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Biomedical subjects

K Iida

Publications and source records attributed to K Iida.

At least 19 recordsLinked to original sources

Hormonal regulation of the human ghrelin receptor gene transcription.

The aim of this study is to clarify the hormonal regulation of the human ghrelin receptor gene expression in GH(3) cells transfected with our previously cloned 5'-flanking region inserted into a luciferase reporter vector. Phorbor 12-tetradecanoate 13-acetate (TPA) with simultaneous addition of Bay K8644 mimicking ghrelin action caused a significant inhibition of the luciferase activity through the ghrelin receptor gene upstream proximal to -669 but not to -608 base pairs (bp). Glucocorticoid caused a weak but significant inhibition of the luciferase activity through the ghrelin receptor gene upstream proximal to -531 but not to -475 bp. Electrophoretic mobility shift assay resulted in binding of oligonucleotides between -669 and -640 bp, and between -520 and -491 bp to GH(3) cell nuclear proteins unlike AP(2) or glucocorticoid receptor. These results suggest that both TPA/Bay K8644 and glucocorticoid downregulate human ghrelin receptor gene expression through the transcriptional mechanism involving some nuclear factors.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Effect of additives on insulin absorption from intratracheally administered dry powders in rats.

The lungs are useful for administration of macromolecules, which are poorly absorbed from the intestine. In the present study, we prepared several dry powder formulations of insulin using a spray drying technique to examine the effect of additives on insulin absorption. The bioavailability of insulin was estimated from the change in the plasma glucose level. The bioavailability of insulin from dry powder with no additive exceeded that obtained from pH 7.4 solution. The absolute bioavailability of insulin administered as a solution with 1.4 mg/dose of bacitracin or 1.0 mg/dose of Span 85 was almost 100%. The bioavailability of dry powder with 0.42 mg/dose of bacitracin was 20% that of the solution with 1.4 mg/dose of bacitracin. The insulin dry powder with 0.21 mg/dose of Span 85 showed a bioavailability less than that for the insulin solution with 0.1 mg/dose of Span 85. Bacitracin and Span 85 were not as effective in dry powder as in solution in the present study. While citric acid was more effective in dry powder that in solution to increase the hypoglycemic effect. The pH 5.0 and pH 3.0 solutions containing 0.19 mg of citric acid in 0.1 ml showed absolute bioavailabilities of 43% and 57%, respectively, while the bioavailabilities for dry powders containing 0.025 and 0.036 mg/dose citric acid were 42% and 53%, respectively. In addition, the hypoglycemic effect of dry powders continued for a longer period and remained at 240 min with the dry powders, while it disappeared at 180 min with the solutions. When the insulin dry powder containing 0.036 mg/dose of citric acid was administered, the lactate dehydrogenase activity, a sensitive indicator of acute toxicity to lung cells, in bronchoalveolar lavage was as low as that for saline administration, suggesting citric acid is a safe additive. Thus, citric acid appears to be a safe and potent absorption enhancer for insulin in dry powder.

Absorption↗

Dual action of eicosapentaenoic acid in hepatoma cells: up-regulation of metabolic action of insulin and inhibition of cell proliferation.

Exogenous administration of eicosapentaenoic acid (EPA) improves insulin sensitivity, but its precise mechanism remains unknown. Here we show that EPA stimulates the intracellular insulin signaling pathway in hepatoma cells. Exposure of these cells to EPA caused up-regulation of several insulin-induced activities including tyrosine phosphorylation of insulin receptor substrate-1, insulin receptor substrate-1-associated phosphatidylinositol 3-kinase, and its downstream target Akt kinase activity as well as down-regulation of gluconeogenesis. In contrast, EPA decreased mitogen-activated protein kinase activity and inhibited cell proliferation. These findings raise the possibility that EPA up-regulates metabolic action of insulin and inhibits cell growth in humans.

Adaptor Proteins, Signal Transducing↗

Eight novel mutations of the FBN1 gene found in Japanese patients with Marfan syndrome.

Marfan syndrome (MFS), an autosomal dominant connective tissue disorder, is caused by mutations in the gene encoding fibrillin 1 (FBN1). The clinical spectrum and severity of MFS disorder varies greatly both between and within families. Since there have been only a few reports on the relationship between FBN1 genotypes and clinical phenotypes in Japanese patients, the FBN1 gene was analyzed in 27 Japanese patients diagnosed with MFS. The nucleotide sequence of the 65 exons of the FBN1 gene was analyzed by PCR and direct sequencing. We have identified six polymorphisms and nine mutations including: four missense mutations (C1652Y, Q2054P, D2127Y, C2221R) in six patients, three nonsense mutations (R215X, S813X, R2220X) in three patients, and two frameshift mutations (2567insT, 7790insT) in three patients. Six of these nine mutations were in the calcium-binding epidermal growth factor-like domains all causative mutations detected except for C2221R were novel. It has been reported that the severe phenotypes of infantile MFS correlate with mutations in the mid region of FBN1, however, mutations were not detected in this region in the population analyzed in this study. Our results suggest that the location of the mutation is not the sole determinant of phenotypic severity; rather there is some difference in the genetic basis of MFS between Japanese and Caucasian populations.

Adolescent↗

Concomitant pituitary adenoma and Rathke's cleft cyst.

We reviewed the clinical, radiological and surgical findings in patients with both pituitary adenoma and Rathke's cleft cyst. We retrospectively selected patients with both lesions from the 374 patients in whom a sellar/juxtasellar lesion was detected on MRI at 1.5 tesla. All patients received intravenous contrast medium. Concomitant pituitary adenoma and Rathke's cleft cyst were found in eight patients (2.1 %). The frequency of the combination was 3.5 % of pituitary adenomas and 11% of Rathke's cleft cysts. Symptoms were always due to the adenoma, secreting adrenocorticotrophin in two patients and growth hormone in six. The adenoma was larger in five patients, and the cyst in three. The cysts gave variable signal. The adenoma was adjacent to the cyst in seven patients, and enclosed it in the other patient. As a result of experience with MRI, concomitant pituitary adenoma and Rathke's cleft cyst are now known not to be as rare as thought previously. When a non-enhancing cyst-like structure is demonstrated in a patient with pituitary adenoma, the possibility of a coexisting Rathke's cleft cyst should be considered.

Adenoma↗

Disease model: hyperinsulinemia and insulin resistance. Part B--polygenic and other animal models.

Deficiency of leptin or its receptor produces hyperinsulinemia with marked obesity. Paradoxically, severe insulin resistance also accompanies lipodystrophy. Animal models of these contrasting conditions have enabled us to observe the profound and complicated aspects of the underlying pathologies. In addition, conventional polygenic rodents with known genetic backgrounds, such as the spontaneously hypertensive rat and the Goto-Kakisaki rat, have also been used to investigate these abnormalities.

Animals↗

Ser-59 is the major phosphorylation site in alphaB-crystallin accumulated in the brains of patients with Alexander's disease.

The phosphorylation state of alphaB-crystallin accumulated in the brains of two patients with Alexander's disease (one infantile and one juvenile type) was determined by means of SDS-PAGE or isoelectric focusing of soluble and insoluble fractions of brain extracts and subsequent western blot analysis with specific antibodies against alphaB-crystallin and each of three phosphorylated serine residues. The level of mammalian small heat shock protein of 25-28 kDa (Hsp27) in the same fraction was also estimated by western blot analysis. The majority of alphaB-crystallin was detected in the insoluble fraction of brain homogenates and phosphorylation was preferentially observed at Ser-59 in both cases. A significant level of phosphorylation at Ser-45 but not Ser-19 was also detected. Hsp27 was found at considerable levels in the insoluble fractions. alphaB-crystallin and phosphorylated forms were detected in the cerebrospinal fluid of patient with the juvenile type. AlphaB-crystallin and phosphorylated forms were also detectable at considerable levels in the insoluble fraction of brain homogenates from patients with Alzheimer's disease and aged controls. The phosphorylation site was mostly at Ser-59 in all cases. Immunohistochemically, alphaB-crystallin was stained in Rosenthal fibers in brains of patients with Alexander's disease and their peripheral portions were immunostained with antibodies recognizing phosphorylated Ser-59. These results indicate that the major phosphorylation site in alphaB-crystallin in brains of patients with Alexander's disease or Alzheimer's disease as well as in aged controls is Ser-59.

Adult↗

Chlorohydrins of bisphenol A diglycidyl ether (BADGE) and of bisphenol F diglycidyl ether (BFDGE) in canned foods and ready-to-drink coffees from the Japanese market.

BADGE.2HCl and BFDGE.2HCl were determined in 28 samples of ready-to-drink canned coffee and 18 samples of canned vegetables (10 corn, 5 tomatoes and 3 others), all from the Japanese market. HPLC was used as the principal analytical method and GC-MS for confirmation of relevant LC fractions. BADGE.2HCl was found to be present in one canned coffee and five samples of corn, BFDGE.2HCl in four samples of canned tomatoes and in one canned corn. No sample was found which exceeded the 1 mg/kg limit of the EU for the BADGE chlorohydrins. However the highest concentration was found for the sum of BFDGE.2HCl anti BFDGE.HCl.H2O at a level of 1.5 mg/kg. A Beilstein test confirmed that all cans containing foods contaminated with BADGE.2HCl or BFDGE.2HCl had at lest one part coated with a PVC organosol.

Benzhydryl Compounds↗

Gynecologic tumors and symptoms in childhood and adolescence.

Although tumors are rarely seen in girls, they should be considered in differential diagnosis because of the high incidence of potential malignancy in genital tumors compared with adults. Ultrasonography can quickly evaluate the underlying cause of genital symptoms or signs and allow timely intervention, while magnetic resonance imaging accurately measures the extent and location of the vaginal lesion. As a result of modern progress in the chemotherapy regimens, the prompt and precise detection of either benign or malignant tumors can lead to both cure and preservation of fertility with conservative surgery whenever possible. With the widespread use of obstetrical ultrasonography, fetal abdominal tumors are being diagnosed with increasing frequency. Most of these tumors will undergo spontaneous resolution within the first few months of life.

Adolescent↗

Comparison of specific serological assays for diagnosing human herpesvirus 6 infection after liver transplantation.

Cross-reactivity between human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) antibodies and the reliability of specific serological assays were analyzed for 12 patients with concurrent HHV-6 and HHV-7 antibody responses after transplantation with a liver from a living relative by using an immunofluorescence assay (IFA). A neutralizing antibody titer assay (NT) and an immunoblot assay (IB) designed to detect immunoglobulin M (IgM) antibody to the HHV-6 immunodominant 101-kDa protein were compared in the diagnosis of an active HHV-6 infection. A total of 9 of 12 patients demonstrated concurrent HHV-6 and HHV-7 antibody responses, including increased IgG titers and/or the presence of IgM by IFA, and were thus analyzed for cross-reactive antibody to heterologous virus. The average percentages of residual antibody to HHV-6 and HHV-7 after absorption with HHV-6 antigen were 32.6% (range, 6 to 50%) and 55.6% (range, 35 to 100%), respectively. All 12 patients were subsequently analyzed for HHV-6 antibody by using IB and NT. IB detected IgM antibody to the 101-kDa protein in 75% (9 of 12) of the recipients. A significant rise in the NT antibody titer was detected in the same nine samples. However, HHV-6 DNA was detected by PCR in only five of nine plasma samples collected from recipients with a specific serologic response against HHV-6.

Adolescent↗

Type 1 fimbriation and its phase switching in diarrheagenic Escherichia coli strains.

Type 1 fimbriae can be expressed by most Escherichia coli strains and mediate mannose-sensitive (MS) adherence to mammalian epithelial cells. However, the role of type 1 fimbriae in enteric pathogenesis has been unclear. Expression of type 1 fimbriae in E. coli is phase variable and is associated with the inversion of a short DNA element (fim switch). Forty-six strains of diarrheagenic E. coli were examined for the expression of type 1 fimbriae. Only four of these strains were originally type 1 fimbriated. Seventeen strains, originally nonfimbriated, expressed type 1 fimbriae in association with off-to-on inversion of the fim switch, after serial passages in static culture. The switching frequencies of these strains, from fimbriate to nonfimbriate, were greater than that of the laboratory strain E. coli K-12. None of the 16 strains of serovar O157:H7 or O157:H(-) expressed type 1 fimbriae after serial passages in static culture. The nucleotide sequence analysis of the fim switch region revealed that all of the O157:H7 and O157:H(-) strains had a 16-bp deletion in the invertible element, and the fim switch was locked in the "off" orientation. The results suggest that expression of type 1 fimbriae may be regulated differently in different E. coli pathogens causing enteric infections.

Bacterial Adhesion↗

Evaluation of flow properties of dry powder inhalation of salbutamol sulfate with lactose carrier.

The effects of the flow and packing properties of a drug/carrier powder mixture on emission of drug adhering to the carrier from capsules and inhalation devices were investigated. Model powder mixtures were designed consisting of lactose carriers with different particle shapes were prepared by surface treatment and micronized salbutamol sulfate. These powder mixtures were aerosolized by a Spinhaler, and in vitro deposition properties of salbutamol sulfate were evaluated by a twin impinger. The flow properties of the mixed powders were evaluated by the Carr's flowability index (FI) and Hausner's ratio (HR). The packing properties of the mixed powders were determined employing the tapping method. Compared with the powder mixed with the untreated lactose carrier, the FI, HR, and the constant K in Kawakita's equation of the powder mixture prepared using the surface-treated lactose carrier were significantly different, showing that the flow and packing properties of the drug/carrier powder mixture were improved. Using this surface-treated system, the handling of the powder mixture when packing into capsules is improved, which is desirable for handling dry powder inhalants. The fraction (%) of drug emitted from capsules and devices (EM) and the FI of the powder mixture were correlated. As the flow properties improved, the outflow of the powder mixture from capsules and devices became easier, and emission of drug adhering on the carrier from capsules and devices improved. Improvement of the inhalation process, such as the drug particles emitted from the inhalation system, is valuable for increasing inhalation properties of dry powder inhalation.

Aerosols↗

Using isoproterenol stress echocardiography to predict the response to carvedilol in patients with dilated cardiomyopathy.

Trials have demonstrated that carvedilol can produce hemodynamic, symptomatic, and prognostic improvements in dilated cardiomyopathy (DCM), but some DCM patients have deteriorated after carvedilol, developing congestive heart failure. The present study investigated the use of isoproterenol (ISP) stress echocardiography to select those patients with DCM who would respond to carvedilol. ISP was infused intravenously in 22 patients with DCM and they were classified into 2 groups based on the left ventricular systolic response: good response to ISP [change in fractional shortening (FS) with ISP > 0.05, n=13] and poor response to ISP (change < or = 0.05, n=9). In the good response group, FS significantly increased from 0.12+/-0.04 to 0.17+/-0.08 (mean+/-SD, p<0.05) with carvedilol, and 7 patients improved symptomatically (New York Heart Association class). However, in the poor response group, no significant difference was observed between FS at baseline and that at the end of follow-up. Moreover, only 1 patient in the poor response group improved symptomatically. ISP stress echocardiography can assist in selecting patients with DCM who will respond positively to carvedilol.

Adrenergic beta-Antagonists↗

[Analysis of main pigments and other ingredients in lac color product].

The contents of the main pigments and other ingredients in commercial lac color products were determined by HPLC using an RP-18 column with 0.1 mol/L citric acid buffer solution-methanol (16:5) as the mobile phase, and a photodiode array (PDA) detector set at 280 nm and 490 nm. The main pigments were confirmed by PDA and electrospray ionization mass spectrometry. Laccaic acids A, B, C and E were detected in all lac color products, and the ratio of content of laccaic acid A in all products was over 50%. The total contents of laccaic acids A, B and C in lac color food additive products and reagent products were 775-858, 797 and 779 g/kg, respectively. As for the contents of ingredients except pigments in commercial food additive products, the maximum moisture content was about 10%, and ether-soluble substances amounted to 0.5-3.6%.

Azo Compounds↗

[A survey of awareness among new patients at the department of oral diagnosis and general dentistry].

The purpose of this study is to know the outline of clinical statistics of new patients at the Clinic for Initial Diagnosis/Emergency, Dental Hospital, Tokyo Medical and Dental University. We examined 1,001 new patients who visited our hospital from 19 October to 8 December 1995. The results were obtained as follows: 1. Our subjects were 1,001 patients, males were 357(35.7%) and females 644(64.3%). The ratio of male to female was 1:1.8. 2. Concerning age distribution, the majorities were in their twenties and fifties in order. 3. 71.5% of patients said it took less than one hour for them to come to our hospital. 4. The rate of introduced patients was 5.5% of all the new patients.

Adult↗

Impaired ability to secrete atrial natriuretic peptide in response to isoproterenol infusion in patients with dilated cardiomyopathy.

OBJECTIVES: The myocardium has 2 functions in vivo, that of pump and endocrine organ. Therefore, simultaneous examinations of cardiac systolic reserve and endocrine reserve are important in evaluating the activities of the myocardial cells. This study investigated the relationship between cardiac systolic reserve and secretion of atrial natriuretic peptide (ANP) in response to isoproterenol infusion in patients with dilated cardiomyopathy. METHODS: Isoproterenol was infused intravenously in 6 healthy individuals (control group) and 32 patients with dilated cardiomyopathy. The left ventricular systolic responses and plasma ANP concentrations were measured. RESULTS: Patients with dilated cardiomyopathy were classified into 2 groups: patients with a good response (change in fractional shortening > 7%, 17 patients) and those with a poor response (change in < or = 7%, 15 patients). There was no significant difference in end-diastolic dimension, fractional shortening, heart rate, or systolic blood pressure between the 2 groups of patients with dilated cardiomyopathy at rest. The resting plasma ANP concentration in the poor-response group (88.8 +/- 59.0 pg/ml) was significantly higher than that in the other 2 groups (good: 47.0 +/- 35.9 pg/ml, p < 0.05, control: 9.8 +/- 4.1 pg/ml, p < 0.01, respectively). The percentage change in ANP after isoproterenol infusion in the poor-response group (-7.1 +/- 16.7%) was significantly less than that in the other 2 groups (good: 12.6 +/- 27.3%, p < 0.05, control: 31.5 +/- 24.6%, p < 0.01, respectively). CONCLUSIONS: The resting plasma ANP concentration can be used to evaluate the cardiac systolic reserve in patients with dilated cardiomyopathy. Decreased myocardial systolic reserve is also associated with impaired ability to secrete ANP.

Adrenergic beta-Agonists↗

[A case of malignant myoepithelioma in the lacrimal gland].

BACKGROUND: A case of malignant myoepithelioma in the lacrimal gland is reported. CASE: The patient, a 77-year-old male with increasing proptosis in the left eye was referred to us. Steroid therapy was not effective, therefore lateral orbitotomy was performed. RESULT: On pathological examination, the proper structure of actini was normal, but the cord of actini revealed the destruction layer tapering into the surrounding area. The tumor was composed of sarcomatoid changes with spindle-shaped cells, collagen fibers, and myxoid pattern. immunohistochemically, tumor cells were positive for epithelial membrane antigen (EMA) and alpha-smooth muscle actin (alpha-SMA). Electronmicroscopy showed desmosomes in intercellular junctions. CONCLUSION: Recently, there have been attempts to distinguish myoepithelioma from pleomorphic adenoma on the basis of cellular organization. In our case, duct formation was less than in pleomorphic adenoma. Therefore we diagnosed this tumor as malignant myoepithelioma.

Aged↗

Performance of a conventional enzyme immunoassay for hepatitis C virus core antigen in the early phases of hepatitis C infection.

There are periods within the early phase of hepatitis C virus (HCV) infection in which the anti-HCV antibody test is unable to confirm HCV viremia. To reduce the risk of transmitting HCV through transfusions, we developed a simple and highly sensitive enzyme immunoassay (EIA) which detects the core antigen of HCV (HCVcAg). This assay employed a conventional colorimetric EIA system, and was based on a two-step sandwich assay, using a 96- well microplate. The reproducibility of the results was very high. When the cutoff values were set to 30 fmol of recombinant HCVcAg/L, as determined by the distribution of healthy subject sera (n=223), 99.6% of healthy subject sera and 100% of hepatitis B patient sera (n=50) were negative for HCVcAg. The clinical performance of this EIA was examined using 14 commercially available seroconversion panels. In every panel, HCVcAg could be detected at points preceding the seroconversion of anti-HCV antibodies. The points at which HCVcAg was detected were the same as those at which it was detected by an AMPLICOR HCV Monitor test. The EIA's window period for detecting the HCVcAg in all panels was on average 26 days shorter than that of the anti-HCV antibody test. In three panels where the first sample is negative for HCV RNA, the window period was shortened 50 days by this EIA for HCVcAg. There was a positive correlation between the concentration of HCVcAg and HCV RNA in anti-HCV antibody negative specimens. This assay was simpler to perform than assays based on gene amplification technology for the detection of HCV RNA, and the window period was shortened to that of the AMPLICOR HCV Monitor test. Thus, the EIA for HCVcAg would be useful in screening seroconverting donors and could reduce the residual risk of secondary HCV infections through transfusions.

Case-Control Studies↗