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Biomedical subjects

M Sekiguchi

Publications and source records attributed to M Sekiguchi.

At least 307 records · Page 17Linked to original sources
PubMed1993

The effect of superoxide production on the replantation of rat limbs after cold ischemia.

In order to clarify the effect of superoxide anion radicals on the "no-reflow phenomenon," the authors examined the utility of simple cold preservation of rat limbs in replantation. They quantified such radicals, derived from erythrocytes and plasma in the preserved limb, using a chemiluminescence method employing a derivative of luciferin (CLA). Eighty-four Lewis rat limbs were preserved at 4 degrees C in Euro-Collins solution for 10 to 120 hr, and grafted orthotopically to isogeneic rats by microsurgical technique. To determine the extent of oxidative stress, heparinized blood from the recipient animals was collected before, or at 5, 30, and 60 min after reperfusion, and chemiluminescence was measured in a total of 51 replantations. Cold ischemic groups at 0, 24, and 48 hr, with high rates of vascular patency, did not show a marked increase in superoxide anion concentration. However, there were significant differences in the production of superoxide between patent and non-patent cases in all groups, excluding a 120-hr ischemic group. This study showed that the increase in superoxide anion concentration after reperfusion following ischemia, correlates closely with the no-reflow phenomenon.

Animals↗
PubMed1993

Establishment of a human small cell lung carcinoma cell line carrying amplification of c-myc gene and chromosomal translocation of t(3p;6p) and t(12q;17p).

A transplantable tumor and an in vitro culture cell line (GK-T3) were established from metastatic liver tissue of human small cell lung carcinoma (SCLC). Southern blot analysis revealed about 30-fold amplification of c-myc gene in the tumor cells in liver, xenografts, and in vitro cell line. The degree of c-myc amplification was essentially conserved through serial passages in nude mice and cultivation in vitro. The level of c-myc mRNA was significantly increased in these cells. Cytogenetically, numerical and complex structural abnormalities were observed in GK-T3 cells, including t(3p;6p), t(12q;17p), two homogeneously staining regions (hsrs) and several double minutes (dmins). These results suggest that activation of c-myc gene and alteration of gene(s) around these chromosomal breakpoints may play a role in tumorigenesis of GK-T3 SCLC.

Aged↗
PubMed1993

Pharmacokinetic evaluation of (glycolato-O,O')diammine platinum(II) in lung lymph in sheep.

The pharmacokinetics of (glycolato-O,O')diammine platinum(II) (254-S), especially the distribution and behavior in the lung lymph in sheep, was investigated and compared with that of cis-diamminedichloroplatinum(II) (CDDP). The blood and lung lymph fluid were collected from the carotid artery and a lung lymph fistula, respectively, in conscious sheep following intravenous infusion of 100 mg/body of 254-S and CDDP for 30 min. The concentrations of these platinum complexes were measured by using atomic absorption spectrometry. We analyzed the data using an anatomically based model including part of the lymphatic circulation. The ultrafilterable platinum of 254-S showed much larger area under the curve (AUC) and transfer rate constants than that of CDDP, even though the mean residence times were the same. The total platinum showed the opposite pharmacokinetic behavior. In anesthetized sheep, when lung tissue samples were obtained by biopsy at the same times as those of blood and lung lymph sampling after infusion of these drugs, 254-S distributed in lung tissue appeared to move more easily into lung lymph than CDDP, which tended to be retained in lung tissue. These differences in pharmacokinetic behavior between 254-S and CDDP seemed to be caused by differences in their strength of protein binding; the association constants of 254-S for plasma and lymph protein were much less than those of CDDP. From these results, 254-S may have favorable therapeutic effects on intrathoracic malignancies such as lung cancer and lymph metastasis.

Anesthesia↗
PubMed1993

Inhibitory activity of camptothecin derivatives against acetylcholinesterase in dogs and their binding activity to acetylcholine receptors in rats.

A camptothecin derivative, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), shows a potent antitumour activity in experimental tumour models and in clinical trials. However, CPT-11 induced early diarrhoea and vomiting at high dose levels in clinical studies and showed an acetylcholine-like action on the guinea-pig ileum and trachea. In the present study, we investigated the activities of camptothecin derivatives in inhibiting acetylcholinesterase (AChE) and in binding to muscarinic acetylcholine receptors (AChR). CPT-11 inhibited AChE and binding of the specific ligand to AChR with respective 50% inhibition concentrations of 0.2 and 5 microM. These inhibitions were induced by camptothecin derivatives having an amino group at the C-10 position (or the C-4 position of hexacyclic derivatives), but were not or were only slightly induced by the others. Early defecation and vomiting in dogs were observed after intravenous injection of DU-6596 and DU-6888, two hexacyclic derivatives having the aminomethyl group at the C-4 position, and of CPT-11. DU-6174, however, which has a hydroxy group at this position, induced no early defecation and little vomiting. Plasma concentrations of CPT-11, DU-6596 and DU-6888 after intravenous treatment at doses causing such early adverse effects were maintained for 1 h or longer at levels sufficient to inhibit AChE. These results suggest that the inhibition of AChE by camptothecin derivatives with an amino group at the C-10 position (or the C-4 position) relates to the early defecation or diarrhoea and vomiting.

Animals↗
PubMed1993

The Ada protein is a class I transcription factor of Escherichia coli.

The methylated Ada protein of Escherichia coli, a regulatory protein for the adaptive response, binds to a target DNA from positions -62 to -31 upstream of the ada gene and facilitates the binding of RNA polymerase to the promoter. Mutant RNA polymerases consisting of C-terminal-deleted alpha subunits are virtually inactive in response to activation by the Ada protein. Thus, we conclude that the Ada protein is a class I transcription factor which requires the C-terminal region of the RNA polymerase alpha subunit for transcription activation.

Bacterial Proteins↗
PubMed1993

Proliferative activation of quiescent Rat-1A cells by delta FosB.

Fos and Jun transcription factors are induced during the normal course of the proliferative response of quiescent cells to serum or to growth factors. We have shown that delta FosB, an alternatively spliced form of FosB, is formed as rapidly as FosB in serum-stimulated Rat-1A cells. Although delta FosB lacks the C-terminal region of FosB carrying the transactivation function, constitutive expression of delta FosB transforms Rat-1A cells as does expression of FosB. The transforming ability of delta FosB suggests that delta FosB may lead to proliferative activation of quiescent cells without activating AP-1-responsive genes. To address this question, FosB or delta FosB was expressed as a fusion protein with the ligand binding domain of the human estrogen receptor (ER) in Rat-1A cells. After estrogen treatment, the fusion protein accumulates in nuclei and forms stable complexes with Jun proteins. We have shown that ER-delta FosB or to a lesser extent ER-FosB triggers quiescent Rat-1A cells to transit G1, initiate DNA replication, and ultimately undergo cell division at least once. Since ER-FosB, but not ER-delta FosB, induced expression of the AP-1-responsive transin/stromelysin gene, we concluded that the N-terminal region and the DNA binding domain of FosB or delta FosB itself have the potential to regulate cell proliferation and that the transactivation function carried by the C-terminal region of FosB is not essential for the proliferative activation of quiescent cells.

Animals↗
PubMed1993

Effects of recombinant human superoxide dismutase on tumor necrosis factor-induced lung injury in awake sheep.

Tumor necrosis factor alpha (TNF) is a mediator of acute lung injury after endotoxemia, but the precise mechanism of TNF-induced lung injury remains unclear. To clarify the role of oxygen radicals, especially superoxide anion, in TNF-induced lung injury, we examined the effects of recombinant human superoxide dismutase (rhSOD; 4,200 U/mg) on lung physiological and biochemical changes after TNF infusion in awake sheep (n = 17). We prepared chronically instrumented sheep for lung lymph collection and hemodynamic monitoring. Recombinant human TNF (3.5 micrograms/kg iv) induced a biphasic response in awake sheep. Pulmonary hypertension peaked within 15 min of initiation of TNF and remained elevated for 3 h, followed by increased lung vascular permeability. rhSOD attenuated the pulmonary hypertension in both early and late phases but caused no change in the timing or magnitude of lung fluid balance changes during the late phase. Thromboxane A2 (thromboxane B2) and prostacyclin (6-ketoprostaglandin F1 alpha) metabolite levels in plasma and lymph increased after the TNF infusion, and rhSOD attenuated these changes. The intravenous infusion of rhSOD resulted in the appearance of significant levels of SOD activity in both plasma and lung lymph before and after TNF infusion. These findings suggest that superoxide anion may be implicated in the pathogenesis of the pulmonary hypertension induced by TNF in sheep.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Relation of phasic coronary flow velocity profile to clinical and hemodynamic characteristics of patients with aortic valve disease.

BACKGROUND: Our objective was to assess phasic coronary blood flow and velocity characteristics of the proximal portion of the left anterior descending artery and to evaluate their relation to the clinical and hemodynamic manifestations in patients with aortic valve disease. METHODS AND RESULTS: We examined 26 patients with chronic aortic regurgitation (AR), 12 patients with predominant aortic stenosis (AS), and 11 control subjects using an intravascular Doppler catheter with spectral analysis. Angiographic assessment of AR identified 10 patients with mild regurgitation and 16 with severe regurgitation. The resting systolic coronary flow velocity-time integral (VTI) was significantly higher and the diastolic VTI was slightly but significantly higher in patients with severe regurgitation than in those with mild regurgitation (11.8 +/- 4.2 vs 4.1 +/- 1.1 cm, P < .001; 18.5 +/- 5.8 vs 13.2 +/- 3.2 cm, P < .05) and control subjects (4.0 +/- 1.0 cm, P < .001 and 13.3 +/- 3.6 cm, P < .05), respectively. Patients with AS had a slightly lower resting systolic VTI (3.8 +/- 1.4 cm) and a higher diastolic VTI (14.6 +/- 3.7 cm) than control subjects. Resting coronary blood flow was greater in patients with aortic valve disease than in control subjects. There was a significant correlation between the ratio of the resting systolic to diastolic VTI (S/D ratio) and the ratio of the aortic systolic to diastolic pressure (r = .75, P < .001) in patients with AR. The S/D ratio was inversely correlated with left ventricular systolic pressure (r = -.92, P < .001) and positively correlated with the ratio of the aortic systolic to diastolic pressure (r = .68, P < .05) in patients with AS. CONCLUSIONS: Our results indicate that hemodynamic changes related to aortic valve disease contribute to alterations in the resting phasic coronary blood flow and velocity profiles observed in these patients.

Aortic Valve Insufficiency↗
PubMed1993

Granulocyte colony-stimulating factor does not exacerbate endotoxin-induced lung injury in sheep.

Because it has been suggested that neutrophils play a role in endotoxin-induced lung injury, we examined the effects of increased peripheral blood-neutrophils induced by recombinant human granulocyte-colony-stimulating factor (rhG-CSF) on the lung dysfunction when induced by endotoxin in awake sheep. We prepared chronically instrumented awake sheep with lung lymph fistulae and catheters for hemodynamic monitoring. We compared alterations of pulmonary hemodynamics, lung lymph balance, circulating leukocytes, plasma and lung lymph concentrations of thromboxane B2 and 6-keto-prostaglandin F1 alpha, and arterial blood gases in sheep that received Escherichia coli endotoxin infusion intravenously (1 microgram/kg) in the following two groups: Group 1 (n = 6) received endotoxin alone, and Group 2 (n = 7) received rhG-CSF (125 micrograms/day) intravenously for 3 days before endotoxin was administered in the same manner as in Group 1. The rhG-CSF remarkably increased circulating neutrophils to 24,600 +/- 2,500/microliters in Group 2 sheep at baseline when compared with the level in Group 1 (5,700 +/- 550 microliters). After endotoxin infusion, we observed significant decreases in circulating neutrophils in both groups. There were no differences between the two groups in the time course of changes in pulmonary hemodynamics, arterial blood gases, or arachidonate products after endotoxemia. However, lung lymph flow and lung lymph protein clearance during the late phase were lower in rhG-CSF-treated sheep than in those that received only endotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Insulin-like growth factor I receptors in human cardiac myocytes and their relation to myocardial hypertrophy.

Specific binding sites for insulin-like growth factor I (IGF-I) and their expression during cardiac myocyte hypertrophy were studied by autoradiographic analysis of right ventricular biopsy specimens from patients with hypertrophic cardiomyopathy (9 cases), dilated cardiomyopathy (8 cases), and sick sinus syndrome (5 cases). Frozen specimens were cut into 5 microns-thick sections and thaw-mounted on albumin-coated slides. After incubation with [125I]IGF-I, with or without excess cold IGF-I, autoradiography was performed, and grains over myocytes were counted microscopically. Binding of [125I]IGF-I was inhibited in a dose-dependent manner by unlabeled IGF-I and competed for by IGF-I > IGF-II > insulin. The maximal grain density was higher in hypertrophic cardiomyopathy (186 +/- 47/1.8 x 10(-2) mm2) than in dilated cardiomyopathy (124 +/- 13/1.8 x 10(-2) mm2) or sick sinus syndrome (98 +/- 18/1.8 x 10(-2) mm2) (p < 0.01). There was a strong correlation between the maximal grain density and the diameter of right ventricular myocytes in hypertrophic cardiomyopathy (r = 0.83), but no similar correlation was observed in dilated cardiomyopathy or sick sinus syndrome. These data suggest that IGF-I receptors are present in adult human cardiac myocytes, and that IGF-I receptors are related to the development of myocyte hypertrophy in hypertrophic cardiomyopathy.

Adolescent↗
PubMed1993

High-altitude pulmonary edema with pulmonary thromboembolism.

High-altitude pulmonary edema (HAPE) is a form of noncardiogenic pulmonary edema. The pathophysiology of HAPE remains unclear. A case of HAPE was associated with pulmonary thromboembolism of a left upper pulmonary artery. Pulmonary thromboembolism was an important factor in development of HAPE in this case.

Acute Disease↗
PubMed1993

[A case of sleep apnea syndrome with significant alteration of apnea index by sleep position].

An obese 37-year-old man (130% ideal body weight) was admitted to our hospital with the complaint of excessive daytime sleepiness. During all-night polysomnography, he showed predominantly obstructive sleep apnea and an apnea index (AI) of 57.5, and was diagnosed as having obstructive sleep apnea syndrome (OSAS). However, AI values calculated separately for the time in the supine position (AI-S) and in the lateral decubitus position (AI-L) were 82.4 and 5.9, respectively. Moreover, duration of apnea, lowest SaO2, and the quality of sleep were improved when sleeping in the lateral compared to the supine position. After weight reduction of 7 kg, AI in total decreased to 33.2, although AI-S was 77.3 and AI-L was 3.8. The improvement of AI in total to be due to a relative increase during sleep in the lateral position. These results suggest that in some OSAS patients, the sleep position should be taken into account in assessing the severity of the disease or in evaluating the effects of therapy. This study also suggests the efficacy of sleep position adjustment in the treatment of OSAS.

Adult↗
PubMed1993

[A case of rheumatoid arthritis with obstructive bronchiolitis appearing after D-penicillamine therapy].

A 56-year-old woman was diagnosed as having rheumatoid arthritis in 1983. She was treated with D-penicillamine in addition to non-steroid anti-inflammatory drugs from April 1990. In August she noticed shortness of breath on exertion. Chest X-ray films showed bilateral interstitial shadows, and chest CT revealed bilateral multiple wedge-shaped shadows extending distally. Blood gas analysis showed severe hypoxemia and pulmonary function tests demonstrated decreased %VC, FEV1.0% and diffusion capacity. Open lung biopsy specimens revealed infiltration of inflammatory cells and fibrotic change in the walls of bronchioles. She was diagnosed as having obstructive bronchiolitis. Corticosteroid therapy and discontinuation of D-penicillamine therapy stopped the progression of her symptoms, and she was discharged on corticosteroid maintenance treatment and home oxygen therapy.

Arthritis, Rheumatoid↗
PubMed1993

[A case report of acute mid-graft occlusion of the left internal mammary artery to the left anterior descending artery after PTCA].

A 66 year-old woman underwent coronary artery bypass grafting for postinfarction angina. A left internal mammary artery graft was joined to the left anterior descending artery. Coronary and graft angiography revealed a 90% stenosis in the anastomotic site of the left internal mammary artery. During PTCA with a 2.0 mm balloon catheter, acute occlusion of the graft body occurred. Intragraft injection of isosorbide dinitrate failed to dilate the graft. Thus, careful consideration should be given to several complications such as acute occlusion of the graft when PTCA for anastomotic site of the graft is performed.

Acute Disease↗
PubMed1993

[Tumor metastasis].

Explore the source record for details and available documents.

Angiogenesis Inducing Agents↗
PubMed1993

[Analysis of bronchoalveolar lavage fluid in a case of high altitude pulmonary edema].

A 29-year-old male climber developed high altitude pulmonary edema (HAPE), progressing from headache and dyspnea to disturbance of consciousness in the Japan Alps. He was admitted to Shinshu University Hospital. Physical examination on admission revealed a cyanotic patient with coarse crackles and wheezes in bilateral lungs. Chest X-ray film showed bilateral patchy infiltrates. Arterial blood gases indicated severe hypoxemia, and respiratory alkalosis; pH 7.452, PO2 35.5 Torr, PCO2 31.6 Torr. Right heart catheterization showed noncardiogenic pulmonary edema, analysis of bronchoalveolar lavage (BAL) fluid was as follows; cells 2.05 x 10(5)/ml (alveolar macrophages 61.5%, neutrophils 25.5%, lymphocytes 13.0%), protein concentration 91 mg/dl. Cellular and protein analysis of BAL has been shown to be of value to clarify the pathogenesis of the permeability edema in patients with HAPE.

Adult↗
PubMed1992

Hydrolytic elimination of a mutagenic nucleotide, 8-oxodGTP, by human 18-kilodalton protein: sanitization of nucleotide pool.

8-Oxoguanine nucleotide can pair with cytosine and adenine nucleotides at almost equal efficiencies. Once 8-oxodGTP is formed in the cellular nucleotide pool, this mutagenic nucleotide is incorporated into DNA and would cause transversion mutations. The MutT protein of Escherichia coli possesses enzyme activity to hydrolyze 8-oxodGTP to the corresponding nucleoside monophosphate and thus may be responsible for preventing the occurrence of such mutations. Here we show that the human cell has an enzyme specifically hydrolyzing 8-oxodGTP in a fashion similar to that seen with MutT protein. The human 8-oxodGTPase has been found in cell-free extracts from Jurkat cells and purified > 400-fold. Analyses by gel filtration and gel electrophoresis revealed that the molecular mass of the native form of human 8-oxodGTPase is 18 kDa. Mg2+ ion is required for the enzyme action and the optimum pH for the reaction is pH 8.0. The enzyme hydrolyzes 8-oxodGTP to 8-oxodGMP with a Km value of 12.5 microM. dGTP and dATP are also degraded to dGMP and dAMP, respectively, with Km values 70 times greater than that for 8-oxodGTP. dTTP and dCTP are not hydrolyzed. These properties of the human 8-oxodGTPase are similar to those observed with the E. coli MutT protein, suggesting that the function of protecting the genetic information from the threat of endogenous oxygen radicals is widely distributed in organisms.

Chromatography, Affinity↗