydroxystilbene) is a dietary polyphenol with chemopreventive properties present in grapes, red wine, peanuts and other edible products. The antiproliferative and proapoptotic effect of resveratrol in breast cancer cells can be traced to the accumulation of ceramide. In this study we demonstrate that resveratrol can also exert antiproliferative/proapoptotic effects in association with the accumulation of endogenous ceramide in the androgen receptor (AR)-negative prostate cancer cell line, PC3. Notably, resveratrol shares with other ceramide-inducing agents a phenolic moiety on its structure. For this reason we hypothesize that the phenolic moiety is critical for the ceramide-associated growth-inhibitory effects of resveratrol. We compared the ability to induce both ceramide increase and growth inhibition in PC3 cells of resveratrol and three resveratrol analogs: piceatannol (3,3',4',5-trans-tetrahydroxystilbene), with an additional hydroxyl group in the 3' position; trans-stilbene, the nonhydroxylated analog; and the semisynthetic 3,4',5-trimethoxy-trans-stilbene (TmS), with methoxyl groups in lieu of the hydroxyl groups. Of the three stilbenoids, only piceatannol (and not stilbene or TmS) produced ceramide-associated growth inhibition. These data point to the phenolic moiety of stilbenoids as a critical structural feature necessary to induce ceramide-associated growth inhibition.

Anticarcinogenic Agents↗

PubMed2002

Improvement over time in outcome for children with acute lymphoblastic leukemia in second remission given hematopoietic stem cell transplantation from unrelated donors.

Aims of this study were to verify whether reduction in transplant-related mortality (TRM) of children with acute lymphoblastic leukemia (ALL) in second complete remission (CR) given allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated volunteers has occurred over time and to investigate the role of other variables on the probabilities of relapse, TRM and event-free survival (EFS). We compared results obtained in 26 children given HSCT before January 1998 with those of 37 patients transplanted beyond that date. In all donor-recipient pairs, histocompatibility was determined by serology for HLA-A and -B antigens and by high-resolution DNA typing for DRB1 antigen. High-resolution molecular typing of HLA class I antigens was employed in 20 of the 37 children transplanted more recently. Probability of both acute and chronic GVHD was comparable in the two groups of patients. In multivariate analysis, children transplanted before January 1998, those with T-lineage ALL and those experiencing grade II-IV acute GVHD had a higher relative risk of TRM at 6 months after transplantation. Relapse rate was unfavorably affected by a time interval between diagnosis and relapse <30 months. The 2-year probability of EFS for children transplanted before and after 1 January 1998 was 27% (10-44) and 58% (42-75), respectively (P = 0.02), this difference remaining significant in multivariate analysis. EFS of unrelated donor HSCT in children with ALL in second CR has improved in the last few years, mainly due to a decreased TRM. This information is of value for counseling of patients with relapsed ALL.

Adolescent↗

PubMed2001

Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO).

One hundred nine patients with hematologic malignancies, undergoing bone marrow transplants (BMT) from unrelated donors, were randomized in 2 consecutive trials to receive or not to receive antithymocyte globulin (ATG) in the conditioning regimen, as follows: (A) 54 patients (median age, 28 years; 39% with advanced disease) were randomized to no ATG (n = 25) versus 7.5 mg/kg rabbit ATG (Thymoglobulin; Sangstat, Lyon, France) (n = 29); (B) 55 patients (median age, 31 years, 71% with advanced disease) were randomized to no ATG (n = 28) versus 15 mg/kg rabbit ATG (n = 27). Grade III-IV graft-versus-host disease (GVHD) was diagnosed in 36% versus 41% (P =.8) in the first and in 50% versus 11% (P =.001) in the second trial. Transplant-related mortality (TRM), relapse, and actuarial 3-year survival rates were comparable in both trials. In fact, despite the reduction of GVHD in the second trial, a higher risk for lethal infections (30% vs 7%; P =.02) was seen in the arm given 15 mg/kg ATG. Extensive chronic GVHD developed overall more frequently in patients given no ATG (62% vs 39%; P =.04), as confirmed by multivariate analysis (P =.03). Time to 50 x 10(9)/L platelets was comparable in the first trial (21 vs 24 days; P =.3) and delayed in the ATG arm in the second trial (23 vs 38 days; P =.02). These trials suggest that (1) 15 mg/kg ATG before BMT significantly reduces the risk for grade III-IV acute GVHD, (2) this does not translate to a reduction in TRM because of the increased risk for infections, and (3) though survival is unchanged, extensive chronic GVHD is significantly reduced in patients receiving ATG.

Adolescent↗

PubMed2001

Detection of breast cancer cells in ductal lavage fluid by methylation-specific PCR.

If detected early, breast cancer is curable. We tested cells collected from the breast ducts by methylation-specific PCR (MSP). Methylated alleles of Cyclin D2, RAR-beta, and Twist genes were frequently detected in fluid from mammary ducts containing endoscopically visualised carcinomas (17 cases of 20), and ductal carcinoma in situ (two of seven), but rarely in ductal lavage fluid from healthy ducts (five of 45). Two of the women with healthy mammograms whose ductal lavage fluid contained methylated markers and cytologically abnormal cells were subsequently diagnosed with breast cancer. Carrying out MSP in these fluid samples may provide a sensitive and powerful addition to mammographic screening for early detection of breast cancer.

Breast↗

PubMed2000

Molecular structure and evolution of DNA sequences located at the alpha satellite boundary of chromosome 20.

We have isolated and characterised one PAC clone (dJ233C1) containing a linkage between alphoid and non-alphoid DNA. The non-alphoid DNA was found to map at the pericentromeric region of chromosome 20, both on p and q sides, and to contain homologies with one contig (ctg176, Sanger Centre), also located in the same chromosome region. At variance with the chromosome specificity shown by the majority of non-alphoid DNA, a subset of alphoid repeats derived from the PAC yielded FISH hybridisation signals located at the centromeric region of several human chromosomes, belonging to three different suprachromosomal families. The evolutionary conservation of this boundary region was investigated by comparative FISH experiments on chromosomes from great apes. The non-alphoid DNA was found to have undergone events of expansion and transposition to different pericentromeric regions of great apes chromosomes. Alphoid sequences revealed a very wide distribution of FISH signals in the great apes. The pattern was substantially discordant with the data available in the literature, which is essentially derived from the central alphoid subset. These results add further support to the emerging opinion that the pericentromeric regions are high plastics, and that the alpha satellite junctions do not share the evolutionary history with the main subsets.

Animals↗

PubMed2000

Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription.

Dentato-rubral and pallido-luysian atrophy (DRPLA) is one of the family of neurodegenerative diseases caused by expansion of a polyglutamine tract. The drpla gene product, atrophin-1, is widely expressed, has no known function or activity, and is found in both the nuclear and cytoplasmic compartments of neurons. Truncated fragments of atrophin-1 accumulate in neuronal nuclei in a transgenic mouse model of DRPLA, and may underlie the disease phenotype. Using the yeast two-hybrid system, we identified ETO/MTG8, a component of nuclear receptor corepressor complexes, as an atrophin-1-interacting protein. When cotransfected into Neuro-2a cells, atrophin-1 and ETO/MTG8 colocalize in discrete nuclear structures that contain endogenous mSin3A and histone deacetylases. These structures are sodium dodecyl sulfate-soluble and associated with the nuclear matrix. Cotransfection of ETO/MTG8 with atrophin-1 recruits atrophin-1 to the nuclear matrix, while atrophin-1 and ETO/MTG8 cofractionate in nuclear matrix preparations from brains of DRPLA transgenic mice. Furthermore, in a cell transfection-based assay, atrophin-1 represses transcription. Together, these results suggest that atrophin-1 associates with nuclear receptor corepressor complexes and is involved in transcriptional regulation. Emerging links between disease-associated polyglutamine proteins, nuclear receptors, translocation-leukemia proteins, and the nuclear matrix may have important repercussions for the pathobiology of this family of neurodegenerative disorders.

Animals↗

PubMed2000

Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas.

BACKGROUND: Retinoic acid plays an important role in lung development and differentiation, acting primarily via nuclear receptors encoded by the retinoic acid receptor-beta (RARbeta) gene. Because receptor isoforms RARbeta2 and RARbeta4 are repressed in human lung cancers, we investigated whether methylation of their promoter, P2, might lead to silencing of the RARbeta gene in human lung tumors and cell lines. METHODS: Methylation of the P2 promoter from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines and tumor samples was analyzed by the methylation-specific polymerase chain reaction (PCR). Expression of RARbeta2 and RARbeta4 was analyzed by reverse transcription-PCR. Loss of heterozygosity (LOH) was analyzed by PCR amplification followed by electrophoretic separation of PCR products. Statistical differences were analyzed by Fisher's exact test with continuity correction. RESULTS: The P2 promoter was methylated in 72% (63 of 87) of SCLC and in 41% (52 of 127) of NSCLC tumors and cell lines, and the difference was statistically significant (two-sided P:<.001). By contrast, in 57 of 58 control samples, we observed only the unmethylated form of the gene. Four tumor cell lines with unmethylated promoter regions expressed both RARbeta2 and RARbeta4. Four tumor lines with methylated promoter regions lacked expression of these isoforms, but demethylation by exposure to 5-aza-2'-deoxycytidine restored their expression. LOH at chromosome 3p24 was observed in 100% (13 of 13) of SCLC lines and 67% (12 of 18) of NSCLC cell lines, and the difference was statistically significant (two-sided P: =.028). CONCLUSIONS: Methylation of the RARbeta P2 promoter is one mechanism that silences RARbeta2 and RARbeta4 expression in many lung cancers, particularly SCLC. Chemical demethylation is a potential approach to lung cancer therapy.

Carcinoma, Non-Small-Cell Lung↗

PubMed2000

Evidence of epigenetic changes affecting the chromatin state of the retinoic acid receptor beta2 promoter in breast cancer cells.

Retinoic acid (RA)-resistance in breast cancer cells has been associated with irreversible loss of retinoic acid receptor beta, RARbeta, gene expression. Search of the causes affecting RARbeta gene activity has been oriented at identifying possible differences either at the level of one of the RARbeta promoters, RARbeta2, or at regulatory factors. We hypothesized that loss of RARbeta2 activity occurs as a result of multiple factors, including epigenetic modifications, which can pattern RARbeta2 chromatin state. Using methylation-specific PCR, we found hypermethylation at RARbeta2 in a significant proportion of both breast cancer cell lines and primary breast tumors. Treatment of cells with a methylated RARbeta2 promoter, by means of the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR), led to demethylation within RARbeta2 and expression of RARbeta indicating that DNA methylation is at least one factor, contributing to RARbeta inactivity. However, identically methylated promoters can differentially respond to RA, suggesting that RARbeta2 activity may be associated to different repressive chromatin states. This supposition is supported by the finding that the more stable repressive RARbeta2 state in the RA-resistant MDA-MB-231 cell line can be alleviated by the HDAC inhibitor, trichostatin A (TSA), with restoration of RA-induced RARbeta transcription. Thus, chromatin-remodeling drugs might provide a strategy to restore RARbeta activity, and help to overcome the hurdle of RA-resistance in breast cancer.

Antimetabolites, Antineoplastic↗

PubMed2000

Clinical relevance of office underestimation of usual blood pressure in treated hypertension.

Average 24-h blood pressure (BP) is more representative of usual BP than office BP. However, the clinical relevance of 24-h BP in treated hypertensive subjects is incompletely known. Thus, we studied 395 uncomplicated hypertensive subjects (209 men, 53+/-10 years) who were receiving antihypertensive drug therapy from >1 year. All subjects underwent 24-h ambulatory BP monitoring and M-mode echocardiography. Subjects were classified by tertile of the difference between observed and predicted 24-h systolic BP (the latter determined by regressing 24-h systolic BP on office systolic BP): higher-than-predicted (III tertile), around the regression line (II tertile), and lower-that-predicted (I tertile) 24-h BP. Despite similar office BP (144/89, 141/88, and 144/89 mm Hg in the III, II, and I tertile, P = not significant), age, body mass index, and duration of hypertension, left ventricular mass was greater in the subjects with higher-than-predicted 24-h systolic BP (50+/-14 g x m(-2.7)) than in the other two groups (46+/-13 g x m(-2.7) and 42+/-10 g x m(-2.7), both P < .05). The III tertile also showed a more concentric left ventricular geometric pattern (relative wall thickness was 0.42+/-0.08, 0.40+/-0.07, and 0.38+/-0.07 in the III, II, and I tertile, P < .001) and a reduced systolic function at the midwall level (16.8+/-3, 17.7+/-3, and 18.2+/-3, P < .001). In conclusion, treated hypertensive subjects whose 24-h BP is notably higher than one would predict from office BP are more likely to develop left ventricular hypertrophy, a strong adverse prognostic marker. In a sizable subset of treated hypertensive subjects, BP measured in the physician's office underestimates usual BP and its impact on left ventricular structure.

Antihypertensive Agents↗

PubMed2000

Alternative donor transplants for patients with advanced hematologic malignancies, conditioned with thiotepa, cyclophosphamide and antithymocyte globulin.

Preparative regimens without total body irradiation (TBI) have been reported for alternative donor hemopoietic stem cell transplants (HSCT). Between 7 September 1994 and 7 June 1999 48 patients with advanced hematologic malignancies were conditioned with thiotepa (THIO) 15 mg/kg, cyclophosphamide (CY) 150 mg/kg and antithymocyte globulin (ATG). Donors were HLA mismatched family members (1-2 antigens) (FAM) (n = 24, median age 31 years) or HLA matched unrelated donors (UD) (n = 24, median age 34 years). GVHD prophylaxis was cyclosporine and methotrexate. Stem cell source was peripheral blood (n = 8) or bone marrow (n = 40). Hematologic recovery was seen in 42/46 (91%) evaluable patients and complete chimerism in 31/37 patients (85%). Acute GVHD grades III-IV were seen in 10/46 patients surviving 10 days (21%) and extensive chronic GVHD in 2/36 patients surviving 100 days (5%). Twenty-six patients died (54%), eight of recurrent disease (17%) and 18 of transplant-related complications (37%): main causes of TRM were GVHD (15%), infections (15%) and graft failure (4%). Twenty-two patients (46%) survive with a median follow-up of 877 days (287-1840). The actuarial 3-year survival is 49% for FAM and 42% for UD transplants. Results obtained with this regimen in unrelated grafts for advanced CML (n = 15) were not significantly different when compared to 21 concurrent UD grafts for advanced CML prepared with CY-TBI. In conclusion, the combination of THIO-CY-ATG allows engraftment of alternative donor hemopoietic stem cells. Results are similar when using unrelated matched donors or partially mismatched family donors, and not significantly different when compared to patients conditioned with CY-TBI.

Actuarial Analysis↗

PubMed2000

Long-term effects of losartan and enalapril, alone or with a diuretic, on ambulatory blood pressure and cardiac performance in hypertension: a case-control study.

BACKGROUND: The long-term effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on ambulatory blood pressure and cardiac performance have never been examined comparatively. OBJECTIVE: We compared losartan and enalapril in their long-term effects on office and ambulatory blood pressure, cardiac structure and function, and routine biochemical tests. DESIGN: In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study, 22 hypertensive subjects were studied with ambulatory blood pressure monitoring and echocardiography before and after an average of 3.3 years of treatment with losartan 50mg daily. These subjects were matched in a 1:3 ratio with a group of 66 subjects treated with enalapril 20mg daily. Case-control sampling was based on age (+/-5years), sex, pre-treatment office blood pressure (+/-5mmHg) and ambulatory blood pressure (+/-5mmHg), and duration of treatment (+/-6months). An additional group of subjects who interrupted their treatment with enalapril (n=18) or losartan (n =2) because of unwanted effects before execution of the follow-up study was not included in the analysis. RESULTS: Hydrochlorothiazide was added during follow-up in order to optimize blood pressure control (office blood pressure <140mmHg systolic and 90mmHg diastolic) in 10 subjects (45%) in the losartan group and 34 subjects (52%) in the enalapril group. Office and ambulatory blood pressures were lowered to a similar extent by losartan and enalapril. Left ventricular mass decreased from 98 to 87g/m(2) with losartan (P <0.01) and from 98 to 89 g/m(2) with enalapril (P <0.01). The change in left ventricular mass over time was more closely associated with the change in ambulatory blood pressure than with office blood pressure in both groups. Left ventricular internal diameter did not change with either drug. The endocardial shortening fraction, mid-wall shortening fraction and Doppler indexes of active diastolic relaxation did not change with either drug. None of the biochemical parameters showed a significant change. Serum uric acid showed a slight and non-significant reduction only in the losartan group. CONCLUSION: In this case-control study in uncomplicated subjects with essential hypertension, losartan and enalapril, alone or combined with a diuretic, effectively and equally lowered office and ambulatory blood pressure and induced a significant reduction in left ventricular mass during long-term treatment. Left ventricular systolic and diastolic function remained unchanged with either regimen.

Adult↗

PubMed2000

Persistence of increased left ventricular mass despite optimal blood pressure control in hypertension.

BACKGROUND: Left ventricular hypertrophy is an adverse risk marker in essential hypertension and its regression has a favorable effect on prognosis. It is unclear whether blood pressure normalization induced by long-term therapy is able to normalize left ventricular mass completely. METHODS: In the setting of a prospective cohort study, 107 consecutive hypertensive patients who achieved blood pressure normalization (clinic blood pressure < 140/90 mmHg on > or = 3 consecutive visits) under long-term (1-10 years, average 2.9) drug treatment were individually matched with 107 healthy normotensive controls by gender, age (+/- 5 years), body mass index (+/- 3 kg/m2), and clinic systolic blood pressure (+/- 5 mmHg) in a case-control design. All subjects underwent 24-hour blood pressure monitoring and M-mode echocardiography. RESULTS: Treated hypertensive patients and normotensive controls did not differ by age, body mass index, clinic blood pressure (128/82 vs 128/81 mmHg), and 24-hour blood pressure (120/77 vs 120/76 mmHg). Left ventricular mass and relative wall thickness were greater in the hypertensive than in the normotensive group (97 +/- 24 vs 86 +/- 17 g/m2 and 0.40 +/- 0.08 vs 0.37 +/- 0.08, both p < 0.001). CONCLUSIONS: Left ventricular mass is greater in well-controlled hypertensive patients than in normotensive controls matched by age, obesity, gender, and clinic and 24-hour blood pressure. This finding is consistent with the lower than epidemiologically expected reduction in coronary heart disease risk during antihypertensive therapy and might reflect the persistent effect on left ventricular mass of hemodynamic and/or non-hemodynamic factors other than blood pressure in treated patients with essential hypertension.

Antihypertensive Agents↗

PubMed1999

Oligomerization properties of fragile-X mental-retardation protein (FMRP) and the fragile-X-related proteins FXR1P and FXR2P.

The absence of fragile-X mental-retardation protein (FMRP) results in fragile-X syndrome. Two other fragile-X-related (FXR) proteins have been described, FXR1P and FXR2P, which are both very similar in amino acid sequence to FMRP. Interaction between the three proteins as well as with themselves has been demonstrated. The FXR proteins are believed to play a role in RNA metabolism. To characterize a possible functional role of the interacting proteins the complex formation of the FXR proteins was studied in mammalian cells. Double immunofluorescence analysis in COS cells over-expressing either FMRP ISO12/FXR1P or FMRP ISO12/FXR2P confirmed heterotypic interactions. However, Western-blotting studies on cellular homogenates containing physiological amounts of the three proteins gave different indications. Gel-filtration experiments under physiological as well as EDTA conditions showed that the FXR proteins were in complexes of >600 kDa, as parts of messenger ribonuclear protein (mRNP) particles associated with polyribosomes. Salt treatment shifted FMRP, FXR1P and FXR2P into distinct intermediate complexes, with molecular masses between 200 and 300 kDa. Immunoprecipitations of FMRP as well as FXR1P from the dissociated complexes revealed that the vast majority of the FXR proteins do not form heteromeric complexes. Further analysis by [(35)S]methionine labelling in vivo followed by immunoprecipitation indicated that no proteins other than the FXR proteins were present in these complexes. These results suggest that the FXR proteins form homo-multimers preferentially under physiological conditions in mammalian cells, and might participate in mRNP particles with separate functions.

Animals↗

PubMed1999

[The Italian Registry of Bone Marrow Donors].

Following a synthetic statement of the scientific, genetic and practical assumptions of the bone marrow transplantation (BMT) from marrow unrelated donor (MUD), which, in turn, have represented the basis for the establishment of the Italian Bone Marrow Donor Registry (IBMDR), the paper reports the registry activity on 30 November 1998. At that date, Italian volunteers were 232,876, number which put the IBMDR as the fourth registry all over the world and as the third in Europe. The mean age of the donors is 34 years, and this means that IBMDR is one of the youngest among international registries. Using Italian donors, 426 BMT, altogether, have been performed, (248 for Italian patients and 178 for foreign patients). Donor search activations performed by national and international transplant centres have been, at the same date, 5729 (1821 for Italian patients and 3908 for foreign patients). Operating standards and guidelines for all centres participating in the IBMDR are reported in this issue.

Age Distribution↗

PubMed1999

[The Italian Registry of Bone Marrow Donors: genetic structure and recruitment strategy].

The genetic structure of the Italian bone marrow donor population was analysed by estimating the HLA-A, -B and -DR gene and haplotype frequencies for the total population and for the Italian administrative regions. The haplotype frequencies were used to predict the probability of finding HLA-compatible donors for Italian patients depending on the registry size, and the probability of recruiting in the different Italian regions a donor with a new phenotype. The analysis of these probabilities allows us to propose strategies for donors recruitment in order to increase the phenotypic variability of the registry, then its efficiency.

Algorithms↗