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Biomedical subjects

I Ohtsu

Publications and source records attributed to I Ohtsu.

13 recordsLinked to original sources

A demand valve device decreases exhaust nitric oxide and nitrogen dioxide by nitric oxide inhalation with a nasal cannula in the human.

To improve patients' quality of life and decrease pollution risks to medical personnel, we tested the usefulness of a nitric oxide (NO) inhalation system consisting of a nasal cannula and a demand valve in an open circuit system. To estimate the content of NO entering the lung with the open system, concentrations of NO and nitrogen dioxide (NO2) were measured in a mechanical lung model, and then nitrocylhaemoglobin (NO-Hb), methaemoglobin (Met-Hb), and nitrite (NO2-) + nitrate (NO3-) concentrations in venous blood were measured in eight healthy subjects. Exhaust NO and NO2 in the open system were also observed in 14 healthy subjects. In the lung model, NO concentration delivered with the open system was approximately 1/11 of that in the gas tank. Increases in Met-Hb and NO2- + NO3- with the open system showed that the concentration of delivered NO was approximately 1/9 of that in the gas tank. The open system reduced exhaust NO to 1/10 in human subjects. These data suggest that this NO inhalation system delivers sufficient NO to spontaneously breathing patients. In addition, these findings indicate that there is little environmental toxicity associated with the open circuit system.

Adult↗

[Quantitative analysis of pulmonary functional damage due to heavy ion particle irradiation therapy for lung cancer].

Seventeen patients with clinical stage I lung cancer were given irradiation therapy with heavy ion radioactive rays at 73.1 +/- 11.2 GyE. Lung injury due to irradiation was evaluated by measuring routing parameters of pulmonary function. No statistically significant changes in these parameters were observed after irradiation, even in patients followed up for a period of 1 year. Chest X-ray examinations, including CT scan images, disclosed the development of nonsegmental consolidations in the irradiated areas, changing into minor fibrosis 1 year later. We concluded that heavy ion particle irradiation has minimal impact on pulmonary function, and is of therapeutic valve to elderly patients and patients with complications.

Aged↗

Random mutagenesis into the conserved Gly154 of subtilisin E: isolation and characterization of the revertant enzymes.

We analyzed the role played by the conserved Gly154, a constituent of the P1 substrate-binding pocket of Bacillus subtilis subtilisin E, in the catalytic properties of the protease. Using an Escherichia coli expression system, the termination codon at position 154 in subtilisin E was first introduced to abolish the catalytic activity through truncation of the C-terminus from amino acid residues 154-275. We then attempted to obtain revertants with substitutions of various amino acids at position 154 by the polymerase chain reaction using a mixture of oligonucleotides. In addition to the Gly residue (wild-type), six amino acid substitutions (Ala, Arg, Leu, Phe, Pro and Thr) gave caseinolytic activity. When assayed with synthetic peptide substrates, most of the revertants showed a considerable decrease in specific activity and a P1 specificity similar to that of the wild-type enzyme. An Ala154 mutant purified from the periplasmic space in E. coli, however, resulted in an up to 2.3-fold preference for Val rather than Pro as a P2 substrate relative to the wild-type. Further, a significant 2-10-fold increase in the catalytic efficiency occurred in the Gly127Ala plus Gly154Ala combination variant, relative to the single Gly127Ala variant, without any change in the restricted specificity. The kinetic data and molecular modeling analysis demonstrate the important role of position 154 in the catalytic efficiency as well as in the substrate specificity of subtilisin E.

Amino Acid Sequence↗

Inhaled nitric oxide in patients with pulmonary hypertension due to valvular heart disease and chronic lung disease.

The objective of this study was to investigate the effects of inhaled nitric oxide (NO) on chronic pulmonary hypertension (PH). Thirty patients with valvular heart diseases (n=8, group A), chronic lung diseases (n=16, group B), primary PH or PH due to collagen disease (n=6, group C) were studied. NO was delivered for 20 min at concentration of 5, 10, and 20 ppm in spontaneous respiration. After inhalation, percentages of systolic pulmonary artery pressure (%SPAP) levels in group A were significantly decreased compared with those for pre-inhalation by 12%, 14%, and 14% at 5, 10 and 20 ppm, respectively (p<0.05). In group B, %SPAP also significantly decreased by 7, 10, and 14% at 5, 10, and 20 ppm, respectively (p<0.05). However, inhaled NO did not significantly affect %SPAP in group C (p=0.4). There was no significant difference in gas exchange in any of the groups. However, 4 out of 8 patients in group A and 10 out of 16 patients in group B showed decreased partial pressure of arterial oxygen in response to inhaled NO. This study demonstrated that inhaled NO is a selective pulmonary vasodilator in decreasing pulmonary artery pressure (PAP); however, the reaction was different in line with the background disease cause of PH. NO inhalation was most effective on patients with moderate PAP. Furthermore, higher concentrations of NO would be risky in some patients with chronic PH.

Administration, Inhalation↗

[One year follow-up of pulmonary rehabilitation in patients with pulmonary emphysema--physiological outcome].

To evaluate the long-term effects of pulmonary rehabilitation on physiological outcome, 12 patients with pulmonary emphysema were enrolled in an inpatient pulmonary rehabilitation program for 6 weeks. After discharge from the hospital, they were followed up for 1 year. The pulmonary rehabilitation program consisted of breathing retraining, thoracic mobilization, exercise training, and patient education. Although the subjects did not participate in outpatient maintenance group sessions after their discharge, they continued breathing retraining and exercise training at home. Their vital capacity improved significantly, and was sustained over the course of the year; other pulmonary functions, however, did not change significantly. Maximum exercise load increased 31% after the rehabilitation program; although it was 18% higher than baseline at follow-up one year later, that was not a significant change. The follow-up data on exercise traming had generally deteriorated 1 year after the rehabilitation program. The change in maximum exercise load from baseline before and after the inpatient pulmonary rehabilitation program correlated closely with the change in maximum exercise load thereafter to follow-up one year later (R = 0.62). We conclude that it is pessible to estimate long-term change in exercise capacity on the basis of short-term changes achieved during inpatient pulmonary rehabilitation. It may be necessary to develop maintenance programs of some kind to help pulmonary emphysema patients retain the benefits of pulmonary rehabilitation over the longer term.

Aged↗

Construction of novel subtilisin E with high specificity, activity and productivity through multiple amino acid substitutions.

Through three cumulative amino acid substitutions, we constructed novel mutant subtilisins E of Bacillus subtilis, all with high specificity, activity and productivity. The substitution of conserved Gly127, constituting P1 substrate-binding pocket, with Ala and Val showed a marked preference for the small P1 substrate. Leu was then substituted for Ile31 next to the catalytic Asp32 to enhance the catalytic activity. Both double mutants (I31L/G127A and I31L/G127V) showed a 3-5-fold increase in catalytic efficiency due to a large kcat, without any change in the specificity of the mutants at position 127. Molecular modeling suggests that large P1 residues were unable to access the pocket because of steric hindrance. A third mutation was introduced by replacing Tyr(-1) with Ala in the propeptide essential for autoprocessing to active mature subtilisin in vivo. A prominent 7-20-fold increase in active enzyme production occurred in the triple mutants (Y-1A/I31L/G127A and Y-1A/I31L/G127V).

Amino Acid Substitution↗

Effect of respiratory rate on respiratory patterns in patients with chronic obstructive pulmonary disease.

We enrolled 22 patients with chronic obstructive pulmonary disease (COPD) and 20 normal subjects as controls. Using a hot-wire flow meter, we obtained tidal volume (VT), duty ratio (Ti/Ttot), and mean inspiratory flow (VT/Ti) as measures of respiratory pattern at two different respiratory rates; 0.5 Hz and 1.5 Hz. At 0.5 Hz, there were significant differences in Ti/Ttot and VT/Ti. At 1.5 Hz, patients with COPD had significantly lower values of VT and VT/Ti. Furthermore, we calculated the change ratios from 0.5 Hz to 1.5 Hz in these parameters as new parameters of respiratory pattern change by respiratory rate. VT0.5/1.5 and VT/Ti0.5/1.5 significantly correlated with FEV1.0/FVC. The findings suggest that the parameters of the respiratory pattern may change depending on respiratory rates, and that the ratios of those parameters obtained at two different rates could be helpful in diagnosing airflow obstruction.

Aged↗

[Associations between breathing pattern during submaximal exercise and exercise capacity in patients with pulmonary emphysema].

We sought to clarify the factors associated with exercise capacity in patients with pulmonary emphysema. Exercise capacities of 20 men with pulmonary emphysema were evaluated by bicycle ergometery, and the results were used to divide the subjects into two groups: high exercise capacity (n = 10) and low exercise capacity (n = 10). Pulmonary-function tests were done, emphysema scores were computed from CT scans, breathing pattern was recorded during submaximal exercise (up to 20 watts), and index of rapid shallow breathing was computed. Neither FEV1 nor airway resistance differed between the two groups, and patients with lower exercise capacity tended to have lower tidal volumes and higher values of the index of rapid shallow breathing during submaximal exercise. Functional residual capacity measured by body plethysmography and emphysema scores were inversely associated with exercise capacity. We speculate that among patients with pulmonary emphysema and a given degree of airway obstruction, a high functional residual capacity causes breathing during submaxinal exercise to be rapid and shallow, and that this rapid and shallow breathing makes ventilation inefficient, increases the work of breathing, and limits exercise capacity.

Aged↗

Restriction of substrate specificity of subtilisin E by introduction of a side chain into a conserved glycine residue.

Substitution of the conserved Gly127 for residues having a side chain markedly changed the substrate specificity of subtilisin E from Bacillus subtilis. The crystallographic findings suggested that Gly127 is responsible for accepting even the large P1 substrates, and the marked change of specificity was attributed to the introduction of a side chain in this position. To test this hypothesis, Gly127 was replaced with 3 non-charged amino acids, Ala, Ser and Val. When assayed with synthetic peptide substrates, all mutants purified from the periplasmic space in Escherichia coli showed a marked preference for small P1 substrate up to 150-fold relative to the wild-type. The kinetic data and molecular modeling analysis suggest that large hydrophobic P1 residues were unable to access the binding pocket due to steric hindrance.

Amino Acid Sequence↗

[Invasive thymoma associated with pure red cell aplasia and lung cancer].

A 71-year-old man was admitted to our hospital with vertigo and general fatigue. Examination of his blood and bone marrow showed pure red cell aplasia. His chest X-ray film revealed an anterior mediastinal mass and a nodular shadow in the right lower lobe. Extended thymothymectomy and right lower lobectomy were done. The mediastinal mass appeared to be an invasive thymoma and the nodular shadow in the right lower lobe proved to be from an adenocarcinoma. The patient was treated with radiation and steroids. Thymoma, pure red cell aplasia, and lung cancer had not recurred and he was alive and well as of 2 years after surgery.

Adenocarcinoma, Papillary↗

[Effects of pulmonary rehabilitation on vital capacity in patients with chronic pulmonary emphysema].

To evaluate the effects of pulmonary rehabilitation on pulmonary function, 15 patients with chronic pulmonary emphysema underwent pulmonary rehabilitation for six weeks as inpatients. Pulmonary rehabilitation consisted of relaxation techniques, breathing retraining, thoracic massage, physical exercise, and walking. In 8 of the 15 patients vital capacity increased by more than 200 ml (over 10%), and in 7 of the 15 patients the load of maximal exercise increased by more than 5 watts (over 10%). Increases in vital capacity were not associated with increases in maximal exercise load. The percent change in vital capacity associated with pulmonary rehabilitation correlated significantly with the percent change in tidal volume and the percent change in expiratory minute ventilation at the maximal load. The percent change in tidal volume at the maximal load correlated significantly with the percent change in maximum oxygen uptake. We attribute the increase in vital capacity to an improvement in thoracic cage movement. These findings suggest that pulmonary rehabilitation can increase vital capacity in some patients with chronic pulmonary emphysema, and that such an increase is not directly connected to increases in exercise capacity.

Aged↗

[Psychological and physiological changes accompanying pulmonary rehabilitation in patients with chronic pulmonary emphysema].

In 14 patients with chronic pulmonary emphysema, the relations between changes in psychological status associated with pulmonary rehabilitation and exercise tolerance were studied with the Cornell Medical Index and the Yatabe-Guiford Personality Inventory. Although the scores on the latter did not change, the cardio-respiratory score on the Cornell Medical Index improved significantly (p < 0.05). The only index of exercise tolerance that improved significantly was the distance walked in 10 minutes (p < 0.05). The changes in the scores of "Lack of Objectivity" and "Rhathymia" correlated negatively with the change in the distance walked in 10 minutes (R = -0.80, p < 0.01; R = -0.81, p < 0.01). The change in psychological status that accompanied pulmonary rehabilitation has been related to the improvement in the distance walked in 10 minutes.

Aged↗

[Diagnosis of respiratory system diseases using radio isotopes].

Common respiratory diagnostic imaging techniques using radioisotopes are ventilation-perfusion, perfusion, aerosol inhalation and tumor scintigraphy. The special features of respiratory imaging diagnostic techniques using radioisotopes are the possibility of early detection of disease and the non-invasiveness of the procedure. Also, no patient effort is required. The kinds of isotopes used are as follows: ventilation-perfusion (133Xe, 13N, 99mTc-pseudogas), perfusion (131I, 99mTc), aerosol inhalation (99mTc), tumor (67Ga, 201Tl). The advantages of these procedures are expected to lead to further developments in respiratory examinations using radio isotopes.

Female↗