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Biomedical subjects

D Hendrick

Publications and source records attributed to D Hendrick.

17 recordsLinked to original sources
PubMed1998

Effects of treatment with formoterol on bronchoprotection against methacholine.

PURPOSE: In addition to their bronchodilatory effects, beta(2)-agonists protect against bronchoconstriction, such as that caused by methacholine challenge. However, tachyphylaxis to this beneficial effect develops after chronic use of beta(2)-agonists. We studied whether the frequency or dose of treatment with a long-acting beta(2)-agonist (formoterol) affects the degree of bronchoprotection afforded against methacholine challenge and to compare this with the effects of a short-acting beta(2)-agonist (terbutaline). PATIENTS AND METHODS: In a randomized, parallel group, double-blind study at two centers, patients with stable asthma of mild to moderate severity who were treated with inhaled corticosteroids were treated with formoterol 6 micrograms twice daily, 24 micrograms twice daily, 12 micrograms once daily; terbutaline 500 micrograms four times daily; or placebo. Treatments were given by dry powder inhaler for a period of 2 weeks. Of the 72 patients who were enrolled, 67 completed the study. Methacholine challenge was performed to calculate the provocative dose that caused a 20% fall in forced expiratory volume in 1 second at baseline (unprotected) after an initial 1-week run-in without beta(2)-agonists, 1 hour after the first dose of study treatment, and again 1 hour after 7 and 14 days of study treatment. RESULTS: Each of the four active treatments exhibited significant tachyphylaxis (P < 0.05) to protection against methacholine challenge when comparing first/last dose (as geometric mean protection ratio versus baseline): formoterol 24 micrograms twice daily (9.6-fold/1.6-fold), 12 micrograms once daily (7.1-fold/2.2-fold), 6 micrograms twice daily (6.2-fold/2.3-fold), and terbutaline 500 micrograms four times daily (2.9-fold/2.0-fold). There were no significant differences among treatments after 2 weeks in bronchoprotection against methacholine challenge. For all formoterol regimens, the bronchodilator response 1 hour after inhalation was maintained over the 2-week treatment period. Diurnal control of morning and evening peak flow was significantly better with formoterol 24 micrograms twice daily than with terbutaline. CONCLUSIONS: Tachyphylaxis to bronchoprotection against methacholine challenge develops after 2 weeks of therapy with formoterol, a long-acting beta(2)-agonist, at all three dosage regimens that were tested. In contrast, the bronchodilator effects of formoterol were maintained during the 2 weeks of treatment.

Adolescent↗
PubMed1989

The effect of filtration on absolute and differential cell counts in fluid obtained at bronchoalveolar lavage.

We have studied the effects of filtering mucus from bronchoalveolar lavage (BAL) fluid on its cellular contents. We examined BAL fluid from 18 patients without excessive endobronchial mucus, and from three patients with bronchiectasis. In the non-bronchiectatic subjects there was a fall of 18% in mean absolute cell count from 2.66 +/- SD 1.9 x 10(9) l-1 to 2.18 +/- 1.4 x 10(9) l-1 (P less than 0.05) as a result of filtration. This was due to a selective loss of macrophages and there were no significant changes in the absolute numbers of either lymphocytes or neutrophils. The differential macrophage count fell from a mean of 82 +/- 14% to 76 +/- 16%, while the mean differential lymphocyte count rose from 14 +/- 7% to 19 +/- 9% and the mean differential neutrophil count increased slightly from 4 +/- 4% to 5 +/- 4%. In the three patients with bronchiectasis the absolute cell counts were grossly raised, due almost entirely to an excess of neutrophils. In these patients, filtration reduced the absolute macrophage count by 61% and the absolute neutrophil count by 27%. Overall, change in absolute cell count correlated significantly with mucus volume (r = 0.76, P less than 0.05). Removal of mucus by filtration affects absolute cell count and may have a selective effect on cell numbers. If filtration of BAL fluid is unavoidable, its effect on cell counts should be clearly established if data from different centres are to be meaningfully compared.

Adult↗
PubMed1988

The effect of bronchoalveolar lavage on bronchial responsiveness in patients with airflow obstruction.

This study assessed the effect of bronchoalveolar lavage (BAL) on nonspecific bronchial responsiveness in 31 patients. Of these, 20 had airflow obstruction; 11 control subjects had normal pulmonary function. Bronchial responsiveness to methacholine, expressed as the dose of inhaled methacholine required to provoke a 20 percent fall in forced expiratory volume in one second (PD20 FEV1), was measured before and after BAL. We found no evidence for the induction of responsiveness by BAL in 11 control subjects with negative methacholine tests prior to the procedure. There were small but significant falls in FEV1 following BAL in both the control group and in patients with airflow obstruction. Thus, BAL does not appear to induce nonspecific bronchial hyperresponsiveness in subjects without airflow obstruction, nor does it affect airway responsiveness in emphysema patients. Among asthmatics, bronchial responsiveness can be increased as a result of BAL; this increase was greatest in patients who were most responsive initially.

Adolescent↗
PubMed1981

Expression of human and mouse nonhistone chromosomal proteins in hybrid mouse erythroleukemia cells containing a single human chromosome.

The nonhistone chromosomal proteins of a series of hybrid mouse erythroleukemia cell lines containing human chromosome 16 were investigated by two-dimensional gel electrophoresis to determine if such cells contained nonhistone chromosomal proteins of both human and mouse origin. Comparison of the two-dimensional gel electrophoretograms of the nonhistone chromosomal proteins of mouse and human cell lines showed 400 and 280 chromosomal proteins, respectively, of which about 75% were electrophoretically identical. The two-dimensional gel electrophoretogram of a cloned hybrid mouse erythroleukemia cell line that retained a tetraploid complement of mouse chromosomes and human chromosome 16 (as the only human chromosome) displayed a nonhistone chromosomal protein of pI 6.2 and Mr 65,000. This protein, which comigrates with a nonhistone chromosomal protein present in the human cell line used to produce this hybrid cell and which is also present in two additional human cells lines studied, could not be detected in the mouse erythroleukemia parent before fusion. This polypeptide also was shown by similar techniques to be associated with the presence of human chromosome 16 in four out of five other independently derived hybrid mouse erythroleukemia cell lines that contained a near tetraploid complement of mouse erythroleukemia chromosomes.

Animals↗
PubMed1980

Expression of human alpha-globin genes in hybrid mouse erythroleukaemia cells depends on differentiated state of human donor cell.

We have developed a system which can be used to study the mechanisms that may govern the expression of human alpha-globin genes in human erythroid and non-erythroid haematopoietic cells. Human chromosome 16, which has been shown to bear the human alpha-globin genes, is introduced by cell fusion into mouse erythroleukemia (MEL) cells to generate continuously proliferating cell lines that retain permanently the human alpha-globin genes. We have shown that hybrid diploid MEL cells with human alpha-globin genes from erythroid donor cells express these genes fully through globin chain synthesis, while hybrid diploid MEL cells containing human alpha-globin genes from non-erythroid human haematopoietic donor cells contain very low levels of human alpha-globin mRNA and no detectable human alpha-globin chains. The levels of human alpha-globin mRNA in these hybrid cells were found to depend on factors present in the MEL recipient cell as well as on the differentiated state of the human donor cell, suggesting that this system may be suitable for characterisation of mechanisms governing haematopoietic differentiation in man.

Animals↗
PubMed1979

Activation of phenotypic expression of human globin genes from nonerythroid cells by chromosome-dependent transfer to tetraploid mouse erythroleukemia cells.

Chromosome-dependent gene transfer mediated by cell fusion was used to show that it is possible to activate phenotypic expression of human alpha globin genes derived from nonerythroid cells. Hybrid cells containing the human alpha globin structural genes were derived by fusion of populations of adult human peripheral blood mononuclear cells (devoid of identifiable erythroid cells) with adenine phosphoribosyl-transferase-deficient mouse erythroleukemia cells that contained close to a tetraploid complement of mouse chromosomes. The hybrid cells retained a near tetraploid complement of mouse chromosomes but had lost 80% of the chromosomes of the human parent cell. All of these hybrid cells and their subclones, which contained human chromosome 16, exhibited synthesis of human alpha globin chains. Human alpha globin mRNA was also demonstrated to be present in one of these hybrid cells by RNA.cDNA molecular hybridization analysis. We conclude that the mechanism responsible for restricting expression of the human globin genes in nonerthroid cells is not irreversible, at least for those globin structural genes that are actively transcribed in erythroid cells during adult life. Moreover, some genetic factor or process in the tetraploid mouse erythroleukemia cell is, under the conditions of our experiments, capable of reactivating phenotypic expression (production of globin chains) of human globin genes derived from nonerythroid hematopoietic cells after chromosome-dependent gene transfer.

Animals↗
PubMed1977

Enrichment for the globin coding region in a chromatin fraction from chick reticulocytes by endonuclease digestion.

A nuclease-sensitive fraction was obtained from chick reticulocyte chromatin by brief digestion with an endonuclease (DNAase II, deoxyribonucleate 3'-oligonucleotidohydrolase, EC 3.1.4.6). The nuclease-sensitive fraction typically contained less than 1% of the chromatin-DNA but about 50% or more of the nascent chromatin-bound RNA. Hybridization of chick globin complementary DNA to the DNA component of the nuclease-sensitive fraction of reticulocyte chromatin indicated a 3--5 fold enrichment for the globin coding region of the chromatin. The control experiment utilizing DNA from a nuclease-sensitive fraction of chick liver chromatin did not show a comparable enrichment for the globin coding region. This suggests that the endonuclease-effected enrichment for the globin coding region in the nuclease-sensitive fraction of reticulocyte chromatin is to some degree specific for structural genes transcribed in reticulocytes.

Animals↗
PubMed1976

Molecular weights, poly(A)--content, and partial separation of chick globin mRNAs.

Poly(A)-containing 9S RNA from chick reticulocytes was electrophoresed on formamide-polyacrylamide gels. The molecular weight was determined to be 211 000 +/- 10 000 daltons. The RNA was separated into three different fractions with respect to molecular weight. These RNAs were translated in a wheat germ cell-free system. The lower molecular weight RNA directed up to 95% alpha-chain synthesis, compared to 60% for the higher molecular weight RNA. This was accompanied by a relative increase for beta-chain synthesis with increasing molecular weight. It could also be shown by hybridization with labelled poly(U) that the average poly(A) length decreased from about 83 nucleotides for fraction I to 36 nucleotides for fraction III. Our results suggest that fractionation of avian 9 S globin mRNA by electrophoresis on formamide-polyacrylamide gels is dependent upon two parameters, namely differences in the lengths of the non-poly(A)-containing portion of the alpha and beta mRNAs and differences in the poly(A) lengths.

Animals↗
PubMed1976

Chicken globin gene number.

Using complementary DNA prepared from adult chicken globin messenger RNA, we show the existence of 2-3 non-cross-hybridising globin sequences in the chicken genome, each of which is present in only one copy per haploid genome. This was done by solution hybridization to total DNA under conditions of cDNA excess. The data agreses with results of RNA-driven hybridisation of globin complementary DNA, and with protein data.

Animals↗
PubMed1975

Globin messenger sequences in nuclear ribonucleoprotein particles of avian erythroblasts.

Nuclear ribonucleoprotein particles were isolated from chick erythroblast nuclei. The particles were found to sediment as heterogeneous material. The major fraction of the rapidly synthesized RNP sedimented at 30 S, whereas the nuclei were found to contain a major, apparently more stable, RNP component sedimenting at about 40 S. The RNA isolated from the RNP particles was assayed for globin messenger activity in a wheat germ cell-free system. RNP sedimenting at relatively low S values (approx. 15 S) as well as RNP-particles of larger size code for globin. In addition to globin, the RNA of the particles codes also for other, not yet identified, proteins.

Amino Acid Sequence↗