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Biomedical subjects

M Motomiya

Publications and source records attributed to M Motomiya.

At least 55 records · Page 3Linked to original sources

[Changes in pulmonary epithelial permeability due to thoracic irradiation].

The changes in pulmonary epithelial permeability during and following radiation therapy were studied in 10 patients with malignant diseases of the chest; 9 patients with bronchogenic carcinoma and one with thymoma. 99mTc-DTPA aerosol was inhaled during tidal breathing with the patient in supine position, and radioactivity was measured anteriorly by a gamma camera and recorded on a computer. Half time clearance (t1/2) was calculated from exponential fitting of time activity curves by regression analysis in various regions of interest in the initial 7 min following completion of aerosol inhalation. Studies were made every two weeks. In patients who developed radiation pneumonitis, t1/2 values decreased and reached the nadir at the time of manifest pneumonitis, indicating increased pulmonary epithelial permeability. Increased pulmonary epithelial permeability was observed not only in the pneumonic regions but also in the contralateral normal lung regions. Steroid therapy reversed these changes. Increased pulmonary epithelial permeability was observed in 2 out of 5 patients who did not develop radiation pneumonitis. In summary, pulmonary epithelial permeability changes occur not only in regions of radiation pneumonitis but also in non-irradiated lung regions following radiation therapy. We consider that the judicious use of this method enables detection of changes in pulmonary epithelial permeability prior to the development of clinical manifestations of radiation pneumonitis.

Aerosols↗

Incidence of pulmonary embolism in a chest hospital in Japan and importance of preoperative perfusion lung imaging in the diagnosis of postoperative pulmonary embolism.

The incidence of pulmonary embolism was retrospectively studied in a University Chest Institute and its affiliated hospital in Sendai, Japan, whose annual numbers of discharged patients from chest medical wards and lung operations as a whole are about 600 and 400, respectively. Before 1975 there was no documented patient with pulmonary embolism. Since then 70 patients had been clinically suspected of having pulmonary embolism and 31 of the 70 were diagnosed as having pulmonary embolism; 15 without and 16 with surgical operations in the immediate past. Fourteen of the 31 patients required combined perfusion and aerosol inhalation lung imaging for diagnosis. Twelve postoperative patients could be diagnosed as pulmonary embolism by comparing postoperative perfusion lung images taken at the time of suspicion with preoperative perfusion counterparts. Although it is said to be rising, the incidence of pulmonary embolism in a chest hospital still seems to remain low compared with that in western countries. For postoperative patients, comparison with preoperative studies was found very useful in diagnosing postoperative pulmonary embolism. The importance of preoperative perfusion lung imaging cannot be overstressed not only as a preoperative lung function test but as a baseline study to be compared with postoperative perfusion images when pulmonary embolism is clinically suspected in postoperative patients.

Female↗

Increased levels of mitochondrial DNA in an etoposide-resistant human monocytic leukaemia cell line (THP-1/E).

Electron microscopic observations of THP-1/E (an etoposide-resistant human monocytic leukaemia cell line) showed a remarkable change of mitochondrial structure. Mitochondria were swollen and cristae were relatively intact. There was no difference in the activity of cytochrome oxidase, an enzyme which contains three subunits coded by mitochondrial DNA (mtDNA) between THP-1/E and THP-1 (the parent cell of THP-1/E). No measurable quantitative change of mitochondrial RNA was observed, but the level of mtDNA in THP-1/E was increased by a factor of about 4 compared with that of mtDNA in THP-1. These results suggest that, on acquisition of resistance to etoposide, some factors affect mitochondria, change its morphology and amplify its DNA.

Blotting, Northern↗

Myosin light chain kinase inhibitors ML-7 and ML-9 inhibit mouse lung carcinoma cell attachment to the fibronectin substratum.

We studied the effects of various protein kinase inhibitors on the attachment of mouse lung carcinoma 3LL cells to the fibronectin (FN) substratum. Calmodulin antagonists (W-7 and W-13) and myosin light chain kinase inhibitors (ML-7 and ML-9) exhibited the inhibitory effect for the attachment, while inhibitors of protein kinases A and C were ineffective. Since Arg-Gly-Asp-containing hexapeptide blocked the attachment, cell surface FN receptor appeared to be involved in this mechanism. These results support the hypothesis that the cell attachment requires the rearrangement of the cytoskeleton in association with the phosphorylation of myosin light chain which would lead to the clustering of the cell surface FN receptors.

Animals↗

Technegas for inhalation lung imaging.

Technegas, an aerosol generator recently devised in Australia, produces aerosol particulates called 'technegas' which have characteristics of both an aerosol and a gas. The majority of the particulate is below 200 nm in size as measured by electron microscopy. Four normal subjects and 31 patients with various lung diseases were studied by imaging the lungs following inhalation of technegas. The penetration of inhaled technegas to the lung periphery was excellent; the average alveolar deposition ratio (ALDR) was 85%. Comparative studies with lung images obtained either with an ultrasonic nebulizer or jet nebulizers also confirmed better penetration of inhaled technegas to the lung periphery. There was no significant statistical difference in the ALDRs between normals and patients. Aerosol studies were comparable to perfusion counterparts, and evaluation of regional ventilatory status was greatly facilitated. Because of the large ALDR and the low airway deposition ratio (ADR), actual imaging could be done not only immediately after aerosol inhalation but also some time later without losing too much radioactivity from the lungs. One disadvantage was that technegas immediately after generation was anoxic.

Administration, Inhalation↗

Association between restriction fragment length polymorphism of the human cytochrome P450IIE1 gene and susceptibility to lung cancer.

Cytochrome P450IIE1 (P450IIE1) is involved in metabolic activation of carcinogenic nitrosamines, aniline and benzene. We detected a restriction fragment length polymorphism of the human P450IIE1 gene with the restriction endonuclease DraI. The population was thus divided into three genotypes, namely, heterozygotes (CD) and two forms of homozygotes (CC and DD). The distribution of these genotypes among lung cancer patients differed from that among controls with statistical significance of P less than 0.05 (chi 2 = 7.01 with 2 degrees of freedom). This result strongly suggests that host susceptibility to lung cancer is associated with the DraI polymorphism of the P450IIE1 gene.

Adenocarcinoma↗

Detection of methicillin-resistant Staphylococcus aureus (MRSA) using polymerase chain reaction amplification.

Polymerase chain reaction (PCR) was applied for the detection of methicillin-resistant Staphylococcus aureus (MRSA). This procedure amplified a segment of MRSA-PBP (penicillin-binding protein) gene of DNA extract from the clinical isolates of S. aureus. A 1339-base-pair fragment of MRSA-PBP gene in DNA from S. aureus (MIC of methicillin, greater than or equal to 16 micrograms/ml) was amplified and detected by a specific oligonucleotide probe. Moreover, a 4.3 kb HindIII fragment containing MRSA-PBP gene was detected by using the same oligonucleotide probe. On the other hand, no PCR-amplified product was detected in DNA from methicillin-sensitive S. aureus (MIC of methicillin, less than 16 micrograms/ml).

Base Sequence↗

[Pulmonary epithelial permeability in normal subjects and patients with idiopathic interstitial pneumonia].

99mTc-DTPA is a low molecular weight substance which is believed to pass through the pulmonary epithelium when it is inhaled as an aerosol. We performed 99mTc-DTPA inhalation studies in 10 nonsmoking normal subjects and 10 patients with biopsy proven idiopathic interstitial pneumonia prior to therapy. 99mTc-DTPA aerosol was inhaled for 3 min with the subject in the supine position and radioactivity was measured anteriorly with a gamma camera and recorded on a computer. Measurements were performed for 3 min with the subject inhaling aerosol and for the subsequent 30 min with the subject in the same position. Time activity curves from the five regions of interest (ROIs) including the entire left lung, the entire right lung, and the upper, middle and lower third of the right lung were separately fitted to a single exponential function for the initial 7 min following cessation of inhalation, and the respective clearance half life (t1/2) in min was calculated. Lung function data, arterial blood gas tensions and blood chemistry were also obtained for comparison with the t1/2 values. The t1/2 values were significantly smaller in all ROIs in patients with idiopathic interstitial pneumonia than in normal subjects, indicating a increased pulmonary epithelial permeability in these patients. There was no relationship between t1/2 and %DLco, %DLco/VA, PaO2, or LDH. Although the true pathophysiologic significance of t1/2 measured using 99mTc-DTPA aerosol is still not known, we consider that this measurement may be an important indicator of nonrespiratory lung function, in particular the degree of alveolar epithelial damage.

Administration, Inhalation↗

Effect of respiratory phases and gravity on mucociliary transport in the normal lungs.

Effect of gravity and respiratory phase on mucociliary transport was studied in 11 normal subjects. After inhaling 99mTc-human serum albumin aerosol, each subject was positioned in right lateral decubitus and then supine position before a scintillation camera. Data in list mode and simultaneous respiratory curve were stored in a computer for 15 min each. The respiratory curve was sequentially marked at the beginning of inspiration, expiration and pause of each respiratory cycle and list mode data was converted into frame mode, respectively. The frame mode data was then sequentially connected according to the respective respiratory phase. The data in count-per-second from each lungs versus time was fitted to a straight line by regression analysis and the slope of the line was compared with each other for respective respiratory phase. Slopes of net radioactivity changes in the right and left lungs were compared to evaluate gravity effect. Neither respiratory phases nor gravity had any significant effect on mucociliary transport. Theoretical calculations have also supported the present findings.

Adult↗

beta-Lactamase activity in sputum and indirect pathogenicity.

beta-Lactamase activity of sputum of 39 patients with respiratory infections and that of bacterial isolates from their sputum were determined by nitrocefin method. Forty-six microbial strains (16 different species) were recovered from 39 sputum samples. The beta-lactamase activity was negative only in nine of the 46 strains. beta-lactamase-positive strains were recovered from 35 of 39 sputum samples. Of these 35 sputum samples, the beta-lactamase activity was positive in 23 and negative in 12. beta-lactamase-negative strains were recovered from 4 of 39 sputum samples, and the beta-lactamase activity was negative in all of these four sputum samples. Both beta-lactamase producing and non-producing strains were recovered in 5 of 6 sputum samples from which two to three microbes were isolated. The ratio of beta-lactamase-positive sputum sample was higher in patients who had received antibiotics than in those who had received no antibiotics. This difference was statistically significant (P < 0.025). It is possible that non-causative beta-lactamase-positive organisms enhance the pathogenicity of causative organisms that are beta-lactamase-negative.

Anti-Bacterial Agents↗

[A phase II study of CPT-11, a camptothecin derivative, in patients with primary lung cancer. CPT-11 Cooperative Study Group].

A Phase II study of CPT-11, a new camptothecin, was performed in patients with primary lung cancer. Patients with previously untreated non-small cell carcinomas (group A), or previously treated non-small cell carcinomas (group B), and with small cell carcinomas (group C), were enrolled in this study. CPT-11 was given at a dose of 100 mg/m2 i.v. infusion once a week for three weeks or more. Out of 153 patients enrolled, 128 (A: 67; B: 26; C: 35) were assessed to be evaluable for response by an extramural review committee. Response rates were 34.3% (23/67) for A, 0% (0/26) for B and 37.1% (13/35) for C. The response rate was 50% for previously untreated patients (4/8), and 33.3% for previously treated patients (9/27) including 2 complete responses in the group C. Major toxicities were leukopenia, nausea/vomiting, diarrhea, anorexia and alopecia. Leukopenia and diarrhea were considered to be dose limiting toxicities, but they were reversible. It was, however, suggested that some patients should be monitored carefully for severe reactions and delay in recovery. The results showed that CPT-11 was highly effective against non-small cell and small cell carcinomas of the lung.

Adenocarcinoma↗

Changes of polyphosphoinositides, lysophospholipid, and free fatty acids in transient cerebral ischemia of rat brain.

Phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4, 5-bisphosphate (PIP2), 1, 2-diglyceride (DG), lysophosphatidylcholine (LPC), and free fatty acids (FFA) contents, as well as their fatty acid composition, were measured in transient global cerebral ischemia. ATP and CTP were also studied. Male Wistar rats were subjected to 1, 5, and 30 min of ischemia and 10, 30, and 60 min of recirculation following 30 min of ischemia. In addition, for the quantification of PI, PIP, and PIP2, rats were also subjected to 30 and 60 min of recirculation following 5 min of ischemia. PIP2 and PIP decreased rapidly during 5 min of ischemia and recovered completely after recirculation. DG increased almost at the same rate during ischemia and returned to normal after recirculation. PI showed almost no changes throughout entire course. LPC increased during 5 min of ischemia and returned to normal after recirculation. Stearic acid and arachidonic acid contained in DG increased during 5 min of ischemia, whereas saturated fatty acids increased in LPC. Among the FFA accumulated during ischemia, stearic acid and arachidonic acid increased rapidly and were followed by increases of other FFA. From these results, the pathways for the increase of FFA during ischemia and the fate of FFA after recirculation are discussed. In addition, the importance of the changes of PIP, PIP2, and LPC is also discussed.

Adenosine Triphosphate↗

Flow patterns at the major T-junctions of the dog descending aorta.

Using a novel technique developed in our own laboratory, an isolated transparent arterial segment containing the whole descending aorta and its four major branches was prepared from a dog. The flow patterns at each aortic T-junction were studied in detail under the conditions of steady flow by means of flow visualization and cinemicrographic techniques. It was found that a standing recirculation zone consisting of a pair of thin-layered spiral secondary flows located symmetrically about the common median plane of the aorta and side branches was formed at each T-junction over a wide range of flow conditions including the time-averaged estimated mean values of physiological flow rates and flow rate ratios. The results support the recent in vivo findings by other investigators that flow reversal occurs at some junctions of the dog abdominal aorta during each cardiac cycle. The flow patterns at the aortic T-junctions were very much similar to those previously observed in various glass model T-junctions. However, due to the particular anatomical structure of the vessel wall at each branching site (the curvature of the wall was very sharp at the flow divider, but gently rounded at the bend opposite to it) no recirculation zone was formed in the side branches. At a given flow rate ratio, the measured critical Reynolds numbers for the formation of spiral secondary flows and fully developed disturbed flows were much higher in aortic T-junctions than those in glass model T-junctions having equivalent branching angles and diameter ratios. These results indicate that, in the circulation, conditions at arterial T-junctions appear to be optimal for minimizing the formation of disturbed flows.

Animals↗

[Studies on respiratory infections in primary care clinic (III). Distribution of bacteria isolated from patients with respiratory infections visiting 21 private clinics in the Tohoku District of Japan].

The bacteriology of the isolates from the throat swab and the sputum respectively of 2,539 patients with respiratory infections visiting 21 private clinics in Tohoku district of Japan during the period from January to April in 1989 was documented. Of the 2,539 patients, 1,694 had an acute upper respiratory infection, 609 had acute bronchitis, 46 had acute pneumonia, 84 had acute exacerbation of chronic respiratory infections and 106 had respiratory infections without diagnosis registered. 1887 (74.3%) strains of potential pathogens were recovered from 1507 (59.4%) of the 2539 cases. The rate of recovery of potential pathogens was very high in patients of the younger age. These patients had elevated body-temperature. There were statistically significant differences in recovery rate when classified by diagnosis, prefecture and the period of investigation. Of the 1,887 strains, 996 (52.8%) were gram-positive and 891 (47.2%) were gram-negative bacteria. The rate of recovery of gram-negative bacteria was high in patients who were less than 10 years old and more than 51 years old, in patients with pneumonia and chronic respiratory infections, and in patients with fever. Of the 1,887 strains, those which exceeded 100 were Staphylococcus aureus (481 strains), Haemophilus influenzae (340 strains), Streptococcus pneumoniae (329 strains), Streptococcus pyogenes (117 strains) and Acinetobacter spp. (100 strains). Species other than those mentioned above had less than 100 strains. In this group there were 39 strains of Branhamella catarrhalis, 32 strains of Escherichia coli, 97 strains of Klebsiella spp., 40 strains of Enterobacter spp., 25 strains of Serratia spp., 12 strains of Pseudomonas aeruginosa and 43 strains of Pseudomonas putida. There was a remarkable difference in recovery rate of each species when classified by diagnosis, age class, prefecture and the period of investigation, respectively. The above results indicated that gram-positive bacteria are more frequent than gram-negative bacteria, that enterobacteriaceae and glucose-non-fermentative gram-negative bacteria are only rarely found in primary care clinics, and that the bacteriology in primary care clinic is different from that of medical school-affiliated hospitals.

Adolescent↗

[Studies on respiratory infections in primary care clinic (IV). Antibiotic sensitivity of bacteria isolated from patients with respiratory infections visiting 21 private clinics in the Tohoku District of Japan].

We determined the MICs of ampicillin, methicillin, cefaclor, cefixime, cefteram, ofloxacin and ciprofloxacin against a total of 1,448 strains from 11 species: 464 strains of Staphylococcus aureus, 306 strains of Streptococcus pneumoniae, 114 strains of Streptococcus pyogenes, 37 strains of Branhamella catarrhalis, 329 strains of Haemophilus influenzae, 32 strains of Escherichia coli, 66 strains of Klebsiella pneumoniae, 26 strains of Enterobacter cloacae, 20 strains of Serratia marcescens, 12 strains of Pseudomonas aeruginosa and 42 strains of Acinetobacter calcoaceticus, isolated from the throat swab and the sputum of 2,539 patients with respiratory infections who visited 21 private clinics in Tohoku district of Japan during the period from January to April in 1989. Ciprofloxacin and ofloxacin were more active against S. aureus, B. catarrhalis, P. aeruginosa and A. calcoaceticus than other antibiotics. Ampicillin and cefteram were more active against S. pneumoniae and S. pyogenes than other antibiotics. New-quinolones and cephems of new-generation were active against H. influenzae, E. coli, K. pneumoniae, E. cloacae and S. marcescens. Of 30 strains of S. aureus which were resistant (MIC greater than or equal to 12.5 micrograms/ml) to ampicillin, only one strain was resistant (MIC greater than or equal to 12.5 micrograms/ml) to methicillin. Twenty strains (6.5%) of S. pneumoniae and 49 strains (14.9%) of H. influenzae were resistant (MIC greater than or equal to 1.56 micrograms/ml) to ampicillin. Of 101 strains of H. influenzae of which their beta-lactamase activity was determined by Nitrocephin-method, 27 (26.7%) were beta-lactamase-positive strains. The above results indicated that MRSA is only rarely found in primary care clinics but the incidence of ampicillin-resistant H. influenzae in primary care clinics is almost the same as that of the intensive care clinic, i.e. medical school-affiliated hospitals. Therefore caution should be exercised as regards antibiotic resistance of the causative organism even in primary care clinics.

Ambulatory Care Facilities↗

Phenytoin affects metabolism of free fatty acids and nucleotides in rat cerebral ischemia.

We investigated the effects of phenytoin on the rate of enzymatic release of free fatty acids and on the levels of energy metabolites and nucleoside phosphates in ischemic brain. Phenytoin (10 mg/kg i.v.) was administered 30 minutes before the onset of ischemia induced in 30 male Wistar rats by occluding the basilar and both common carotid arteries. The rats' brains were frozen in situ after 0, 5, or 30 minutes of ischemia or 10, 30, or 60 minutes of recirculation following 30 minutes of ischemia (n = 5 at each time). Nucleoside triphosphate levels were higher in the phenytoin-treated rats than in corresponding untreated rats at each time during and after ischemia. Phenytoin significantly attenuated the accumulation of lactate and free fatty acids (arachidonic acid and stearic acid) during ischemia and accelerated their recovery during recirculation. These results suggest that phenytoin has favorable protective effects on ischemic brain and that phenytoin may inhibit calcium-mediated phenomena, especially the inositol cycle, in cerebral ischemia.

Animals↗