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Biomedical subjects

M Sekiguchi

Publications and source records attributed to M Sekiguchi.

At least 343 records · Page 19Linked to original sources

Pulmonary hemodynamics and lung function during chronic paraquat poisoning in sheep. Possible role of reactive oxygen species.

The purpose of this study was to establish a chronic model of paraquat-induced lung injury. To examine the role of reactive oxygen species in this form of lung injury, we measured malondialdehyde (MDA) and superoxide dismutase (SOD) activity in the lungs. Paraquat (5 mg/kg intramuscularly) caused a significant decrease in dynamic lung compliance from 128.5 +/- 9.2 to 63.3 +/- 11.8 ml/cm H2O (p less than 0.05), with a significant increase in AaPO2 3 wk after paraquat. Histologic findings in the lungs showed a gradual increase in the number of granulocytes and alveolar wall thickening with proliferation of reticular fibers and were coincident with the changes in physiology. A transient decrease in pressor responses to hypoxia was observed 1 wk after paraquat, although pulmonary hemodynamics did not change. The amount of lung MDA 3 wk after paraquat increased from the baseline value of 0.73 +/- 0.04 to 1.12 +/- 0.10 nmol/mg protein (p less than 0.05). SOD activity in the lung tissue significantly decreased from 6.47 +/- 0.20 to 4.82 +/- 0.25 U/mg protein (p less than 0.05) 1 wk after paraquat and remained at low levels for 3 wk. These findings suggest that a small dose of paraquat causes chronic lung injury characterized by granulocyte infiltration and lung fibrosis. Reactive oxygen species may play an important role in this chronic lung injury, and the inability to increase antioxidant defense may contribute to the reaction.

Animals↗

Effect of metal ions on transcription of the ada gene which encodes O6-methylguanine-DNA methyltransferase of Escherichia coli.

The effect of metal ions on transcription of the ada gene of Escherichia coli which is promoted by Ada protein in the presence of methylated deoxyribonucleic acid (DNA) was examined in a reconstituted system. Their effect on the O6-methylguanine-DNA methyltransferase (MGTase) activity of Ada protein was also examined. Ag+, Cd2+, Cu2+ and Hg2+ severely inhibited transcription of the ada gene at a dose which inhibited neither transcription of the lacUV5 gene nor MGTase activity. Zn2+ inhibited both transcription and MGTase activity in the same dose range. Al3+ and Fe3+ inhibited transcription of both ada and lacUV5 genes without affecting the MGTase activity of Ada protein. Inhibitory mechanisms are discussed.

Escherichia coli↗

Absorption, distribution and excretion of zenarestat, a new aldose reductase inhibitor, in rats and dogs.

1. The absorption, distribution and excretion of zenarestat have been studied in male rats and dogs after i.v. and oral administration of 14C-zenarestat. 2. The bioavailability of zenarestat was 93% in rats and 65% in dogs. A major proportion of the plasma 14C in rats and dogs was due to unchanged drug. The terminal elimination half-life of zenarestat in plasma was 6 h in rats and dogs. 3. Except for organs associated with absorption and elimination, tissue 14C levels were lower than plasma levels in rats. The distribution to, and elimination from sciatic nerve were slower than those of other tissues. 4. Most of the 14C from 14C-zenarestat administered orally and i.v. to rats and dogs was excreted in the faeces. After i.v. dosing to bile duct-cannulated rats, 96% of the radioactive dose was excreted in the bile.

Absorption↗

Molecular mechanisms for controlling spontaneous and induced mutagenesis.

Errors in the replication of DNA are a major source of spontaneous mutations, and a number of cellular functions are involved in correction of these errors to keep the frequency of spontaneous mutations very low. We report here a novel mechanism which prevents replicational errors by degrading a potent mutagenic substrate for DNA synthesis. We also deal with suppression of alkylation-induced mutations by O6-methylguanine-DNA methyltransferase.

Alkylation↗

[Clinical applications of ion-sensor].

The coulometric measurement technique offers a rapid, accurate and precise method for measuring iron in liquid samples. It is well-known that analytical interferences common to colorimetric methods essentially do not exist in this procedure. However, this study shows that various drugs, such as chondroitin iron sulfate, deferoxamine mesylate, and salazosulfapyridine have strongly positive effects on the most contemporary determination of serum iron. The study of the analytical interference of drugs is important for precise and accurate measurement of desirable or undesirable pharmacological effects. New drugs and new methods should be systematically studied in this manner.

Biosensing Techniques↗

Endomyocardial biopsy approach in cases with ventricular arrhythmias.

Right ventricular endomyocardial biopsies were performed in patients with ventricular tachycardia (VT: n = 20) and idiopathic premature ventricular contraction (PVC: n = 23). Active myocarditis was found in one case and postmyocarditic change in 9 cases. Significant pathology according to our definition was found in 9 out of the total of 43 cases (20.5%). The pathological features of the 9 cases were interstitial fibrosis in 5, disarrangement of muscle bundles in 6, degeneration of myocytes in one and increase in fatty tissue in 7. Increase in fatty tissue was characteristically observed in 6 out of the 20 cases with VT and it was noteworthy that the VT cases with left bundle branch block configuration showed high incidence of the fatty tissue (5/12 cases, 42%).

Adolescent↗

[A case of superior vena cava syndrome due to extensive venous thrombosis of an idiopathic nature].

A 37-year-old man was admitted with facial edema and right arm swelling. Venography, computed tomography and magnetic resonance imaging showed massive organizing thrombi in the superior vena cava and bilateral internal jugular as well as subclavian veins, and showed no mass lesions occluding the veins in the mediastinum. Angioscopy demonstrated a white thrombus at the entrance of the right subclavian vein. All results of blood coagulation tests were normal. The patient was diagnosed as having superior vena cava syndrome caused by idiopathic venous thrombosis. Anti-coagulant therapy with intravenous tissue plasminogen activator injection and continuous urokinase and heparin infusion into the thrombi through a catheter were not effective in lysing the thrombi. Collateral circulation gradually developed and his symptoms decreased. We decided to follow this patient on warfarin medication because of the difficulty in removing the thrombi surgically.

Adult↗

[A fatal case of acute mediastinitis caused by periodontal infection].

A 57-year-old man had suffered from poorly controlled diabetes mellitus and liver cirrhosis due to alcohol and hepatitis C for about 10 years. He developed fever and swelling of the right cheek and neck due to periodontal infection. The symptoms worsened in spite of antibiotic therapy and were accompanied by dyspnea. He was therefore referred to our hospital. Chest radiographs and computed tomographs revealed widening of the superior mediastinum, pulmonary infiltrates and right pleural effusion. He was diagnosed as having mediastinitis, right pyothorax and pneumonia caused by periodontal infection. Tracheotomy and mechanical ventilation were performed. Antibiotic therapy resulted in improvement of the mediastinitis and pyothorax. However, renal and liver dysfunction developed and the patient died of multiorgan failure after 35 days of hospitalization. Death due to periodontal infection is rare. We give a review of the literature.

Acute Disease↗

Cytoarchitectonic abnormalities in cerebellum and hippocampal formation of beige mutant mouse.

Abnormalities in the cerebellum and hippocampal formation of the beige mouse were revealed by histological and immunohistochemical examination. In the cerebellum, Purkinje cells and clusters of granule cells, plus an occasional Bergmann glia cell, were located ectopically in the molecular layer. In the hippocampus, ectopically situated pyramidal cell were found in the stratum oriens of area CA3. The infrapyramidal mossy fiber layer (IPMFL) was formed by fiber bundles emerging from two districtly separated areas of the dentate gyrus. The IMPFL was not compact, but appeared as clumps of scattered fiber bundles. The neuronal heterotopias and cytoarchitectonic disorganization observed in the beige mutant mouse cerebellum and hippocampus may prove to be very useful parameters in analyzing the relationship between the immune system and the development of the central nervous system.

Animals↗

Clinical and pathologic features of chronic myocarditis: four autopsy cases presenting as dilated cardiomyopathy in life.

Four patients who appeared to suffer from dilated cardiomyopathy in life were found at autopsy to have had chronic myocarditis (two males and two females, aged 7 to 42 years). Before the appearance of cardiac symptoms, a flu-like illness was observed in two cases and fever in two others. The duration of illness was from 7 months to 10 years and 11 months (mean: 3 years and 8 months) and the heart weight in three adult patients varied from 510 to 940 g (mean: 720 g). Histologic observation of a transverse ventricular section in each patient showed 10 to 187 clusters of small round cells, and massive fibrosis was also found at these sites. The mean percent area of interstitial fibrosis was 26.3% in the ventricular septum, 31.2% in the left ventricular free wall, and 21.6% in the right ventricular free wall. These histologic findings indicated the presence of myocarditis, which was presumably chronic. Our findings suggest that some of the patients diagnosed as having dilated cardiomyopathy may in fact have chronic myocarditis.

Adult↗

[A case of pulmonary tuberculosis associated with severe skin eruption, prominent eosinophilia, and liver dysfunction induced by streptomycin].

A 42-year-old woman was admitted because of cough, sputum, and fever. A chest roentgenogram revealed a nodular density in the left upper lung field with satellite lesions compatible with tuberculoma. Mycobacterium tuberculosis was detected from sputum. Five weeks after starting the treatment with 0.4 g/day of isoniazid, 0.45 g/day of rifampicin, and 0.75 g/day of streptomycin, she showed itching erythema in the trunk. The white blood cell count was 4,500/mm3 with 14% eosinophils, and serum transaminases were slightly increased (GOT 101 U/L, GPT 74 U/L). Although isoniazid and rifampicin were stopped, the erythema with exfoliation spread to her extremities, suggesting exfoliative dermatitis. The white blood cell count reached 15,990/mm3 with 68% eosinophils (10,810/mm3). Stimulation indices measured with the lymphocyte stimulation test (LST) were 109% with rifampicin, 140% with isoniazid, and 275% with streptomycin, suggesting streptomycin-induced allergy. After cessation of streptomycin, the symptoms gradually improved. After the reaction had subsided, the treatment with isoniazid, rifampicin, and ethambutol was resumed, but she showed no further adverse reactions. LST seems to be very useful to identify the drug or drugs responsible for the reactions occurred during the treatment by antituberculosis drugs.

Adult↗

Radiological evaluation on allograft reconstruction of the acetabulum combined with supporting device in revision total hip replacement.

We reviewed the radiographs of 25 hips of 20 patients who had received revisions of the acetabular components of total hip replacement supplemented by allograft for bone defects. Bone defects in 20 hips (80%) were classified into type D (cranio-central defect) according to Itoman's classification. In eight, sockets were installed directly on the allografts (group A). A metallic supporting device was used for reinforcing the grafts in 17 hips (group B). The position of the acetabular socket was measured on a radiograph, taken immediately after revision surgery and again at the latest follow-up. Using a MEM template, cranial and central migrations were determined. Mean cranial migration in hips of group A was 3.6 mm. Group B was 0.2 mm. Maintenance of thickness of the allografts was 60.6% in the cranial region and 75% in the central in group A. In the hips of group B, however, almost 100% of the initial thickness was maintained cranially and centrally. Allograft reconstruction of acetabular bone defect in revision total hip replacement is a beneficial procedure. The remaining pelvic bone is usually in poor condition, therefore, it is necessary to ensure primary fixation by the metallic supporting device.

Acetabulum↗

Valgus-flexion osteotomy for middle-aged patients with advanced osteoarthritis of the hip: a clinical and radiological evaluation.

We followed up 34 secondary osteoarthritis patients with 38 hips treated by valgus-flexion osteotomy between 1979 and 1985. The average age of the patients at surgery was 45 years and the follow-up period ranged from 5 to 11 years. After surgery, the clinical evaluations were made according to the JOA Hip Score which remained unchanged in all 38 hips for 5 years. After 6 years there were some hips whose score declined with time. It was found that the preoperative extension-flexion range was the factor that was most closely associated with the result of the surgery (p less than 0.01). Radiological examination at 5 years revealed that the joint space had been widely broadened and the trabecular structure nearly normalized in 23 hips (60.5%), while 15 hips (39.5%) showed a slight degree of joint space broadening and were left with sclerosis and pseudocysts. After a lapse of 10 years or more, in 13 hips out of 10 patients, seven were found to have osteoarthritic changes and revision had to be done by THR in 2 patients. Valgus-flexion osteotomy can therefore be said to provide one of the useful means to preserve joints when employed in middle-aged patients with secondary OA.

Adult↗

[A successful treatment of patient with paraquat poisoning].

A 60-year-old man was admitted 1 hour after ingesting approximately 40 ml of Gramoxon (paraquat) in an attempt to commit suicide. Gastrointestinal lavage, compulsory urination, and direct hemoperfusion (DHP) were immediately performed to remove the paraquat. He was then administered Vitamin E and high dose methylprednisolone therapy to prevent lung injury. Chest roentgenogram on the 3rd day showed ground glass appearance in the outer zone of bilateral lung fields. Chest CT scans on the 9th day revealed a faint high density area in the same area, suggesting interstitial change. The shadows gradually improved and had disappeared on the 35th day after admission. Serum superoxide dismutase (SOD) activity, measured by electron spin resonance spectroscopy, was undetectably low until the 22nd day, and then increased into the normal range. It was suggested that SOD was consumed to neutralize the paraquat toxicity. Serum SOD activity changed according to the paraquat activity, and was a useful indicator of paraquat toxic activity. He was discharged without any symptoms 50 days after admission.

Female↗

Mutational specificity of the dnaE173 mutator associated with a defect in the catalytic subunit of DNA polymerase III of Escherichia coli.

We developed a system to examine forward mutations that occurred in the rpsL gene of Escherichia coli placed on a multicopy plasmid. Using this system we determined the mutational specificity for a dnaE173 mutator strain in which the editing function of DNA polymerase III is impeded. The frequency of rpsL- mutations increased 32,000-fold, due to the dnaE173 mutator, and 87 independent rpsL- mutations in the mutator strain were analyzed by DNA sequencing, together with 100 mutants recovered from dnaE+ strain, as the control. While half the number of mutations that occurred in the wild-type strain were caused by insertion elements, no such mutations were recovered from the mutator strain. A novel class of mutation, named "sequence substitution" was present in mutants raised in the dnaE173 strain; seven sequence substitutions induced in the mutator strain occurred at six sites, and all were located in quasipalindromic sequences, carrying the GTG or CAC sequence at one or both endpoints. While other types of mutation were found in both strains, single-base frameshifts were the most frequent events in the mutator strain. Thus, the mutator effect on this class of mutation was 175,000-fold. A total of 95% of the single-base frameshifts in the mutator strain were additions, most of which occurred at runs of A or C bases so as to increase the number of identical residues. Base substitutions, the frequency of which was enhanced 25,000-fold by the mutator effect, occurred primarily at several hotspots in the mutator strain, whereas those induced in the wild-type strain were more randomly distributed throughout the rpsL sequence. The dnaE173 mutator also increased the frequency of duplications 28,000-fold. Of the three duplications recovered from the mutator strain, one was a simple duplication, the region of which was flanked by direct repeats. The other duplications were complex, one half part of which was in the inverted orientation of a region containing two sets of inverted repeats. The same duplications were also recovered from the wild-type strain. The present data suggest that dnaE173 is a novel class of mutator that sharply induces sequence-directed mutagenesis, yielding high frequencies of single base frameshifts, duplications with inversions, sequence substitutions and base substitutions at hotspots.

Base Sequence↗

Abnormalities of foliation and neuronal position in the cerebellum of NZB/BINJ mouse.

To analyze developmental abnormalities related to neural migration in the NZB/BINJ mouse, the pattern of cerebellar foliation and neural position were compared with that of a normal mouse (C57BL/6J). Three abnormalities of cerebellar foliation--(1) lobe isolated from other cerebellar lobes, (2) lobes imbalanced in relative amounts or ratio of granular cell layer and molecular layer, (3) lobes in which some Purkinje cells and the molecular layer was embedded in the granular cell layer--were observed in NZB/BINJ mice. These morphological abnormalities were not limited to a specific lobe. On the other hand, abnormalities of neural position were observed in both granule and Purkinje cells. The pattern of ectopically-situated granule cells, in general, could be divided into 3 types: (1) large cell clusters extending from granular cell layer to the pia mater or middle part of the molecular layer, (2) clusters of various sizes scattered within the white matter and (3) clusters formed by combination of granule cells extending from two opposed granular cell layers to the molecular layer. The pattern of ectopically-situated Purkinje cells could be divided into 4 types: (1) ectopia of a group of cells from one part of the Purkinje cell layer, (2) ectopia of a single Purkinje cell observed in the molecular layer, (3) single Purkinje cell scattered within the white matter accompanied by clusters of ectopic granule cells and (4) ectopic Purkinje cells embedded in the granular cell layer. The abnormalities in position of both granule cells and Purkinje cells was not limited to a particular cerebellar lobe.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗