Molecular genetics of antigen receptors and associated chromosomal abnormalities in human leukemias.
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Biomedical subjects
Publications and source records attributed to R Baer.
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The structure and rearrangement of the human T-cell receptor alpha-chain gene have been analysed. The constant region segment is comprised of four exons, with the 3' non-coding region present as a separate exon. Two J alpha segments have been identified by sequence analysis about 4 X 10(3) and 15 X 10(3) base-pairs upstream from the constant region segment. Analysis of alpha-chain rearrangements in a panel of T-cells reveals the presence of at least four more J alpha segments within 19 X 10(3) base-pairs of C alpha and suggests the existence of additional J alpha segments further upstream. This dispersed organization of the J alpha region contrasts with the clustered organization observed in other lymphoid rearranging genes. The use of J alpha probes in diagnostic purposes for T-cell leukaemia is not, therefore, convenient and will require a number of different probes to ensure complete analysis of the locus.
We reported previously that rats kept for 5 weeks on a liquified diet by which masticatory movements were eliminated show widespread reductions of mitotic rates in oral epithelia, the rate in buccal epithelium being a third that in pair fed controls. This report deals with ultrastructural changes in the buccal epithelium of 7 rats subjected to the same experiment. In 43% of control basal cells and 24% of 1st row spinous cells, chromatin showed the full dispersal seen in buccal keratinocytes between the second and fifth spinous row. In all experimental animals, the proportion of these cells was elevated, averaging an 80% increase in the basal layer and more than a 100% increase in the first spinous row. The size of the nucleus was unchanged; the size of the nucleolus was 33% smaller in the basal layer and 30% in the 1st spinous layer. The number of lysosomes and keratohyaline granules per cell and the proportion of cells having these organelles were reduced in both layers, in proportion to the reduced nucleolar size. We conclude (1) that the reduced mitotic rate, entailing lengthened mean cell cycle time and lengthened mean stay in the progenitor compartment, allowed higher proportions of cells in this compartment to reach the chromatin dispersal characteristic of cells in the maturation compartment, and (2) that compared to controls formation of the nucleolus lagged behind the dispersal of chromatin. We suggest that the cells reaching this degree of dispersal might be the post-cycling cells.
An inversion of chromosome 14, inv(14)(q11,q32), is frequently observed in human T cell tumors; the cytogenetic breakpoints are of interest because the T cell receptor alpha-chain and immunoglobulin heavy chain genes reside on chromosome bands 14q11 and 14q32, respectively. We have investigated the structure of the alpha-chain genes in a T cell line harboring the chromosome 14 inversion. On the normal chromosome 14, a V alpha segment has rearranged nonproductively with a J alpha segment. In contrast, the inverted chromosome features an unprecedented rearrangement in which an immunoglobulin heavy chain variable gene segment (VH) on chromosome band 14q32 has joined with a J alpha segment from band 14q11. The VH-J alpha C alpha rearrangement is productive at the genomic level and therefore may encode a hybrid immunoglobulin/T cell receptor polypeptide.
The H-DNA repeat unit of Herpesvirus saimiri strain 11 was cloned in plasmid vector pAGO, and the nucleotide sequence was determined by the dideoxy chain termination method. One unit of repetitive DNA has 1,444 base pairs with 70.8% G+C content. The structural features of repeat DNA sequences at the termini of intact virion M-DNA (160 kilobases) and orientation of reiterated DNA were analyzed by radioactive end labeling of M-DNA, followed by cleavage of the end fragments with restriction endonucleases. The termini appeared to be blunt ended with a 5'-phosphate group, probably generated during encapsidation by cleavage in the immediate vicinity of the single ApaI recognition site in the H-DNA repeat unit. The sequence did not reveal sizeable open reading frames, the longest hypothetical peptide from H-DNA being 85 amino acids. There was no evidence for an mRNA promoter or terminator element, and H-DNA-specific transcription could not be found in productively infected cells.
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A 22-month-old girl with the syndrome of hypoventilation, pulmonary hypertension, cor pulmonale and pulmonary edema due to adenoidal hypertrophy is described. Adenoidectomy resulted in relief of all symptoms and signs within 24 h. Hemodynamic study using pulmonary artery catheter showed that the pulmonary artery pressure returned to normal 48 h after relief of the obstruction. The normal left ventricular end-diastolic pressure, measured throughout the period of obstruction, in the presence of severe pulmonary edema, could suggest a non-cardiogenic "low pressure" pulmonary edema. However, the highly negative pleural pressure which existed during upper airway obstruction indicated an elevation of transmural left ventricular end diastolic pressure (compared to pulmonary wedge pressure) and thus, suggested that the pulmonary edema in this syndrome is secondary to both - right and left heart failure.
Burkitt's lymphoma cells are characterized by the presence of specific chromosomal translocation bringing the immunoglobulin and the c-myc proto-oncogenes into the proximity of each other. Different translocations involve each of the three immunoglobulin loci but the breakpoint with respect to the c-myc gene is shown to be very variable. In t8/14 the breakpoint occurs upstream from the c-myc gene whilst in the variant lymphomas it occurs downstream from the gene. Possible ways in which the translocation affects the c-myc gene are discussed.
An analysis of the approximately 12,440 base-pair sequence of the EcoRI Dhet fragment isolated from the circular episomal form of the B95-8 strain of Epstein-Barr virus is presented. This fragment contains the covalently joined ends of the intracellular episomal form of the molecule. In the viral capsid the DNA is linear and the joining is mediated via the terminal repeated DNA. Four copies of tandem repeated DNA were present in this clone, three with a repeat size of 538 and one of 523. The positions of a number of possible protein coding regions and transcription signals are discussed. In particular a possible spliced coding region for an approximately 45,000 Mr protein expressed in latently infected transformed cells is proposed. The predicted protein sequence contains hydrophobic regions separated by charged amino acids reminiscent of a membrane protein.
The 17,180 base-pair Eco-RI-C fragment of Epstein-Barr virus has been sequenced in its entirety. This same fragment has also been analyzed for RNA polymerase II promoters, which are active in a soluble in vitro assay. These data are compared to the availability of predicted open reading frames and potential nucleotide signals associated with transcription. In addition, the DNA sequence of a number of previously undetected repeated DNA sequences from this and several nearby regions of the viral genome are reported.
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The 220 3'-terminal nucleotides of the small ribosomal subunit RNA (13S) of hamster (BHK-21) cell mitochondria have been sequenced and the positions of post-transcriptionally methylated residues within this sequence have been established. Also, we have derived the secondary structure of the 3'-terminus of mitochondrial 13S rRNA by 1) searching nucleotide sequences of 13S rRNA, procaryotic 16S rRNA and eucaryotic 18S rRNA for common secondary structures and 2) using single-strand specific endonucleases to map secondary interactions in 13S rRNA. The pyrimidine tract CCUCC in E. coli 16S rRNA, which participates in base-pairing with bacterial mRNA, is absent in mitochondrial 13S rRNA. We believe that the binding of mRNA to mammalian mitochondrial ribosomes is not mediated by a conventional Shine-Dalgarno interaction.
After the introduction of the term "Zwangsvorstellungen" (compulsive ideas) into german psychiatry in 1867, there were intensive psychopathological discussions concerning the role of the affective component of this disturbance. The conviction that an affective causation of compulsion has to be repudiated, that a primary compulsive idea is just followed by a secondary affect, contrasted with the belief that alterations of mood are a prerequisite of compulsive symptoms. The latter hypothesis led to the identification of a typical course of illness in the compulsive depressions. After a short review of Lauter's casuistry, some of our own cases are presented. A differentiation between two types of compulsive depression seems to fulfill the requirements of the clinic. The distinguishing criterion is the pattern of the premorbid personality. To the widespread therapeutic pessimism we oppose various psychotherapeutic techniques for the treatment of non-psychotic compulsive phenomenal; for the manifestations occurring in the course of psychotic illnesses, the appropriate psychotropic drugs will be used in the first place, although they are of limited importance in these types of illness which oppose serious difficulties to all methods of treatment.
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Different heterologous sera including human, rabbit, bovine and fetal calf serum (FCS) showed a strong inhibiting effect on the migration of guinea pig peritoneal macrophages (GPPM), compared to the migration of GPPM in homologous guinea pig serum. The inhibiting effect of these sera on the migration of horse monocytes on the other hand was much less marked. Fractionation of human and rabbit serum showed the 4 S fraction to be most inhibitory on GPPM migration. The migration inhibiting effect of heterologous sera on GPPM was prevented by addition of homologous (GP) serum, by absorption of the sera by various guinea pig cells, by heating at 56 degrees and by addition of alpha-L-fucose. Human sera were found to be strongly cytotoxic for 51Cr-labelled guinea pig erythrocytes and lymphocytes, but not for horse lymphocytes. Upon absorption with guinea pig erythrocytes, lymphocytes and kidney cells, the cytotoxicity of the human sera was strongly reduced. Accordingly, the role of heterophilic antibodies and/or of heat-labile MIF-like factors in heterologous sera has to be considered in al macrophage migration experiments where heterologous sera are being used. These factors may differ from the heat-stable MIF activity generated upon antigen- or mitogen-induced stimulation of cultured lymphocytes.
Numerous studies have demonstrated that disruptive classroom behavior can be decreased by delivering tokens contingent upon periods of time during which children do not engage in it or by removing tokens contingent upon its occurrence. To date, the best controlled of these studies have consistently reported the two procedures to be qually effective. However, in these studies, token the two procedures to be equally effective. However, in these studies, token contingencies have been combined with instructions regarding the contigencies. The present study compared these two procedures when no instructions were given regarding the token contingencies. Token delivery was not effective in decreasing disruptive behavior in any of the children, while a combination of token delivery and removal was effective for three of four children. The results token delivery and removal was effective for three of four children. The results suggest that the combined procedure may be effective with certain populations that are not readily controlled by instructions.