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Biomedical subjects

K Asano

Publications and source records attributed to K Asano.

At least 235 records · Page 13Linked to original sources

Effect of roxithromycin on respiratory bacterial infection in mice.

The effects of roxithromycin (RXM), an antibiotic of the macrolide family, on respiratory bacterial infection in mice were examined. BALB/c mice were administered with RXM orally at a dose of 5.0 or 2.5 mg/kg once per day for 14 days. On day 2 after the final drug administration, the mice were nasally infected with Haemophilus influenzae. RXM dose dependently inhibited the pathological changes in lung tissues induced by H. influenzae infection. RXM also enhanced 2',5'-oligoadenilate synthetase production in response to infection.

Animals↗

[A case of non-small-cell primary lung cancer invading distal aortic arch and left subclavian artery].

A 71-year-old male patient was referred to our institute for abnormal mediastinal shadow. It was proved to be squamous cell carcinoma arising in left S1 + 2 and involving distal aortic arch and left subclavian artery (T4N2M0 Stage IIIB). The cancer responded well to the preoperative induction therapy and it was resected completely with associated resection of distal aortic arch and left subclavian artery. Both arteries were replaced with Dacron grafts. With induction therapy and extended operation, this patient of non small cell T4 primary lung cancer is expected to acquire long term survival.

Aged↗

[Role of serotonin in impaired gas exchange during pulmonary embolism].

Although serotonin has been reported to play a substantial role in cardiopulmonary dysfunction, the quantitative effects of serotonin, released from activated platelets, on the development of alveolar flooding and on impaired gas exchange in pulmonary embolism have not been systematically investigated. To elucidate the effects of serotonin on pulmonary hemodynamics, accumulation of edema fluid in alveolar space, and impairment of gas exchange in acute pulmonary embolism, 20 mongrel dogs were given 0.4-0.6 g/kg of glass beads with a diameter of 100 microns, via the internal jugular vein. Before and after embolization, pulmonary hemodynamics, systemic hemodynamics, blood gases, and the distribution of ventilation-perfusion ratios (VA/Q) in the lung were measured, with and without a newly developed selective antagonist of the serotonin S2 receptor, DV-7028. VA/Q distribution was determined by applying the multiple inert gas elimination technique. After glass-bead embolization, the animals that did not receive DV-7028 showed significant increases in pulmonary arterial pressure and in extravascular lung water, widened alveolar-arterial O2 tension differences, and appreciable development of low VA/Q areas (0 < VA/Q < or = 0.1). These changes were prevented in the animals that received DV-7028. However, DV-7028 did not affect the formation of high VA/Q areas (VA/Q > 10). In conclusion, in acute canine pulmonary embolism serotonin not only induces pulmonary hypertension and pulmonary edema, but also worsens gas exchange through the formation of low VA/Q areas.

Acute Disease↗

[Nitric oxide synthase in lung epithelial cells in culture].

To identify the molecular nature of nitric oxide synthase (NOS) and its regulation and function in the airway, NOS activity and NOS mRNA expression were measured in cultured lung epithelial cell. All epithelial cells exhibited constitutive NOS activity that was calcium-dependent, and inducible, lesser calcium-dependent activity in the presence of interferon-gamma, interleukin-1 beta, tumor necrosis factor-alpha, and lipopolysaccharide. Two distinct NOS mRNA species (neuronal and inducible) were found with the reverse transcription polymerase chain reaction. The co-existence of constitutive and inducible NOS in human alveolar and bronchial epithelial cells indicates that nitric oxide may have many roles in normal and diseased lungs.

Calcium↗

[Acoustic neurinomas with large cystic components: a clinical and pathological study of 3 cases].

Acoustic neurinomas containing cystic parts are fairly common, but it is extremely rare for acoustic neurinomas to be mainly composed of cysts. So far, we have encountered three such cases. We studied these cases retrospectively to correlate their characteristic clinical symptoms and their respective pathological findings. Referring to reviews of the relevant literature and our three cases, we would like to discuss the possible mechanism of cyst formation and clinical symptoms. Compared with the patients with ordinary acoustic neurinomas, the patients in our three cases and in some cases in the literature have some distinct and possibly common clinical features. First of all, in spite of the cysts being large, hearing loss was less severe. Secondly, sudden onset of headache and hearing loss were frequently experienced, probably due to intratumoral hemorrhages. Thirdly, intratumoral hemorrhages with niveau formations were frequently able to be identified on CT or MRI scannings. Histologically, our three cases revealed lots of abnormal sinusoid or telangiectasis vessels. Small hemorrhages, hemosiderin deposits and hemosiderin-containing phagocytes were also more abundant than in solid-type neurinomas. The exact mechanism of the formation of these cysts is still controversial. Our hypotheses concerning the probable causes of cyst formation are presented in this study. In our three cases. the most distinct finding was the presence of abundant abnormal sinusoid or telangiectasis-like vessels. We suggest therefore that, in these cases, repeated small hemorrhages from these abnormal vessels, along with subsequent intratumoral changes, are the most probable cause of the formation of these cysts.

Adult↗

Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation.

Nitric oxide (NO) produced by murine macrophages is important in murine resistance to ectromelia virus, herpes simplex virus, and vaccinia virus infection. In contrast, NO production by human mononuclear cells has been difficult to demonstrate, and a role for NO in human responses to infection is uncertain. We report constitutive, low level, macrophage-type NO synthase (iNOS) expression in Epstein-Barr virus (EBV)-transformed human B lymphocytes and Burkitt's lymphoma cell lines. Immune NOS activity is involved in maintaining EBV latency through down-regulation of the expression of the immediate-early EBV transactivator Zta. NO also inhibits apoptosis in B lymphocyte cell lines. The effects of NO are largely independent of cGMP and influential on signaling pathways regulated by (sulfhydryl) redox status. These results suggest that NO plays a physiological role in human B cell biology by inhibiting programmed cell death and maintaining viral latency.

Adult↗

Inhibition of cytokine production from human peripheral blood leukocytes by anti-allergic agents in vitro.

The influence of anti-allergic drugs on lymphocyte function was investigated by examining the blastic activity and cytokine production of human peripheral blood leukocytes in response to concanavalin A stimulation in vitro. Addition of ketotifen, disodium cromoglycate and oxatomide did not influence peripheral blood leukocyte blastic activity even when high concentrations (10.0 micrograms/ml) of these drugs were added to cell cultures. However, azelastine and terfenadine caused inhibition of peripheral blood leukocyte activation. Interleukin-2, interleukin-3, interleukin-4 and interleukin-5 production from peripheral blood leukocytes was strongly suppressed when the cells were cultured in the presence of these agents. This suppression was observed even when lower concentrations (1.0 and 0.5 micrograms/ml) of these agents were added to the cultures.

Cells, Cultured↗

Constitutive and inducible nitric oxide synthase gene expression, regulation, and activity in human lung epithelial cells.

Histochemical activity and immunoreactivity of nitric oxide synthase (NOS, EC 1.14.13.39) have been recently demonstrated in human lung epithelium. However, the molecular nature of NOS and the regulation and function of the enzyme(s) in the airway is not known. A549 cells (human alveolar type II epithelium-like), BEAS 2B cells (transformed human bronchial epithelial cells), and primary cultures of human bronchial epithelial cells all exhibited constitutive NOS activity that was calcium dependent and inhibitable by the NOS inhibitor NG-monomethyl-L-arginine. Nitric oxide production by epithelial cells was enhanced by culture in the presence of interferon gamma, interleukin 1 beta, tumor necrosis factor alpha, and lipopolysaccharide; the NOS activity expressed under these conditions showed less dependence on calcium, reminiscent of other inducible forms of NOS. Two distinct NOS mRNA species, homologous to previously identified constitutive brain (type I) and inducible hepatic (type II) NOS, were demonstrated by reverse transcription-polymerase chain reaction in all cell lines. Northern analysis confirmed the expression of inducible NOS mRNA. Cell culture with epidermal growth factor, a principal regulator of epithelial cell function, decreased inducible NOS activity by posttranscriptional action but did not affect constitutive NOS activity. The coexistence of constitutive and inducible NOS in human alveolar and bronchial epithelial cells is consistent with a complex mechanism evolved by epithelial cells to protect the host from microbial assault at the air/surface interface while shielding the host from the induction of airway hyperreactivity.

Adenocarcinoma↗

Suppressive effects of IPD-1151T (suplatast-tosilate) on induction of mast cells from normal mouse splenocytes.

The influence of IPD-1151T (suplatast-tosilate) on murine mast cell induction was examined by in vitro cell culture. Splenocytes from BALB/c mice suspended in RPMI-1640 medium supplemented with interleukin-3 were cultured in the presence or absence of IPD-1151T. Half of the total volume of the medium was changed every 4-5 days. The number of mast cells increased with culture time and reached a peak on the 16th day when the cells were cultured without IPD-1151T. However, the growth of mast cells from the splenocyte culture was dose dependently inhibited by IPD-1151T. Furthermore, IPD-1151T inhibited the proliferation of mast cell progenitor cells, IC-2, but not that of splenocytes or mature mast cells.

Animals↗

Muscle energetics in short-term training during hypoxia in elite combination skiers.

Four well-trained combination skiers were studied through pre- and post-training for the effects of short-term intermittent training during hypoxia on muscle energetics during submaximal exercise as measured by Phosphorus-31 nuclear magnetic resonance and maximal aerobic power (VO2max). The hypoxia and training in the cold was conducted in a hypobaric chamber and comprised 60-min aerobic exercise (at an intensity equivalent to the blood lactate threshold), using a cycle ergometer or a treadmill twice a day for 4, consecutive days at 5 degrees C, in conditions equivalent to an altitude of 2000 m (593 mm Hg). No change in VO2max was observed over the training period, while in the muscle energetics during submaximal exercise, the values of phosphocreatine/(phosphocreatine+inorganic phosphate) and intracellular pH were found to be significantly increased by training during hypoxia. During recovery, the time constant of phosphocreatine was found to have been significantly reduced [pre, 27.9 (SD 6.7) s; post, 22.5 (SD 4.7) s, P < 0.01]. The observed inhibition of phosphocreatine as well as that of intracellular pH changes after training during hypoxia and quicker recovery of phosphocreatine in submaximal exercise tests, may indicate improved oxidative capacity (i.e. a high adenosine 5'-triphosphate formation rate) despite the short-term hypoxia training.

Adult↗

Oxidative stress induced by intermittent exposure at a simulated altitude of 4000 m decreases mitochondrial superoxide dismutase content in soleus muscle of rats.

The effects were examined of 6-month intermittent hypobaric (4000 m) exposure on the antioxidant enzyme systems in soleus and tibialis muscles of rats. At the end of the 6-month experimental exposure, the six rats in both the exposed group and the control group were sacrificed. Immunoreactive mitochondrial superoxide dismutase (Mn-SOD) contents were measured as well as the activities of antioxidant enzymes [Mn-SOD, cytosolic SOD (Cu,Zn-SOD), catalase (CAT), and glutathione peroxidase (GPX)]. Thiobarbituric acid-reactive substances (TBARS) were also determined as an indicator of lipid peroxidation. The high altitude exposure resulted in a marked increase in TBARS content in soleus muscle, suggesting increased levels of oxygen free radicals. Conversely, significant decreases in both Mn-SOD content and activity in soleus muscle were noted after exposure. Such trends were not noticed in tibialis muscle. On the other hand, no significant changes in Cu,Zn-SOD, CAT, or GPX were observed in either muscle. These results suggested that the increases in lipid peroxidation were most probably a result of decreased Mn-SOD function which was more depressed in oxidative than in glycolytic muscle.

Altitude↗

Adoptive transfer of protection to Taenia taeniaeformis infection in rats with immune spleen cells.

The effector mechanism of the protection against re-infection with eggs of Taenia taeniaeformis was evaluated in rats by analysing protection dynamics against an ongoing primary infection. Immune spleen cells were prepared from F344 donor rats 10 days after oral inoculation with 200 eggs and used for adoptive transfer experiments. When F344 recipient rats were injected intravenously with immune spleen cells (2 x 10(8)) from 2 to 48 h after a primary egg inoculation, there was a statistically significant reduction in the number of metacestodes recovered at day 30 of the infection. The highest protection figures were obtained in rats given immune cells at 12 or 24 h of the primary infection. The maximum reduction induced with immune cells was 92% when they were injected at 12 h of the ongoing infection. It is strongly suggested that the vulnerable stage of the parasite damaged by immune spleen cells is the initial stage of infection (oncosphere and post-oncosphere stages in the liver within 2 days, especially between 12 and 24 h).

Animals↗

Ventilation-perfusion inequality and diffusion impairment in acutely injured lungs.

To assess the significant role of diffusion impairment and its unequal distribution in acutely injured lungs with alveolar flooding, oleic acid was intravenously injected into twenty-five mongrel dogs. The animals were divided into two groups, A and B. 0.1% CO in air was delivered, as an inspired gas, to the animals of group A. Simultaneously, saline containing a trace amount of six foreign inert gases was infused through a peripheral vein. While allowing the animals in group B to breathe air, saline containing ethylene, acetylene and freon 22 was infused. After injection of oleic acid, group A revealed increase in intrapulmonary shunt accompanied by a marked broadening of ventilation-perfusion (VA/Q) and diffusing capacity-perfusion (G/Q) distributions. A considerable amount of total cardiac output was received by the lung areas with low G/Q ratios where significant diffusion limitation was predicted to occur. Group B showed that excretion of freon 22 (gas with lower diffusivity) in injured lungs was considerably distorted as compared to those of ethylene and acetylene (gases with higher diffusivities), again ascertaining the importance of diffusion limitation in lungs with exudate in alveolar regions.

Animals↗

Pharmacological effects of recombinant human granulocyte colony-stimulating factor modified by polyethylene glycol on anticancer drug-induced neutropenia in mice.

1. To clarify the pharmacological effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) conjugated to polyethylene glycol (PEG), its effects on the number of circulating neutrophils in mice made neutropenic by cyclophosphamide (CPA) or 5-fluorouracil (5-FU) were compared with rhG-CSF lacking PEG. 2. In normal mice, PEG-conjugated rhG-CSF (PEG-rhG-CSF, 10 micrograms protein/kg) induced an increase in neutrophils which lasted for 72 h after injection whereas the effect of rhG-CSF (10 micrograms protein/kg) disappeared by 24 h after injection. 3. In CPA or 5-FU-induced neutropenic mice, PEG-rhG-CSF inhibited neutropenia or accelerated recovery from neutropenia and its potency was higher than that of rhG-CSF. 4. These results indicate that PEG-rhG-CSF has a longer duration of action than rhG-CSF and is more effective in the recovery from neutropenia.

Animals↗