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Biomedical subjects

R Berger

Publications and source records attributed to R Berger.

At least 307 records · Page 17Linked to original sources
PubMed1995

Safety, immunogenicity, and pilot efficacy of Plasmodium falciparum sporozoite and asexual blood-stage combination vaccine in Swiss adults.

This study was part of a larger program to develop a vaccine effective against Plasmodium falciparum infection caused by sporozoites and clinical malaria caused by asexual blood stages. In a phase 1 study of safety and immunogenicity, two recombinant proteins (Ro 46-2717, a circumsporozoite [CS] protein) construct with a molecular mass of 35 kD, and Ro 46-2924, a merozoite surface antigen [MSA-2] construct with a molecular mass of 25 kD) adsorbed onto alum were injected in two low (20 micrograms) or two high (100 micrograms) doses in the right and left deltoid muscles of 33 healthy Swiss volunteers; six other volunteers received a placebo (alum alone). Twenty-six participants reported 51 immunization-related adverse events, mainly pain at the injection site. Mean antibody titers to CS protein and MSA-2 in an indirect immunofluorescence assay peaked four weeks after the second immunization without evidence of boosting (i.e., sharp increase in titer). By that time, 56% and 31% of the vaccinees seroconverted to CS protein and MSA-2, respectively, with the increase in MSA-2 titer being weaker than that for the CS protein. After a third immunization, five vaccinees volunteered to be challenged by three or four infective bites of Anopheles stephensi. Prepatent and incubation periods in all five were comparable with unvaccinated historic controls challenged under similar conditions, and all had symptoms of clinical falciparum malaria. We conclude that the vaccine components were safe and immunogenic but there was no evidence that this immunization regimen with the CS protein plus MSA-2 component was able to prevent infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Chromosomal localization of two KOX zinc finger genes on chromosome bands 7q21-q22.

Human cDNAs encoding Krüppel-type zinc finger domains, designated KOX 1-32, have been cloned from human T lymphocyte cell line libraries. We report here the regional localizations by in situ hybridization of KOX 18 and KOX 25 on chromosome bands 7q21q22. Pulse-field gel electrophoresis (PFGE) analysis showed that these genes are physically located within a DNA fragment of 250 kb. The genes KOX 4 and KOX 9, mapped on chromosome 8q24, were found to be located within a DNA fragment of 450 kb. From the present and previous data, eighteen different KOX genes have been located at least two by two within nine DNA fragments of 200 to 580 kb.

Animals↗
PubMed1995

Partial duplication of HRX in acute leukemia with trisomy 11.

The HRX gene has recently been shown to be involved in most of the chromosomal abnormalities of band 11q23 frequently present in human hematological malignancies. Rearrangements are strikingly diverse, but most affect a restricted area of the HRX gene and lead to gene fusion between HRX and a gene located on the partner chromosome. Another kind of HRX alteration seen in human acute leukemia is a partial duplication of the NH2 part of the HRX locus. We have characterized two cases of partial HRX duplication in acute leukemias bearing trisomy 11 as the sole chromosomal abnormality. In one patient analyzed at the genomic level, an Alu repeat was involved within exon 6 but not within intron 1. Splicing of exon 6 to exon 2 was observed in this patient while splicing of exon 8 to exon 2 was observed in the other. Our data indicated that HRX duplication is highly similar to the translocation affecting the HRX locus both in the restricted diversity of the fusion points and the involvement of Alu repeats within the breakpoint cluster region (exon 5 to 10).

Acute Disease↗
PubMed1995

[Cellular senescence and survival of T lymphocytes].

In order to study cellular senescence in T lymphocytes and its link with aging, we have undertaken long-term cultures from adult individuals (aged from 20 to 40) and centenarians. The proliferative advantage of CD4+ over CD8+ T cells is reversed after the second stimulation. Periodically stimulated cultures remained exponentially growing during nearly 200 days, whereas 2 of them that were continued for 300 days stopped proliferating. However, once this phase of senescence is reached, the cells do not die out. Six other cultures remained viable for 34 months without proliferation but with conservation of the cell number. Three of these cultures have clonal karyotypic abnormalities: trisomy 2 and telomeric fusions.

Adult↗
PubMed1995

Recent advances in fluorescence in situ hybridization (FISH) in hematology.

Fluorescence in situ hybridization (FISH) techniques has been considerably developed over the past years. They have brought new important data when applied to hematological malignancies: studies of aneuploidies on interphase nuclei at diagnosis and in the follow-up of the patients, combination with immunophenotype studies allowing to determine the lineage of the cells studied, simultaneous use of several molecular probes by multicolor hybridization, detection of chromosome rearrangements difficult to ascertain with usual techniques, delineation of the breakpoints in chromosome abnormalities. Examples of these applications are presented and discussed.

Chromosome Aberrations↗
PubMed1995

X-linked liver phosphorylase kinase deficiency is associated with mutations in the human liver phosphorylase kinase alpha subunit.

Two Dutch patients with liver phosphorylase kinase (PhK) deficiency were studied for abnormalities in the PhK liver alpha (alpha L) subunit mRNA by reversed-transcribed-PCR (RT-PCR) and RNase protection assays. One patient, belonging to a large Dutch family that expresses X-linked liver PhK deficiency, had a C3614T mutation in the PhK alpha L coding sequence. The C3614T mutation leads to replacement of proline 1205 with leucine, which changes the composition of an amino acid region, containing amino acids 1195-1214 of the PhK alpha L subunit, that is highly conserved in different species. The patient showed normal levels of PhK alpha L mRNA. The second patient, from an unrelated family, was found to have a TCT (bp 419-421) deletion in the PhK alpha L coding sequence, resulting in a phenylalanine 141 deletion. The same deletion was found in the PhK alpha L coding sequence from lymphocytes of the patient's mother, together with a normal PhK alpha L coding sequence. The phenylalanine that is absent in the PhK alpha L coding sequence of the second patient is a highly conserved amino acid between species. Both the C3614T mutation and the TCT (bp 419-421) deletion were not found in a panel of 80 control X chromosomes. On the basis of these results, it is postulated that the mutations found are responsible for liver PhK deficiency in the two patients investigated.

Amino Acid Sequence↗
PubMed1995

The proteinase 3 (PRTN3) gene is localized on 19p13.3 and is distal to the E2A gene.

The gene encoding the proteinase 3. (PRTN3, myeloblastin) was localized to chromosomal band 19p13.3 by radioactive and fluorescent in situ hybridization (FISH) to normal metaphase chromosomes. This localization was shown to be telomeric to the E2A gene by performing FISH to metaphases with balanced translocation t(1;19)((q23;p13) characteristic for a pre-B subtype of acute leukemia. In the unbalanced form of this translocation, a monoallelic loss of the PRTN3 locus was observed with FISH.

Chromosome Mapping↗
PubMed1994

[Immunogenicity and stability of an aluminum-free liposomal hepatitis A vaccine (Epaxal Berna)].

The high immunogenicity of the liposomal hepatitis A vaccine (Epaxal Berna) after a single dose and after a booster dose one year later has been confirmed in several studies with healthy adult volunteers: 95-100% and 96-100% seroconversion (> or = 20 mIE/ml) after 1 and 12 months respectively, as well as a booster effect in 100% of the cases after revaccination. The tolerability of this new, alum-free vaccine has been excellent with 6-25% local and 0-13% mild systemic reactions after a dose of 0.5 ml. Stability testing with and without detergent indicated partial internalization of the hepatitis A virions in the phospholipid bilayer of the liposome vesicles with storage. Immunization of 10 healthy adult volunteers with vaccine stored for 32 months at 4 degrees C showed, however, that the duration of storage has no influence on immunogenicity and tolerability of the vaccine.

Adult↗
PubMed1994

Detection of minimal residual disease in acute myelomonocytic leukemia with abnormal marrow eosinophils by nested polymerase chain reaction with allele specific amplification.

Acute myelomonocytic leukemia with bone marrow eosinophilia (AML-M4Eo in the French-American-British FAB] classification) is frequently associated with pericentric inversion of chromosome 16, inv(16)(p13q22). Recently, the molecular cloning of teh breakpoints has led to the identification of the two fused genes, CBFB on 16q and MYH11 on 16p. We have analyzed 24 patients with AML-M4Eo at diagnosis and 47 patients with AML of other FAB subtypes, by a reverse-transcriptase polymerase chain reaction (RT-PCR) assay for the CBFB/MYH11 fusion mRNAs. Three types of fusion mRNAs were detected in 22 samples of AML-M4Eo (type A, n = 20; type C, n = 1; and type D, n = 1). Among these 22 positive samples, inv(16) was found in the 20 cytogenetically studied cases. No fusion transcript was detected in two patients with AML-M4Eo and in patients with other types of AML. These results confirm that CBFB/MYH11 transcripts (with a predominant type A form) are present in most cases of inv(16) AML. Moreover, detection of the hybrid transcript is closely associated with the finding of abnormal bone marrow (BM) eosinophils in AML-M4Eo as it is not found in other, FAB subtypes of AML, including AML-M4. To assess the presence of type A CBFB/MYH11 fusion transcripts in five AML-M4Eo patients in remission, we designed a sensitive assay combining nested PCR and allele-specific amplification (NPASA). Residual leukemia cells were detected in four patients who were in remission from 4 to 22 months, but not in one patient in long-term remission (5 years). The clinical relevance of persistent CBFB/MYH11 fusion transcripts in remission remains to be established by studying a large prospective series of patients. NPASA provides a useful and sensitive tool for the detection of minimal residual disease in inv(16) AML and, potentially, in other leukemias associated with translocations that result in a predominant fusion transcript.

Alleles↗
PubMed1994

Leucine-zipper dimerization motif encoded by the AF17 gene fused to ALL-1 (MLL) in acute leukemia.

Chromosome region 11q23 is involved in reciprocal chromosome translocations associated with human acute leukemias. These aberrations fuse the ALL-1 gene located at 11q23 to a series of partner genes positioned on a variety of human chromosomes. The fused genes encode chimeric proteins. Here we report the cloning and characterization of the ALL-1 partner at 17q21, the AF17 gene. The AF17 gene encodes a protein of 1093 amino acids, containing a leucine-zipper dimerization motif located 3' of the fusion point and a cysteine-rich domain at the N terminus. The latter can be arranged in three zinc fingers and shows homology to a domain within the protein Br140 (peregrin). AF17 contains stretches of amino acids previously associated with domains involved in transcriptional repression or activation. Based on features of AF17 and of the proteins encoded by the other partner genes analyzed and in conjunction with other recent studies, we propose a model in which ALL-1 rearrangements result in loss of function of the gene. In this model, the partner polypeptide plays an accessory role either by repressing activity of the truncated ALL-1 protein or by blocking the function of the normal protein presumably present in the leukemic cells.

Amino Acid Sequence↗
PubMed1994

A YAC contig in 6p23 based on sequence tagged sites.

A yeast artificial chromosome (YAC) contig located in 6p23 and spanning roughly 2.5 Mb has been constructed from the content of 10 sequence tagged sites (STSs) for YAC clones in 66 yeast colonies. Nine of the STSs have been genetically mapped in CEPH families. The order of STSs mapped with the contig is consistent with that of the genetic map. The order of loci that did not recombine with each other on the genetic map was inferred from the contig. Various regions of the contig are covered by multiple YAC clones that complement observed STS deletions. The STS for the CAG repeat sequence contained in the gene for spinal cerebellar ataxia 1 (gene symbol SCA1) is localized in the contig. It is likely that this gene is located in 6p23. The frequency of chimeric YAC clones in this contig is 35%. Eleven yeast colonies were found to carry two or more YACs. YAC subclones from some of these colonies showed size variation, and for several subclones, evidence consistent with deletion of a sequence tagged site.

Base Sequence↗
PubMed1994

The prognostic value of magnetic resonance imaging for the management of breech delivery.

In patients with breech presentation secondary cesarean section is often caused by a failure to progress in labor due to a disproportion between fetal breech and maternal pelvis. The aim of the present study was to select such patients for primary cesarean section by prenatal use of magnetic resonance imaging. In 39 patients with breech presentation at term, maternal obstetric conjugate, transversal inlet diameter, sagittal mid-pelvis diameter, and interspinal distance, as well as fetal transversal and sagittal breech diameters, were measured by magnetic resonance imaging 1-7 days before delivery. All obstetricians that were involved in this study were blind to the measured values. For statistical evaluation the Mann-Whitney U-test was used. In 13 of these patients a secondary cesarean section was performed due to failure to progress in labor and in 9 due to other indications (intrauterine asphyxia, etc.). Seventeen women were delivered vaginally. The proportion between maternal pelvic inlet and fetal breech diameters was significantly less favourable in patients with failure to progress in labor (n = 13) than that in patients who were delivered vaginally (n = 17) (0.97 +/- 0.06 vs. 0.86 +/- 0.05, P < 0.001). Furthermore, by comparing the maternal pelvic inlet diameters with the corresponding fetal breech diameters, three groups of patients could be selected: one group (A; n = 8), in which the patients could be delivered only by cesarean section, a second group (B; n = 10), in which delivery by both cesarean section and vaginally was possible, and a third group of patients (C; n = 12), in which vaginal delivery was exclusively successful.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed.

In a previous study of a t(4;16)(q26;p13) translocation, found in a human malignant T-cell lymphoma the BCMA gene, located on chromosome band 16p13.1, has been characterized. In this study we show that the BCMA gene is organized into three exons and its major initiation transcription site is located 69 nucleotides downstream of a TATA box. RNase protection assays demonstrated that the BCMA gene is preferentially expressed in mature B cells, suggesting a role for this gene in the B-cell developmental process. A cDNA complementary to the BCMA cDNA was cloned and sequenced and its presence was assessed by RNase protection assay and anchor-PCR amplification. This antisense-BCMA RNA is transcribed from the same locus as BCMA, and exhibits mRNA characteristic features, e.g. polyadenylation and splicing. It also contains an ORF encoding a putative 115 aa polypeptide, presenting no homology with already known sequences. RNase protection assays demonstrated the simultaneous expression of natural sense and antisense-BCMA transcripts in the majority of human B-cell lines tested.

Amino Acid Sequence↗
PubMed1994

Extensive small intestinal T-cell lymphoma of low-grade malignancy associated with a new chromosomal translocation.

BACKGROUND: Primary T-cell lymphoma of the small intestine is rare, and most cases have proved rapidly fatal. METHODS: We describe a case of lymphoma involving the small intestine uniformly and extensively in a 28-year-old man on initial examination seen with long-standing diarrhea, malabsorption, and recurrent episodes of intestinal obstruction. Clinical remission was obtained with pentostatin (2'-deoxycoformycin, supplied by Professor Catovsky, London UK) after the patient had failed to improve under conventional chemotherapy. Tumor specimens as well as mesenteric lymph node, liver, and bone marrow specimens were studied with conventional pathology and immunochemistry. Additionally, mesenteric lymph nodes and peripheral blood cells were studied for T-cell receptor (TCR) gene rearrangement and karyotype. RESULTS: Lymphoma cells were small T-lymphocytes with irregular pleomorphic nuclei, bearing the CD3, CD4 and TCR alpha-beta phenotype. Peripheral-blood cytology and bone marrow biopsy were normal. Southern blot analysis of the TCR beta-chain gene revealed the same monoclonal rearrangement in the mesenteric lymph nodes and peripheral blood lymphocytes. An as yet undescribed t(4;16)(q26;p13) translocation, involving the region where the interleukin-2 (IL-2) gene has been mapped, was present in the mesenteric lymph nodes and peripheral blood lymphocytes. CONCLUSION: We believe this is the first description of an extensive, small intestinal lymphoma of low-grade malignancy made up of monoclonal T-cells with a TCR alpha-beta and helper/inducer phenotype, associated with a novel chromosomal translocation.

Adult↗
PubMed1994

t(12;21): a new recurrent translocation in acute lymphoblastic leukemia.

A t(12;21)(p11-p12;q22) was detected by chromosome painting in three patients with acute lymphoblastic leukemia (ALL) among eight ALL cases with 12p- abnormalities. The three leukemias had similar immunophenotypes (DR+, CD10+, CD19+). Fluorescence in situ hybridization (FISH) experiments using YAC clones from 21q21-q22 were performed to better localize the breakpoint on chromosome 21. This breakpoint was localized to 21q22.2 in one patient. Although only one case of ALL with t(12;21) has been reported previously, the present results suggest that t(12;21) is a recurrent translocation in ALL.

Adolescent↗
PubMed1994

Localization of a new type of X-linked liver glycogenosis to the chromosomal region Xp22 containing the liver alpha-subunit of phosphorylase kinase (PHKA2).

We describe here a new type of X-linked liver glycogen storage disease. The main symptoms include liver enlargement and growth retardation. The clinical and biochemical abnormalities of this glycogenosis are similar to those of classical X-linked liver glycogenosis due to phosphorylase kinase deficiency (XLG). However, in contrast to patients with XLG, the patients described here have no reduced phosphorylase kinase activity in erythrocytes and leukocytes, and no enzyme deficiency could be found. Linkage analysis of four families with this X-linked type of liver glycogenosis assigned the disease gene to Xp22. Lod scores obtained with the markers DXS987, DXS207, and DXS999 were 3.97, 2.71, and 2.40, respectively, all at 0% recombination. Multipoint linkage analysis localized the disease gene between DXS143 and DXS989 with a maximum lod score of 4.70 at theta = 0, relative to DXS987. As both the classical XLG gene and the liver alpha-subunit of PHK (PHKA2) are also located in Xp22, this variant type of XLG may be allelic to classical XLG, and both diseases may be caused by mutations in PHKA2. Therefore, we propose to classify XLG as XLG type I (the classical type of XLG) and XLG type II (the variant type of XLG).

Adolescent↗