Biomedical subjects

T Ohwada

Publications and source records attributed to T Ohwada.

At least 19 recordsLinked to original sources

PubMed2001

Effect of neutral endopeptidase inhibitor on bradykinin-induced bronchoconstriction.

To evaluate whether neutral endopeptidase (NEP) inhibitors have adverse respiratory effects, the influence of a NEP inhibitor on bradykinin (BK)-induced bronchoconstriction was investigated. In anesthetized and artificially ventilated guinea pigs, changes in airway opening pressure (Pao) were measured as an index of bronchoconstriction. An infusion of phosphoramidon (3 mg kg(-1) h(-1)), a NEP inhibitor, significantly enhanced the bronchoconstriction induced by high-dose BK (30 nmol kg(-1), i.v.). Capsaicin (0.1 mg kg(-1), i.v.) and SR48968 (0.3 mg kg(-1), i.v.), an NK2 receptor antagonist, significantly inhibited the phosphoramidon-induced enhancement of BK-induced bronchoconstriction, although FK888 (3 mg kg(-1), i.v.), an NK1 receptor antagonist, did not. Both neurokinin A (NKA) (0.1-3 nmol kg(-1), i.v.) and substance P (SP) (0.1-3 nmol kg(-1), i.v.) induced dose-dependent bronchoconstriction which was enhanced by phosphoramidon infusion, although these enhancements were more prominent in the NKA series. Phosphoramidon partially inhibited BK degradation in lung homogenate, and both NKA and SP degradation in the lung homogenate were significantly suppressed by phosphoramidon. In bronchoalveolar lavage fluid (BALF), levels of NKA and SP were significantly elevated after a bolus of BK with a phosphoramidon infusion. These results suggest that NEP inhibitors may have adverse respiratory effects resulting from inhibition of the degradation of neurokinins, but mainly of NKA, when a large amount of BK is generated.

Animals↗

PubMed2001

Anchoring and bola cationic amphiphiles for nucleotide delivery. Effects of orientation and extension of hydrophobic regions.

Novel cationic amphiphiles, based on lithocholic acid derivatives with two structural motifs, anchoring lipids and bola lipids, were designed and synthesized. Both bear extended hydrophobic space-filling substituents. A significant effect of the orientation and extension of hydrophobic regions around the ether linkage at the 3-position was found on the efficiency of DNA delivery.

3T3 Cells↗

PubMed2001

Structural features of aliphatic N-nitrosamines of 7-azabicyclo[2.2.1]heptanes that facilitate N-NO bond cleavage.

N-Nitrosamines can be considered as potential nitric oxide (NO)/nitrosonium ion (NO(+)) donors. However, the relation of the structures of N-nitrosamines, in particular of aliphatic N-nitrosamines, to the characteristics of release of NO or NO(+) remains unclear. Here we show that aliphatic N-nitrosoamines of 7-azabicyclo[2.2.1]heptanes can undergo heterolytic N-NO bond cleavage. On the basis of the observation of reduced rotational barriers of the N-NO bonds in solution and nitrogen-pyramidal structures of the N-nitroso group in the solid state, we postulate that N-NO bond cleavage of N-nitrosamines is enhanced by a reduction of the resonance in the N-NO group. Computational studies suggest that these structural features of the N-nitrosamines of 7-azabicyclo[2.2.1]heptane are derived from angle strain imposed on the CNC angles.

Bridged Bicyclo Compounds, Heterocyclic↗

PubMed2001

Mutation spectrum of o-aminoazotoluene in the cII gene of lambda/lacZ transgenic mice (MutaMouse).

The o-aminoazotoluene (AAT) has been evaluated as a possible human carcinogen by the International Agency for Research on Cancer. In rodents, it is carcinogenic mainly in the liver, and also in lung following long term administration. We previously examined in lambda/lacZ transgenic mice for the induction of lacZ mutations in liver, lung, urinary bladder, colon, kidney, bone marrow, and testis. AAT induced gene mutations strongly in the liver and colon. In the present report, we reveal the molecular nature of mutations induced by AAT in the lambda cII gene (the cII gene, a phenotypically selectable marker in the lambda transgene, has 294bp, which makes it easier to sequence than the original target, the 3kb lacZ gene). The cII mutant frequency in liver and colon was five and nine times higher, respectively, in AAT-treated mice than in control mice. Sequence analysis revealed that AAT induced G:C to T:A transversions, whereas spontaneous mutations consisted primarily of G:C to A:T transitions at CpG sites.

Animals↗

PubMed2001

Gluteal muscle necrosis following transcatheter angiographic embolisation for retroperitoneal haemorrhage associated with pelvic fracture.

Transcatheter angiographic emobilisation has been used as an effective control of haemorrhage associated with pelvic fracture. Although few complications of this procedure have been reported, gluteal muscle necrosis occurs occasionally. We assessed the type of pelvic fracture, concomitant injury, embolic site, embolic materials, and outcome in cases of gluteal muscle necrosis associated with angiographic embolisation for pelvic fracture-related haemorrhage, and investigated the factors associated with the development of gluteal muscle necrosis, one of the fatal complications of transcatheter angiographic embolisation. Five out of the 151 patients (incidence, 3.3%) who underwent transcatheter angiographic embolisation for haemorrhagic shock due to pelvic fracture developed gluteal muscle necrosis after embolisation. The five cases had injury severity scores ranging from 26 to 59 (mean 46.4). Three patients died (mortality, 60%) of subsequent sepsis and disseminated intravascular coagulation. These cases showed that transcatheter angiographic embolisation with gelatin sponge and/or steel coil, while effectively controlling bleeding, may also result in gluteal muscle necrosis. Aggressive management including intraarterial antibiotic treatment may have a role, but our numbers are too small to confirm this.

Adolescent↗

PubMed2001

Space-filling effects in membrane disruption by cationic amphiphiles.

We studied the hemolytic activity towards bovine erythrocytes of novel synthetic steroid-polyamine conjugates consisting of a rigid hydrophobic steroid unit, and a flexible hydrophilic polyamine unit connected by a linker. The steroid structure, polyamine chain length, and the presence of a hydrophobic substituent on the steroid, all influenced the activity. Analysis of the time dependence of hemolysis suggested that these structurally related cationic amphiphiles have different mechanisms of membrane perturbation.

Algorithms↗

PubMed2001

Partial characterization of genes whose transcripts accumulate preferentially in cell clusters at the earliest stage of carrot somatic embryogenesis.

We attempted to identify genes that are preferentially expressed immediately after somatic cells divide to form cell clusters at the earliest stage of carrot somatic embryogenesis when they are not or barely expressed in non-embryogenic suspension-cultured cells in the presence of 2,4-D. Using the differential display technique, we isolated three cDNA clones, designated No. 43, No. 87 and No. 93. The No. 43 transcript was preferentially expressed in the earliest cell clusters, its level decreased drastically at the globular and heart-shaped and torpedo-shaped stages, and it was not detected in non-embryogenic suspension-cultured cells. No. 43 cDNA encoded a protein with homology to thaumatin-like proteins and the deduced positions of seven cysteine residues in the 63 amino acid sequence from the carboxyl terminus were identical to those in thaumatin-like proteins. The full-length nucleotide sequence of No. 93 cDNA was determined and its product was about 80% homologous to precursor of the 14 kDa proline-rich DC 2.15 protein of carrot at the amino acid level. However, the deduced amino acid sequence lacked the characteristic core of repeating Pro-X motifs found in DC 2.15. The No. 93 transcript accumulated preferentially in the earliest cell clusters but it was also detected at a low level in non-embryogenic suspension-cultured cells, unlike DC 2.15 transcripts that begin to accumulate in heart-shaped embryos before their level falls in torpedo-shaped embryos. No. 87 transcripts were expressed preferentially in the earliest cell clusters that has been incubated with 2,4-D but were also detected at a low level in suspension-cultured cells subcultured in the continued presence of 2,4-D. The No. 87 cDNA exhibited no significant homology to any sequences in databases.

2,4-Dichlorophenoxyacetic Acid↗

PubMed2001

Alkaline esophagitis evaluated by endoscopic ultrasound.

CASE REPORT: Two patients with corrosive esophagitis caused by alkaline household agents were examined with endoscopic ultrasound using a 20-MHz probe. In the first case, endoscopic ultrasound revealed circumferentially thickened mucosa and muscularis propria, and lack of differentiation between the mucosa and submucosa. However, esophageal stricture did not develop during 3 months of follow-up, suggesting that the deep lesion may have involved a narrow section of esophagus only. In the second case, a markedly thickened mucosa was seen, resulting in no sequelae. Endoscopic ultrasound offers a more accurate evaluation of the depth of the lesions in alkaline esophagitis compared to standard endoscopy or computed tomography. Longitudinal studies are needed to identify lesions at greatest risk for progression to stricture.

Adult↗

PubMed2001

[Nitrogen pyramidal amides and related compounds].

A planar amide bond is a fundamental linkage in the structures of peptides and proteins. The rigid planarity of the amide linkage, due to a conjugation between carbonyl and amine groups, may be requisite for encoded protein folding and many other biological processes. Non-planar amides in the ground state will decode the significance of the planarity and rigidity of the amide linkage. We show here that simple amides of 7-azabicyclo[2.2.1]heptane, free from steric bias, including parent N-benzoyl 7-azabicyclo[2.2.1]heptane, are nitrogen-pyramidal amides in the crystalline state. We can suggest that pyramidalized amide nitrogen is a general feature and intrinsic to the 7-azabicyclo[2.2.1]heptane motif. Low rotational barriers of the amide C-N bond in a series of N-benzoyl amides of 7-azabicyclo[2.2.1]heptane, compared to monocyclic amides, may imply that ground-state nitrogen pyramidalization of the former amides also exist in solution. The 7-azabicyclo[2.2.1]heptane motif also favors nitrogen pyramidalization of sulfonamides and N-nitrosoamines, which can lead to pharmacophores after appropriate modification.

Amides↗

PubMed2001

Usefulness and limitation of DiBAC4(3), a voltage-sensitive fluorescent dye, for the measurement of membrane potentials regulated by recombinant large conductance Ca2+-activated K+ channels in HEK293 cells.

The usefulness of bis-(1,3-dibutylbarbituric acid)-trimethine oxonol (DiBAC4(3)), a voltage-sensitive fluorescent dye, for the measurement of membrane potentials (MPs) was evaluated in HEK293 cells, where alpha or alpha plus beta1 subunits of large conductance Ca2+-activated K+ (BK) channels were expressed (HEKBK alpha and HEKBK alphabeta). The fluorescent intensity of DiBAC4(3) was measured at various potentials under voltage-clamp for calibration to estimate the absolute MP semi-quantitatively. The resting MPs measured with DiBAC4(3) were roughly comparable to those recorded with a microelectrode; the MP in HEKBK alphabeta was 10-20 mV more negative than that in native HEK. In HEKBK alpha, the membrane hyperpolarization induced by 10 microM Evans blue, a BK channel opener, was detected with DiBAC4(3). NS-1619, another BK channel opener, induced gradual but substantial change in F/F(K) even in native HEK, while the BK channel opening effect was detected. Oscillatory membrane hyperpolarization was induced in HEKBK alphabeta by application of 10 microM acetylcholine via increase in intracellular Ca2+ concentration. The oscillatory hyperpolarization was, however, detected only as a slow hyperpolarization with DiBAC4(3). It can be concluded that relatively slow effects of BK channel modulators can be semi-quantitatively measured by use of DiBAC4(3) in HEKBK, while the limited temporal resolution and possible artifacts should be taken into account.

Barbiturates↗

PubMed2001

Tight Sylvian cisterns associated with hyperdense areas mimicking subarachnoid hemorrhage on computed tomography--four case reports.

Four patients with supratentorial mass lesions (two chronic subdural hematomas, one acute epidural hematoma, and one acute subdural hematoma) showed hyperdense sylvian cisterns on computed tomography (CT). Association of subarachnoid hemorrhage was suspected initially, but was excluded by intraoperative observation or postoperative lumbar puncture. CT showed disappearance of the hyperdense areas just after evacuation of the mass lesions. The hyperdense areas are probably a result of the partial volume phenomenon or concentrations of calcium deposits rather than abnormally high hematocrit levels, which were not found in these patients.

Accidental Falls↗

PubMed2001

Traumatic basilar artery occlusion caused by a fracture of the clivus--case report.

A 56-year-old man presented with a rare traumatic basilar artery occlusion caused by a fracture of the clivus. He fell from the height of 2 meters and immediately fell into a coma. Head computed tomography (CT) revealed an open depressed fracture, an acute epidural hematoma 1 cm thick in the left middle frontal fossa, and a longitudinal fracture of the clivus. Emergency removal of the hematoma was performed with cranioplasty. Head CT 8 hours 50 minutes after injury showed infarctions in the brain stem, cerebellum, and occipital lobes. Cerebral angiography revealed occlusion of the basilar artery in the middle part of the clivus. The patient died after 3 days. Autopsy revealed that the basilar artery was trapped in the clivus fracture site. Vertebrobasilar artery occlusion due to trapping in a clivus fracture has a very poor prognosis. Diagnosis is difficult and generally only confirmed at autopsy. Cerebral angiography is recommended in a patient in a deep coma without massive brain contusion at the early stage of head injury to identify the possibility of vertebrobasilar artery occlusion in a clivus fracture.

Accidental Falls↗

PubMed2001

Case report: right subclavian artery pseudoaneurysm due to perforation of esophageal cancer.

A 51-year-old man presented with massive hematemesis. Perforation of upper esophageal cancer, which had already occurred at least six days earlier, progressed to upper mediastinitis. The mediastinitis contiguous to the right subclavian artery was considered to have caused a pseudoaneurysm. Rupture of the pseudoaneurysm into the esophagus resulted in massive hematemesis. Both enhanced computed tomography and angiography were diagnostic for the pseudoaneurysm. Transluminal endovascular stent-grafts placement was successful in preventing subsequent hemorrhage.

Aneurysm, False↗

PubMed2001

Acute mercuric chloride poisoning: effect of co-ingested milk on outcome and continued hyperamylasemia.

Thirty-six h after intentionally ingesting 25 g of mercuric chloride powder mixed with 5O mL of milk, an elderly woman presented to the emergency department with diffuse upper gastrointestinal erosions and acute renal failure. The patient was treated with dimercaprol and hemodialysis, and was discharged from the hospital without clinically apparent sequelae. However, elevated serum concentrations of amylase and proteases persisted for several months despite normal findings by computed tomography including contrast administration. Delayed absorption and weakened corrosive effect may have resulted from the binding of mercuric chloride to thiol-containing proteins in milk, improving the clinical outcome.

Administration, Oral↗

PubMed2000

Gene transfection activities of amphiphilic steroid-polyamine conjugates.

The design and evaluation of a novel potent class of DNA delivery agents based on steroid-polyamine conjugates bearing a flexible linker are reported. The hydrophobic regions are based on steroids, i.e. chlolestane and lithocholic acid motifs. The linker, which couples a hydrophobic steroid and a hydrophilic polyamine, in this study can be regarded as a two-atom extension of the conventional carbamate linker. We found that the gene transfection activity of the steroid-polyamine conjugates is influenced by the polyamine chain length and steroid structure. Molecular modeling of the relevant amphiphilic molecules revealed low-energy structures in which the polyamine chains are folded rather than stretched. This work suggests a significant effect of space-filling, i.e. the shape and orientation of the hydrophilic and hydrophobic regions, upon the efficiency of gene transfection.

3T3 Cells↗

PubMed2000

The effect of a hemofilter during extracorporeal circulation on hemodynamics in patients with SIRS.

OBJECTIVE: To evaluate the hypothesis that extracorporeal hemopurification with a hemofilter contributes to the stabilization of hemodynamics in patients with systemic inflammatory response syndrome (SIRS) due to a mechanism other than the removal of cytokines. DESIGN: Prospective study. SETTING: Intensive care unit (ICU) in a university hospital. PATIENTS: Seven critically ill patients who met criteria for SIRS with unstable hemodynamics requiring vasopressors after emergency surgery. INTERVENTIONS: Before initiation of continuous hemofiltration (CHF) extracorporeal circulation through the hemofilter (ECC) with a hollow-fiber polyacrylonitrile hemofilter was performed for 6 h. MEASUREMENTS AND RESULTS: Vital signs were monitored continuously and hemodynamics were evaluated intermittently. The blood level of endotoxin and the plasma levels of cytokines were measured at 0 and 6 h. Changes in plasma levels of cytokines passing through the hemofilter were evaluated at 3 h. A significant decrease of body temperature (P < 0.05 at 3 and 6 h vs 0 h), a significant elevation of mean arterial pressure (P < 0.05 at 0.5 h, P < 0.01 at 3 and 6 h vs 0 h), and a significant increase of urinary flow rate (P < 0.05 at 0 to 3 h vs -3 to 0 h) were observed with ECC. Neither the blood level of endotoxin nor the plasma levels of cytokines decreased. A significant increase of plasma IL-6 as it passed through the hemofilter was noted. CONCLUSIONS: The beneficial effects of hemopurification with a hemofilter on SIRS patients are possibly due to mechanisms other than the elimination of cytokines with ultrafiltration, diffusion, or adsorption.

Aged↗

PubMed2000

Pulse steroid therapy in adult respiratory distress syndrome following petroleum naphtha ingestion.

CASE REPORT: A suicide attempt by a 23-year-old woman involved ingestion of 1000 mL of petroleum naphtha. Early chemical pneumonitis was complicated by life-threatening, diffuse interstitial lung consolidation with pneumatoceles. Pulse steroid therapy beginning on day 17 was associated with remarkable resolution of interstitial consolidation, although an enlarging secondarily infected pneumatocele ruptured to produce a bronchopleural fistula. Thoracic surgery and antibiotic therapy resulted in improvement of the patient's respiratory condition, and she was discharged with no residual respiratory symptoms. High-dose corticosteroid therapy appears to be a useful addition to aggressive supportive treatment in late adult respiratory distress syndrome following hydrocarbon ingestion.

Adult↗

PubMed2000

Cardiovascular response and stress reaction to flumazenil injection in patients under infusion with midazolam.

OBJECTIVES: To evaluate the cardiovascular response and acute stress reaction after arousal induced by a benzodiazepine antagonist, flumazenil, in patients sedated with midazolam. DESIGN: Prospective study. SETTING: Emergency center in a university hospital. PATIENTS: A total of 12 patients were ventilated mechanically under sedation with midazolam. INTERVENTIONS: We monitored the consciousness level, heart rate, systemic blood pressure, pulmonary artery pressure, and pulmonary artery occlusion pressure before and after a bolus injection of 0.5 mg of flumazenil. The score for the consciousness level represents the sum of the scores for eye opening and best motor response, as determined by the Glasgow Coma Scale. We measured the cardiac output, concentrations of norepinephrine, epinephrine, and 3-methoxy-4-hydroxyphenylethyleneglycol in plasma, and concentration of cortisol in serum. We calculated the left ventricular ejection fraction, cardiac index, systemic vascular resistance index, pressure-rate product, systemic oxygen delivery, and systemic oxygen consumption at 0, 10, 30, and 60 mins after injection of flumazenil. MEASUREMENTS AND MAIN RESULTS: The serum benzodiazepine's receptor binding activity in serum was in the range from 50 to 1000 ng/mL before injection of flumazenil. Flumazenil improved the consciousness level from 6.7+/-2.0 to 8.9+/-1.6 and induced transient elevations in heart rate, blood pressure, systolic pulmonary artery pressure, and pulmonary artery occlusion pressure. Left ventricular ejection fraction, oxygen delivery index, and pressure-rate product increased significantly, from 61%+/-8%, 640+/-170 mL/min/m2, and 13,300+/-2600 mm Hg/min at 0 mins to 67% +/-5%, 710+/-220 mL/min/m2, and 16,500+/-4400 mm Hg/min at 10 mins, respectively. Concentrations of norepinephrine and epinephrine in plasma increased significantly, from 890+/-840 pg/mL and 220+/-360 pg/mL, respectively, at 0 mins to 990+/-850 pg/mL and 270+/-300 pg/mL, respectively, at 10 mins. There were no significant changes in the plasma concentration of 3-methoxy-4-hydroxyphenylethyleneglycol, the serum concentration of cortisol after the administration of flumazenil. CONCLUSIONS: Flumazenil did not result in a significant acute stress reaction in midazolam-sedated patients, but it increased myocardial oxygen consumption by enhancing sympathetic nervous activity or antagonizing cardiovascular depression induced by midazolam.

Acute Disease↗