[Respiratory failure in elderly patients with chronic obstructive pulmonary disease].
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Biomedical subjects
Publications and source records attributed to F Kishi.
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LexA protein is a repressor of several chromosomal genes involved in the SOS response in Escherichia coli. In previous experiments, we found that LexA protein may also be a repressor of the colicin E1 gene. We now present evidence that the purified LexA protein strongly repressed the in vitro transcription of the colicin E1 gene. As determined in DNase I protection experiments, LexA protein bound with a high affinity to the approximately 40-base pair long sequence between the Pribnow box and the start codon of the colicin E1 gene. The sequence of the binding site was composed of two overlapped "SOS boxes" to which the LexA protein bound in a cooperative manner.
We studied the relation of oxygen delivery, mixed venous oxygenation, and pulmonary hemodynamics to prognosis in 50 randomly selected patients with chronic obstructive pulmonary disease. Cardiac catheterization was performed when the patients were clinically stable. Four years later, 27 patients (54 per cent) had died of respiratory failure. At the time of catheterization, patients who subsequently lived were similar to those who died in age, physical characteristics, and hematocrit. Nonsurvivors had significantly lower arterial and mixed venous oxygen tension and significantly higher arterial and mixed venous carbon dioxide tension. The mean pulmonary arterial pressure, pulmonary arteriolar resistance, right ventricular work, coefficient of oxygen delivery, and cardiac index did not differ between the two groups. After inhalation of 100 per cent oxygen for one hour, the mixed venous oxygen tension of nonsurvivors rose to a level equivalent to that of survivors, and their mean pulmonary arterial pressure fell significantly. These results indicate that, with respect to oxygen supply to the tissues, mixed venous oxygenation is one of the important prognostic factors in chronic obstructive pulmonary disease. Pulmonary and right ventricular hemodynamics measured during periods of clinical stability do not differentiate nonsurvivors from survivors.
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From the cells of an Escherichia coli K-12 strain, a 22,000-dalton protein which has an affinity for the superhelical DNA molecule was purified to apparent homogeneity by monitoring the DNA-binding activity using the filter binding assay. In the sedimentation analysis of the DNA-protein complex, the protein has an affinity for the superhelical or single-stranded DNA molecule but neither for the open-circular nor for the linear DNA molecule. The amino acid composition of the protein resembled those of the other prokaryotic histone-like proteins and also to eukaryotic histones H2A and H2B. The protein precipitated upon heating, which is in contrast to the heat-stable feature of the other histone-like proteins. Furthermore, DNA and RNA syntheses in vitro were not affected by the presence of the protein. In view of these characteristics, this protein may play a role in maintaining the bacterial nucleoid structure.
Spontaneous colicin E1 production by plasmid RSF2124 in a recA lexA(spr) strain of Escherichia coli was about 10-fold greater than that observed in a wild-type strain. The synthesis was repressed nearly to the level of a recA strain in the presence of the plasmid pMCR551, which carries the lexA gene.
In 58 patients with chronic obstructive pulmonary disease, pulmonary gas exchange efficiency was assessed by the ratio: arterial to mixed venous PO2 difference (efficient part) versus alveolar to mixed venous PO2 difference (driving pressure for O2 transport). Patients with PaO2 below 75 mm Hg had a ratio lower than 50%. Patients with PaO2 below 60 mm Hg had lower values for arterial to mixed venous O2 content difference and higher blood lactic acid concentration than patients with PaO2 over 60 mm Hg. Arterial to mixed venous PO2 difference decreased linearly against PaO2 till PaO2 reached 60 mm Hg from which the difference began to attenuate. These figures in PaO2 are in close agreement with the criteria for pulmonary failure presented by the Ciba guest symposium (PaO2 below 75 mm Hg) and for respiratory failure by the National Heart, Lung and Blood Institute (PaO2 below 60 mm Hg).
The product of the lexA gene of Escherichia coli has been shown to regulate expression of the several cellular functions (SOS functions) induced by treatments which abruptly inhibit DNA synthesis. We have cloned and mapped the lexA gene on a small segment of approximately 600 base pairs. The lexA promotor was located by transcription R-loop analysis, and the lexA product of 22,000 daltons was identified by protein synthesis in vitro. An unknown gene was found which directed the synthesis of a protein of 35,000 daltons in a region downstream from the lexA gene. Nucleotide sequence of the regulatory region of the lexA gene was determined. The sequence contained inverted repeats homologous to that of the recA regulatory region. These inverted repeats may be recognized by the lexA protein, because the protein is considered to repress both the genes as a common repressor.
The nucleotide sequence of 570 bp, covering the N-terminal portion of the colicin E1 gene, was determined. The sequence of the N-terminal four amino acids of the colicin E1 protein, determined by manual Edman degradation, agreed with that predicted from the nucleotide sequence. From analysis of the 5'-terminal sequences of RNAs synthesized in vitro, the promoter and operator regions of the colicin E1 gene were assigned. These data indicate the existence of two promoters, one of which is located in the coding region for colicin E1. DNA sequence homology of 16 bp was found between the putative operator regions of the colicin E1 and recA genes.
We labeled proteins with [14C]phenylalanine in rats breathing air and assessed the rate of proteolysis in the isolated ventilated lung by measuring the accumulation of [14C]phenylalanine in the medium perfusing the lung. Ventilation with 0% O2 decreased the rate of proteolysis and the ATP content in the lung 60%. Medium from lungs ventilated with 0% O2, when used to perfuse lungs ventilated with 95% O2, decreased the rate of proteolysis 60% without lowering the ATP content of the lung. Correcting the pH of "used" medium or dialyzing used medium did not decrease its ability to inhibit proteolysis. Used medium from nonhypoxic lungs, or exogenous lactate (50 mM), diminished proteolysis only 20%. In a cell-free system the degradation by cathepsin D of radioactive lung proteins and radioactive hemoglobin was decreased by used medium from hypoxic lungs. We conclude that the hypoxic perfused lung releases a factor(s) that decreases the rate of proteolysis in nonhypoxic lungs and that this factor may be a protease inhibitor.
In 11 normal subjects (mean age = 22.8 years) and 8 patients with pulmonary emphysema (mean age = 70.4 years), the role of chemosensitivity in determining ventilation, cardiac output, lactic acid, and cyclic AMP and GMP was evaluated quantitatively during 150 or 30 W exercise and simulated exercise. Simulated exercise was done while the subjects took a rest by regulating arterial blood gases at exercise levels in patients and at PaO2 = 65 mm Hg and PaCO2 = 48 mm Hg in normal subjects. In normal subjects, the role of arterial blood gases in determining exercise ventilation, cardiac output, cyclic AMP and GMP are large, while those contributed much less to lactic acid. In patients, PaO2 contributed only half of the exercise ventilation. It accounted for a negligibly small portion of exercise cardiac output, lactic acid, and cyclic GMP. These results indicate, by deduction, that either augmentation of chemosensitivity, pH, or humoral factors is responsible for about half of the changes of exercise ventilation in patients with pulmonary emphysema. These factors seem to influence cardiac output, lactic acid, and cyclic AMP and GMP more strongly than PaO2 alone in exercising patients.
A sex-, age-, obesity, and protease inhibitor-matched study of pulmonary function and ventilatory control was performed on 26 sons of 19 patients with chronic obstructive pulmonary disease (COPD) and 26 control subjects. Mean values for FEV1/FVC and V25 were significantly lower and CV/VC was significantly higher in sons of patients than in the controls. VC, airway resistance, static pulmonary compliance. delta N2, arterial blood gases and pH were not different between sons and controls. When the sons of patients were divided into two groups according to the arterial blood gases of their parents, sons of hypoxemic, hypercapnic parents showed significantly lower hypoxic ventilatory responses than sons of normoxemic, normocapnic parents. Hypercapnic ventilatory responses were not different between sons and controls. Abnormal pulmonary function and low ventilatory responses were more frequently detected in sons than in controls. The association of smoking with abnormalities of pulmonary function was not clearly seen in sons. These results suggest that familial factors (either genetic or environmental) play a significant role in determining the pathogenesis and clinical types of COPD.
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