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Biomedical subjects

T Bando

Publications and source records attributed to T Bando.

At least 19 recordsLinked to original sources

Influence of the perfusate temperature on lung preservation: is there an optimum?

The optimal temperature of the pulmonary flush perfusate is still a matter of controversy. At present, a temperature of 10 degrees C is favored. This study deals with the structural and functional impact of different perfusate temperatures on lung preservation. In an extracorporeal rat heart-lung model lungs were preserved with Perfadex solution of 4, 15 and 25 degrees C and submitted to 2 h ischemia. Heart-lung blocks harvested from male rats were perfused with Krebs-Henseleit solution and ventilated with room air. Lungs were perfused with deoxygenated perfusate via the working right ventricle while the coronary arteries were retrogradely perfused with oxygenated perfusate. Oxygenation capacity (dPO2), peak inspiratory pressure (PIP) and pulmonary vascular resistance were measured. After establishment of baseline functional parameters hearts were arrested with 10 ml St. Thomas cardioplegia and lungs were flushed with 20 ml Perfadex solution. The heart-lung block was then stored for 2 h at 10 degrees C. Reperfusion was performed thereafter under the same conditions. At the end of the trial the lung tissue water was measured by the wet/dry ratio. The perfusion time of the groups flushed with 15 or 25 degrees C perfusate was significantly lower than that of the 4 degrees C group. After 20 min reperfusion dPO2 of the groups flushed with 15 or 25 degrees C was superior to those submitted to a 4 degrees C flush perfusion. PIP was significantly lower in the 15 degrees C group than in the 4 and 25 degrees C groups. The wet/dry ratio revealed the smallest water content in the 15 degrees C group. We conclude that the post-ischemic lung function is dependent on the temperature of the flush perfusate. Among the tested temperatures, perfusion at 15 degrees C showed the best results. The optimum may therefore lie in this range.

Animals

Ultrastructural changes in canine lung preserved in newly developed solutions.

The present study was undertaken to clarify the effect of differences in the ionic composition of a preservation solution by investigating ultrastructures of pulmonary endothelial cells and oxygenation ability of preserved lungs after reperfusion. The relation between the ultrastructural changes and the oxygenation ability was also examined. Canine lungs flushed with an extracellular-type (ET)-Kyoto solution (group A, n = 6), with an intracellular-type-Kyoto solution and prostaglandin El (group B, n=6), or with Euro-Collins solution and prostaglandin E1 (group C, n=6) were stored at 4 degrees C for 20 hr. In transmission electron microscopic findings, the frequency of ultrastructural changes (protrusion of endothelial cells and cellular vacuolization) was significantly less in group A (23.3 +/- 9.1 and 13.3 +/- 5.2%, respectively) than in group B (64.4 +/- 6.1 and 42.2 +/- 8.8%, respectively). In group A, PaO2 after 40, 70, and 130 min of reperfusion was uniformly excellent (289.4 +/- 5.7, 303.3 +/- 7.0, and 303.0 +/- 19.6 mm Hg, respectively) and significantly higher than in groups B and C (202.6 +/- 32.0 and 185.9 +/- 23.0 mm Hg, respectively) after 70 min and higher than in group C (155.7 +/- 36.3 mm Hg) after 130 min of reperfusion. A negative correlation was noted between the frequency of cellular vacuolization and the PaO2 after reperfusion. These results indicated that extracellular ion composition has significantly better effect on pulmonary vascular ultrastructures than intracellular ion composition. This may be a factor making ET-Kyoto solution superior to the other two solutions in oxygenation ability after reperfusion. When attempting to develop better lung preservation solution, the ability to preserve the ultrastructures of preserved lung may be an important consideration in the evaluation.

Animals

Modulation of sensitivity to mitomycin C and a dithiol analogue by tempol in non-small-cell lung cancer cell lines under hypoxia.

We examined the mechanisms involved in the bioactivation of mitomycin C (MMC) and a newly developed MMC analogue: 7-N-(2-([2-(gamma-L-glutamylamino)ethyl]dithio)ethyl)mitomycin C, KW-2149, in non-small-cell lung cancer (NSCLC) cell lines under aerobic and hypoxic conditions. To investigate these mechanisms, we used MMC-resistant non-small-cell lung cancer cell lines (PC-9/MC4) that had been established in our laboratory from the parent PC-9 cell line by continuous exposure to MMC. We previously reported that the MMC-resistant cell line (PC-9/MC4) was poor in NAD(P)H dehydrogenase (quinone) activity and approximately 6-fold more resistant than the parent cells (PC-9) to MMC on 2-h exposure under aerobic conditions. In this study, the subline PC-9/MC4 was 6.7-fold more resistant to MMC than PC-9, the parent cell line, under aerobic conditions, and 5.2-fold more resistant under hypoxic conditions after 2-h exposure to MMC. However, on co-incubation with tempol, an inhibitor of the one-electron reduction pathway, the sensitivity of PC-9/MC4 to MMC was impaired under hypoxic conditions, but the impairment was not evident under aerobic conditions. KW-2149, the newly developed MMC analogue, was cytotoxic for both PC-9/MC4 and PC-9 cells, and the sensitivity of both cell lines to KW-2149 was not changed by exposure to hypoxic conditions or by coincubation with tempol. There were no significant differences in the intracellular uptake of MMC and the activities of cytosolic detoxification enzymes between the PC-9 and PC-9/MC4 cell lines. These results support the hypothesis that the one-electron reduction pathway plays a partial role in the bioactivation of MMC, but not of KW-2149, and that KW-2149 is excellent at circumventing resistance to MMC in NSCLC.

Antineoplastic Agents

Analysis of thrombocytopenia due to carboplatin combined with etoposide in elderly patients with lung cancer.

Thrombocytopenia induced by carboplatin combined with etoposide for elderly lung cancer patients was analyzed in relation to the predicted thrombocytopenia by the equations advocated by Egorin et al. and Taguchi et al. The thrombocytopenia actually observed was strongly correlated with and significantly more severe than that predicted if carboplatin had been administered as a single agent. The AUC (area under the curve) of carboplatin predicted by Calvert's equation significantly affected the degree of thrombocytopenia. These data suggested that dosing of carboplatin should be determined individually on the basis of renal function, as recommended earlier. The reason for the enhancement of thrombocytopenia is yet to be determined in future trials.

Aged

ET-Kyoto solution for 48-hour canine lung preservation.

BACKGROUND: ET-Kyoto (ET-K) solution, proven safe for 20-hour lung preservation, was modified to achieve longer preservation: ET-K2 solution with more buffer capacity and ET-K3 with less potassium. METHODS: Lungs were preserved with one of the three solutions (with prostaglandin E1 at 4 degrees C for 48 hours (n = 5 for each). Left lung transplantation was performed and evaluated for 6 hours. RESULTS: Each solution became acidic after preservation (p < 0.01), though the change was lowest in the ET-K2 solution. All animals in the ET-K and ET-K3 groups survived for 6 hours after reperfusion, but only 1 survived in the ET-K2 group (p < 0.05). In all groups, partial pressure of oxygen in arterial blood decreased gradually after reperfusion. Pulmonary vascular resistance after reperfusion was significantly lower in the ET-K group than in the ET-K3 group (p < 0.01). Scanning electron microscopic examination showed that endothelial cell swelling and disruption were milder in the ET-K group (with the solution containing potassium of 44 mEq/L) than in the ET-K3 group. CONCLUSION: Lung preservation can be achieved for 48 hours in ET-K and ET-K3 solutions. Enhancement of buffer capacity provides no advantage. Potassium at 44 mEq/L does not cause deterioration of endothelial cells.

Animals

Effective 30-hour preservation of canine lungs with modified ET-Kyoto solution.

BACKGROUND: With the aim of developing a preservation solution that can preserve donor lungs reliably for a long time, we prepared a modified ET-Kyoto solution by adding N-acetylcysteine, nitroglycerin, and dibutyryl adenosine 3', 5'-cyclic phosphate to the previously reported ET-Kyoto solution, which contains trehalose, gluconate, and hydroxyethyl starch. In this study, we examined the efficacy of modified ET-Kyoto solution in 30-hour lung preservation. METHODS: Twenty five pairs of adult mongrel dogs were divided into four groups. Donor lungs were flushed with modified ET-Kyoto solution (n = 9), with ET-Kyoto solution (n = 6), with University of Wisconsin solution group (n = 6), or with ET-Kyoto solution plus the solvents of nitroglycerin (ethanol and propylene glycol) (n = 4), then stored at 4 degrees C for 30 hours. All animals were treated with prostaglandin E1. Left lungs were transplanted and reperfused for 6 hours. RESULTS: With respect to arterial oxygen tension, peak inspiratory pressure, and wet-to-dry lung weight ratio, modified ET-Kyoto solution was significantly superior to ET-Kyoto solution. The modified ET-Kyoto solution was significantly superior to University of Wisconsin solution with respect to survival rate, arterial oxygen tension, and wet-to-dry lung weight ratio. Ultrastructural findings supported these results. CONCLUSIONS: These results suggest that modified ET-Kyoto solution is superior to University of Wisconsin solution for 30-hour lung preservation.

Acetylcysteine

Roles of the lateral suprasylvian cortex in convergence eye movement in cats.

Ocular convergence and lens accomodation were evoked by microstimulation in the lateral suprasylvian area (LS cortex) in the parieto-occipital cortex in the cat. Electrolytic lesions in LS cortex reduced the amplitude and velocity of ocular convergence. Neurons in LS cortex discharged in relation to ocular convergence and/or lens accommodation. These results support the hypothesis that the LS cortex plays an important role in controlling ocular convergence The LS cortex receives visual inputs from cortical visual areas 17, 18 and 19, and in addition from the superior colliculus through the LP nucleus of the thalamus. Electrophysiological recordings have revealed that these visual inputs, which include cues about 3-dimensional target motion, are integrated in the LS cortex. The integrated output from LS cortex may provide the brainstem motor centers with the neural signals that facilitate eye movements, especially when the target is moving at high speeds. Outputs from the LS cortex travel directly to brainstem structures including the superior colliculus and pretectum. Evidence from monkey suggests that information may also travel to the mesencephalic reticular formation, where neurons have been recorded that are related to ocular convergence, lens accomodation or both. Although comparable data is lacking in the cat, it is suggested that the efferent circuit from the LS cortex to the motor nuclei in the brainstem included both the superior colliculus and the mesencephalic reticular formation. It is also suggested that this pathway is rather short, given that the mean latency of the early component of evoked disjunctive eye movements was approximately 60 ms.

Animals

Modulation of sensitivity to cis-diamminedichloroplatinum (II) by thromboxane A2 receptor antagonists in non-small-cell lung cancer cell lines.

We examined the effect of selective thromboxane A2 (TXA2) receptor antagonists, calcium 5(Z)-1R, 2S, 3S, 4S-7-[3-phenylsulphonylaminobicyclo [2.2.1] hept-2-yl]-5-heptonoate hydrate (S-1452) and +/- -7-(3,5,6,-trimethyl-1,4-benzoquinon-2-yl)-7-phenylhaptanoic acid (AA-2414), on sensitivity to cis-diamminedichloroplatinum (II) (CDDP) in non-small-cell lung cancer cell lines. IC50 values to CDDP using MTT assay were decreased 2.1- and 4.6-fold respectively by treatment with 250 or 500 microM S-1452, for a 2 h simultaneous drug exposure, and those of PC-9/CDDP, a CDDP-resistant cell line, were decreased 3.1- and 6.1-fold. Sensitivity to carboplatin was also enhanced by the treatment with S-1452. IC50 values to CDDP and carboplatin were decreased by treatment with AA-2414 in a dose-dependent manner. Isobologram analysis showed that the combination of CDDP with S-1452 or AA-2414 produced supra-additive or additive effects in each cell line. Neither glutathione content nor glutathione S-transferase activity was changed in either cell line by treatment with 500 microM S-1452. Accumulation of platinum into PC-9 and PC-9/CDDP was increased by the treatment in a dose-dependent manner. Na+, K+-ATPase activity of PC-9 and PC-9/CDDP was enhanced by the treatment of S-1452 in a dose-dependent manner. These data show that the TXA2 receptor antagonists may enhance the sensitivity of non-small-cell lung cancer cell lines to platinum agents. Increase in Na+, K+-ATPase activity induced by S-1452 may be the mechanism of its sensitising effect through increase in platinum accumulation.

Adenocarcinoma

Changes in oculomotor functions before and after loading of a 3-D visually-guided task by using a head-mounted display.

Changes in visual and oculomotor functions were tested in eight young volunteer subjects after performing a 3-D visually-guided task for 25 min. The visual stimuli were given by using a head-mounted display. No significant change was detected in the AC/A ratio and the stereo acuity. Changes were found in refraction and ocular convergence. Slight but significant hyperopic changes were detected in refraction after the task. The mean amplitude of convergence eye movement elicited by test stimuli after the task was significantly changed in the pooled data. They were significantly reduced when the subjects were tested by the disparity step of 0.7 degrees, but significantly increased when tested by the step of 6 degrees. The mean amplitudes were not significantly changed after the task when the subjects were tested by the intermediate disparity steps of 1.5 and 3 degrees. In data obtained for each subject, the amplitude of ocular convergence evoked by test stimuli after the task was reduced significantly in most subjects. In the majority of subjects, however, the results were not consistently significant when they were tested by step stimuli with different disparities. In only a few subjects, the changes were consistently significant except when the largest disparity was tested. On the other hand, the mean peak velocities of ocular convergence after the task were not significantly changed in the pooled data. In individual subjects, the changes of velocities of ocular convergence evoked by test stimuli after the task were more variable: they increased in some subjects but decreased in other subjects. Consequently, in only one subject, both amplitudes and peak velocities of ocular convergence tested by the disparity steps of 0.7, 1.5 and 3 degrees were consistently reduced after the task. The changes in refraction or ocular convergence found in this study were relatively small, and were not in the pathological range. The significance of these data are discussed. The results of the present study provide the basis for the more detailed analyses of the human factor in the head-mounted display.

Adult

Rhabdomyolysis following status asthmaticus.

A case of rhabdomyolysis following an asthmatic attack is reported. A 71-year-old man was admitted because of wheezing and hypoxemia. Brown urine was present on admission. Although these symptoms completely disappeared with the treatment with aminophylline, salbutamol and corticosteroid, transiently elevated serum creatine phosphokinase and myoglobinuria were present. Rhabdomyolysis has rarely been reported in cases of bronchial asthma. This case represents an extremely rare case of rhabdomyolysis following status asthmaticus.

Aged

[A comparative study on the efficacies of ritipenem acoxil and cefotiam hexetil in bacterial pneumonia by the double-blind method].

To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against bacterial pneumonia, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as the control drug. Both RIPM-AC and CTM-HE were orally administered at 200 mg t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 208, of which 152 cases (RIPM-AC group: 73, CTM-HE group: 79) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent + good) were 91.8% (67/73) in the RIPM-AC group and 94.9% (75/79) in the CMT-HE group. There was no significant difference between the two groups, and the clinical equivalency of RIPM-AC to CTM-HE was demonstrated. 2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 84.6% (22/26) in the RIPM-AC group and 91.7% (22/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 9 cases (9.6%) of the RIPM-AC group and 5 cases (4.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 23 cases (26.7%) of the RIPM-AC group and 15 cases (15.6%) of the CTM-HE group. There was no significant differences between the two groups in the incidence of side effects nor of abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 64 cases (68.1%) and CTM-HE in 82 cases (80.4%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 86.5% (64/74) in the RIPM-AC group and 92.5% (74/80) in the CTM-HE group. There was no significant difference between the two groups. Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of bacterial pneumonia.

Adolescent

[Effects on visual functions following several hours' usage of a head mounted display].

We investigated the effects of viewing video movies with a head-mounted display (HMD) for 4 to 6 hours on visual functions such as refraction, visual acuity, and accommodation-vergence system. Two or three video movies were watched without any breaks by 13 normal volunteers (age: 22 approximately 40). Measurements were made of (1) objective and subjective refraction, (2) corrected visual acuity, (3) tonic level and step response of accommodation with a computer-assisted infrared optometer, and (4) near and far phorias and AC/A ratio. Significant transient myopia was found following 4 hours' viewing, but not following 6 hours' viewing. Scrutinizing individual data, myopia was consistently found in some subjects, and hyperopia in others. We presumed that many subjects might have been influenced by initial instrumental myopia when they adjusted the focus by using the mechanism built in the HMD. No significant change was observed in any other examination. However, there was a tendency for the AC/A ratio to change after a short time, and then to recover to its original value. Based on the results in this study, it appears that some changes in accommodation and vergence systems are caused by viewing video movies with the HMD. Although the amount of changes was within normal physiological variation in this study, the possibility still remains that usage for a longer time may lead to other changes in visual function. Care is also necessary when using the HMD in subjects with subclinical problems.

Accommodation, Ocular

Influence of dextrans on lung preservation: is the molecular weight important?

BACKGROUND: The addition of dextran with a molecular weight of 40,000 Dalton in pulmonary preservation solutions has proved to be beneficial. However, dextrans of other size have not yet been investigated. Therefore, it is unclear whether dextran 40,000 represents the optimal additive for lung preservation solutions. METHOD: In a working rat heart-lung model, lung were preserved with regular Euro-Collins solution or with Euro-Collins solution containing 5% dextran of different sizes: 40,000 Dalton molecular weight; 70,000 Dalton molecular weight; 160,000 Dalton molecular weight. After 2 hours of ischemia functional (oxygenation; pulmonary vascular resistance) and structural (wet/dry-ratio, light microscopy) data were assessed and the amount of dextran in the lung tissue was measured. RESULTS: Lungs preserved with Euro-Collins solution 70,000 Dalton molecular weight or Euro-Collins solution 160,000 Dalton molecular weight exhibited superior functional and structural results when compared with Euro-Collins solution and Euro-Collins solution 40,000 Dalton molecular weight. Additionally, the least amount of dextran in the lung tissue was found in organs preserved with Euro-Collins solution 160,000 Dalton molecular weight after ischemia and reperfusion. CONCLUSIONS: Dextrans are useful additives for lung preservation solutions. However, the size of the molecules is important because dextrans of 160,000 Dalton molecular weight were superior to dextrans of lower molecular weight in our study.

Animals

[Comparative study on the efficacy of ritipenem acoxil and cefotiam hexetil in chronic lower respiratory tract infections by the double-blind method].

To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against chronic lower respiratory tract infections, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as a control drug. RIPM-AC was orally administered at 200 mg, and CTM-HE at 400 mg, t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 202, of which 151 cases (RIPM-AC group: 75, CTM-HE group: 76) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent+good) were 85.3% (64/75) in the RIPM-AC group and 80.3% (61/76) in the CTM-HE group. There was no significant difference between the two groups, hence the clinical equivalency of RIPM-AC to CTM-HE was demonstrated. 2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 50.0% (13/26) in the RIPM-AC group and 75.0% (18/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 10 cases (11.0%) of the RIPM-AC group and 10 cases (10.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 8 cases(9.5%) of the RIPM-AC group and in 14 cases (16.7%) of the CTM-HE group. There were no significant differences between the two groups in the incidence of side effects and abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 73 cases (80.2%) and CTM-HE in 71 cases (77.2%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 79.5% (62/78) in the RIPM-AC group and 76.9% (60/78) in the CTM-HE group. There was no significant difference between the two groups. Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of chronic lower respiratory tract infections.

Adult

Characteristics of antitumor activity of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]- 2(1H)-quinolinone (vesnarinone) against a human adenoid squamous carcinoma-forming cell line grown in athymic nude mice.

The tumors produced by transplantation into nude mice of human adenoid squamous carcinoma-forming cell line TYS, presumably derived from a minor salivary gland, were treated with a differentiation-inducing agent, vesnarinone, which was given per o.s. daily at a dose of 200 mg/kg for 35 days. They were then examined morphologically and immunohistochemically. The vesnarinone treatment resulted in a significant suppression of tumor growth. In addition, tumor nests indicating keratinocyte and acinar cell differentiation were often observed in the treated tumors, but not in untreated controls. Tissue sections from vesnarinone-treated and untreated TYS tumors were stained with monoclonal antibody (NAb) directed to carbohydrate antigen LeY or proliferating cell nuclear antigen (PCNA) and with rabbit polyclonal antibody to p53. Antibody staining patterns were compared with morphological characteristics of cells as revealed by hematoxylin and eosin staining, and DNA fragmentation patterns as revealed by 3'-OH nick-end labelling techniques. Tissue sections from vesnarinone-treated TYS tumors showed positive reaction with nick-end labelling and were extensively stained strongly by anti-LeY MAb, whereas the untreated tumors showed negative reaction with nick-end labelling and were infrequently stained by anti-LeY MAb. Within LeY-positive areas of tissue sections from the vesnarinone-treated tumors, keratinocyte and acinar cell differentiation as well as DNA fragmentation were frequently observed, although not all LeY-positive cells showed such signs of apoptosis. LeY-positive cells showed consistent negative staining by anti-PCNA MAb and anti-p53 rabbit serum. From these findings, it can be considered that vesnarinone has differentiation and apoptosis-inducing activity against TYS cells grown in athymic nude mouse.

Animals