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Biomedical subjects

A Umeda

Publications and source records attributed to A Umeda.

At least 55 records · Page 3Linked to original sources

[Mycobacterium kansasii lung infection associated with myelofibrosis--a case refractory to treatment with antitubercular agents].

A case of Mycobacterium kanasasii lung infection associated with myelofibrosis is reported. A 32-year-old woman was admitted to Keio University Hospital because of fever. One year before admission, a diagnosis of myelofibrosis was made at another hospital. The initial chest X-ray film showed bilateral diffuse infiltrative shadows and right hilar enlargement. Sputum cultures yielded Mycobacterium kansasii on 3 occasions. A fever of 38 degrees C or higher persisted for about 4 months despite the use of antitubercular agents, including INH, RFP, SM, and PZA. During the course of treatment, the hilar and mediastinal lymph node enlargement became more severe, and this was followed by calcification of the nodes. The fever and chest X-ray findings improved in response to the addition of treatment with EB, Ofloxacin, TH, and an increase in the doses of INH (from 300 to 500 mg/day) and RFP (from 450 to 600 mg/day). The patient was discharged 14 months after admission. It is rare especially in Japan for a Mycobacterium kansasii lung infection (not disseminated) to persist in spite of treatment with antitubercular drugs, including RFP or TH. The response to treatment may have been impaired by an immunological disorder associated with the myelofibrosis.

Adult↗

Effects of pH and SO2 on solubility coefficients of inert gases in human whole blood.

We systematically investigated the quantitative importance of pH and O2 saturation (SO2) of hemoglobin on the solubility coefficients (alpha) for six inert gases: sulfur hexafluoride, N2, ethane, cyclopropane, halothane, and diethyl ether. Measurements of alpha were made at 37 degrees C with SO2 of 0-1.0 and pH of 7.2-7.7 by use of whole blood obtained from three healthy subjects. No significant dependence of alpha on pH was demonstrated for sulfur hexafluoride, N2, halothane, or diethyl ether, but an appreciable augmentation of alpha with increasing pH was found for ethane and cyclopropane. No alpha value obtained for oxygenated blood differed statistically from that for deoxygenated blood. In addition to the basic findings on the effects of pH on alpha values of ethane and cyclopropane with the multiple inert gas elimination technique (data obtained from 22 patients with either interstitial pneumonia or chronic obstructive pulmonary disease), we also found that dependence of alpha on blood pH exerted no significant influence on the recovery of ventilation-perfusion distribution in the lung. We concluded that: 1) pH plays an appreciable role in determining gas solubilities in blood, 2) SO2 is not a decisive factor for gas solubilities in blood, and 3) the influence of various pH values in pulmonary capillaries on inert gas exchange is negligible.

Adult↗

Molecular cloning and chromosomal mapping of feline p53 tumor suppressor gene.

Alterations of the p53 tumor suppressor gene have been observed in a variety of human and mouse tumors. For investigation of the role of this gene in tumors in cats, feline p53 cDNA was molecularly cloned by PCR amplifications using primers based on the sequences conserved among several species. The cloned cDNA appeared to cover approximately 90% of the open reading frame of the feline p53 gene and had characteristic structures in common with the p53 genes of several other species. The amino acid sequence similarities of the feline p53 with the human, mouse, rat and chicken counterparts were 82.9%, 75.6%, 76.5% and 57.2% respectively. Moreover, using a panel of feline x rodent somatic cell hybrids, the feline p53 gene was assigned to feline chromosome E1. These data will be useful for determining the role of the p53 tumor suppressor gene in feline tumors.

Amino Acid Sequence↗

[Roles of serotonin in glass-bead pulmonary microemboli].

We investigated the role of serotonin release from aggregating platelets in glass-bead microemboli on isolated perfused rabbit lungs. The perfusion was performed at 70 ml/min with a roller pump. The temperature of the perfusion circuit was maintained at 37 +/- 1 degrees C by means of a heat exchanger. 100 microns-diameter glass beads (1 g) were infused via the main pulmonary artery. We examined the concentration of serotonin and the number of platelets in the perfusate and the mean pulmonary arterial pressure before and after glass bead embolization. Administration of PRP (platelet-rich plasma) to the perfusate caused the concentration of serotonin to significantly increase after microembolization. Specific serotonin S2 receptor antagonist (DV-7028) inhibited the increase of serotonin concentration in the perfusate, platelet aggregation, and vasoconstriction. We concluded that in the glass-bead embolization model, serotonin was released from aggregating platelets surrounding the glass beads, and constricted pulmonary microvessels via serotonin S2 receptors on the vascular smooth muscles cells.

Animals↗

[Pulmonary disease due to Mycobacterium xenopi].

A 54-year old man with pulmonary disease due to Mycobacterium xenopi is described. He had a history of pulmonary tuberculosis at 8 years of age. He was admitted to our hospital in October 1992, complaining of productive cough and fever. A chest X-ray on October 20 showed an infiltrative shadow with a cavity, although chest X-ray picture on October 2 showed only inactive shadow, in the right upper lobe. Acid-fast organisms were seen in his sputum specimens and M. xenopi was identified by culture. The isolates were confirmed to be M. xenopi by the DNA-DNA hybridization method. He was treated with isoniazid, rifampicin and streptomycin. The fever decreased within a week. After two months of therapy, sputum cultures became negative and chest X-ray findings improved. It was concluded that this is a case of rapidly progressed pulmonary disease caused by M. xenopi in the normal host. This patient's condition responded to antituberculosis drugs.

Humans↗

[A study of localized inflammatory pulmonary lesions by ultra-thin bronchofiberscope].

We used a new type of endoscope developed by the authors in 10 patients with localized inflammatory pulmonary lesions in the peripheral areas which were far from the 3 branch and needed to be distinguished from lung cancer. Endoscopic findings revealed reddening, obstruction, stenosis, hypersecretion and dilation in the peripheral airway. The endoscopic findings in this disease were different from those peripheral lung cancer. The combination of thin-section CT, endoscopy and lung biopsy was the best method for determining the morphological changes in localized pulmonary lesions.

Adult↗

[Effect of diffusion limitation on gas exchange in the lung--analysis in oleic acid-induced lung injury].

To assess the effect of diffusion limitation on gas exchange in injured lungs with non-cardiogenic pulmonary edema, an experimental model of acute lung injury with alveolar flooding was produced in six mongrel dogs by intravenously injecting oleic acid at 0.06 ml/kg. The effect of diffusion limitation was quantitatively examined by measuring the excretion (E) of three indicator gases (acetylene, ethylene and freon-22) with differing solubility (lambda) and tissue diffusivity (d). The indicator gases were dissolved in normal saline and infused at a constant rate through a peripheral vein. Since acetylene and ethylene have nearly identical of d but differing lambda, the difference in E values of these two gases may solely reflect the effect of uneven distribution of ventilation-perfusion ratios (VA/Q) in the lung. Thus, measured E values of acetylene and ethylene allowed us to approximately predict the E of freon-22, the value corresponding to the condition where d of freon-22 was taken to be equal to that of acetylene or ethylene. The difference between predicted and measured E values of freon-22 is indicative of the limitation of diffusion in the lung periphery. In all the lungs studied, measured E values of freon-22 were consistently smaller than those predicted from acetylene and ethylene, leading to the conclusion that gas exchange in injured lungs with widespread pulmonary edema was partly impaired by diffusion in aqueous media.

Animals↗

[Effects of antioxidant enzymes in erythrocytes on pulmonary arterial pressure during hypoxic gas breathing].

Using isolated rabbit lungs (n = 72) perfused at a constant flow of 70 ml/min, we analyzed whether the antioxidant system in erythrocytes significantly contributes to maintaining pulmonary vascular responsiveness to alveolar hypoxia (HPV) in normal lungs. As a measure of HPV, we observed the difference (delta P) between mean pulmonary arterial pressure during ventilation with normoxic gas mixture (21% O2, 5% CO2 in N2) and that during hypoxic gas breathing (3% O2, 5% CO2 in N2). Autologous erythrocytes obtained from the animals treated with various substances inhibiting either superoxide dismutase (SOD), the anion channel of the membrane, catalase (CAT) or glutathione peroxidase (GSH-Px). Subsequently, delta P was systematically measured in the perfusate, whose hematocrit was adjusted to 6-7% with normal or treated erythrocytes as described above. Further, the effects of adding SOD (75 U/ml) or CAT (1000 U/ml) to the perfusate on delta P were examined. The following results were obtained. (1) Inhibition of the superoxide scavenging mechanism in erythrocytes (SOD and anion channel) exerted no significant influence on delta P. (2) Inhibition of hydrogen peroxide scavengers in erythrocytes did not alter the scope of delta P. (3) Addition of either SOD or CAT to the perfusate did not show any significant effect on delta P. The findings are highly consistent with the idea that HPV in normal lungs is essentially independent of antioxidant enzymes in erythrocytes, which are expected to be one of the important factors determining the total capacity to deal with oxidant stress in the lung.

Animals↗

[Mechanism of constriction and dilatation of pulmonary artery induced by hydrogen peroxide].

Hydrogen peroxide (H2O2) is known to cause transient pulmonary vasoconstriction in isolated lungs perfused with a solution containing no blood components, by inducing vasoactive arachidonate metabolites such as thromboxane A2 (TXA2). However, the exact site of production of the vasoactive arachidonates in the lung tissue is unclear. Using isolated main pulmonary arterial rings obtained from male Sprague-Dawley rats (B.W. 300-350 g), we attempted to examine the arachidonate metabolism, especially that mediated by cyclooxygenase, in the vascular wall of pulmonary artery without endothelium. Changes in isometric tension were used to measure contraction or dilatation of the ring preparation. H2O2 caused transient contraction of the ring, which was treated previously with a solution containing a high concentration of potassium (20 mM). The contractile response was enhanced in parallel with the concentration of H2O2 in the presence or absence of endothelium. Catalase (1000 U/ml), a H2O2 scavenger, completely inhibited the response of the isolated ring (without endothelium) to H2O2. OKY-046 (10(-5) and 10(-4) M), a TXA2 synthetase blocker, partially attenuated the contractile response induced by H2O2. ONO-3708 (10(-5) M), a TXA2 and prostaglandin H2 receptor blocker, fully inhibited the vasoconstriction and caused relaxation of the ring without endothelium after addition of H2O2. Indomethacin (5 microM), a cyclooxygenase inactivator, completely inhibited both vasoconstriction and vasodilation of the denuded ring. H2O2 also induced the release of 6-keto-prostaglandin F1 alpha, a stable metabolite of the vasodilator, prostacyclin, from the pulmonary artery without endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Attenuation of hypoxic pulmonary vasoconstriction in acute oleic acid lung injury--significance of vasodilator prostanoids.

To assess a significant role of hypoxic pulmonary vasoconstriction, HPV, on maintaining the gas exchange efficiency in acute lung injury, 24 mongrel dogs were treated with intravenously injecting 0.07 ml/kg of oleic acid. Hemodynamic and gas-exchange parameters were investigated at varied inspired O2 concentration, FIO2. To know a possible contribution of vasoactive prostanoids in regulating vascular reactivity under these circumstances, observations were repeated after infusion of indomethacin. The impairment of gas exchange in injured lungs was examined by measuring the fractional retention, R, of the gas in arterial blood. For this evaluation, a normal saline containing five foreign inert gases such as sulfur hexafluoride, SF6, ethane, cyclopropane, halothane and diethyl ether was infused at a constant rate through a peripheral vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were simultaneously taken for the inert-gas analysis. The concentrations of the indicator gases in the samples were measured in terms of a gas chromatograph equipped with an electron capture detector for SF6 and a flame ionization detector for the other four gases. Although pulmonary vascular resistance, PVR, after injecting oleic acid at FIO2 0.60 was significantly smaller than that obtained at FIO2 0.21, cardiac output, QT as well as extravascular lung water were not different between the two conditions. R value for the indicator gas was consistently lower at FIO2 0.60 irrespective of the gas species. As increasing FIO2, R estimate concerning SF6, RSF6, rational index of the fractional blood flow perfusing shunt area, decreased significantly. Administration of indomethacin caused the rise in PVR without an appreciable change in either QT or extravascular lung water but a considerable diminution in R value for the inert gas. RSF6 after infusion of indomethacin decreased from 0.35 to 0.27, accompanied by a significant rise in arterial PO2 from 84 to 99 Torr. The findings are highly compatible with the idea that HPV is distinctly attenuated in diseases areas induced by oleic acid probably due to a local accumulation of vasodilator prostanoids. Inhibiting prostanoid biosynthesis may selectively enhance the vascular reactivity to O2 in shunt vessels and may redistribute the perfusion from shunt to relatively normal areas, thereby improving gas exchange at alveolar region without altering the total amount of extravascular lung water.

Animals↗

Bactericidal activities of rat defensins and synthetic rabbit defensins on Staphylococci, Klebsiella pneumoniae (Chedid, 277, and 8N3), Pseudomonas aeruginosa (mucoid and nonmucoid strains), Salmonella typhimurium (Ra, Rc, Rd, and Re of LPS mutants) and Escherichia coli.

Rat defensins were purified and tested for in vitro bactericidal assay against gram-positive and gram-negative bacteria. Staphylococcus aureus (209P, Cowan I, Smith diffuse and Smith compact) were resistant to defensins, whereas Staphylococcus epidermidis, Staphylococcus saprophyticus, Micrococcus lysodeikticus and Bacillus subtilis were less sensitive. Gram-negative bacteria, such as Pseudomonas aeruginosa (mucoid and K) and Klebsiella pneumoniae (Chedid, 277, and 8N3 which were heavily capsulated, moderately capsulated and noncapsulated, respectively) were all very sensitive to defensins and killed within 20 min. Escherichia coli was moderately sensitive and the rough mutants of lipopolysaccharide (LPS) of Salmonella typhimurium LT2, such as Ra, Rc, Rd, and Re were equally sensitive to defensins, being killed within 40 min. Lysozyme did not show any bactericidal activity except against M. lysodeikticus and B. subtilis, whereas it enhanced the bactericidal activity of defensins against P. aeruginosa, E. coli, and K. pneumoniae and suppressed the killing activity of defensins against S. typhimurium and S. aureus. With regard to the three synthetic rabbit defensins, NP1, NP4, and NP5, NP1 showed strong bactericidal activity against K. pneumoniae 277, comparable to that of rat defensins. Neither NP4 nor NP5 showed any bactericidal activity, while NP5 rather enhanced the bactericidal activity of NP1 against K. pneumoniae 277.

Animals↗

[Alteration of oxygen extraction and blood flow in various organs under acute hypoxia].

To assess the compensatory mechanisms involved in maintaining aerobic metabolism in various organs during exposure to acute hypoxia, five anesthetized and paralyzed dogs were ventilated with either normoxic (FIO2: 0.21) or hypoxic gas mixture (FIO2: 0.13). Under both conditions, we examined systemic and pulmonary hemodynamic parameters, and took samples of arterial and mixed venous blood as well as venous blood from various organs including the heart, brain splanchic organs (hepatic vein) and kidney. Based on PO2, PCO2 and pH values as measured with electrodes, we calculated O2 and CO2 contents in each blood sample. The values thus obtained were then used to estimate the O2 extraction ratio (ER), gas exchange ratio (R) and difference of base excess between arterial and venous blood (avBE) in the whole body as well as in each organ. In addition, both O2 delivery (DO2) and O2 consumption (VO2) in the whole body were calculated. Although the whole body showed a decrease in DO2 and an increase in ER during hypoxic gas breathing, other parameters including R, avBE and VO2 did not change significantly. Higher ER values were found in the heart and brain than those in the splanchic organs and kidney, the qualitative trend being the same irrespective of FIO2. On the other hand, increase in ER during hypoxic gas breathing was considerably larger in the splanchic organs and kidney than that in the heart and brain. There was no significant difference in R and avBE in any of the organs between normoxic and hypoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Location of peptidoglycan and teichoic acid on the cell wall surface of Staphylococcus aureus as determined by immunoelectron microscopy.

Anti-peptidoglycan (PG) and anti-teichoic acid (TA) antibodies were prepared from sera of rabbits immunized with the cell wall fraction of Staphylococcus aureus Cowan I by the specific adsorption technique with purified teichoic acid or peptidoglycan. The anti-PG antibody recognized the trichloroacetic acid-treated walls (TCA wall) prepared from S. aureus, Bacillus subtilis, and Micrococcus luteus but did not react with teichoic acid or proteins extracted from the cell wall of Staphylococcus. The anti-TA antibody specifically reacted with cell wall teichoic acid of beta-type sugar configuration. The reaction sites of these antibodies on the cell wall of S. aureus Wood 46 were determined by immunoelectron microscopy using colloidal gold as a probe. The anti-TA antibody reacted mostly with the fibrous electron-dense mass on the cell surface. The reaction was also seen on the inner surface of the cell wall. The anti-PG antibody reacted with the fibrous structures and also directly on the cell wall surface. The distribution of the probes on the cell wall surface examined with the scanning electron microscope showed that there was no localized distribution in respect to the cell division. We knew from these observations that the external surface of the cell wall of Staphylococcus is covered with the fibrous mass which consists mostly of teichoic acid but partially of peptidoglycan.

Antibodies, Bacterial↗

Distribution of ventilation and of diffusing capacity to perfusion in the lung.

We developed a method for estimating the distribution of ventilation (VA) and of diffusing capacity (G) to perfusion (Q) in the lungs. We used O2, CO2 and CO together with six inert gases of widely differing solubility and assumed that mass transfer efficiency of each gas in a gas exchange unit is limited by both VA/Q and G/Q ratios. The underlying lung model comprised 20 units along both the VA/Q and G/Q axes. Using numerical analysis, we transformed the data into a virtually continuous distribution of Q in the VA/Q-G/Q field. We tested the precision of the numerical procedure by examining the recovery of various artificial distributions, and found that distributions with up to two modes could be recovered with reasonable accuracy. Analytical results from 15 patients with interstitial pneumonia of unknown etiology (IPF) revealed the following features. (1) In an early disease stage, most of the lung was operating in the range of normal VA/Q, without a significant contribution of diffusion limitation. (2) An advanced stage of the disease exhibited a widening of VA/Q distribution and either broad unimodal or bimodal distribution of G/Q, extending to G/Q below 10(-3) ml (STPD)/(ml.Torr) with diffusion-limited O2 exchange. (3) Severe diffusion limitation causing disequilibrium of inert gas across the blood-gas barrier was observed in three (far advanced fibrosis; active interstitial inflammation) out of 15 patients. These findings suggest that inhomogeneity of G/Q does exist and may play an appreciable role in causing impairment of gas exchange in patients with interstitial pneumonia.

Animals↗

Accumulation of phosphate-containing granules in the nucleoid area of Pseudomonas aeruginosa.

Many electron-dense granules were found in the nucleoid area of Pseudomonas aeruginosa strain K by electron microscopy with the technique of the freeze-substitution method. These granules contained phosphorus and calcium as determined by X-ray microanalysis. The size and the numbers of the granules decreased when the bacteria was cultured in the medium from which phosphate-containing compounds were depleted. From these observations we concluded that the granule was a phosphate-containing granule and possibly a polyphosphate granule. The excellent preservation of the fine structures by the freeze-substitution technique enables us to show very small polyphosphate granules in the nucleoid area of the bacterial cells which cannot be revealed by the conventional chemical fixation method. As we could not see the granules in other bacteria cultured in nutrient medium such as Serratia, Escherichia, Bacillus and Vibrios, the accumulation of the phosphate granules in Ps. aeruginosa might be a unique character of this bacteria and might be related to the growing capability of this bacteria in extremely low nutrient supply.

Cytoplasmic Granules↗

Distribution of capsular materials on the cell wall surface of strain Smith diffuse of Staphylococcus aureus.

The fine structure of the capsule of Staphylococcus aureus Smith diffuse was examined by the technique of freeze-substitution and immunoelectron microscopy. The cell surface was covered with a thick layer consisting of fine fibrous structures which were absent from an unencapsulated strain, Smith compact. Anti-teichoic acid antibody did not react with this surface layer but reacted with the surface of strain Smith compact. Anti-capsular antibody, made from the serum of a rabbit immunized with strain Smith diffuse and specific absorption with unencapsulated strain Wood 46, reacted with the fibrous layer of the Smith diffuse strain. Since the anti-teichoic acid antibody did not react with the encapsulated strain Smith diffuse, the capsular layer acts as a barrier to penetration of the anti-teichoic acid antibody through the capsular layer. A portion of a few cell surfaces of the encapsulated strain remained accessible to the anti-teichoic acid antibody. The capsular layer in this portion of the cell surface was thin, and this surface seemed to be a new cell wall surface created by the cell separation.

Bacterial Adhesion↗

[Two cases of primary lung cancer with initial symptoms due to ocular metastases].

Two cases of primary lung cancer with initial symptoms due to metastasis to the eye or the orbit are reported. Case 1 had orbital metastasis, while case 2 had intraocular metastasis. It has been reported that the survival period is short after the metastasis was found. In our cases, the survived periods for case 1 and case 2 were 3.5 months and one month, respectively.

Adenocarcinoma↗

[Impairment of gas exchange in acute lung injury].

To demonstrate the characteristics of impaired gas exchange in acute respiratory distress syndrome (ARDS), an experimental model of lung injury was produced in 24 mongrel dogs by intravenously injecting 0.07 ml/kg of oleic acid. While allowing the animal to breathe a mixture of 0.1% CO in air, normal saline, which contained appropriate amounts of six inert gases such as SF6, ethane, cyclopropane, halothane, ether and acetone, was infused at a constant rate through a peripheral vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were taken simultaneously. The concentrations of the nine indicator gases (O2, CO2, CO and six inert gases) in the samples were measured in terms of a gas chromatograph, permitting analysis of the distribution of ventilation to perfusion (VA/Q) as well as the diffusing capacity to perfusion (G/Q) in injured lungs. To determine the role of hypoxic pulmonary vasoconstriction (HPV) in maintaining gas exchange in ARDS, hemodynamic and gas-exchange parameters were investigated at inspired O2 concentrations (FIO2) of either 21 or 60%. The impairment of gas exchange was examined by measuring the fractional retention (R) of the inert gases in arterial blood. Furthermore, to assess the possible contribution of vasoactive prostanoids in regulating vascular reactivity in ARDS, observations at FIO2 of 60% were repeated after administered indomethacin at a dose of 5 mg/kg. Analytical results revealed that shunt flow in experimental dogs with lung damage caused by oleic acid averaged 17%. Furthermore, widening of VA/Q distribution was found accompanied with significant contribution of extremely low VA/Q areas. In addition, most of the lung was operating in G/Q units with values ranging from 10(-3) to 10(-2) but 9.8% of total Q(QT) was received by the area with G/Q less than 10(-3), which might limit O2 exchange between the alveolar gas phase and capillary blood. Although pulmonary vascular resistance (PVR) in injured lungs observed at FIO2 of 60% was significantly smaller than the value obtained at FIO2 of 21%, QT as well as extravascular lung water did not differ in the two conditions. The R value for the indicator gas was consistently lower at FIO2 of irrespective of gas species. Administration of indomethacin caused a considerable diminution of the R value for inert gas but a rise in PVR without an appreciable change of either QT or extravascular lung water. This was followed by a significant rise in arterial PO2 from 84 to 99 Torr.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗