S-nitrosoglutathione (SNOG) accumulates hypoxia inducible factor-l alpha in main pulmonary artery endothelial cells but not in micro pulmonary vessel endothelial cells.
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Cell Line↗
Biomedical subjects
S Osanai
Publications and source records attributed to S Osanai.
Doxapram inhibits carotid sinus baroreceptors in rabbits.
1 To clarify the effects of doxapram on the baroreflex, we recorded carotid sinus nerve (CSN) activity in isolated and perfused carotid artery bifurcations of rabbits. 2 The CSN activity due to chemoreceptor stimulation was blocked by resection of the nerve branches from the carotid body. After the resection, the CSN activity was correlated to increase of carotid sinus (CS) pressure. 3 Administration of doxapram reduced the CSN activity originating from baroreceptors. The effect of doxapram on baroreceptors was dose dependent and reversible. 4 It is unlikely that doxapram altered CS wall mechanics because CS pressure did not change in the presence of the drug. 5 We conclude that doxapram acts on the cardiovascular system in part by inhibiting the negative feedback loop that originates in CS baroreceptors.
Animals↗
Extrinsic allergic alveolitis induced by the yeast Debaryomyces hansenii.
A 65-yr-old female developed cough, fever and dyspnoea following repeated exposure to a home ultrasonic humidifier. High-resolution computed tomography showed ground-glass opacity in both lung fields. Arterial blood gas analysis gave an oxygen tension of 8.38 kPa (63 Torr). Pulmonary function testing revealed restrictive ventilatory impairment with a reduction in the diffusing capacity. The diagnosis of extrinsic allergic alveolitis (EAA) was confirmed by radiographic findings, pathological evidence of alveolitis and reproductive development by a provocation test to the humidifier water. The yeast Debaryomyces Hansenii was the only microorganism cultured from the water of the humidifier. The double diffusion precipitating test and lymphocyte proliferative response was positive for an extract of D. Hansenii, providing evidence to incriminate this fungus. This is the first described case of EAA caused by D. Hansenii.
Aged↗
Conditions for chiral asymmetry generation in the preparation of the chiral octahedral cobalt complex.
We have reported that the random chiral asymmetry generation, which is a spontaneous preferential generation of one enantiomer, was observed in the synthesis of a chiral octahedral cobalt complex, cis-[CoBr(NH(3))(en)(2)]Br(2). In this article, we review our studies to explain in this system the autocatalytic growth of small enantiomeric excess that arises due to statistical fluctuations. One important experimental finding was that the rate of chiral autocatalysis increased with increasing the degree of supersaturation. Furthermore, our numerical simulation indicates that even small inhomogeneities in the reaction system may play a significant role because their effect is amplified by the autocatalytic reaction under appropriate conditions. In a small volume, fluctuations in concentration can grow if the autocatalytic growth overcomes the diffusional loss of the excess concentration from this volume. This may makes the enantiomeric excess of the chiral complex randomly fluctuate from run to run.
Journal Article↗
Hypoxic ventilatory depression in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.
We describe a case of a 21-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) who presented with hypoxic ventilatory depression. He had chronic hypoventilation, which was not explained by weakness of respiratory muscles. His hypercapnic ventilatory response was not impaired. In contrast, hypoxic ventilatory depression was observed in the isocapnic progressive hypoxic response test. After exposure to hypoxic conditions, his respiratory frequency decreased and tidal volume was unchanged. The hypoxic ventilatory depression was partially blocked by pretreatment with aminophylline. In conclusion, we need to be careful with patients with MELAS who are hypoxaemic because a vicious circle of hypoxia and hypoventilation can occur.
Adenosine↗
Flow-mediated release of nitric oxide in isolated, perfused rabbit lungs.
The effects of changing perfusate flow on lung nitric oxide (NO) production and pulmonary arterial pressure (Ppa) were tested during normoxia and hypoxia and after N(G)-monomethyl-L-arginine (L-NMMA) treatment during normoxia in both blood- and buffer-perfused rabbit lungs. Exhaled NO (eNO) was unaltered by changing perfusate flow in blood-perfused lungs. In buffer-perfused lungs, bolus injections of ACh into the pulmonary artery evoked a transient increase in eNO from 67 +/- 3 (SE) to 83 +/- 7 parts/billion with decrease in Ppa, whereas perfusate NO metabolites (pNOx) remained unchanged. Stepwise increments in flow from 25 to 150 ml/min caused corresponding stepwise elevations in eNO production (46 +/- 2 to 73 +/- 3 nl/min) without changes in pNOx during normoxia. Despite a reduction in the baseline level of eNO, flow-dependent increases in eNO were still observed during hypoxia. L-NMMA caused declines in both eNO and pNOx with a rise in Ppa. Pulmonary vascular conductance progressively increased with increasing flow during normoxia and hypoxia. However, L-NMMA blocked the flow-dependent increase in conductance over the range of 50-150 ml/min of flow. In the more physiological conditions of blood perfusion, eNO does not reflect endothelial NO production. However, from the buffer perfusion study, we suggest that endothelial NO production secondary to increasing flow, may contribute to capillary recruitment and/or shear stress-induced vasodilation.
Acetylcholine↗
Role of airway nitric oxide on the regulation of pulmonary circulation by carbon dioxide.
The effects of hypercapnia (CO(2)) confined to either the alveolar space or the intravascular perfusate on exhaled nitric oxide (NO), perfusate NO metabolites (NOx), and pulmonary arterial pressure (Ppa) were examined during normoxia and progressive 20-min hypoxia in isolated blood- and buffer-perfused rabbit lungs. In blood-perfused lungs, when alveolar CO(2) concentration was increased from 0 to 12%, exhaled NO decreased, whereas Ppa increased. Increments of intravascular CO(2) levels increased Ppa without changes in exhaled NO. In buffer-perfused lungs, alveolar CO(2) increased Ppa with reductions in both exhaled NO from 93.8 to 61.7 (SE) nl/min (P < 0.01) and perfusate NOx from 4.8 to 1.8 nmol/min (P < 0.01). In contrast, intravascular CO(2) did not affect either exhaled NO or Ppa despite a tendency for perfusate NOx to decline. Progressive hypoxia elevated Ppa by 28% from baseline with a reduction in exhaled NO during normocapnia. Alveolar hypercapnia enhanced hypoxic Ppa response up to 50% with a further decline in exhaled NO. Hypercapnia did not alter the apparent K(m) for O(2), whereas it significantly decreased the V(max) from 66.7 to 55.6 nl/min. These results suggest that alveolar CO(2) inhibits epithelial NO synthase activity noncompetitively and that the suppressed NO production by hypercapnia augments hypoxic pulmonary vasoconstriction, resulting in improved ventilation-perfusion matching.
Animals↗
Spontaneous rupture of the amyloid spleen in a case of usual interstitial pneumonia.
We describe a rare case of secondary amyloidosis associated with usual interstitial pneumonia (UIP), who died from spontaneous rupture of the amyloid spleen. A 68-year-old man was admitted to evaluate to his interstital lung disease. Chest radiography showed reticular shadow in bilateral lower lung fields. Two years later, he suddenly felt severe abdominal pain. In spite of maximum therapy, he died from hypovolemic shock. Postmortem examination revealed massive intraabdominal hemorrhage. The diagnosis of lung disease was UIP and amyloid A type deposits were observed in various organs including the ruptured spleen.
Aged↗
[Effectiveness of a new toothbrush with irrigation and suctioning capabilities (ty e-Brush) for removing supragingival plaque].
Patients with dysphagia typically have poor oral health. Because of improper swallowing, they cannot easily and safely clean their mouths. As a solution for such a problem, a manual toothbrush with both irrigation and suctioning functions has been developed, called the "e-Brush". The purpose of this study was to evaluate the cleaning effectiveness of the new e-Brush (9 mm and 11 mm in bristle length) for removing supragingival plaque, compared with a conventional toothbrush, GUM # 211 by Butler. In this study, 12 subjects (12 female of average age 20.6) were selected, and plaque control record (PCR) and scrubbing method were used. The following results were obtained: 1. Significant differences (p < 0.05) were recognized between e-Brush/9 mm (55.54 +/- 18.27%) and the others (e-Brush/11 mm: 30.88 +/- 8.14%, GUM # 211: 35.42 +/- 9.32%). 2. Bristles 9 mm in length were more effective than 11 mm bristles (p < 0.05). 3. Irrigation/suctioning function is more effective than the conventional tooth-brushing method. 4. The irrigation function of e-Brush was meritorious in making almost all users comfortable. These results suggest that this new oral hygiene device, "e-Brush/9 mm", is effective for improving oral care management for patients with dysphagia.
Adult↗
Sequence analysis and expression of the P450 aromatase and estrogen receptor genes in the Xenopus ovary.
Recent studies point to a key role for the estrogen synthesizing enzyme P450 aromatase (P450 arom) in ovary determination in fish, birds and reptiles. It is unclear whether estrogen synthesis is important in sex determination of Xenopus gonad. To determine whether the aromatase gene is transcribed in the gonads of Xenopus tadpoles during the sex determination, we cloned a P450 arom cDNA and examined the level of P450 arom and estrogen receptor (ER) gene expression in association with estrogen activity. cDNA clones for P450 arom were isolated from a Xenopus ovarian cDNA library. There was an open reading frame (ORF) of 1500 bp from the ATG start to TAA stop codons encoding 500 predicted amino acids. cDNAs for P450 arom have previously been cloned from various vertebrates. The homology between the Xenopus P450 aromatase and the human P450 arom was higher. The expression of the P450 arom gene was mainly limited to reproductive organs. To determine the beginning of estrogen activity in gonads of embryos, expression of the aromatase and ER gene was also examined by RQ-RT-PCR. Both Xenopus aromatase and ER mRNA was detected at stage 51 in gonads. These observations are consistent with estrogens having a key role in ovarian development in various other vertebrates.
Amino Acid Sequence↗
The metabolic hypothesis revisited.
High levels of CO are used to mimic the stimulatory response of the CSN initiated by hypoxia. Using light of different wavelengths we show that the stimulatory effects of high CO can be pinpointed to the cytochrome c oxidase in the mitochondrial respiratory chain. This supports the metabolic theory of oxygen sensing in the mitochondria.
Animals↗
Effects of complexation between liposome and poly(malic acid) on aggregation and leakage behaviour.
The design and development of novel pH-sensitive liposomes were investigated to improve the release of liposome-encapsulated chemicals. Stable liposomes comprising of L-alpha-dipalmitoylphosphatidylcholine (DPPC) and poly(carboxylic acid) were prepared and characterized. Poly(malic acid) (PMLA) was chosen as a fusogen, because of its excellent biodegradability in physiological regions. Octyl groups introduced in the poly(malic acid) worked as anchors at the surface of the liposomes and made a remarkable contribution to complexing. The interaction between the liposomes and the polyacids was studied in terms of the change in size of the liposomes. The influences of molecular weight and amounts of polymer upon their characteristics, especially fusion, were discussed. The influences of pH change with respect to the association behavior of the liposomes such as aggregation and fusion were estimated by the particle size of the liposomes, turbidimetry of the solution and resonance energy transfer assay. From the results of these studies, it was shown that more tightly complexed liposomes aggregated and fused more positively with increasing acidity of the solution. The leakage of calcein entrapped in the inner aqueous phase of the liposomes increased with decreasing pH. The effect of pH on the liposome aggregation in a solution qualitatively paralleled that found in the leakage behavior.
Drug Carriers↗
Reduced nasal nitric oxide in diffuse panbronchiolitis.
Diffuse panbronchiolitis (DPB) is a pulmonary disease of unknown origin with inflammation in the respiratory bronchioles, bronchiectasis, and recurrent sinusitis. Patients with DPB suffer from chronic airway infections resulting from mucociliary dysfunction. Whereas a high concentration of nasal nitric oxide (NO) has been documented in healthy subjects, only two diseases are known to reduce nasal NO: primary ciliary dyskinesia syndrome and cystic fibrosis. We hypothesized that patients with DPB have abnormal levels of nasal NO. To test our hypothesis, we measured NO with the chemiluminescence technique. Air was sampled directly from the nose in 15 healthy subjects and eight patients with DPB. Nasal NO was 88% lower in DPB patients than in the age-matched control subjects (69 +/- 70 versus 556 +/- 87 nl/min; p < 0.001). Treatment with erythromycin for 2 wk did not alter the nasal NO in four control subjects. DPB is the third pulmonary disease in which nasal NO is low. The reduced nasal NO may well be involved in the pathogenesis of DPB, and NO measurements may serve as a noninvasive test in the diagnosis of DPB.
Adult↗
Extensively calcified hemangioma of the diaphragm with increased 99mTc-hydroxymethylene diphosphonate uptake.
A 31-year-old woman visited an out-patient clinic, because of low-grade fever and general fatigue. She was referred to our hospital and admitted for examination of an abnormal shadow which had been found on the chest radiograph. She had experienced faint right lateral chest pain several times on the deep inspirations. Chest radiography showed a mass shadow with calcification in the right lower lung field on the mediastinal side. Chest radiographic computed tomography showed a 6x6 cm tumor in the right lung field. There were low-density areas with septae inside the tumor. Bone scintigraphy showed extremely high uptake of (99m)Tc-HMDP in the tumor. After surgical resection and pathological examination, we concluded that the tumor was an extensively calcified benign hemangioma of the diaphragm.
Adult↗
[Exhaled nitric oxide].
We introduce the standard method of measurement of nitric oxide recommended by American thoracic society in 1999 and report the results of exhaled NO and nasal NO in patients with obstructive sleep apnea syndrome(OSAS). Our data showed lower exhaled NO output in the patients with OSAS than that of normal volunteers(NV) and that of patients with simple obesity(SO). On the other hand, nasal NO in the OSAS patients is higher than that of NV and that of SO patients. Also, there were significant relationships between apnea index and exhaled NO and between desaturation during sleep and nasal NO. These findings suggested that NO from lower and upper airway will be a non-invasive maker of sleep disordered breathing in future.
Breath Tests↗
Regulation of pulmonary circulation by alveolar oxygen tension via airway nitric oxide.
The effects of airway (AH) and vascular hypoxia (VH) on the production of nitric oxide (NO; VNO) were tested in isolated buffer-perfused (BFL) and blood-perfused rabbit lungs (BLL). To produce AH and/or VH, the lung was ventilated with 1% O(2) gas, and/or the perfusate was deoxygenated by a membrane oxygenator located on the inlet limb to the pulmonary artery. We measured exhaled NO (VNO), accumulation of perfusate NOx, and pulmonary arterial pressure (Ppa) during AH (inspired O(2) fraction = 0.01) and/or VH (venous PO(2) = 26 Torr). In BFL, a pure AH without VH caused decreases in VNO and NOx accumulation with a rise in Ppa. However, neither VNO, NOx accumulation, nor Ppa changed during VH. Similarly, in BLL, only AH reduced VNO, although NOx accumulation was not measurable because of Hb. When alveolar PO(2) was gradually reduced from 152 to 0 Torr for 20 min, AH reduced VNO curvilinearly from 73.9 +/- 8 to 25.6 +/- 8 nl/min in BFL and from 26.0 +/- 2 to 5. 2 +/- 1 nl/min in BLL. This plot was analogous to that of a substrate-velocity curve for an enzyme obeying Michaelis-Menten kinetics. The apparent Michaelis-Menten constant for O(2) was calculated to be 23.2 microM for BLL and 24.1 microM for BFL. These results indicate that the VNO in the airway epithelia is dependent on the level of inspired O(2) fraction, leading to the tentative conclusion that epithelial NO synthase is O(2) sensitive over the physiological range of alveolar PO(2) and controls pulmonary circulation.
Animals↗
Depression of peripheral chemosensitivity by a dopaminergic mechanism in patients with obstructive sleep apnoea syndrome.
In the present study, respiratory drives to chemical stimuli and peripheral chemosensitivity were evaluated in patients with obstructive sleep apnoea (OSAS). The effects of oral administration of domperidone, a selective dopamine D2-receptor antagonist, were also examined, to study the respiratory effects of endogenous dopamine on peripheral chemoreceptors. Sixteen patients with OSAS and nine normal control subjects were studied. Respiratory responses to hypercapnia and hypoxia were measured using the rebreathing method and isocapnic progressive hypoxia method, respectively. The hypoxic withdrawal test, which measures the decrease in ventilation caused by two breaths of 100% O2 under mild hypercapnic hypoxic conditions (end-tidal oxygen and carbon dioxide tensions approximately 8.0 kPa and 5.3-6.7 kPa, respectively), was used to evaluate peripheral chemosensitivity. In the patients with OSAS, ventilatory responses to hypercapnia and hypoxia were significantly decreased compared with those of control subjects. Hypoxic withdrawal tests showed that peripheral chemosensitivity was significantly lower in patients with OSAS than in normal subjects. Hypercapnic ventilatory response and peripheral chemosensitivity were enhanced by administration of domperidone in the patients with OSAS, although no changes in either of these were observed in the control subjects. The hypoxic ventilatory response and peripheral chemosensitivity in the patients with OSAS were each significantly correlated with severity of hypoxia during sleep. These findings suggest that peripheral chemosensitivity in patients with obstructive sleep apnoea syndrome may be decreased as a result of abnormality in dopaminergic mechanisms and that the reduced chemosensitivity observed in patients with obstructive sleep apnoea syndrome may affect the severity of hypoxia during sleep.
Adult↗
High PCO does not alter pHi, but raises [Ca2+]i in cultured rat carotid body glomus cells in the absence and presence of CdC12.
We measured the effect of high PCO (500-550 Torr) on the pHi and [Ca2+]i in cultured glomus cells of adult rat carotid body (CB) as a test of the two models currently proposed for the mechanism of CB chemoreception. The metabolic model postulates that the rise in glomus cell [Ca2+]i, the initiating reaction in the signalling pathway leading to chemosensory neural discharge, is due to [Ca2+] release from intracellular Ca2+ stores. The membrane potential model postulates that the rise in [Ca2+]i comes from influx of extracellular Ca2+ through voltage-dependent Ca2+ channels (VDCC) of the L-type. High PCO did not change pHi at PO2 of 120-135 Torr, showing that CO-induced changes in [Ca2+]i are not due to changes in pHi. High PCO caused a highly significant rise in [Ca2+]i from 90+/-12 nM to 675+/-65 nM, both in the absence and in the presence of 200 microM CdCl2, a potent blocker of L-type VDCCs. This result is fully consistent with release of Ca2+ from glomus cell intracellular stores according to metabolic model, but inconsistent with influx of extracellular Ca2+ through VDCCs according to the membrane potential model.
Animals↗