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Biomedical subjects

S Teramoto

Publications and source records attributed to S Teramoto.

At least 199 records · Page 11Linked to original sources

Successful canine bilateral single-lung transplantation after 21-hour lung preservation.

A canine bilateral single-lung transplantation model was used to evaluate 21-hour lung preservation with low-potassium dextran glucose solution. Donor lungs were flushed with low-potassium dextran glucose solution (50 mL/kg), inflated with 100% oxygen (35 mL/kg), and preserved at 8 degrees C. Bilateral single-lung transplantation was performed without using cardiopulmonary bypass. The ischemic times to the right and left lungs were designed to be 3 and 6 hours, respectively, in group 1 (n = 5) and 18 and 21 hours in group 2 (n = 6). After bilateral single-lung transplantation, animals were maintained on a ventilator for 12 hours and lung function, including arterial blood gas and pulmonary hemodynamics, was measured. All 5 dogs in group 1 and 5 of 6 dogs in group 2 completed bilateral single-lung transplantation successfully and survived for 12 hours with excellent lung function. Arterial oxygen tension and mean pulmonary artery pressure were stable during the 12-hour assessment period in both groups and did not differ significantly from donor values. Twelve hours after reperfusion, mean arterial oxygen tension (inspired oxygen fraction = 1.0) was 590 +/- 18 mm Hg in group 1 and 604 +/- 8 mm Hg in group 2. After the 12-hour assessment period, the animals were extubated and immunosuppressed. Two dogs in group 2 survived for 7 and 8 days, respectively, with a mean arterial oxygen tension of 74 mm Hg on room air at 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Synthesis of key analogs of bleomycin A2 that permit a systematic evaluation of the linker region: identification of an exceptionally prominent role for the L-threonine substituent.

The synthesis of a full series of analogs 2b-k of deglycobleomycin A2 (2a) containing systematic variations in the linker domain of bleomycin A2 (1) is described. The agents 2b-k, which are not accessible through structural modification of 1 or 2a, constitute key substructure analogs incorporating deep-seated structural modifications in the linker domain capable of delineating the contribution of the individual backbone substituents to the DNA cleavage efficiency, characteristic DNA cleavage selectivity, and double strand to single strand DNA cleavage ratio. The comparative examination of the DNA cleavage properties of the Fe(II) and Fe(III) complexes of 2a-k upon activation by O2-thiol or H2O2, respectively, revealed several characteristic features and trends. First, none of the substituents affect the characteristic 5'-GC, 5'-GT > 5'-GA DNA cleavage selectivity of bleomycin A2. In contrast, an exceptionally prominent role for the L-threonine substituent and an important role for the C4-methyl substituent of the (2S,3S,4R)-4-amino-3-hydroxy-2-methylpentanoic acid subunit were observed on the DNA cleavage efficiency of the agents. Similarly, the L-threonine substituent was found to substantially increase the ratio of double strand to single strand DNA cleavage events (2-3 times). In a w794 DNA cleavage assay, shortening the linker region by two carbons resulted in an exceptionally large reduction in DNA cleavage efficiency (125 times) and provided an agent that was only 1.3 times more effective than Fe(III) indicating that this deep-seated modification essentially destroys the DNA cleavage capabilities of the agent. The L-threonine substituent contributes in an exceptional manner, and its removal resulted in a 25 times reduction in DNA cleavage efficiency. A substantial contribution was observed for the C4-methyl group on the 4-aminobutanoic acid subunit and its removal resulted in a 7 times reduction in DNA cleavage efficiency. Little effect for the C3-hydroxyl and C2-methyl substituents on the 4- aminobutanoic acid subunit was observed (0-2.5 times) and even their inversion of stereochemistry had little impact on DNA cleavage efficiency or selectivity. Notably, the magnitude of the previously unappreciated L-threonine substituent contribution to the DNA cleavage efficiency and on the ratio of double to single strand DNA cleavage events is the largest effect observed to date including the well recognized disaccharide potentiation (6 times) of the DNA cleavage properties. Consequently, the past role and relative importance of the L-threonine subunit and substituent has been underestimated. Moreover, the cumulative effect of the two important linker chain substituents clearly illustrate that the functional role of this domain is much more important than its simply serving as a linker.

Antineoplastic Agents↗

Effect of adenoviral vector infection on cell proliferation in cultured primary human airway epithelial cells.

Although recombinant adenoviruses are used as vectors for delivering therapeutic genes to the airways of cystic fibrosis (CF) patients, the effects of these vectors on the kinetics of airway epithelial cell growth have not been investigated. We tested whether E1, E3-deleted Ad vectors (Ad5-CMV-lacZ) affect the kinetics of cell proliferation of human airway epithelial cells in primary culture. There was a dose-dependent relationship between the vector multiplicity of infection (moi) and the efficiency of Ad-mediated lacZ gene transfer. Growth curves of cells exposed to vector were shifted to the right as compared to vehicle in a dose-dependent manner. The vector-induced slowing of cell proliferation resulted from both (i) increased apoptotic cell death and (ii) lower recruitment into S phase. UV inactivation of the vector genes abolished the effects on cell proliferation. These data demonstrate that as the moi of vectors is increased to achieve effective gene transfer, apoptosis and slowing of the cell cycle of infected cells increases concomitantly. The identification and inactivation of these vector effects on human airway cells may be important for reducing the toxicity of adenovirus vectors for gene therapy of CF airways.

Adenoviruses, Human↗

Improvements in exercise capacity and dyspnoea by inhaled anticholinergic drug in elderly patients with chronic obstructive pulmonary disease.

To test the effects of the inhaled anticholinergic drug, oxitropium bromide (OTB), on exercise capacity and dyspnoea in elderly patients (more than 75 years old) with chronic obstructive pulmonary disease (COPD), we performed cycle exercise testing on 12 elderly patients with COPD [mean age 78.7 (SD 1.1) years; FEV1% 41.3 (2.0)%] as well as 12 middle-aged COPD patients [mean age 60.1 (1.0) years; FEV1% 38.9 (2.4)%] before and after inhalation of OTB or placebo in a double-blind and placebo-controlled design. Spirometry was repeated immediately before and 30 min after OTB or placebo inhalation. Dyspnoea was quantitatively evaluated using the slope of the regression line between Borg scale and oxygen uptake (VO2) during exercise (Borg scale slope: BSS). After OTB inhalation, spirometric indices, exercise capacity as indexed by maximal VO2, and dyspnoea index (BSS) were improved compared with pre-inhalation value in both the elderly and middle-aged patients. The magnitude of improvements in these indices in the elderly patients was not different from that in the middle-aged. We conclude that the inhaled anticholinergic drug produces useful improvements in dyspnoea and exercise capacity in both elderly and middle-aged COPD patients.

Administration, Inhalation↗

A comparison of ventilation components in young and elderly men during exercise.

To elucidate the influence of age on ventilation components during exercise, we investigated the change in fractional contribution of abdomen or thorax during exercise in 12 elderly (71.9 +/- 5.3, mean +/- SD years) and 12 young (25.0 +/- 4.9 years) normal male subjects using respiratory-inductive plethysmography. At rest, abdominal/thoracic contribution was not different between elderly and young. During exercise, abdominal contribution to total ventilation was decreased in the young compared to that at rest (rest: 53.6 +/- 2.9% vs exercise: 50.4 +/- 1.9-48.9 +/- 1.8%; p < .01), but significantly increased in the elderly (rest: 53.9 +/- 1.8% vs exercise: 57.3 +/- 1.7-59.8 +/- 2.0%; p < .01). Only in the elderly, respiratory frequency was increased during exercise compared to that at rest (rest: 20.1 +/- 0.8 [/min] vs exercise; 25.6 +/- 1.5-27.8 +/- 1.6 [/min]; p < .05). The breathing pattern in the elderly during exercise was partly simulated in the young by reducing thoracic compliance using chest strapping. This study demonstrates the greater participation of diaphragmatic motion together with rapid shallow breathing during lower graded exercise in the elderly as compared with the young. This ventilatory pattern during exercise may result from a stiffening of the thorax with advancing age.

Abdomen↗

[Determination of the neutrophil function in the respiratory infection by chemiluminescence (CL). III: Changes in neutrophil and whole blood CL after chemotherapy against the acute respiratory infection].

We measured the chemiluminescent activity (CL-index) in both the whole blood and isolated neutrophils from 12 patients with acute respiratory infection (7 cases; pneumonia, 4 cases; in the exacerbated phase, chronic lower tract infection, and one; acute bronchitis) two times per each case: before and after chemotherapy. Before the initiation of chemotherapy, neutrophil and whole blood CL was high but whole blood CL was higher. After the completion of chemotherapy, whole blood CL was decreased more significantly than neutrophil CL. There was no correlation between neutrophil CL and whole blood CL. However the neutrophil CL-index.N (neutrophil numbers x neutrophil CL-index) was correlated with the whole blood CL. Thus, we think the number of neutrophils is a critical factor for phagocytic function of neutrophils as determined by CL.

Acute Disease↗

Lymphoepithelial cysts in the mediastinum with an opening to the trachea.

A case of lymphoepithelial cysts (LECs) in the mediastinum, manifested radiographically by paratracheal air collection, is reported. Percutaneous injection of radiopaque material and indocyanine green into a cyst showed an opening to the trachea. During surgical resection, three well-circumscribed cysts were isolated. Pathologically the cysts were lined by a ciliated columnar epithelium and surrounded by lymphoid tissue with germinal centers. Judging from the level of the duct opening onto the airway, these LECs might have derived from a remnant of the fourth branchial pouch. To the authors' knowledge, this is the first case described.

Branchioma↗

Biochemical characteristics of lungs in senescence-accelerated mouse (SAM).

This study examined age-related biochemical changes of the lung in an animal model of senile lung, senescence-accelerated mouse (SAM). Bronchoalveolar lavage (BAL) was performed on two strains of SAM, the senescence-prone strain (SAM P2) and the senescence-resistant strain (SAM R1), as well as on normal ageing C57 black mice (C57BL), aged 1-24 months. Elastase-like and elastase inhibitory activity of BAL fluid (BALF), glutathione (GSH) and oxidized GSH (GSSG) content both of BALF and lung tissue, and oxygen radical generation of free lung cells obtained by BAL were examined in the three strains of mice. Cell populations did not change throughout the life in SAM strains and C57BL. The elastolytic activity in SAM was greater than in C57BL, but there was no change with age. Both a decreased content of GSH and an increased oxidation of the GSH in BALF were markedly observed with ageing in SAM P2. In the lung tissue, the GSSG/GSH ratio in SAM strains was consistently greater than that in C57BL, suggesting that the GSH redox cycle of the lung may be impaired in SAM strains. The oxygen radical generation by free lung cells increased with age in all three strains, but the increase was earlier and more pronounced in SAM P2 than in the other two strains. In conclusion, an impaired GSH redox cycle and an increased formation of oxygen radicals are observed in the lungs of SAM with increasing age.

Aging↗

Ultrastructural and morphometrical analyses of Leydig and Sertoli cells in the testes of rats with hereditary polydactylism.

Rats of the polydactylous (PD) strain carry an autosomal recessive gene pd that causes polydactylism in homozygotes (pd/pd). Male homozygotes are sterile owing to an abnormality of spermatogenesis. In the present study, Leydig and Sertoli cells of 12-week-old pd/pd male rats were examined for ultrastructural alterations in an attempt to clarify the cause of the abnormal spermatogenesis. The relative volumes of the organelles were also determined with morphometry. Phenotypically normal pd/+ males served as controls. No morphological or morphometrical abnormalities were noted in the Leydig cells. However, two different types of Sertoli cell were evident: light cells and dark cells. The incidence of the dark Sertoli cells in pd/pd males was high (27%) compared with that in pd/+ males (6%). These dark cells contained quantities of lipid droplets in the cytoplasm and exhibited a significant increase in the relative volume of lipid droplets compared with the value for the light cells. The nuclei of the dark Sertoli cells were irregular in shape and were invaginated. These results suggest that dark Sertoli cells may have lower lipid metabolism, and in pd/pd males, the high number of these dark Sertoli cells may be related to abnormal spermatogenesis.

Animals↗

Mechanical left ventricular support in patients with Marfan's syndrome: a report of two cases.

Left ventricular assist device (LVAD) was utilized for the treatment of postcardiotomy heart failure in two patients with Marfan's syndrome. Patient 1 (a 22-year-old) with annuloaortic ectasia (AAE) and DeBakey type II dissection had been supported by LVAD for 87h after composite graft replacement of the ascending aorta and aortic valve. Patient 2 (a 52-year-old) with AAE and DeBakey type I dissection had been supported by LVAD for 91 h after aortic valve replacement. During the assist, both patients complicated bleeding from the fragile left atria near the sites of cannulation. Patient 1 died of multiple organ failure on the 62nd postoperative day, but patient 2 returned to work after surgery.

Adult↗

[Congenital cystic adenomatoid malformation of the lung: a case report in a newborn infant with severe respiratory failure and a review of the literature].

The patient was newborn infant with severe respiratory failure. The left upper lobe of her lung was occupied by multiple small cysts and it was getting worse in her condition soon after birth. So left upper lobectomy was underwent urgently four days later. Then she was recovering her strength. Pathological examination of resected specimen revealed congenital cystic adenomatoid malformation (CCAM) of the lung (type II lesion of Stocker's classification). It is reported that about seventy percent of CCAM present between birth and one month of age. Its prognosis is poor without operation. The lesion is showed by Chest-abdominal X-ray and ultrasonography, and recognized to best advantage by computed tomography. Neonatal CCAM must be rapidly diagnosed and decided its indication of lobectomy, then its prognosis may be improved.

Cystic Adenomatoid Malformation of Lung, Congenita↗

[A surgical case of invasive thymoma with postaortic left innominate vein].

We report a surgical case of invasive thymoma with post-aortic left innominate vein (PALIV). The patient was a 59-year-old female, and admitted due to abnormal shadow on chest X-p. Preoperative chest CT demonstrated a invasive thymoma with the swelling of mediastinal lymph nodes. During the operation, we found no swelling of mediastinal lymph nodes, and the left innominate vein ran below the aortic arch and behind the ascending aorta. Thymothymomectomy combined resection of pericardium, lung and phrenic nerve was performed, with taking care of no injurying the PALIV. PALIV is a very rare anomary of vessels, and 32 cases have reported in the literature and only 15 cases in that of Japan.

Brachiocephalic Veins↗

Morphogenetic study of the eyelids in NC-eob mice fetuses with an open-eyelid malformation at birth.

The NC-eob mice are mutants having open eyelids at birth with complete penetrance. Detailed scanning electron microscopy and light microscopy for study of the eyelid development of NC-eob embryos/fetuses were performed at days 13 to 17 of gestation and compared with normal NC mice, with the aim of investigating the etiopathogenesis of the open eyelids at birth. No difference was observed between NC and NC-eob embryos by scanning electron microscopy and histologic examination at days 13 and 14 of gestation. At day 15 the epithelium at the tip of the eyelids had 2 to 3 layers, and clumps of round periderm cells appeared on the outer surface of the margin of the lids in NC and NC-eob embryos. However, these clumps in NC-eob embryos were not as remarkable in number and in size compared with NC embryos. At day 16 the eyelids of NC fetuses extended over the cornea and began to fuse. The epithelium at the tip of the eyelids consisted of 4 to 5 layers with the following elongated area. The surface of the tip of the elongated epithelium was covered with a large number of round periderm cells. In NC-eob fetuses the epithelium remained stationary at 2 to 3 layers. Only a small number of round cells were noted at the tip of the eyelids, and fusion did not occur. At day 17, although the upper and lower eyelids of NC fetuses were entirely fused, no change occurred in NC-eob fetuses, either in the periderm or in the epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pathogenetic changes in the lung bud of mutant rats with heritable pulmonary lobation anomalies.

The present study aimed at investigating pathogenesis of pulmonary lobation anomalies in fpl/fpl mutant rats. Day 12-15 embryos were first examined for pulmonary lobation. Lung serial sections were then made and examined for bronchial branching and distribution of extracellular matrices (ECMs). The lung buds of both fpl/fpl embryos and their phenotypically normal fpl/+ littermates were formed as bilateral protrusion of the foregut on gestation day 12. In fpl/+ embryos, three processes appeared on the right lung bud on day 13, and fissures were completely formed by day 14. In fpl/fpl embryos, the right lung bud had no clear process on gestation day 13, and fissures were not formed on day 14 and thereafter, with the exception of incomplete separation between the cranial and middle lobes. Histological observation revealed that the right main bronchial bud of fpl/+ embryos ramified all lobar bronchial buds by gestation day 13. ECMs, a borderline between endodermal bronchial buds and surrounding mesenchyme, disappeared at the distal end of each lobar bronchial bud. By contrast, in fpl/fpl embryos, the right main bronchial bud did not ramify the middle and intermediate lobar bronchial buds at its lateral and ventral portions, but swelled on gestation day 13. It was covered with ECMs at the lateral side but not at the ventral region, from which the middle and intermediate lobar bronchial buds arose on gestation day 14. These observations suggest that altered distribution of ECMs causes branching abnormalities of the lobar bronchial buds and subsequent lobation anomalies in fpl/fpl embryos.

Animals↗