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A Dahan

Publications and source records attributed to A Dahan.

86 records · Page 5Linked to original sources

On a pseudo-rebreathing technique to assess the ventilatory sensitivity to carbon dioxide in man.

1. The ventilatory sensitivity to carbon dioxide obtained from a step-ramp CO2 challenge was compared to the CO2 sensitivity from the steady-state method. 2. Experiments were performed in nine healthy male subjects against a background of hyperoxia and in two subjects against a background of normoxia. 3. In each subject experiments were performed in which the stepwise increase in end-tidal PCO2 above its resting value (A) was varied (range 0-2 kPa) and the subsequent rate of rise of end-tidal PCO2 in time (R) kept constant at 0.6 or 0.8 kPa min-1. 4. The results of the hyperoxic experiments show that the slope of the non-steady-state ventilatory response to CO2 (Sn) is greatly influenced by the magnitude of A. An increase of A of 1 kPa results in a 54% increase of the ratio non-steady-state ventilatory CO2 sensitivity to steady-state ventilatory CO2 sensitivity (Ss). The magnitude of R plays a minor role in determining Sn. The normoxic experiments gave similar results. 5. In experiments performed during hyperoxia Sn approximates Ss when the magnitude of A is 0.5 kPa. 6. The results are discussed and related to a physiological model. Simulations with representative values for the model parameters are in fair agreement with experimental values.

Carbon Dioxide↗

The influence of oxygen on the ventilatory response to carbon dioxide in man.

1. The ventilatory response to isoxic square-wave challenges in end-tidal PCO2 was investigated at three levels of end-tidal PO2 (PET, O2) in nine healthy male subjects. 2. Twenty-seven responses against a background of mild hypoxia (PET, O2 approximately 10 kPa), sixty-seven against a background of normoxia (PET, O2 approximately 14.5 kPa) and seventy-six against a background of hyperoxia (PET, O2 approximately 70 kPa) were collected. 3. The breath-to-breath data were partitioned into a fast and a slow ventilatory component using a two-compartment model. 4. In the normoxic and hypoxic experiments the CO2 sensitivity of the fast component averaged to about 30 and 40% of the total CO2 sensitivity, respectively. In the hyperoxic experiments three subjects had no fast component in their response while in three others the CO2 sensitivity of the fast component averaged to about 24% of the total CO2 sensitivity. In the remaining three subjects the presence of a fast component was doubtful. 5. We argue that the fast component is due to the peripheral chemoreflex loop and the slow component to the central chemoreflex loop. 6. The central CO2 sensitivity and the apnoeic threshold (extrapolated end-tidal CO2 at zero ventilation in the steady state) were 15% smaller in hyperoxia than those in normoxia and hypoxia. In normoxia and mild hypoxia the central CO2 sensitivities were not significantly different. 7. We argue, that apart from peripheral oxygen-carbon dioxide interaction, there is evidence for central oxygen-carbon dioxide interaction in human subjects. 8. We conclude that in general there is a contribution to ventilation of the peripheral chemoreceptors during hyperoxia in man.

Adult↗

Somatic hyperconversion diversifies the single Vh gene of the chicken with a high incidence in the D region.

The chicken heavy chain locus contains a single JH segment and a unique functional VH gene (VH1) 15 kb upstream, with approximately 15 D elements in between. A cluster of pseudogenes (psi VH) spans 60-80 kb, starting 7 kb upstream from VH1, with an average density of one pseudogene per 0.85 kb and an almost systematic alternation of polarity. Diversification of the unique rearranged VH1 gene takes place during bursal ontogeny by the same hyperconversion mechanism that was described for the chicken light chain, with psi VH segments acting as donors. The hyperconversion mechanism also operates within the D region, as all pseudogenes analyzed are fused VD elements; this D region possesses distinct characteristics, allowing higher combinatorial possibilities in the gene conversion process. Allelic exclusion appears to be performed by restriction of a complete VDJ rearrangement to a single allele.

Alleles↗

The ventilatory CO2 sensitivities from Read's rebreathing method and the steady-state method are not equal in man.

1. The ventilatory response to changes in end-tidal carbon dioxide tension during hyperoxia, obtained with Read's rebreathing method and a steady-state technique, were compared. 2. In ten young male subjects, forty successful rebreathing and thirteen steady-state experiments were performed on thirteen different morning sessions. 3. In all subjects the ventilatory CO2 sensitivities obtained with the rebreathing method (Sr) were appreciably larger than the steady-state CO2 sensitivities (Ss). The ratio Sr/Ss ranged from 1.40 to 2.59 with a mean value of 1.85. 4. We argue that these results can be explained by considering the effect of changes in cerebral blood flow upon increasing the arterial CO2 tension during rebreathing and the steady state. 5. We conclude that in general the CO2 sensitivity obtained with Read's rebreathing method does not represent the steady-state CO2 sensitivity.

Adult↗

On the immune reaction to autologous human lymphoblasts: evidence for the stimulation by activating factors rather than induction by autoantigens.

This report questions the nature of stimulation in the lymphoblast-induced autologous mixed leukocyte reaction (AMLR). Using immobilized phytohemagglutinin (PHA) and pokeweed mitogen (PWM), we show that the AMLR generated with PHA lymphoblasts (PHA X AMLR) was not significantly different from the AMLR generated with untreated stimulators. The PWM lymphoblasts of 15 out of 33 apparently normal blood donors generated an AMLR (PWM X AMLR) greater than their respective normal AMLR. The positive PWM X AMLR was not related to the expression of HLA-DR or surface IgM, since expression of both was increased by both PHA and PWM, yet only PWM blasts stimulated in the AMLR. Fixation of PWM-stimulated cells prior to the AMLR completely abolished stimulatory capacity, indicating further against new or increased antigen expression. Inactivation by uv irradiation of surface HLA-D on the stimulators had no effect upon the PWM X AMLR, while intact protein synthesis was required in order to stimulate. The ability of cells to stimulate was associated with the release of soluble helper factors capable of stimulating autologous cells independently. These factors were neither contaminating PWM nor secreted IL-1 or IL-2, although IL-1-like activity was released by all cells regardless of their ability to stimulate. The individual variation in the PWM X AMLR response and secretion of helper factors is discussed in relation to B-cell hyperproliferation and altered immunoglobulin production in autoimmune manifestations.

Adult↗

A single rearrangement event generates most of the chicken immunoglobulin light chain diversity.

The chicken immunoglobulin lambda locus contains a single C lambda gene with a unique J lambda element, 1.9 kb upstream. The same V lambda gene (V lambda 1) is rearranged in most cells of the Bursa of Fabricius. This V lambda 1 gene is located, in germ-line configuration, 1.7 kb upstream from J lambda and in the same transcriptional orientation. Eight to twelve variable genes of the same set are found adjacent to the V lambda 1 gene, indicating that V-gene amplification did occur. Three of these genes were sequenced and proved to be pseudogenes, one of them having an inverted polarity. Data suggesting extensive somatic diversification of the V lambda 1 sequence are reported, including the possible use of nonfunctional V elements in a somatic gene-conversion-like process.

Animals↗

Nucleotide sequence of the constant region of a chicken mu heavy chain immunoglobulin mRNA.

We have recently reported the sequence of a chicken Ig lambda light chain cDNA clone, isolated from a spleen partial cDNA library (1). In this paper, we describe the characterization of a cDNA clone coding for the chicken constant (C) region of the secreted mu chain. This is the first report on the nucleotide and amino acid sequence of a chicken Ig heavy chain constant region. It contains the 3' untranslated region of the mu mRNA up to the poly(A) tail, and, in comparison with the mouse Cmu sequence, displays the overall domain size and organization of a secreted mu chain, i.e.: a characteristic COOH-terminal region, a Cmu4, a Cmu3, a Cmu2, and part of a Cmu1 domain. The sequence homology between these two species ranges from 45% for the Cmu4 to 18% for the Cmu2. Thus, the Cmu sequence appears much less conserved between chicken and mouse than their respective lambda light chain constant regions (1). These results, together with some distinctive features of the Cmu2 domain, may be of evolutionary relevance and will be further discussed.

Amino Acid Sequence↗

Complete sequence of a chicken lambda light chain immunoglobulin derived from the nucleotide sequence of its mRNA.

Recombinant cDNA plasmids have been constructed from chicken spleen poly(A)-containing RNA. Two clones have been selected and provide the sequence determination of a chicken lambda immunoglobulin light chain: they include the complete variable, constant, and 3' untranslated regions of the chicken lambda light chain mRNA and part of the leader sequence. Comparison of the chicken light chain constant region with both human and mouse lambda constant sequences indicates 61% homology at the amino acid level. Unexpectedly, the chicken variable sequence is 53-63% homologous to human variable sequences when it is compared to the various lambda subgroups and only 42% homologous to the mouse V lambda 1 sequence. The degree of homology between the variable regions of these three species does not easily correlate with their phylogenetic relationship.

Amino Acid Sequence↗