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Biomedical subjects

T Uno

Publications and source records attributed to T Uno.

At least 127 records · Page 7Linked to original sources

Hemin binding to DNA with bis-dentate acridine intercalator.

Hemin was covalently connected to two 9-aminoacridines (9AA) through its two propionates, and the binding properties of this bis-dentate compound (hemin(9AA)2) to DNA were examined by visible absorption spectroscopy. The binding affinity of the hemin(9AA)2 was found to be higher than that of the hemin, and this should be attributed to the two linked acridine moieties. The binding constant (K) and the number of binding sites per nucleotide (n) were estimated by Scatchard plot analyses. Though the order of the K value of hemin(9AA)2 was similar to that of 9AA, the hemin(9AA)2 was analyzed to have a smaller n value, the order of which was of about 10(-4). The small n value may reflect the sequence specificity of the bis-dentate hemin(9AA)2 on binding to the DNA.

Aminacrine↗

Calcitonin gene-related peptide-like immunoreactive motoneurons innervating the canine inferior pharyngeal constrictor muscle.

The percentage of the calcitonin gene-related peptide-immunoreactive motoneurons (Mn) in the nucleus ambiguus (NA) innervating the canine inferior pharyngeal constrictor muscle was examined using the cholera toxin B subunit-gold (CTBG) as a retrograde tracer and by immunohistochemistry. Labeled neurons with CTBG (CTBG MNs) from the thyropharyngeal muscle (TP) were located in the dorsomedial division of the rostral part of the NA and the average percentage of neurons with CGRP immunoreactivity was 70.3%. CTBG MNs from the cricopharyngeal muscle (CP) were located in the dorsal division of the rostral part of the NA and the average percentage of neurons with CGRP immunoreactivity was 21.2%. This low percentage of CGRP immunoreactivity is noteworthy and supports the idea that the CP is a particular striated muscle in function and innervation manner.

Animals↗

[Intra-ocular pressure changes during laparoscopic cholecystectomy].

Intra-ocular pressure (IOP) was measured during laparoscopic cholecystectomy (n = 20) under continuous epidural block and nitrous oxide-oxygen anesthesia. There was a slight but significant increase in IOP and peak airway pressure when the abdominal CO2 insuffration was started, and the IOP recovered to the preoperative level after the postural change to the head-up position. It was not associated with any significant change in mean arterial pressure and end-tidal CO2. In one ocular hypertension case undergoing laparoscopic chorecystectomy and appendectomy, however, there was profound increase in IOP during abdominal CO2 insuffration with head down position. We speculate that it was due to the effect of increased CVP with abdominal CO2 insuffration and postural change on the IOP. Thus the laparoscopic operation with head-down position should be avoided in patients with ocular hypertension.

Anesthesia, Epidural↗

Intracranial blood flow measured with single photon emission computer tomography (SPECT) during transient -6 degrees head-down tilt.

Regional cerebral blood flow (CBF) during a transient head-down tilt of -6 degrees (-6 degrees HDT) was measured with single photon emission computer tomography (SPECT). CBF was measured and averaged for both sides of the brain areas; e.g., the bilateral anterior cerebral artery (bACA) area, the middle cerebral artery (bMCA) area, the posterior cerebral artery (bPCA) area, bilateral basal ganglia, and the cerebellum. Among these areas, a significant increase in CBF was observed in the basal ganglia and the cerebellum during -6 degrees HDT compared to pre-HDT. When CBF was measured separately in the left or right brain area, these significances disappeared, although a trend of increase or decrease was still observable. A trend of increase was observed in the left anterior cerebral artery (IACA) area, the right middle cerebral artery (rMCA) area, the right posterior cerebral artery (rPCA) area, the left and right basal ganglia, and the cerebellum. In rACA, IMCA and IPCA areas, a slight decrease in CBF was observed. At the same time, cardiac parameters were measured. Heart rate (HR), stroke volume (SV) and cardiac output (CO) did not change significantly, although SV slightly increased and HR slightly decreased during -6 degrees HDT.

Adult↗

Cytochrome d axial ligand of the bd-type terminal quinol oxidase from Escherichia coli.

Using various spectroscopic techniques, we studied the structure of the dioxygen reduction site of the bd-type terminal quinol oxidase in the aerobic respiratory chain of Escherichia coli. Resonance Raman and FT-IR spectroscopies identified the v(Fe(2+)-CO) and v(C-O) stretching frequencies at 471 and 1980.7 cm-1, respectively, at the cytochrome d center of the dithionite-reduced CO-bound enzyme. The CO ligation in the cytochrome bd complex is considerably different from those of the heme-copper terminal oxidases. Anaerobic addition of NO to the air-oxidized enzyme caused an exchange of cytochrome d-bound dioxygen with NO leading to an appearance of cytochrome d-NO EPR signal. But there is no superhyperfine structure originating from the cytochrome d proximal 14N ligand in the central resonance of the NO EPR signal. These results suggest that cytochrome d axial ligand of the cytochrome bd complex is likely a histidine residue in an anomalous condition or other than a histidine residue and, therefore, the molecular structure around the dioxygen-binding site is different from that of the heme-copper terminal oxidases.

Binding Sites↗

Synthesis of antimicrobial agents. 5. In vivo metabolism of 7-(4-hydroxypiperazin-1-yl)quinolones.

A series of novel pyridone carboxylic acids having a 4-hydroxypiperazin-1-yl, a 4-hydroxy-3-methylpiperazin-1-yl, and a 4-hydroxy-3,5-dimethylpiperazin-1-yl group was prepared, and their metabolism to corresponding piperazinyl derivatives after oral administration to mice and rats was studied. This reductive metabolism appeared to be more extensive in mice than in rats. Moreover, the introduction of a methyl group into the alpha-position of the 4-hydroxy group depressed the metabolism in both species.

4-Quinolones↗

Distribution of the afferent neurons from the canine recurrent laryngeal nerve.

Localization of the afferent neurons from the canine recurrent laryngeal nerve in the nodose ganglia (NG) and jugular ganglia was studied using the horseradish peroxidase technique. Labeled cells were detected in the ipsilateral NG and presented no distinct pattern of distribution, but rather were scattered throughout the ganglion. No labeled cells were found in the contralateral NG or bilateral jugular ganglia. The size of labeled cells varied from 15 microns to 60 microns. Two to six labeled cells larger than 45 microns were detected in each dog. Most of the labeled cells (62%) had a diameter between 30 microns and 45 microns. The percentage of labeled cells with a diameter between 15 microns and 30 microns was 30% and between 45 microns and 60 microns was 8%. This difference in size of labeled cells in the NG may be related to functional differences among the receptors mediated.

Animals↗

Importance of successive prolines in the carboxy-terminal region of P450 2C2 and P450 2C14 for the hydroxylase activities.

Proline-480 and proline-481 are highly conserved in the P450 2 family. When these successive prolines of P450 2C2 were replaced by Ala-Thr, its activities of laurate (omega-1)-hydroxylation and benzphetamine N-demethylation were lost. On the other hand, the mutated P450 which retained one of the proline residues was 60-100% active in the (omega-1)-hydroxylation and 100-120% active in the N-demethylation. Pro-Pro (480, 481) to Ala-Thr mutated P450 2C14 was also inactive in testosterone 16 alpha-hydroxylation and benzphetamine N-demethylation, the activities of the wild-type P450 2C14. In the carboxyterminal region of the P450 2C subfamily, the sequence of P450 2C2 from residues 469-473 is noticeably different from those of the other members of this subfamily. The Ser-473 to Val mutation of P450 2C2 caused a decrease in the (omega-1)-hydroxylase activity to one-fifth but the N-demethylase activity was not much affected. When the sequence of P450 2C2 from residues 469-473 was replaced by that of P450 2C14 (mutation at four residues), the 16 alpha-hydroxylase and N-demethylase activities were increased by seven- and three-fold, respectively, and the (omega-1)-hydroxylase activity was decreased to one-third. The mutated P450 2C2, in which the carboxy-terminal four residue sequence or the proline cluster adjacent to the amino-terminal membrane-anchor signal sequences was deleted, was not accumulated in yeast cells transformed with plasmids directing the synthesis of such P450s.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Effect of protease inhibitor on ischemia/reperfusion injury of the rat liver.

The purposes of this study were to clarify the role of neutrophilic proteases in the pathogenesis of hepatic ischemia/reperfusion injury and to determine whether urinary trypsin inhibitor (UTI) pretreatment attenuated liver ischemia/reperfusion injury in rats. Livers from male Sprague-Dawley rats were subjected to 90 min of no-flow warm ischemia followed by 120 min of reperfusion. Rats were divided into a UTI group and a control group. In the control group, 120-min reperfusion of the liver produced a significant increase in myeloperoxidase activity, a significant decrease in ATP and energy charge, and a marked increase in the serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels. In the UTI group, the myeloperoxidase activity was significantly attenuated (P < 0.01), ATP and energy charge were significantly improved (P < 0.01 and P < 0.05, respectively), and the elevation in serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase was also markedly suppressed (P < 0.05, P < 0.01, and P < 0.05, respectively) compared with the control group. Sections through the livers of control rats showed severe hepatocyte necrosis with neutrophil infiltration. In the UTI group, there was slight congestion and hepatocyte necrosis. The survival rate after 90-min liver ischemia was significantly improved compared with that in the control group (P < 0.05). The results of this study suggest that pretreatment with UTI significantly attenuates liver reperfusion injury, perhaps by inhibiting neutrophil proteases.

Adenosine Triphosphate↗

Effect of ibudilast, a novel antiasthmatic agent, on anaphylactic bronchoconstriction: predominant involvement of endogenous slow reacting substance of anaphylaxis.

The effect of ibudilast on anaphylactic bronchoconstriction was studied in guinea pigs sensitized actively with ovalbumin (OA). Animals were treated with indomethacin, tripelennamine and propranolol prior to the antigen challenge. Anaphylactic bronchoconstriction was prevented by ibudilast (1-4 mg/kg i.v. and 5-20 mg/kg p.o.) dose-dependently. FPL55712 and phenidone were also effective. Even when administered at the maximum development of bronchoconstriction, ibudilast (0.5 and 2 mg/kg i.v.) and FPL 55712 caused significant reduction of the increased airway tone, while phenidone did not. Ibudilast (1-4 mg/kg i.v.) and FPL55712 inhibited leukotriene D4-induced airway responses in nonsensitized guinea pigs pretreated with indomethacin and propranolol. Ibudilast (1.6 and 4 mg/kg i.v.) inhibited platelet-activating-factor (PAF)-induced airway responses in nonsensitized guinea pigs pretreated with indomethacin and propranolol, however, FPL 55712 inhibited PAF-induced airway responses only at a high dose such as 10 mg/kg i.v. Ibudilast (4 mg/kg i.v.) did not inhibit acetylcholine-induced airway response. Ibudilast showed inhibition of the release of slow-reacting substance of anaphylaxis (SRS-A) from guinea pig chopped lung sensitized with OA, which was significantly diminished by indomethacin. The drug little affected the activity of phospholipase A2 and 5-lipoxygenase in guinea pig polymorphonuclear leukocytes. These results indicate that ibudilast inhibits anaphylactic bronchoconstriction which is considered to be largely mediated by endogenously released SRS-A. The inhibitory effect of ibudilast on anaphylactic bronchoconstriction in the presence of indomethacin is considered to be exerted through its antagonism to SRS-A.

Acetylcholine↗

[Autonomic neurons sending fibers into the canine laryngeal nerves--using a retrograde tracer technique with cholera toxin].

The distribution of the autonomic neurons sending fibers into the canine superior and inferior laryngeal nerves was investigated by an immunohistochemical technique with cholera toxin B subunit as a retrograde tracer. Cholera toxin was applied to the right internal branch of the superior laryngeal nerve (SLNI), external branch of the superior laryngeal nerve (SLNE) or inferior laryngeal nerve (ILN) in 2-month-old dogs. In every case of cholera toxin application, labeled neurons were seen mainly in the caudal portion of the ipsilateral superior cervical ganglion, whereas none were seen in the stellate ganglion. The number of labeled neurons in the superior cervical ganglion after application of cholera toxin to the SLNI was over 20 times that observed after application to the SLNE or ILN. When cholera toxin was applied to the SLNI or SLNE, labeled neurons were found mainly in the ipsilateral dorsal motor nucleus of the vagus (DMNV), and a few labeled neurons were found in the ipsilateral reticular formation. The neurons in the DMNV were localized, on the average, between 2.7 mm and 5.3 mm rostral to the obex. The number of neurons in the DMNV labeled retrogradely from the SLNI was much larger than that from the SLNE. In contrast, no labeled neurons were detected in the DMNV after application to the ILN. These results demonstrate the following: 1) The sympathetic neurons innervating the canine larynx are distributed mainly in the caudal portion of the superior cervical ganglion and they send their fibers mainly into the SLNI. 2) The parasympathetic neurons innervating the canine larynx have a limited distribution in the dorsal motor nucleus of the vagus and their main pathway is also the SLNI.

Animals↗

[The alteration of right ventricular performance in patients with pneumonectomy and pulmonary lobectomy].

Elevation of right ventricular afterload associated with the decrease of pulmonary vascular bed is a serious problem immediately after pneumonectomy. We studied the alteration of right ventricular performance and hemodynamics by using an RVEF thermodilution catheter, and compared them among 6 patients after pneumonectomy and 8 patients after pulmonary lobectomy. Results demonstrate that 1) PVRI increased significantly immediately after the pneumonectomy, and recovered to the preoperative level on the 1st postoperative day. On the other hand, in the lobectomy patients, PVRI showed no significant change throughout the operation, because the decrease of pulmonary vascular bed after pneumonectomy was larger than that after pulmonary lobectomy. 2) In the pneumonectomy group, CI and RVEF were preserved and right ventricular works (RCWI and RSWI) increased in spite of an increase of right ventricular afterload after the ligation of the pulmonary artery. We considered that immediately after pneumonectomy the increase of right ventricular afterload associated with decreased pulmonary vascular bed was compensated by increasing right ventricular work. 3) On the 1st postoperative day, CI and RVEF did not change, but mRAP decreased significantly, and PVRI and right ventricular works recovered to the preoperative level in the pneumonectomy patients. From the above results, we considered that after the pneumonectomy, increased right ventricular afterload was compensated by the decreased circulating blood volume.

Hemodynamics↗

[Expression of major histocompatibility complex antigens, and kinetics of infiltrated lymphocytes in murine herpetic keratitis].

Immunohistochemical techniques were used to study expression of HSV-1 antigen, induction of class I and II major histocompatibility complex (MHC) antigens, and infiltration of L3T4+ and Lyt2+ cells were analyzed during the acute phase of herpetic keratitis. The results were as follows: 1) HSV-1 antigens were detectable in the corneal epithelium at 2 days post infection (p.i.), then localized in the stroma after 5 days p.i.. 2) Class I MHC antigens (H-2d) were evenly expressed in all layers of infected as well as uninfected corneas. On the other hand, class II MHC antigens (Iad) were induced in the superficial corneal stroma 2 days p.i., then gradually spread in the entire corneal stroma with increased intensity. 3) L3T4+ (helper/inducer) cells penetrated the stroma at 2 days p.i.. These cells infiltrated the central stroma at 5 days p.i.. Lyt2+ (suppressor/killer) cells were first seen in the corneal stroma as late as at 5 days p.i.. These results imply that L3T4+ cells play a role in the early immunological events concerning class II MHC antigens and viral antigens, both concomitantly expressed in the corneal stroma.

Animals↗

[Evaluation of blood purification in perioperative acute renal failure].

The technical aspects of blood purification have made a great progress during 1980's. We reviewed our experiences of blood purification for the past six years. Between 1986 to 1991, we treated 48 perioperative patients with acute renal failure (ARF). Four were intraoperative cases and 46 were postoperative cases. Three of four intraoperative patients received major cardiovascular surgery, and hemodialysis was connected directly to ECC in these three cases, and in other one case, ARF was treated with continuous hemofiltration (CHF). There was no intraoperative complication. One patient died of septic multiple organ failure (MOF), but other three patients were discharged uneventfully. Thirty five postoperative ARF patients showed oliguric ARF, and their major causes were LOS (65%) and septic shock (29%). We treated these ARF patients with CHF combined with HD (63%), CHF only (28%) and HD only (9%). There were 21 deaths (60%) in this group and most common cause of death was septic MOF. Eleven postoperative ARF patients showed non-oliguric renal failure, and major cause of this type of ARF was thought to be aortic dissection and relative hypotension (45%). We treated these non-oliguric ARF patient with HD only (73%) and HD combined with CHF (27%). One of these non-oliguric ARF patients died from ARDS.

Acute Kidney Injury↗

[Results of radiation therapy of extrahepatic bile duct carcinoma].

From January 1975 to August 1988, 40 patients with extrahepatic bile duct carcinoma were treated by external irradiation at Chiba University Hospital and the National Medical Center Hospital. Thirty-four patients (male: 20, female: 14) were evaluable. Eighteen patients were postoperative cases because the surgical margin was positive for tumor cells in the postoperative pathological examination; the other 16 were inoperable cases. Survival in postoperative and inoperable cases was not significantly different, with median survival times of 13.8 and 8.1 months, respectively. Survival in the recanalization-positive and negative-groups was significantly different (p less than 0.05) after irradiation, with median survival times of 13.5 and 6.0 months, respectively. Complications of therapy were recognized in 68% of all cases. They were mainly gastrointestinal symptoms such as nausea, vomiting, erosive gastritis and loss of appetite, but they were not severe. Distant metastasis was recognized in only 4 patients (10%): three had bony metastasis and one had supraclavicular and pulmonary hilar lymph node metastasis. Ninety percent of all cases died from hepatic failure or peritonitis carcinomatosa due to failure to obtain local control by external irradiation. A more effective modality of treatment is necessary to cure these patients.

Aged↗

Distribution of tyrosine hydroxylase immunoreactive nerve fibers in the canine larynx.

The sympathetic innervation of the canine larynx was investigated using tyrosine hydroxylase (TH) immunohistochemistry. Many tyrosine hydroxylase immunoreactive (TH-IR) nerve fibers were observed around arteries and arterioles in the laryngeal mucosa and intrinsic laryngeal muscles. In the glandular region, TH-IR fibers were also found, with some of these fibers terminating around the basement membranes of the glandular cells. The quantity of TH-IR fibers in the mucosa differed among regions of the larynx. Many of these fibers could be found in the laryngeal surface of the epiglottis as well as the posterior glottis. These findings suggest that TH-IR fibers may directly innervate muscles in the intrinsic larynx.

Adrenergic Fibers↗

Distribution of calcitonin gene-related peptide nerve fibers in the canine larynx.

Immunohistochemistry was used to investigate the distribution pattern of calcitonin gene-related peptide (CGRP) nerve fibers in the laryngeal mucosa, glands and intrinsic muscles of the dog. CGRP immunoreactive nerve fibers were found more frequently than substance P immunoreactive nerve fibers in every region of the larynx. In the epithelia, CGRP nerve fibers were mainly found in the epiglottis, arytenoid region and subglottis. Many taste buds were observed in the arytenoid region and were densely innervated by the CGRP nerve fibers. In the lamina propria, the plexus of CGRP nerve fibers was present, with some of these fibers associated with blood vessels. Laryngeal glands were also innervated by a few CGRP nerve fibers. In the intrinsic laryngeal muscles, abundant immunoreactivity was observed and many motor end-plate-like structures were found with CGRP immunoreactivity. These findings strongly suggest that CGRP plays an important role in all of the sensory, motor and autonomic nervous systems of the larynx.

Animals↗