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M Zamani

Publications and source records attributed to M Zamani.

At least 19 recordsLinked to original sources
PubMed2006

Detection of spallation neutrons and protons using the (nat)Cd activation technique in transmutation experiments at Dubna.

Various spallation sources have been used to transmute long-lived radioactive waste, mostly making use of the wide energy neutron fluence. In addition to neutrons, a large number of protons and gamma rays are also emitted from these sources. In this paper (nat)Cd is proved to be a useful activation detector for determining both thermal-epithermal neutron as well as secondary proton fluences. The fluences measured with (nat)Cd compared with other experimental data and calculations of DCM-DEM code were found to be in reasonable agreement. An accumulation of thermal-epithermal neutrons around the center of the target (i.e. after approx. 10 cm) and of secondary protons towards the end of the target is observed.

Journal Article↗
PubMed2003

Application of activation methods on the Dubna experimental transmutation set-ups.

High spallation neutron fluxes were produced by irradiating massive heavy targets with proton beams in the GeV range. The experiments were performed at the Dubna High Energy Laboratory using the nuclotron accelerator. Two different experimental set-ups were used to produce neutron spectra convenient for transmutation of radioactive waste by (n,x) reactions. By a theoretical analysis neutron spectra can be reproduced from activation measurements. Thermal-epithermal and fast-super-fast neutron fluxes were estimated using the 197Au, 238U (n,gamma) and (n,2n) reactions, respectively. Depleted uranium transmutation rates were also studied in both experiments.

Journal Article↗
PubMed2001

Linkage and association of HLA class II genes with vitiligo in a Dutch population.

BACKGROUND: Serological typing of HLA has shown discrepancies in HLA associations with vitiligo in different ethnic populations. OBJECTIVES: To perform genotyping of HLA class II genes on a Dutch vitiligo population in order clearly to identify susceptible and protective HLA alleles in vitiligo. METHODS: HLA typing was carried out by amplifying genomic DNA by polymerase chain reaction (PCR) followed by dot-blot hybridization with sequence-specific oligonucleotides (SSO). Fifty Dutch vitiligo probands, and their parents (150 individuals) and 204 healthy controls were studied. RESULTS: Family-based case-control association studies and linkage disequilibrium analysis showed the linkage and association of DRB4*0101 allele with vitiligo (P(c) = 0.0016, relative risk = 2.21). The family-based association study also provided evidence for linkage and association of DQB1*0303 allele with vitiligo (chi(2) = 7.36, P = 0.006). We measured the clinical relevance of the test by calculating the prevalence corrected positive predictive values (PcPPV). The PcPPV of disease for the DRB4*0101 allele was 0.017 and for the DRB4*0101/0101 genotype was 0.0358. In other words, a DRB4*0101/0101 genotype carries a 3.58% risk of developing vitiligo. CONCLUSIONS: Both DRB4*0101 and DQB1*0303 alleles provide significant susceptibility for vitiligo.

Adolescent↗
PubMed2000

Primary role of the HLA class II DRB1*0301 allele in Graves disease.

The association of the Graves disease (GD) with HLA DR3 and DQA1*0501 in Caucasians has been described previously. From these studies it could not be determined whether one specific locus was primarily involved. Using a case-control study design, we have examined the role of HLA class II gene polymorphisms in the predisposition for GD in a group of Belgian subjects. We demonstrated that both DRB1*0301 and DQA1*0501 alleles conferred significant susceptibility in the DRB1*0301-DQA1*0501 haplotype. The DRB1*0301 allele was the primary susceptibility allele for GD, however, because the susceptibility provided by DQA1*0501 was most likely due to it being in linkage disequilibrium with DRB1*0301. The DRB1*0701/x and DQA1*0201/x genotypes and the DRB1*0701-DQA1*0201 haplotype provided protection with an equal RR of 0.29. Predictive value calculations showed that testing for DRB1*0301 gave the highest positive predictive value for GD in females and males. This was, however, 10 times higher in females and predicted a 3.63% risk for a random female to develop GD.

Alleles↗
PubMed2000

Object encoding, goal similarity, and analogical transfer.

Although the importance of goal similarity and similarity of encoding are well known in analogical transfer literature, there has never been a study in which one of these factors was maintained constant and the other manipulated. This point was studied in our first experiment. The results show that the interaction between the two factors is not significant. However, the width of the credibility intervals suggests that it is difficult to conclude that there is either a presence or an absence of an interaction. The second experiment concerned more directly the impact of the encoding process on recognition of analogy. The results show that analogical transfer can be highly dependent on the way subjects interpret problems and that the encoding process can be influenced by the visual characteristics of the problems. These results can be related to a recent body of research on the importance of interpretive effects on analogy, as well as to the categorization literature.

Adult↗
PubMed1999

Epistatic effects of genes encoding tumor necrosis factor-alpha, immunoglobulin allotypes, and HLA antigens on susceptibility to non-insulin-dependent (type 2) diabetes mellitus.

Non-insulin-dependent diabetes mellitus (NIDDM) is a complex disease with a very high degree of heritability. Linkage and segregation analyses have not been very productive in identifying genes responsible for polygenic diseases such as NIDDM, and the majority of the genes determining susceptibility to this disorder remain to be identified. Using a case-control study design, we investigated the possible roles of genes coding for HLA class II antigens, tumor necrosis factor-alpha (TNF-alpha), and immunoglobulin (Ig) allotypes (GM and KM) in a group of Caucasians from Belgium (214 NIDDM patients and 200 controls). All genetic markers were determined by polymerase chain reaction-based methods. We demonstrate that particular homozygous genotypes of TNF-alpha and GM and KM allotypes epistatically interact with HLA-DQalpha1(Arg 52) and contribute to an increased relative risk of NIDDM.

Case-Control Studies↗
PubMed1998

Human immunodeficiency virus type 2 lentivirus vectors for gene transfer: expression and potential for helper virus-free packaging.

In addition to the long-term expression of the transgene provided by all retroviral vectors, lentiviruses present the opportunity to transduce nondividing cells and potentially achieve regulated expression. The development of lentiviral vectors requires the design of transfer vectors to ferry the transgene with efficient encapsidation of the transgene RNA and with full expression capability, and of a packaging vector to provide packaging machinery in trans but without helper virus production. For both vectors, a knowledge of packaging signal is required-the signal to be included in the transfer vector but excluded from the packaging vector. Among the human lentiviruses, human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2), we think HIV-2 is better suited for gene transfer than HIV-1. It is less pathogenic and thus safer during design and production; its desirable nuclear import and undesirable cell-cycle arrest functions are segregated on two separate genes. In HIV-1 infection, it is less likely to recombine with the resident HIV-1, and it may itself downregulate HIV-1 expression. Evidently, elements located both upstream and downstream of the splice donor site in the leader sequence participated in RNA encapsidation and these sequences appeared necessary and sufficient. Deletion of both sequence elements resulted in a dramatic curtailment of RNA encapsidation and helper virus production. This was accompanied by some but acceptable loss of gene expression capability. The helper virus-free phenotype and expression capability of the double mutant was maintained upon replacement of its 3' long terminal repeat with a minigene cassette containing a transcriptional termination signal and a drug resistance marker gene. Deletion of the splice donor site itself had a dramatic negative effect on gene expression, supporting the important role of this element in the life of RNA.

Cell Line↗
PubMed1998

Reevaluation of the importance of polymorphic HLA class II alleles and amino acids in the susceptibility of individuals of different populations to type I diabetes.

Several publications have shown that certain alleles at the HLA-DRB1, -DQA1, and -DQB1 loci are associated with insulin-dependent diabetes mellitus (IDDM). Many of these studies have claimed that HLA-DQalpha1Arg52 and DQbeta1Asp57 showed the strongest association with IDDM, but these results could not be confirmed in different populations. We have recently found that DRbeta1Lys71+ provided major susceptibility to IDDM and that DQbeta1Asp57- had an additive effect to DRbeta1Lys71+ [Zamani et al., 1994a: Eur J Hum Genet 2:177-184]. This was confirmed with haplotype analysis in multiplex IDDM families [Zamani et al., 1996a: J Med Genet 33:899-905]. Therefore, we have reanalyzed the data from the literature on the association of the human leucocyte antigen (HLA) DRB1, DQB1, and DQA1 with IDDM in different ethnic groups to determine whether different amino acids in the antigen binding cleft of HLA class II molecules play a preponderant role in the development of IDDM. The results showed that the DRbeta1Lys71+ allele provided the highest relative risk for IDDM in the Belgian, Danish, Greek Taiwanese, and Chinese population while this was not the case in Norwegians, Sardinians, and Algerians. Indeed, in the Sardinian and Algerian population the DRB1*0401 allele encoding Lys71+ is very rare. Nevertheless, the few positive cases were always in the patient group. We also measured the clinical relevance of the testing for DRbeta1Lys71, DQbeta1Asp57, and DQalpha1Arg52 by calculating a prevalence-corrected positive predictive value (PcPPV), a prevalence corrected negative predictive value (PcNPV), the sensitivity and specificity of these tests. The results indicated that the sensitivity of the test for DRbeta1Lys71+ was lower than for DQalpha1Ag52+ and DQbeta1Asp57-, while testing for DRbeta1Lys71+ was more specific than testing for DQbeta1Asp57- and DQalpha1Arg52+ and that the DRbeta1Lys71+ allele had a higher PcPPV than DQalpha1Arg52+ and DQbeta1Asp57- in all studied populations. These results also showed that testing for DRbeta1LyS71+/+ can be useful in IDDM risk assessment particularly in populations with a high prevalence (P) of IDDM such as the Danish (P[IDDM] = 0.65%). PcPPV for DRbeta1Lys71+/+ was 0.2313 in the Danish, indicating a 23.13% risk for an individual who is homozygous for the genotype DRbeta1Lys71+/+ to develop IDDM. Some mechanisms which might explain the role of these HLA class II alleles in susceptibility to IDDM are discussed.

Alleles↗
PubMed1998

Towards developing HIV-2 lentivirus-based retroviral vectors for gene therapy: dual gene expression in the context of HIV-2 LTR and Tat.

Because of the distinct ability of retroviruses to integrate into the target cell genome and thus achieve long-term expression, retrovirus vectors hold great promise for stable gene transfer. Such vectors derived from human immunodeficiency retroviruses (HIVs) and other lentiviruses are envisioned to possess several advantages, especially for in vivo gene therapy of HIV infection and acquired immunodeficiency syndrome (AIDS) where targeting CD4+ T cells/macrophages and pluripotent non-dividing stem cells would be required. Among these is the ability of HIVs to transduce nondividing cells in contrast to the murine retroviruses which require target cell mitosis. The advantages of the lentivirus vectors will be further enhanced by the development of multigenic vectors carrying more than one gene in a dependent or independent transcriptional unit. Separate from the issue of transduction efficiency, information is needed about the impact of the configuration of the genes in a multigenic vector on their expression. Towards this end, we investigated the expression of genes specifically directed by the HIV-2 LTR and Tat in a prototypic minimal transfer vector. We found that the expression of a gene in a dual gene configuration depended upon its position in the transcriptional unit and that the insertion of an internal translational initiation mechanism improved the expression of the downstream gene. Apparently not sufficiently appreciated previously, these effects were promoter and cell-type dependent. Our data also suggest that the commonly used cellular or viral promoters may be orders of magnitude less effective than HIV-2 LTR in the presence of Tat, and thus may not be useful as internal promoters in the context of the HIV-2 LTR:Tat regulatory loop.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Linkage of type I diabetes to 15q26 (IDDM3) in the Danish population.

Affected sib pair and linkage disequilibrium analysis, intrafamilial and case-control association studies were performed on 81 Danish multiplex insulin-dependent diabetes mellitus (IDDM) families (382 individuals) and 82 healthy Danish controls. The results confirm the linkage of D15S107 to IDDM in these Danish IDDM families (P = 0.010). When these data are combined with those of previous studies, an even stronger case for linkage can be made (P = 0.0005). Our analyses show that the D15S107*130 allele provides increased susceptibility (P = 0.02, relative risk = 3.55) and that the D15S107 locus contributes up to 16% of the familial clustering of IDDM. The analysis of affected sib pairs suggests that HLA and D15S107 may possibly act independently of each other. Taken together with our previous findings, our results suggest that three causes of susceptibilities can be discerned in the IDDM patient population: (1) a major susceptibility caused by the HLA-DRB1 alleles; (2) a minor susceptibility caused by the joint action of HLA and other non-HLA gene(s); and (3) a minor susceptibility caused by non-HLA gene(s).

Alleles↗
PubMed1996

Linkage and association of the HLA gene complex with IDDM in 81 Danish families: strong linkage between DR beta 1Lys71+ and IDDM.

Many studies have shown an association of IDDM with polymorphisms in the HLA region on chromosome 6p21. Previously our case-control study in the Belgian population showed significant association between IDDM and certain HLA class II alleles, in particular Lys71+, encoding DRB1 alleles. In the present study, 81 Danish multiplex IDDM families and 82 healthy Danish controls were examined for polymorphisms in the HLA-DRB genes and 54 of the 81 families for polymorphisms in HLA-B, -DQA1, -DQB1, -TNFA, and -TNFB genes. The results confirm our previous studies in the Belgian population and show that DRB1Lya71+/+ homozygotes have a relative risk (RR) of 103.5. Linkage between IDDM and DRB1 alleles that encode Lys71+ was shown by affected zib pair analysis which showed strong linkage (p < 1 x 10(-6). By family based association studies, the DRB1Lys71+ was identified as the allale which increased susceptibility to develop IDDM most in the HLA region (haplotype relative risk = 8.38). Haplotype analysis confirmed the increased risk contributed by DRB1Lys71+ alleles and in addition showed that DRB1Lys71- provides protection against IDDM even in the presence of DQB1Aep47-. These results indicate that DRB1Lys71+ screening is a powerful test compared to full HLA typing to determine the risk for a random person to develop IDDM in the Danish population, with an even higher probability than shown previously for the Belgians.

Alleles↗
PubMed1995

Neutrophil and Platelet Activity and Quantification Following Delayed tPA Therapy in a Rabbit Model of Thromboembolic Stroke.

Although there is considerable interest in the role of neutrophils and platelets in acute cerebral ischemia-reperfusion, there are very little data related to the effect of systemic thrombolytic therapy on these blood elements. In the present study a rabbit model was used to examine the effects of cerebral ischemia, tissue-plasminogen activator therapy, or both on neutrophil and platelet peripheral counts and activity, the latter studied by stimulated neutrophil and platelet impedance aggregation and neutrophil oxygen-free radical chemiluminescence. New Zealand white rabbits (n = 25) were randomized to receive either tissue-plasminogen activator (6.3 mg/kg IV; 20% bolus, remainder as a 2-hour infusion) or vehicle (0.9% saline) 3 hours following either autologous clot embolization or sham carotid artery isolation. Thus, four groups were examined: sham (n = 4), tPA only (n = 4), stroke only (n = 8), and stroke plus tPA (n = 9). Two hours after completion of thrombolytic therapy or vehicle infusion, the experiments were terminated, that is, 7 hours following autologous clot embolization or sham instrumentation. Blood was sampled from the thoracic aorta, and neutrophil and platelet peripheral counts and activity were determined prior to embolization and 0.5, 2.0, 4.0, and 7.0 hours following autologous clot embolization. No significant difference in platelet counts, either over time or between groups, was noted. In contrast to the platelet counts, the neutruphil count significantly increased over time, rising approximately 2.5-fold from baseline in all four groups (p < 0.001). No significant increase in neutrophil accumulation (myeloperoxidase assay; 10 (7) PMNs/g tissue; mean +/- SEM) was noted within infarcted regions of either the stroke (1.26 +/- 0.07; n = 5) or stroke plus tissue-plasminogen activator (1.26 +/- 0.09; n = 5) groups when compared to either viable brain regions within the ischemic hemisphere (1.29 +/- 0.03; n = 4) or in sham controls (1.36 +/- 0.35; n = 4). Neutrophil activity (aggregation, oxygen-free radical release) in both groups undergoing autologous clot embolization demonstrated a trend toward higher values when compared to the two sham-operated groups. Tissue-plasrninogen activator administration did not significantly affect ex vivo neutrophil activity. In contrast, platelet aggregation was significantly reduced by the administration of tPA with (p = 0.001) or without (p < 0.01) autologous clot embolization. Thus, in the present rabbit model platelet but not neutrophil activity is modulated by the administration of tissue-plasminogen activator, while autologous clot embolization results in a trend toward acute neutrophil activation.

Journal Article↗
PubMed1985

Dose rate dependence on the response of CR-39 SSNT-detector.

The dose rate dependence on the response of CR-39 SSNT-Detector was examined. The dose rate region studied was 10(2)-10(6) rad/min for doses 0 up to 1 Mrad. For relatively low and high dose rates a drop in the response of the detector was observed. The behavior changes for low doses and above 1 Mrad. The contribution of recombination and degradation mechanisms on the observed behavior was discussed.

Dose-Response Relationship, Radiation↗