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Biomedical subjects

K Yagi

Publications and source records attributed to K Yagi.

At least 307 records · Page 17Linked to original sources

Effect of recombinant human adult T cell leukemia-derived factor on rat lung reperfusion injury.

The formation of reactive oxygen species (ROS) is a major factor responsible for reperfusion injury in lungs. Adult T cell leukemia derived factor (ADF), a polypeptide made of 104 amino acids, is induced by a variety of stresses including X-ray, ultraviolet, H2O2, and mitogen. ADF has a reducing activity, which catalyzes the proton transfer between thiol-radical of cystein-containing proteins. Furthermore, ADF has a protective activity of ROS which are formed by xanthine oxidase and other alternative pathways in vitro. Using a rat in vivo model of lung ischemia, we examined the protective effect of recombinant human ADF (rhADF) against ischemia reperfusion injury of the lung. Ischemia, lasting for 75 min, was induced in the left lung of rats at 23 degrees C. The lung was then reperfused. These animals were divided into two groups: group 1 (n = 6, treatment with normal saline) and group 2 (n = 6, treatment with 28 micrograms/g of rhADF). One minute after the beginning of reperfusion, arterial oxygen tension (PaO2) decreased significantly in both groups (p < 0.01), without any significant intergroup difference (55.5 +/- 9.8, 49.8 +/- 8.6 mm Hg, respectively). Twenty minutes after reperfusion, PaO2 was significantly higher (p < 0.05) in group 2 (113.0 +/- 8.1 mm Hg) than in group 1 (72.3 +/- 13.6 mm Hg). The wet/dry weight ratio was significantly higher in group 1 (7.31 +/- 0.54) than in group 2 (5.82 +/- 0.36). Histologically, lung injury tended to be milder in group 2 than in group 1. These results suggest that rhADF has a protective effect against ischemia reperfusion injury of the rat lung.

Animals↗

Genetic cholesteryl ester transfer protein deficiency caused by two prevalent mutations as a major determinant of increased levels of high density lipoprotein cholesterol.

Genetic determinants of HDL cholesterol (HDL-C) levels in the general population are poorly understood. We previously described plasma cholesteryl ester transfer protein (CETP) deficiency due to an intron 14 G(+1)-to-A mutation(Int14 A) in several families with very high HDL-C levels in Japan. Subjects with HDL-C > or = 100 mg/dl (n = 130) were screened by PCR single strand conformational polymorphism analysis of the CETP gene. Two other mutations were identified by DNA sequencing or primer-mediated restriction map modification of PCR products: a novel intron 14 splice donor site mutation caused by a T insertion at position +3 from the exon14/intron14 boundary (Int14 T) and a missense mutation (Asp442 to Gly) within exon 15 (D442G). The Int14 T mutation was only found in one family. However, the D442G and Int14 A mutations were highly prevalent in subjects with HDL-C > or = 60 mg/dl, with combined allele frequencies of 9%, 12%, 21% and 43% for HDL-C 60-79, 80-99, 100-119, and > or = 120 mg/dl, respectively. Furthermore, prevalences of the D442G and Int14 A mutations were extremely high in a general sample of Japanese men (n = 236), with heterozygote frequencies of 7% and 2%, respectively. These two mutations accounted for about 10% of the total variance of HDL-C in this population. The phenotype in a genetic compound heterozygote (Int14 T and Int14 A) was similar to that of Int14 A homozygotes (no detectable CETP and markedly increased HDL-C), indicating that the Int14 T produces a null allele. In four D442G homozygotes, mean HDL-C levels (86 +/- 26 mg/dl) were lower than in Int14 A homozygotes (158 +/- 35 mg/dl), reflecting residual CETP activity in plasma. In 47 D442G heterozygotes, mean HDL-C levels were 91 +/- 23 mg/dl, similar to the level in D442G homozygotes, and significantly greater than mean HDL-C levels in Int14 A heterozygotes (69 +/- 15 mg/dl). Thus, the D442G mutation acts differently to the null mutations with weaker effects on HDL in the homozygous state and stronger effects in the heterozygotes, suggesting dominant expression of a partially defective allele. CETP deficiency, reflecting two prevalent mutations (D442G and Int14 A), is the first example of a genetic deficiency state which is sufficiently common to explain a significant fraction of the variation in HDL-C in the general population.

Adult↗

Pharmacodynamics and tumoricidal effect of adriamycin entrapped in ceramide sulfate-containing liposomes.

Ceramide sulfate (N-acylsphingosine-1-O-sulfate), which lacks the galactose residue of sulfatide, was examined as a possibly preferable constituent of liposomes for drug delivery. Multilamellar vesicles prepared from phosphatidylcholine, cholesterol, and N-lignoceroylsphingosine-1-O-sulfate in a molar ratio of 5:4:1 efficiently entrapped adriamycin, and the retention of the drug in the liposomes in saline at 4 degrees C for 8 d was nearly 100%. In terms of entrapment efficiency and retention of the drug in liposomes, N-lignoceroylsphingosine-1-O-sulfate was superior to N-stearoylsphingosine-1-O-sulfate. A pharmacodynamic study revealed that the blood level of adriamycin was far higher with the drug encapsulated in N-lignoceroylsphingosine-1-O-sulfate-containing liposomes than with the free drug. The drug level in the heart was remarkably reduced with the liposome-entrapped drug, which is advantageous in reducing the cardiotoxicity of this drug. The effect of N-lignoceroylsphingosine-1-O-sulfate-containing liposomes on the blood level of adriamycin was superior to that of sulfatide-containing liposomes, though the effect of the former on the heart level was comparable to that of the latter. The tumoricidal effect on ascitic P388 leukemia and Lewis lung carcinoma was higher with adriamycin entrapped in N-lignoceroylsphingosine-1-O-sulfate-containing liposomes than with the free drug.

Animals↗

The UAS of the yeast GAPDH promoter consists of multiple general functional elements including RAP1 and GRF2 binding sites.

The upstream activating sequence (UAS) of TDH3, one of three genes encoding glyceraldehyde phosphate dehydrogenase in Saccharomyces cerevisiae, was characterized by using a series of external and internal deletion mutants of the TDH3 upstream region. The levels of activation by these deletions of transcription mediated through either the segment of TDH3 promoter or the segment of ADH1 (alcohol dehydrogenase 1 gene) promoter were quantitatively examined and the region between -583 and -447 was found to be required for full transcriptional activation with either promoter segment. It has been demonstrated that the protein binding site involved in the formation of two DNA-protein complexes is identical with the consensus RAP1 binding sequence by methylation interference assay. Surprisingly, the UAS fragment composed of the 22-mer sequence containing exclusively a RAP1 binding sequence showed full activation, suggesting that the RAP1-dependent transcriptional activation is a primary positive control in the TDH3 gene expression. In addition, a pair of inverted repeat sequences homologous to the binding sequence for GRF2, another yeast trans-acting factor, and directly repeated sequences containing a CATCC motif were also found upstream and downstream, respectively, of the RAP1 binding site. Deletion analysis suggested that these elements could also function as regulatory elements for transcription.

Base Sequence↗

[Changes in C100-3, and N14 antibodies in patients with chronic hepatitis C treated with interferon].

In interferon therapy for chronic hepatitis type C, we assayed C100-3 and N14 antibodies, and also determined IgM-C100-3 and IgM-N14 antibodies as well as HCV-RNA. N14 antibody was assayed by an end point titer method. In patients responding to interferon therapy, C100-3 and N14 antibody titers were decreased and became negative. In patients irresponsive to interferon therapy, C100-3 antibody titers were hardly changed, while N14 antibody titers were markedly increased. IgM-C100-3 and IgM-N14 antibody levels were significantly higher in the patients non-responding to interferon therapy than in those responding to interferon therapy. The daily assays of C100-3 and N14 antibody titers are considered useful in judging the effectiveness of interferon against chronic hepatitis type C.

Antigens, Viral↗

[Thoracoscopic observation and diagnosis in cases of pleural, mediastinal, and pulmonary lesions].

Thoracoscopy was performed in a total of 424 patients at our institute from January 1970 to December 1993. The indications for thoracoscopy were pneumothorax (121 cases), primary lung cancer (98 cases), mediastinal tumor (45 cases), metastatic lung tumor (23 cases), pleuritis (35 cases), diffuse lung disease (38 cases), tuberculosis (20 cases), benign lung tumor (10 cases), and other (34 cases). By 1990, diagnostic thoracoscopy had been performed in 383 patients. Since 1991, thoracoscopy has been used therapeutically for spontaneous pneumothorax (24 cases), mediastinal and chest wall tumors (9 cases), pulmonary nodules (2 cases), and others (8 cases). Findings useful for diagnosis were obtained in 326 cases and biopsy was performed in 173 cases. Thoracoscopy was especially useful in the diagnosis of diffuse lung disease, pleuritis, and small pulmonary nodules. Recent advances in endoscopic equipment and refinement of thoracoscopic techniques have expanded the application of this procedure. Our experience indicates a markedly expanded role for thoracoscopy in the diagnosis and treatment of thoracic diseases, with less postoperative morbidity.

Humans↗

[A case of acute disseminated encephalomyelitis with pathologically-proven acute demyelinating lesion in the peripheral nervous system].

We present a case of acute severe demyelination affecting both CNS and PNS with pathological evidence. A 62-year-old man presented with acute onset of coma preceded by common cold-like symptoms. He was diagnosed as acute disseminated encephalomyelopathy (ADEM), and died of brain herniation in two weeks. At autopsy, in addition to severe demyelination of the white matter of the central nervous system, there was widespread acute demyelinating process in the peripheral nervous system. Myelin destruction by macrophage was most conspicuous in the spinal nerve root with preservation of the axon cylinder. So far the association of hypertrophic demyelinating neuropathy was reported in cases of multiple sclerosis. However, there have not been any papers in which substantial involvement of both CNS and PNS in cases of ADEM except for the clinical report by Amit. Antigenic cross-reactivity between CNS and PNS against myelin proteins or other antigens like glycolipid may elicit similar immune responses producing demyelination.

Acute Disease↗

[A comparative evaluation of three commercially available peak flowmeters before and after being used 1000 times].

The differences in values, accuracy, reproducibility and interdevice variability of three models of portable peak flowmeters (standard and low range of Assess, mini-Wright, Pulmo-Graph) before use and after they had been used 1000 times. A computerized standard flow generator was used to evaluate. Standard range; The three models showed differences in values before and after 100 uses of less than 3 percent at flow rates below 480 L/min. However, the used flowmeters, especially the Assess, showed higher values compared with the new ones at higher flow ranges. There was no significant difference in accuracy between the new and used mini-Wright and Pulmo-Graph models. The used Assess, howevers, showed higher values at higher ranges, thus demonstrating improved accuracy over the new ones. The reproducibilities of the three models deteriorated at high flow rates. The interdevice variability of the used Pulmo-Graph flowmeter was better than that the new one. No significant changes were observed in the mini-Wright, while the Assess showed deteriorated interdevice variability. Low range; The three models showed no significant differences in values, accuracy, reproducibility or interdevice variability before and after use.

Evaluation Studies as Topic↗

Production by a baculovirus expression system of the APO-protein of L-gulono-gamma-lactone oxidase, a flavoenzyme possessing a covalently-bound FAD.

L-Gulono-gamma-lactone oxidase, an enzyme functioning in L-ascorbic acid biosynthesis in higher animals, possesses a covalently-bound FAD as the prosthetic group. Catalytically-active enzyme was expressed in silkworm cells by a recombinant baculovirus encoding rat L-gulono-gamma-lactone oxidase. When recombinant enzyme was expressed under riboflavin-deficient conditions, most of it was found to be the apoprotein, as evidenced by an increase in enzymic activity upon addition of FAD to the assay mixture. Interestingly, the observed enzymic activity is thought to have been provoked by a noncovalent interaction between FAD and the apoprotein, since the covalent attachment of FAD was not demonstrated by a fluorometric gel-scanning experiment.

Animals↗

Inhibition of reperfusion injury by human thioredoxin (adult T-cell leukemia-derived factor) in canine lung transplantation.

Human thioredoxin, which was previously recognized as adult T-cell leukemia-derived factor, has many physiologic activities, one of which is a radical scavenger effect. Its ability to reduce reperfusion injury was assessed in vivo in a canine lung transplantation model. In 19 dogs, left lung allotransplantation was performed after 100 minutes of warm ischemia. The function of the transplanted lung was assessed after clamping of the contralateral pulmonary artery. In the human thioredoxin group (n = 6), human thioredoxin 30 mg/kg was given to the recipients during reperfusion. In the N-acetylcysteine group (n = 5), N-acetylcysteine 150 mg/kg, known as a radical scavenger, was given in the same manner. In both groups, arterial oxygen tension was significantly higher than in the control group (n = 8). In the human thioredoxin group, peak inspiratory pressure was significantly lower than in the control group. Macroscopic and microscopic examinations showed an almost normal appearance of the lung tissues in the human thioredoxin and N-acetylcysteine groups, in contrast to the abnormal findings in the control group. Thus it would appear that human thioredoxin has a protective effect on transplanted lungs, as does N-acetylcysteine, and that its action may be a radical scavenger effect.

Animals↗

[Diagnosis of mediastinal lymph node metastasis in primary lung cancer: comparing CT scan and mediastinoscopy].

In 105 patients with primary lung cancer who were operated on, the rate of diagnosis of mediastinal lymph node metastasis was determined, and the results of CT scanning and mediastinoscopy were compared. The rate of accuracy of mediastinoscopy was 93.8%, considerably higher than that of CT, which was less than 85%. For the lymph nodes other than #7, which indicate contralateral metastasis, the rate of accuracy of mediastinoscopy was even better and reached 96.3%. In the 9 patients who were proved by mediastinoscopy to have contralateral lymph node metastasis, the rate of accuracy of CT was only 44%. Mediastinoscopy was very effective in the diagnosis of mediastinal lymph node metastases from primary lung cancers.

Humans↗

Interferon-beta endogenously produced by intratumoral injection of cationic liposome-encapsulated gene: cytocidal effect on glioma transplanted into nude mouse brain.

The cytocidal effect of endogenously produced human interferon-beta was tested on glioma transplanted into the brain of nude mice by intracranial injection of a cell suspension of human glioma cell line U251-SP. When plasmid pSV2IFN-beta, bearing the human interferon-beta gene, was encapsulated into cationic multilamellar liposomes composed of N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride, dilauroyl phosphatidylcholine, and dioleoyl phosphatidylethanolamine in a molar ratio of 1:2:2 and injected intratumorally, human interferon-beta was produced in the tumor. The tumor completely disappeared if the injection was done shortly after the transplantation. Even when the tumor did not disappear, survival of the tumor-bearing nude mice was markedly prolonged. In control experiments made with normal brain having no glioma, interferon-beta was not detected.

Animals↗

Effects of newly developed solutions containing trehalose on twenty-hour canine lung preservation.

Trehalose is a nonreducing disaccharide that stabilizes the cell membrane under various stressful conditions. A previous study demonstrated that trehalose was effective in 12-hour canine lung preservation. We have developed new preservation solutions containing trehalose: an extracellular type ET-Kyoto solution (Na 100 mmol/L, K 44 mmol/L) and an intracellular type IT-Kyoto solution (Na 20 mmol/L, K 130 mmol/L). The composition of these solutions is identical except for the electrolyte content. We examined their efficacy in 20-hour lung preservation. Canine lungs were flushed with ET-Kyoto (group A, n = 6), with IT-Kyoto and prostaglandin E1 (25 micrograms/kg) (group B, n = 6), or with Euro-Collins solution and prostaglandin E1 (25 micrograms/kg) (group C, n = 7), and stored for 20 hours at 4 degrees C. Left lung transplantation was performed and evaluated for up to 130 minutes. The flush time was similar in the three groups. Arterial oxygen tensions (inspired oxygen fraction = 0.5) in group A were uniformly excellent (303.3 +/- 7.0 mm Hg 70 minutes after reperfusion and 303.0 +/- 19.6 mm Hg 130 minutes after reperfusion) and significantly higher than in group B (202.6 +/- 32.0 mm Hg, p < 0.05, and 197.8 +/- 44.0 mm Hg, p = 0.054, respectively) or group C (185.9 +/- 23.0 mm Hg, p < 0.01, and 155.7 +/- 36.3 mm Hg, p < 0.05, respectively). Peak inspiratory pressure in group A was significantly lower than in groups B and C (p < 0.05). Wet/dry weight ratio in group A was significantly lower than in groups B (p < 0.05) and C (p < 0.01). Histologic and scanning electron microscopic examinations showed better preservation in group A than in groups B and C. We conclude that ET-Kyoto is superior to IT-Kyoto and to Euro-Collins solution for 20-hour lung preservation.

Animals↗

[An evaluation of three commercially available peak flowmeters].

The accuracy, reproducibility and interdevice variability of three models of portable peak flowmeters (standard and low range) were evaluated by using a computerized standard flow generator. Standard range; The mini-Wright peak flow meter generally overestimated peak flow from 120 L/min to 540 L/min and the Assess peak flowmeter underestimated peak flow at full range. The Pulmo-Graph peak flowmeter showed a similar pattern to the mini-Wright but with more accuracy. The Assess showed the best linearity. The reproducibilities of the three models deteriorated over 20 L/min at high flow rates. The interdevice variability of the mini-Wright was better than those of the Assess or the Pulmo-Graph. Low range: The accuracy and interdevice variability of the Pulmo-Graph were better than those of the Assess or the mini-Wright. The reproducibility of Assess seemed to be inferior to the other's. The measured flow from the low ranges was not the same as that of the standard ranges. The three peak flowmeter models have different spring mechanisms for their readings, and the measured flows by one model should not be compared with other models.

Evaluation Studies as Topic↗

[MRI imaging of purulent cerebral ventriculitis].

This report concerns a 68-year-old male who was diagnosed as having purulent ventriculitis based on CT and MRI findings. He was first admitted to a nearby hospital with fever and impaired consciousness and thought to be suffering from herpes simplex encephalitis based on laboratory findings. In spite of treatment with acyclovir and antibiotics, his symptoms persisted for one and a half months. Because of gradual deterioration of his neurological status, he was transferred to our hospital. On admission he was stuporous with nuchal rigidity and a fever of 38.5 degrees C. The CSF leukocyte count was elevated (217/mm3) with predominantly polymorphonuclear cells (mononuclear 20, polymorphonuclear 197). Gd-DTPA MRI (T1-weighted) showed marked enhancement of the ependyma of the fourth ventricle and both lateral ventricles. A diagnosis of purulent ventriculitis was made and high-dose antibiotics (ABPC 12g, CTX 9g) were started intravenously. Gradual improvement in the clinical signs was observed with rapid normalization of the CSF cell-count. The patient had completely recovered one month after the start of treatment and this was associated with disappearance of abnormal enhancement on the MRI images. Although cerebral ventriculitis occasionally occurs as a complication of neonatal meningitis, it is rare in adult purulent meningitis. In our patient, persistent meningitis combined with impaired drainage of CSF from the ventricles are presumed to have caused ventriculitis. Serial enhanced MRI is particularly helpful in diagnosing ventriculitis, and can serve as a good index for monitoring the effects of treatment.

Aged↗

Combined therapy in children and adolescents with IgA nephropathy.

We retrospectively evaluated renal outcome in a total of 38 children and adolescents with IgA nephropathy who were selected for 6-month therapy for clinical (proteinuria > 1 g/m2/24 hour) and pathologic (mesangial proliferation, crescent formation, and tubulo-interstitial changes) features suggestive of progressive renal failure. Seventeen patients (group A) were treated with a combination of prednisolone, cyclophosphamide and dipyridamole, and the remaining patients (21; group B) were treated with the same drugs plus warfarin. All the patients were followed-up for more than 2 years (range 2-10 years, mean 4.8). In both groups, the mean urinary protein excretion value was significantly reduced after the therapy, compared with that at entry into the therapy. The significant reduction continued for up to 6 years in group A and up to 5 years in group B. Creatinine clearance was stable until 5-6 years after the trial in both groups, but 4 patients progressed to end-stage renal failure after that period. Post-therapy biopsy was performed in 14 patients, and was compared with the pre-therapy biopsy. The activity score had improved in both groups, but the chronicity score did not. These results indicate that there was a temporary effect and limited benefit with this treatment of combined drugs for children and adolescents with IgA nephropathy. The additive effect of warfarin was not substantiated.

Adolescent↗