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A Oppenheim

Publications and source records attributed to A Oppenheim.

At least 55 records · Page 3Linked to original sources
PubMed1996

Assessment of personality functioning in the transition from adolescent to adult life: preliminary findings.

BACKGROUND: The Adolescent to Adult Personality Functioning Assessment (ADAPFA) a modification of the Adult Personality Functioning Assessment (APFA) is described. It may be used to assess specific and general social dysfunction in the transition from childhood to adult life. METHOD: Two raters independently rated 38 audiotaped interviews to test the interrater reliability of the instrument. The relationship between dysfunction in specific domains and overall psychosocial dysfunction was examined. RESULTS: Interrater reliabilities for the total ADAPFA score and for the majority of the domains were high. Agreement on type of dysfunction and on categorical ratings indicating the presence of personality disorder were good. CONCLUSION: The ADAPFA is a useful measure of interpersonal and social role performance in the transition between adolescent and adult life.

Adolescent↗
PubMed1996

Effect of magnesium given 1 hour after head trauma on brain edema and neurological outcome.

Excitatory amino acids (EAA), mainly glutamate and aspartate, are released in excessive amounts from terminals of ischemic or traumatically injured neurons. These excessive levels of EAAs initiate a cascade of events believed to lead to secondary delayed damage to the surrounding brain. The N-methyl-D-aspartate receptor antagonists MK-801 and ketamine are reported to suppress excessive EAA release and to attenuate the development of focal brain edema following neuronal injury. Magnesium is also reported to work at the postsynaptic receptor to reduce the neurotoxic effect of glutamate. The present study was undertaken to examine the effect of postinjury treatment with Mg++ on brain edema and neurological outcome after traumatic brain injury. Sixty-nine rats that survived halothane anesthesia and closed head trauma (CHT) were randomly assigned to one of seven experimental groups: sham, CHT, and CHT with administration of Mg++ 1 hour postinjury. At 48 hours, brain tissue Mg++ concentration (calculated from optical density using a standard curve) was significantly increased compared to baseline levels (10.06 +/- 2.44 mg/g vs. 6.83 +/- 0.81 mg/g, p < 0.01 calculated by one-way analysis of variance). Also at 48 hours postinjury, brain tissue specific gravity in the contused hemisphere of Mg(++)-treated rats was significantly greater than that in the contused hemisphere of untreated rats, indicating attenuation of brain edema formation by Mg++. The neurological severity score (NSS) of rats treated with Mg++ improved significantly at both 18 and 48 hours, compared to baseline values obtained 1 hour after CHT but prior to administration of Mg++ (11.2 +/- 2.5 vs. 15.2 +/- 4.1, p = 0.03; and 12.3 +/- 6.1 vs. 17.3 +/- 3.6, p = 0.004, respectively). In the untreated groups, the NSS at 18 and 48 hours was not significantly different from baseline values (that is, no neurological improvement). The present study indicates that postinjury treatment with Mg++ attenuates brain edema formation and improves neurological outcome after experimental CHT.

Animals↗
PubMed1996

Improved single-step PCR assay for sex identification post-allogeneic sex-mismatched BMT.

A method is presented which allows sex-identification simultaneously of both male and female cells in cell mixtures. The sensitivity of this PCR-based assay is one male cell in 10(6) female cells. The test can be used routinely to analyze bone marrow and peripheral blood lymphocytes post-allogeneic sex-mismatched bone marrow transplantation to detect early engraftment or rejection, as well as host cell regeneration.

Amelogenin↗
PubMed1995

Sex identification of archaeological human remains based on amplification of the X and Y amelogenin alleles.

Sex identification of archaeological human remains is essential for the exploration of gender differences in past populations. Traditional morphometric analyses fail to identify the gender of incomplete skeletal remains and that of immature individuals. In the present work, we have established a sensitive and reliable method, based on amplification of the single-copy amelogenin-encoding gene (AMG). The Y allele carries a small deletion in the first intron, facilitating the design of distinct X- and Y-specific polymerase chain reactions. Amplification with three primers, two of which are allele-specific, allows unambiguous identification of both X and Y chromosome signals in a single reaction, providing an internal control. For added confidence, the reaction may be performed in separate tubes for each allele. Using this method, the sex was determined from the skeletal remains of 18 individuals, including young children, out of 22 examined from periods ranging from 200 to around 8000 years ago. The state of skeletal preservation ranged from poor to good. Cortical and cranial bones, as well as teeth, were found to provide sufficiently preserved DNA. The success of retrieval of amplifiable DNA was not related either to the period or to the burial site. On the other hand, the method of DNA purification was critical. In our hands, direct DNA purification by Chelex from minute samples of bone/tooth powder gave the best results. This study demonstrates the applicability of the method for gender determination in skeletal remains from different periods.

Adult↗
PubMed1995

Analysis of beta-globin mutations shows stable mixed chimerism in patients with thalassemia after bone marrow transplantation.

Beta-thalassemia major (TM) is caused by any of approximately 150 mutations within the beta-globin gene. To establish the degree of chimerism after bone marrow transplantation (BMT), we have performed molecular analysis of beta-globin mutations in 14 patients with TM over a period of 10 years. All patients underwent T cell-depleted allogeneic BMT from HLA-identical related donors, using either in vitro T-cell depletion with CAMPATH 1M and complement or in vivo depletion using CAMPATH 1G in the bone marrow collection bag. To date, at different time periods after BMT, seven patients have some degree of chimerism; six of these patients, all blood transfusion-independent, have donor cells in the range of 70% to 95%, with stable mixed chimerism (MC). The seventh patient has less than 10% donor cells with, surprisingly, only minimal transfusion requirements. The detection of beta-globin gene point mutation, as used here, is a highly specific and sensitive marker for engraftment and MC in patients with thalassemia. In light of its specificity, the method is applicable in all cases of TM, as it is independent of sex and other non-globin-related DNA markers. The high incidence of MC found in our patients may be a consequence of the pre-BMT T-cell depletion. Because MC was associated with transfusion independence, complete eradication of residual host cells for effective treatment of TM and possibly other genetic diseases may prove not to be essential.

Alleles↗
PubMed1995

Sequence analysis reveals a beta-thalassaemia mutation in the DNA of skeletal remains from the archaeological site of Akhziv, Israel.

beta-Thalassaemia is manifested by severe anaemia and extensive bone pathology. Similar pathology may also result from other forms of anaemia. To clarify the precise cause, we performed DNA analyses on archaeological remains of a child with severe bone pathology. We found homozygosity for frameshift in codon 8 of beta-globin, causing a beta-null phenotype. Paradoxically, the child died when eight years old, whereas such patients are transfusion dependent from early infancy. An infrequent polymorphic marker in the child's DNA, and information from present-day patients, indicated that amelioration of the clinical condition was due to elevated fetal haemoglobin production. Thus this analysis provided not only precise diagnosis of a genetic disease but also allowed clarification of the molecular mechanism underlying the clinical presentation.

Base Sequence↗
PubMed1995

Hemoglobin switching in humans is accompanied by changes in the ratio of the transcription factors, GATA-1 and SP1.

BACKGROUND: Understanding the mechanism of developmental regulation of hemoglobin switching has scientific as well as clinical relevance because of the influence of fetal hemoglobin (HbF) production in adulthood on the clinical manifestation of thalassemia and sickle cell anemia. We have previously found that the normal developmental patterns of globin gene expression are recapitulated in an experimental system of primary cultures that support differentiation of erythroid progenitors. We further found that high activities of the transcriptional activators, GATA-1 and SP1, are associated with normal adult erythroid differentiation. MATERIALS AND METHODS: In the present work, we have studied, the activities of GATA-1 and SP1 during differentiation of cultured erythroid progenitors derived from cord blood and from fetal livers, as well as from beta zero-thalassemia patients. RESULTS: The results showed high GATA-1 binding activity and very low SP1 activity in the fetal liver cultures. This pattern was in contrast to cultures derived from normal adult peripheral blood, in which both GATA-1 and SP1 activities were high. Cord blood cultures showed an additive combination of "adult" and "fetal" patterns. The progenitors derived from a beta zero-thalassemia patient with high HbF production showed "fetal" pattern. On the other hand, in cultures of 2 beta zero-thalassemia patients without high HbF, "adult" pattern was observed. CONCLUSIONS: In the present work, we show that human fetal and adult erythroid progenitors are distinct in their transcription factors, and that the commitment to fetal or adult program occurs at a very early differentiation stage. Our studies also demonstrate that under anemic stress, recruitment of fetal progenitors may occur in adulthood.

Adult↗
PubMed1994

Dynamics of the nucleoprotein structure of simian virus 40 regulatory region during viral development.

The regulatory region of SV40 is composed of multiple elements, including the origin of replication (ori), the encapsidation signal (ses) and the enhancer. Here, the structure of the chromatin and nucleoprotein complexes in a region encompassing ses and part of the enhancer was investigated in detail by in situ probing with DNase I. We have used a model experimental system based on plasmids which carry parts of the SV40 regulatory region. The results demonstrate that a specific nucleoprotein structure at the region is formed early after transfection. The overall structure is maintained throughout the viral life cycle. The observed DNase digestion pattern is consistent with the presence of a mixed population of viral minichromosomes with various, but not random, nucleosomal arrangements in that region. Specific modulations, which are associated with the various stages of the viral life cycle, are superimposed on the general structure. The most dramatic changes occur at nucleotides 34 and 113, located at both ends of ses and flanking the GC-box region. Some of the changes depend on the presence of viral gene product(s), probably a late (capsid) protein. The results further suggest that the condensed minichromosome within the viral particle assumes a highly specific configuration in this region. The nucleoprotein structure is sensitive to modifications of the primary nucleotide sequence and to flanking DNA elements. There is good correlation between distortions in the nucleoprotein structure and the inability of mutant plasmids to be packaged, substantiating the requirement for proper chromatin condensation in viral packaging.

Animals↗
PubMed1994

Severe thalassaemia intermedia caused by interaction of homozygosity for alpha-globin gene triplication with heterozygosity for beta zero-thalassaemia.

A 3-year-old child was evaluated for beta-thalassaemia intermedia. Molecular characterization including beta-globin gene sequence analysis revealed heterozygosity for a single beta-thalassaemia mutation, IVSI nt1 (G-->A). In addition the patient was found to be homozygous for alpha-globin gene triplication (alpha alpha alpha anti3.7/alpha alpha alpah anti3.7). The propositus has a significantly more severe phenotype than has been previously reported with this combination of genetic defects. In contrast, four individuals heterozygous for both triplicated alpha and for beta thalassaemia had a phenotype of thalassaemia minor, and a fifth had very mild thalassaemia intermedia.

Blotting, Southern↗
PubMed1993

Promoter resurrection by activators--a minireview.

Frequently, in nature, defective promoters can be resurrected by activator proteins in response to cellular demands. The activators bind to nearby DNA sites for action. Various protein-protein and DNA-protein contacts involving activators, RNA polymerase, and different segments of DNA in and around a defective promoter form a DNA-multiprotein complex (cage) which enhances transcription.

DNA↗
PubMed1993

Erythropoietin triggers a burst of GATA-1 in normal human erythroid cells differentiating in tissue culture.

GATA-1 is a central transcription-activator of erythroid differentiation. In the present work we have studied the kinetics of its expression and activity during development of normal human erythroid progenitors, grown in primary cultures. In response to the addition of erythropoietin (Epo), the cells undergo proliferation and differentiation in a synchronized fashion. This recently developed experimental system allows biochemical dissection of erythroid differentiation in a physiological meaningful environment. No DNA-binding activity of GATA-1 could be detected before the addition of Epo, although a very low level of mRNA was observed. Following Epo addition there was a sharp parallel rise in both mRNA and DNA-binding activity, consistent with positive autoregulation of the GATA-1 gene. After reaching a peak on day 7-9, both mRNA and protein activity decreased. The binding activity of the ubiquitous factor SP1 showed a biphasic pattern; its second peak usually coincided with the GATA-1 peak, suggesting that SP1 also plays a specific role in erythroid maturation. The highest activity of GATA-1 per erythroid cell was found on day 6-8, immediately preceding the major rise in globin gene mRNA and in the number of hemoglobinized cells. The results imply that a high level of GATA-1 activity is necessary for globin gene expression and erythroid maturation, suggesting that a requirement for a threshold concentration of GATA-1 is part of the mechanism that determines the final steps of erythroid maturation.

Adult↗
PubMed1993

G6PD Mediterranean accounts for the high prevalence of G6PD deficiency in Kurdish Jews.

The Jews of Kurdistan are a small inbred population with a high incidence of beta-thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Recently, it was reported that the beta-thalassaemia in this population shows an unusual mutational diversity; 13 different mutations were identified, of which 4 had not previously been observed in any other population. In contrast, we now report that the G6PD deficiency, which has the highest known incidence in the world, and which affects about 70% of males, is almost entirely attributable to a single widespread mutation, G6PD Mediterranean.

Female↗
PubMed1993

Silent carrier beta-thalassaemia due to a severe beta-globin mutation interacting with other genetic elements.

Beta-thalassaemia is caused by the presence of two mutated beta-globin genes, one inherited from each parent. We describe two families in which the diagnosis of beta-thalassaemia intermedia was delayed because one of the parents, an obligatory heterozygote, had normal haematological parameters (silent carrier beta-thalassaemia). DNA analysis revealed that these silent carriers were heterozygous for a point mutation in the polyadenylation signal (AATAAA-AATAAG). This defect is known to cause a moderately severe beta-thalassaemia phenotype. In one case, concurrent deletional alpha-thalassaemia was found in the silent carrier, which may have contributed to the mild phenotype. The increasing availability of DNA analysis should allow prompt diagnosis of such cases. Silent carrier beta-thalassaemia presents a diagnostic challenge to the clinician who evaluates children with anaemia.

Base Sequence↗
PubMed1992

Two mutations in the beta-globin polyadenylylation signal reveal extended transcripts and new RNA polyadenylylation sites.

Two mutations in the beta-globin poly(A) signal were identified in Israeli patients with beta +-thalassemia by sequence analysis following PCR. One is a point mutation (AATAAA----AATAAG) and the other is a 5-base-pair deletion (AATAAA----A----). The mutant genes were used to investigate the function of the poly(A) signal in vivo and to evaluate the mechanism whereby these mutations lead to a thalassemic phenotype. Analysis of RNA derived from peripheral blood demonstrated the presence of elongated RNA species in patients carrying either mutation. Other aspects of RNA processing (initiation, splicing) were unimpaired. RNA obtained from the patients carrying the point mutation contained four discrete, extended RNA species, 1500-2900 nucleotides long, which were found to be polyadenylated. Some normal cleavage-polyadenylylation was also observed. The 5-base-pair deletion completely abolished cleavage at the normal site. This deletion mutation resulted in a phenotype of beta +-thalassemia, thus providing evidence that the extended mRNAs are translatable in vivo. Furthermore, additional transcripts, greater than 5 kilobases, presumably mRNA precursors, were found in all RNA samples, including those of nonthalassemic controls. The extended transcripts of the poly(A) mutants, together with the high molecular weight precursors, suggest that the human beta-globin gene transcription unit is significantly longer than previously recognized.

Base Sequence↗
PubMed1992

Mean corpuscular volume of heterozygotes for beta-thalassemia correlates with the severity of mutations.

The relationship between the degree of microcytosis and the type of mutation carried by beta-thalassemia heterozygotes was investigated. In 113 individuals, 18 different mutations were identified, correlated with mean corpuscular volume (MCV) values, and analyzed statistically. Overall, there was a wide range of MCV (56.3-87.3 fL). In almost all cases, carriers of beta(0) mutations had an MCV below 67 fL, whereas all but a few beta(+) heterozygotes had MCVs above this cutpoint. Mean MCV of beta(0) carriers was statistically significantly lower than those of beta(+) heterozygotes. The various beta(+) mutations were associated with significant differences in mean MCV values. In contrast, all the beta(0) (null) mutations had virtually identical ranges of MCV. The results indicate that degree of reduction in MCV is directly related to the severity of the mutation. Deviations, in four cases, were associated with concurrent alpha gene rearrangements, whereas in three other cases, the MCV was not significantly affected by concurrent alpha rearrangements. The MCV of beta-thalassemia heterozygotes is a valuable parameter in planning strategies for rapid identification of mutations in populations with great mutational diversity. Its use can be particularly advantageous in the setting of prenatal diagnosis. The pattern of mean corpuscular hemoglobin (MCH) values was similar to the MCV pattern. However, our results suggest that MCH may be preferred for carrier detection in population screening.

Erythrocyte Indices↗