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Biomedical subjects

K Okazaki

Publications and source records attributed to K Okazaki.

At least 199 records · Page 11Linked to original sources

Cardioprotective effects of NIP-121, a novel ATP-sensitive potassium channel opener, during ischemia and reperfusion in coronary perfused guinea pig myocardium.

We investigated the effect of NIP-121, a novel ATP-sensitive K+ channel opener, on myocardial damage during ischemia/reperfusion. The action potential and contractile force of coronary-perfused guinea pig right ventricular walls were recorded. The preparations were subjected to 30-min no-flow ischemia with or without NIP-121 or glibenclamide, followed by 60-min reperfusion. In untreated tissues, decreases in action potential duration (APD) and contractile force and an increase in resting tension were observed during the no-flow period. On reperfusion, transient arrhythmias were observed and resting or contractile force returned to <50% of preischemic values. NIP-121, at 0.3 microM, a concentration showing only a slight negative inotropic effect, caused a faster decrease in APD and contractile force but abolished the increase in resting tension (RT) during the no-flow period. On reperfusion, no arrhythmia was observed in NIP-121-treated preparations, and contractile force recovered to approximately 80% of the preischemic value. Glibenclamide 1 microM attenuated the decrease in APD but affected neither the decrease in contractile force nor the increase in RT during the no-flow period. On reperfusion, the incidence of arrhythmia was increased in glibenclamide-treated preparations, and the recovery of basal tension and contractile force was inhibited: Contractile force recovered to only approximately 15% of the preischemic value. NIP-121 was also shown to attenuate the decrease in tissue ATP during ischemia and reperfusion. We demonstrated that NIP-121 may have protective effects against myocardial injury during ischemia and reperfusion. Activation of ATP-sensitive K+ current may be an adaptive mechanism for cardioprotection under compromised blood flow.

Action Potentials↗

Development of immuno-PCR for diagnosis of bovine herpesvirus 1 infection.

A highly sensitive immuno-PCR method specific for the detection of antigens of and antibodies to bovine herpesvirus 1 was established. This assay attained a high sensitivity of up to 10(7.0) times higher than that of enzyme-linked immunosorbent assay (ELISA) or PCR for antigen detection and 10(5.0) times higher than that of ELISA for antibody detection.

Animals↗

The extracellular signal-regulated kinase pathway phosphorylates AML1, an acute myeloid leukemia gene product, and potentially regulates its transactivation ability.

AML1 (also called PEBP2alphaB, CBFA2, or CBFalpha2) is one of the most frequently disrupted genes in chromosome abnormalities seen in human leukemias. It has been reported that AML1 plays several pivotal roles in myeloid hematopoietic differentiation and other biological phenomena, probably through the transcriptional regulation of various relevant genes. Here, we investigated the mechanism of regulation of AML1 functions through signal transduction pathways. The results showed that AML1 is phosphorylated in vivo on two serine residues within the proline-, serine-, and threonine-rich region, with dependence on the activation of extracellular signal-regulated kinase (ERK) and with interleukin-3 stimulation in a hematopoietic cell line. These in vivo phosphorylation sites of AML1 were phosphorylated directly in vitro by ERK. Although differences between wild-type AML1 and phosphorylation site mutants in DNA-binding affinity were not observed, we have shown that ERK-dependent phosphorylation potentiates the transactivation ability of AML1. Furthermore the phosphorylation site mutations reduced the transforming capacity of AML1 in fibroblast cells. These data indicate that AML1 functions are potentially regulated by ERK, which is activated by cytokine and growth factor stimuli. This study provides some important clues for clarifying unidentified facets of the regulatory mechanism of AML1 function.

Acute Disease↗

Results of systematic speech sound monitoring in children with cleft palate.

Using our monitoring system, we report the articulation results in 208 children with competent velopharyngeal function after surgery of cleft palate. The number of children who showed normal articulation at each test during the monitoring period was 138. The other 79 children included 37 who acquired normal articulation after training and whose misarticulation disappeared without training. Factors related to their misarticulation are discussed.

Articulation Disorders↗

[Studies on the synthesis of cholecystokinin A receptor antagonists. II. Synthesis and cholecystokinin A receptor inhibitory activities of sulfur-containing amide-carboxylic acid derivatives].

A number of sulfur-containing amide-carboxylic acid derivatives were synthesized and tested for cholecystokinin A (CCK-A) receptor inhibitory activity in order to study structure-activity relationships. Significant CCK-A receptor inhibitory activities were found in only two series, that is, sulfoxide-carboxylic acid derivatives (9) and sulfone-carboxylic acid derivatives (10). As the most preferred compound, 5-(3,4-dichlorophenylsulfonyl)-4-(N,N-dipentylcarbamoyl)pent anoic acid (10n) was selected.

Animals↗

[Studies on the synthesis of cholecystokinin A receptor antagonists. III. Synthesis and cholecystokinin A receptor inhibitory activities of naphthyl sulfone derivatives].

A number of naphthyl sulfone derivatives were synthesized and tested for cholecystokinin A (CCK-A) receptor inhibitory activity in order to study structure-activity relationships. Significant CCK-A receptor inhibitory activities were found in sulfone-carboxylic acid derivatives (7) having very hydrophobic sidechains. As the most preferred compound, (R)-4-[N-(3-methoxypropyl)-N-pentylcarbamoyl]-5-(2-naphthylsulf onyl) pentanoic acid ((R)-7c) was selected.

Animals↗

Intake ratio of water-insoluble dietary fiber to the water-soluble one in Japanese: an estimation on dietary records and the secular consideration on the national nutrition survey.

Thirty-four foods were analyzed in order to determine the content of water-soluble dietary fiber (SDF) and insoluble dietary fiber (IDF). Using the results with the standard table for 227 foods, the intake ratio of IDF/SDF of an average Japanese was calculated for the period 1946-1990. The ratio was 3.22 in 1990 as calculated on the food intakes shown in the national nutrition survey, and the secular change was not detected since 1946 when the ratio was 3.30. The ratio was also shown to be well preserved between types of households including the age of the head. Using dietary records of 60 healthy city workers (average 42.8 years) for 4 weeks, however, the weekly average ratio for an individual was found to vary in the range of 2.25-5.13 although the total average for 60 individuals was 3.33. Thus, the well preserved IDF/SDF intake ratio for an average Japanese showed, on the contrary, a wide variation of food selection between each person.

Adult↗

[Cardiac output in patients in their 90's].

Cardiac output was measured by the thermodilution method in nine patients aged 90 to 97 years. The patients were capable of walking in their daily lives before the injury or admission to the hospital, after which they were scheduled for operations. The causes for operations were localized and did not markedly influence general conditions of the patients. After heart rate, arterial blood pressure and mental condition of the patients had been stabilized, their cardiac outputs were determined before the induction of anesthesia. The results are as follows: Cardiac output: 3.58 +/- 0.90 l.min-1, cardiac index: 2.72 +/- 0.57 l.min-1.m-2. Previously published reports in Japan and the results of this study about the relationship between cardiac index and age suggest that as a whole there is a tendency for the cardiac index to decrease with aging.

Aged↗

[Use of Warm Touch for intraoperative hypothermia].

A 63-year old man was scheduled for nephrectomy and cholecystectomy. Anesthesia was maintained by oxygen-nitrous oxide-isoflurane (0.5 approximately 1%) and epidural anesthesia. Operation was performed with the patient on left decubitus position. At this time, rectal temperature as his core temperature was 35.8 degrees C. Active warming with electrical warming mattress was started and the room temperature was maintained at 25 degrees C during the operation. Thirty minutes after the abdominal incision, rectal temperature decreased to 34.5 degrees C. Active warming was started with forced-air warming system (Warm Touch, Mallinckrodt Medical Co.) on his upper body. Ten minutes after warming, his body temperatures were restored gradually. Three hours after using Warm Touch, rectal temperature recovered to 36.1 degrees C. The intraoperative course was uneventful. At the end of the operation, the patient showed no shivering and general condition was good. In this case, Warm Touch is useful to restore body temperature against intraoperative hypothermia during abdominal surgery.

Anesthesia, Epidural↗

Endoscopic features of gastric inflammatory fibroid polyps.

OBJECTIVES: The inflammatory fibroid polyp (IFP) is a rare benign lesion that can occur throughout the digestive tract. The aim of this study is to describe endoscopic features of gastric IFPs and to determine the clinical value of endoscopic removal. METHODS: Upper gastrointestinal endoscopy was performed in 13 patients with gastric IFPs. The IFPs were resected either by endoscopic removal or gastrectomy, and confirmed histologically as IFPs. To evaluate the diagnostic value, endoscopic features of the lesions were analyzed. RESULTS: The most frequent features were semi-pedunculated protrusions (61.5%), covered with a smooth surface of normal mucosa (100%), and located in the antrum or prepyloric region (100%). Bridging folds were observed in three of the 13 lesions (23.1%). The central surface of all 10-mm or larger lesions had an erythematous depression (three lesions), ulceration (five lesions), or white cap on the polyp (one lesion). Endoscopic biopsies failed to confirm IFP in any lesions. CONCLUSIONS: IFPs are commonly visualized as semi-pedunculated elevations, covered with a smooth surface of normal mucosa, and located in the antrum or prepyloric region. The 10-mm or larger lesions have central changes. Endoscopic removal of gastric IFPs is a useful method for both accurate diagnosis and treatment in view of negative results with the use of standard biopsy forceps.

Endoscopy↗

DNA typing by triplex affinity capture (TAC) PCR.

Using a triplex affinity capture approach, we extracted PCR-ready DNA from fresh blood, buccal swabs, and bloodstains made on hard objects. We immobilized a biotinylated purine-rich oligonucleotide onto streptavidin-coated magnetic beads, and captured double-stranded DNA via triple-helix formation. We were able to amplify the MCT118, ACTBP2, FGA, D8S320, D11S488, and THO1 loci from the captured DNA. DNA typing by triplex affinity capture PCR is simple, rapid, and well-suited for paternity testing and population studies of microsatellites.

Base Sequence↗

[A case of toxic shock syndrome induced by MRSA after sinus surgery].

We present a case of toxic shock syndrome (TSS) induced by MRSA after sinus surgery. The patient was a 64-year-old woman who had undergone sinus surgery because of chronic sinusitis. Nine days after the surgery, she began to have sore throat, fever, and diffuse erythroderma followed by severe hypotension and renal dysfunction. Culture of sputum, nasal discharge and stool showed MRSA. Blood culture was negative. She was treated with intravenous fluids, catecholamines and antibiotics (vancomycin and fosfomycin). Continuous hemodiafiltration was started because of oliguria. Her condition improved gradually and she was discharged about a month after the onset of her illness. We should recognize that TSS can occur as a fatal complication after nasal surgery.

Chronic Disease↗

[Mild glucose intolerance in the elderly].

Glucose tolerance has been shown to decline with age. Mechanisms of this phenomenon are not yet completely defined. The insulin response to glucose shows little change with age. The primary cause results from resistance to the ability of insulin to stimulate glucose uptake. Many factors, including composition of diet with regard to both caloric adequacy and carbohydrate content, decreased physical activity and decreased lean body mass, probably contribute to the insulin resistance. Mild glucose intolerance in the elderly, as in young adults, increases the risk for the development of overt diabetes mellitus and is a risk factor for the development of atherosclerotic diseases.

Aged↗

STR typing of buccal swabs for paternity testing with reference to Japanese population data on the D20S85, D14S118, and D14S543 loci.

To simplify short tandem repeat (STR) typing of genomic DNA, we used buccal cells instead of blood cells. Buccal swabs taken from paternity-test trios were washed with 1 ml of distilled water by centrifugation, and the pellets were suspended in 20 microliters of distilled water. The suspensions were frozen at -80 degrees C and then thawed. Using a 1/5 volume of each suspension, we were able to type STRs at the TH01, D20S85, D14S118, and D14S543 loci by triplex PCR amplification of the first three markers and by simplex amplification of the other. In addition, we studied the polymorphisms at the D20S85, D14S118, and D14S543 loci in a Japanese population of 320 individuals. The four loci have a combined average exclusion power of 99.37%. In 24 cases of disputed paternity, the results of STR typing of the four loci agreed with those of conventional marker typing. In addition to being simple and rapid, STR typing of buccal swabs involves no painful procedure. It is therefore preferable for paternity tests on infants and small children.

Alleles↗

Detection of viral genome in non-neural tissues of cattle experimentally infected with bovine herpesvirus 1.

To obtain further information on the latent infection with bovine herpesvirus 1 (BHV-1) in the natural host, we examined the nasal secretions and various tissues of experimentally infected calves using virus isolation, polymerase chain reaction (PCR), and immuno-PCR/antigen (Immuno-PCR/Ag) assays. In the nasal secretions, viral DNA was detected in samples with virus isolation titers of 10(4.3) TCID50 or more by PCR. On the same samples, Immuno-PCR/Ag remained positive up to day 19 p.i. the last day of test. BHV-1 DNA was detected from the following tissues in all the calves at day 22 p.i.: trigeminal ganglia, ovaries, lungs, nasal and tracheal mucosae, spleen, prescapular and precrural lymph nodes, and peripheral blood leukocytes (PBL), but not skeletal muscles. Virus was not recovered from any of these tissues. The present findings suggest a possible role of leukocytes in BHV-1 latent infection.

Animals↗

Effect of 60Co gamma radiation on Biomphalaria glabrata (Mollusca, Gastropoda) embryos: mortality, malformation and hatching.

A study was carried out on the radiosensitivity of Biomphalaria glabrata embryos submitted to doses of 5, 10, 15, 20 and 25 Gy of 60Co during the cleavage, blastula, gastrula, young trochophore and trochophore stages. Mortality, malformation and hatching were the parameters used to evaluate the damage induced by ionizing radiation. Estimated LD50 values (15 days) showed that the cleavage stage (4.3 Gy) was approximately four times more radiosensitive than the trochophore stage (17.0 Gy). Susceptibility to malformation induction was higher in the blastula, gastrula and young trochophore stages. Several types of morphogenetic malformations were observed, such as head malformations, exogastrulas, shell malformations, and embryos with everted stomodeum, with nonspecific malformations being the most frequent. The types of malformation induced by radiation probably are not radiation-specific and do not depend on the dose applied. The dose of 15 Gy was sufficient to greatly reduce the number of hatching snails regardless of the embryonic stage irradiated. We conclude that the effect of 60Co gamma radiation on B. glabrata embryos presented a specific pattern.

Animals↗

The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its transforming activity in NIH 3T3 cells.

The c-mos proto-oncogene product, Mos, is a serine/threonine kinase that can activate ERK1 and 2 mitogen-activated protein (MAP) kinases by direct phosphorylation of MAPK/ERK kinase (MEK). ERK activation is essential for oncogenic transformation of NIH 3T3 cells by Mos. In this study, we examined how mitogenic and oncogenic signalling from the Mos/MEK/ERK pathway reaches the nucleus to activate downstream target genes. We show that c-Fos (the c-fos protooncogene product), which is an intrinsically unstable nuclear protein, is metabolically highly stabilized, and greatly enhances the transforming efficiency of NIH 3T3 cells, by Mos. This stabilization of c-Fos required Mos-induced phosphorylation of its C-terminal region on Ser362 and Ser374, and double replacements of these serines with acidic (Asp) residues markedly increased the stability and transforming efficiency of c-Fos even in the absence of Mos. Moreover, activation of the ERK pathway was necessary and sufficient for the c-Fos phosphorylation and stabilization by Mos. These results indicate that c-Fos undergoes stabilization, and mediates at least partly the oncogenic signalling, by the Mos/MEK/ERK pathway. The present findings also suggest that, in general, the ERK pathway may regulate the cell fate and function by affecting the metabolic stability of c-Fos.

3T3 Cells↗

Effect of KN-62, Ca2+/calmodulin-dependent protein kinase II inhibitor, on adriamycin resistance of human ovarian cancer cells.

We examined effects of an isoquinolinesulfonamide derivative, KN-62, on human ovarian cancer cells, NOS3AR, that are resistant to Adriamycin (ADR). MTT assay revealed that 10 microM KN-62 overcame the resistance. KN-62 had little effect on GST activity. In studies on the intracellular accumulation of ADR, KN-62 increased the ADR contents in the resistant cells close to the level seen in the sensitive cells. These results suggest that the reversal of the resistance against ADR in ovarian cancer cells by KN-62 is mainly due to higher accumulation of ADR in NOS3AR cells. Furthermore, we detected Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in NOS3AR cells since KN-62 is a specific inhibitor of the kinase. In this paper, we discussed on modulation of ADR-resistance by KN-62.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗