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Biomedical subjects

A Takagi

Publications and source records attributed to A Takagi.

At least 73 records · Page 4Linked to original sources

Molecular cloning of Frizzled-10, a novel member of the Frizzled gene family.

The Frizzled genes encode WNT receptors. Frizzled-10 (FZD10), a novel member of the Frizzled gene family, has been cloned and characterized. Nucleotide sequence analysis showed that human FZD10 gene encodes a seven-transmembrane-receptor of 581 amino acids, with the N-terminal cysteine-rich domain and the C-terminal Ser/Thr-Xxx-Val motif. Larger amounts of FZD10 mRNA, 4.0 kb in size, were detected in the placenta and fetal kidney, followed by fetal lung and brain. In adult brain, FZD10 mRNA was abundant in the cerebellum. Among cancer cell lines, FZD10 was highly expressed in a cervical cancer cell line, HeLa S3, and moderately in a colon cancer cell line, SW480. The FZD10 gene was mapped to human chromosome 12q24.33. FZD10 shares 65.7% amino-acid identity with Frizzled-9 (FZD9). FZD10 and FZD9 constitute a subfamily among the Frizzled genes.

Adult↗

Overexpression of myotonic dystrophy protein kinase in C2C12 myogenic culture involved in the expression of ferritin heavy chain and interleukin-1alpha mRNAs.

The specific function of myotonic dystrophy protein kinase (DMPK) is still not known. We found that overexpression of human DMPK in C2C12 myogenic culture induces the expression of ferritin heavy chain (FN-H) mRNA using differential display analysis. The quantity of FN-H mRNA was greater in the DMPK transfectant with five CTG triplet repeats in the 3'-untranslated region, while it was lower in the transfectant with 46 CTG repeats, over that of the control clone. We also investigated the quantity of interleukin 1-alpha (IL-1alpha) mRNA in each culture, due to the fact that this cytokine is able to induce FN-H expression, regardless of the concentration of free iron. Quantitative, competitive polymerase chain reaction (PCR) analysis revealed that the quantity of IL1-alpha mRNA is higher in the transfectant with five repeats, compared to the quantity of mRNA in the control clone; however, it is markedly lower in the clone with 46 repeats. These results suggest that overexpression of DMPK in C2C12 cultures may up-regulate IL-1alpha expression, resulting in the induction of FN-H expression. However, a large number of CTG repeats in the 3'-untranslated region of the DMPK gene may affect the pathway of IL-1alpha transcription, thereby resulting in decreased expression of FN-H.

Animals↗

Clinical potential of intravascular ultrasound for physiological assessment of coronary stenosis: relationship between quantitative ultrasound tomography and pressure-derived fractional flow reserve.

BACKGROUND: Little is known regarding intravascular ultrasound (IVUS) criteria to determine the functional severity of coronary stenosis. Recently, fractional flow reserve (FFR) has emerged as a lesion-specific index of the functional severity of a coronary stenosis that is independent of systemic hemodynamic variability. The present study was undertaken to determine the IVUS parameters for the physiological severity of coronary stenosis. METHODS AND RESULTS: Fifty-one lesions in 42 patients were evaluated by means of quantitative coronary angiogram, IVUS, and intracoronary pressure measurements. The FFR was calculated as the ratio of the distal coronary pressure divided by the proximal coronary pressure under hyperemia. We considered a value of the FFR <0.75 as significant in determining inducible ischemia, according to the previous studies. The minimal luminal area (MLA) and the area stenosis were measured by IVUS. By regression analysis, the MLA showed a positive correlation with the FFR value (r(2)=0.62, P<0.0001). The area stenosis had a significant inverse correlation with the value of FFR (r(2)=0.60, P<0.0001). The IVUS thresholds that maximized the sensitivity and specificity were MLA <3.0 mm(2) (sensitivity, 83.0%; specificity, 92.3%) and area stenosis >0.6 (sensitivity, 92.0%; specificity, 88.5%). The combination of both criteria (MLA <3.0 mm(2) and area stenosis <0.6) without exception met a value of the FFR <0.75. CONCLUSIONS: Anatomic parameters obtained by IVUS showed a significant correlation to the FFR values. The present study demonstrated that the combination of the MLA and area stenosis measured by IVUS can be an anatomic predictor for the physiological impact of coronary epicardial stenosis.

Coronary Angiography↗

Inhibitory effect of microfibril wheat bran on azoxymethane-induced colon carcinogenesis in CF1 mice.

Microfibril wheat bran (MFW), a processed dietary fiber prepared by milling of coarse wheat bran (WB), is softer and has a more pleasant taste than WB. In this study, we examined the inhibitory effect of MFW on azoxymethane (AOM)-induced colon carcinogenesis in female CF1 mice and compared its effect with that of WB and cellulose (CL). The mice were fed a modified AIN 76 A diet supplemented with either MFW, WB, or CL at a final concentration of 20% (w/w). Six weekly s.c. injections of AOM (10 mg/kg body weight) were administered per mouse commencing 1 week after the start of the feeding period. Control mice were injected with saline only. Thirty-three weeks after the initial injection, the mice were sacrificed, examined for tumors, and the cecal contents were analyzed to determine the moisture content and the concentrations of short-chain fatty acids (SCFA). The average number of total tumors per mouse in the MFW (2.9 +/- 0.6, P = 0.017) and WB (5.3 +/- 1.3, P = 0.373) diet groups was lower than that of the CL diet group (7.5 +/- 1.3), though there was no significant difference in tumor incidence (94.7%, 90.0% and 94.7%, respectively) between the groups. More than 90% of the tumors in each group were adenocarcinomas. The incidence of adenoma and that of carcinoma in situ in the MFW diet group (5.3% and 0%, respectively) were also lower than those in the CL diet group (26.3 and 26.3%, respectively; P = 0.180 and P = 0.046, respectively). Analysis of the cecal contents revealed a significantly higher moisture content and significantly higher concentrations of SCFA, butyrate in particular, in the MFW and WB diet groups. The results of this study indicate that the source and texture of dietary fiber can influence tumor development in CF1 mice, and more specifically that MFW is a promising and useful dietary supplement with properties serving to protect against the development of colon cancer.

Adenocarcinoma↗

Induction of a critical elevation of povidone-iodine absorption in the treatment of a burn patient: report of a case.

A critical elevation of povidone-iodine absorption which occurred in a burn patient who was topically treated with 10% povidone-iodine (PI) gel is herein reported. A 65-year-old man was admitted to our hospital for deep second- and third-degree burns covering 26% of his total body surface area. The intravenous administration with lactated Ringer's solution and topical treatment with silver sulfadiazine were applied in addition to such treatments as debridement and skin grafting. However, wound infection occurred due to Pseudomonas aeruginosa. Topical treatment with PI gel was effective for this condition. Persistent nodal bradycardia with hypotension, metabolic acidosis, and renal failure occurred 16 days after the start of PI gel treatment. Iodine toxicosis caused by PI gel was suspected with a serum iodine level of 20600 microg/dl (normal range 2-9 microg/dl). The PI gel treatment was therefore discontinued immediately, and hemodialysis was scheduled. However, the patient's family refused hemodialysis and he died 44 days after admission. To our knowledge, only eight patients with iodine toxicosis have been reported in burn patients treated with PI gel.

Absorption↗

Inhibitory effect of oral administration of Lactobacillus casei on 3-methylcholanthrene-induced carcinogenesis in mice.

The present study was designed to determine whether tumor induction by 3-methylcholanthrene (MC), a carcinogenic hydrocarbon, can be inhibited by oral administration of Lactobacillus casei strain Shirota (LC). C3H/HeN mice were divided into four groups and assigned to the following treatments: treated with MC and given control or LC-containing diet; treated with vehicle only and given control or LC-containing diet. MC (1 mg) was injected intradermally at 7 weeks of age and the tumor incidence was monitored; LC was mixed into a diet at a concentration of 0.05% (w/w) and the diet was fed from the day of MC injection throughout the study. Spleen cells were analyzed for the immune parameters at 12 and 16 weeks after the MC injection. Oral feeding of mice with LC reduced tumor incidence (P < 0.05). MC treatment lowered the in vitro response to concanavalin A (Con A) of spleen cells, the secretion of interleukin-2 in spleen cell culture after stimulation of the cells with Con A and the proportions of CD3+ CD4+ and CD8 + splenic cells. However, the analysis of the spleen cells obtained from the mice treated with MC and given the LC-containing diet revealed that these disrupted host immune parameters were maintained at the level of normal controls. These results suggest that oral feeding of mice with LC inhibits MC-induced tumorigenesis by modulating the disrupted host immune responses during MC carcinogenesis.

Animals↗

Identification of compound heterozygous mutations (G188E/W382X) of lipoprotein lipase gene in a Japanese infant with hyperchylomicronemia: the G188E mutation was newly identified in Japanese.

We herein report a case of a 5-month-old Japanese female (patient AN) with fasting hyperchylomicronemia due to a primary lipoprotein lipase (LPL) deficiency. Patient AN was compound heterozygous for a missense mutation (GG818G-->GAG/Gly188-->Glu; G188E) in exon 5 and a nonsense mutation (TGG1401-->TGA/Trp382-->Stop; W382X) in exon 8 of the LPL gene. This resulted in less than 10% of the control levels for both the LPL activity and immunoreactive LPL mass in the postheparin plasma. A G188E mutation was thus identified for the first time in a Japanese, and the haplotype of this G188E allele was different from that of the G188E alleles identified in other ethnic groups. This additional mutation might be useful for early diagnosis of LPL gene aberrations in Japanese patients with fasting hyperchylomicronemia.

Base Sequence↗

Development and evaluation of a direct sandwich enzyme-linked immunosorbent assay for the quantification of lipoprotein lipase mass in human plasma.

OBJECTIVE: The purpose of this study was to develop and evaluate a direct sandwich enzyme-linked immunosorbent assay (ELISA) for quantification of the lipoprotein lipase (LPL) immunoreactive mass in human plasma using monoclonal antibodies (MAbs) directed against LPL purified from human postheparin plasma (PHP) [corrected]. METHODS AND RESULTS: The direct sandwich-ELISA was performed using a combination of two distinct types of MAbs that recognize different epitopes on the LPL molecule. The immunoreactive mass of human LPL was specifically measured using a horseradish peroxidase-labeled anti-human LPL MAb [1(1)D2B2] as an enzyme-linked MAb, and an anti-human LPL MAb [2(10)F8F9] coated on a polystyrene microtiter plate as a solid-phase MAb. Purified human PHP-LPL was used as a standard material. The detection range of the sandwich-ELISA was 3.6-460 ng of LPL protein per mL of plasma. The intra- and interassay coefficients of variation were less than 5.9% and 3.3%, respectively. The validity of this method was additionally assured by the recovery test, which resulted in the variation only between 97.5% and 105.1%, and also by the interference test, which resulted in noninterference of LPL assay with a high concentration of triglyceride, hemoglobin, bilirubin, uric acid, or creatinine. To assess the reliability of the LPL mass values obtained with the direct sandwich-ELISA, they were compared with LPL mass values determined by the one-step sandwich-EIA (MARKIT-F LPL EIA kit) previously established by us. This comparison showed a highly significant correlation (r = +0.990) between the two sets of values. The LPL mass concentrations in PHP from 33 healthy subjects were 267 +/- 53 and 257 +/- 59 ng/mL (mean +/- SD), respectively. CONCLUSION: The present direct sandwich-ELISA is useful for rapidly identifying certain abnormalities of LPL in PHP samples from patients with hypertriglyceridemia [corrected].

Adult↗

A novel sex-determining region on Y (SRY) nonsense mutation identified in a 45,X/47,XYY female.

OBJECTIVE: To determine whether an SRY mutation participated in the phenotypic outcome in the case of a 45,X/47,XYY female. DESIGN: Analysis of genomic DNA for mutations in SRY. SETTING: An academic teaching hospital. PATIENT(S): A family that included one phenotypic female with 45,X/47,XYY mosaicism. INTERVENTION(S): Extraction of DNA, polymerase chain reaction analysis, nucleotide sequencing, and restriction enzyme analysis. MAIN OUTCOME MEASURE(S): Comparison of control and subject DNA sequences. RESULT(S): The patient demonstrated one nucleotide (thymine, T) deletion at position 422, leading to a frame-shift mutation. This mutation changes the codon for Tyr (TAT) to a stop codon (TAG) within the open reading frame just upstream of a conserved DNA-binding motif. Neither other mutations nor nucleotide mosaicisms were found in the remaining regions of the gene. This mutation was not present in the patient's normal father. CONCLUSION(S): The mutant SRY may be assumed to induce a nonfunctional SRY-coded protein that lacks a DNA-binding motif. These results explain the phenotypic female and the gonadal dysgenesis in the 45,X/ 47,XYY sex-reversed offspring.

Amino Acid Sequence↗

Customized EMG needle insertion guide for the muscle afferent block of jaw-deviation and jaw-opening dystonias.

OBJECTIVE: Jaw-opening and jaw-deviation dystonias are characterized by mouth opening or lateral shift of the mandible due to involuntary contraction of the lateral pterygoid muscle, causing difficulties in speech or mastication. We introduce the method of muscle afferent block by using a removable device for inserting a hollow electromyographic needle. STUDY DESIGN: A technique for fabricating a customized needle insertion guide into the lateral pterygoid muscle is described. Using the device, intramuscular injection of lidocaine and ethanol was performed in 3 patients with jaw-opening dystonia and 2 with jaw-deviation dystonia. Subjective improvement was assessed on a linear self-rating scale ranging from 0 (no improvement) to 100 points (complete cure). RESULTS: The overall subjective improvement was 72% +/- 16.4% without major side effects. CONCLUSIONS: The device is very useful for safe and accurate injection into the lateral pterygoid muscle. The muscle afferent block is effective for jaw-opening and jaw-deviation dystonias.

Adult↗

Improved method for non-denaturing polyacrylamide gradient gel electrophoresis for detection of small-sized LDL produced during postprandial hypertriglyceridaemia.

A reliable method for detection of small-sized low-density lipoprotein (LDL) produced during transient hypertriglyceridaemia induced by ingestion of fat is described. Electrophoresis using a commercial non-denaturing 2.0-16% polyacrylamide gradient gel is commonly utilized to determine the size of LDL particles, but it failed to detect a minor change in LDL size induced during postprandial hypertriglyceridaemia. Detection of small-sized LDL was achieved by adjusting the polyacrylamide concentration. Electrophoresis using a non-denaturing 1.5-10% polyacrylamide gradient gel gave the best resolution for detecting small-sized LDL induced during postprandial hypertriglyceridaemia. This improved method may be useful for elucidating the underlying mechanism of production of small-sized LDL (small dense LDL) in subjects with chronic hypertriglyceridaemia.

Dietary Fats↗

The therapeutic effect of bovine lactoferrin in the host infected with Helicobacter pylori.

BACKGROUND: It remains unclarified whether bovine lactoferrin (bLF) can exert a therapeutic effect on the host infected with Helicobacter pylori. METHODS: Germfree BALB/c mice were orally inoculated with H. pylori to induce infection. Three weeks after infection the mice were given bLF orally once daily for 2 or 4 weeks and were then killed to examine the bacterial number in the stomach and the serum antibody titer to H. pylori. To count the number of epithelium-bound H. pylori, the resected stomach was agitated in phosphate-buffered saline to remove non-bound H. pylori before bacterial enumeration. RESULTS: The administration of 10 mg bLF for 3 to 4 weeks decreased the number of H. pylori in the stomach to one-tenth and also exerted a significant inhibitory effect on the attachment of H. pylori to the stomach. As a result, the serum antibody titer to H. pylori, whose level is presumed to represent the size of the immune response by the host, thereby reflecting the degree of bacterial attack, decreased to an undetectable level. CONCLUSIONS: These findings suggest that bLF exerts an inhibitory effect on colonizing H. pylori by detaching the bacterium from the gastric epithelium and by exerting a direct anti-bacterial effect.

Animals↗

MesP1 is expressed in the heart precursor cells and required for the formation of a single heart tube.

The Mesp1 gene encodes the basic HLH protein MesP1 which is expressed in the mesodermal cell lineage during early gastrulation. Disruption of the Mesp1 gene leads to aberrant heart morphogenesis, resulting in cardia bifida. In order to study the defects in Mesp1-expressing cells during gastrulation and in the specification of mesodermal cell lineages, we introduced a (beta)-galactosidase gene (lacZ) under the control of the Mesp1 promoter by homologous recombination. The early expression pattern revealed by (beta)-gal staining in heterozygous embryos was almost identical to that observed by whole mount in situ hybridization. However, the (beta)-gal activity was retained longer than the mRNA signal, which enabled us to follow cell migration during gastrulation. In heterozygous embryos, the Mesp1-expressing cells migrated out from the primitive streak and were incorporated into the head mesenchyme and heart field. In contrast, Mesp1-expressing cells in the homozygous deficient embryos stayed in the primitive streak for a longer period of time before departure. The expression of FLK-1, an early marker of endothelial cell precursors including heart precursors, also accumulated abnormally in the posterior region in Mesp1-deficient embryos. In addition, using the Cre-loxP site-specific recombination system, we could determine the lineage of the Mesp1-expressing cells. The first mesodermal cells that ingressed through the primitive streak were incorporated as the mesodermal component of the amnion, and the next mesodermal population mainly contributed to the myocardium of the heart tube but not to the endocardium. These results strongly suggest that MesP1 is expressed in the heart tube precursor cells and is required for mesodermal cells to depart from the primitive streak and to generate a single heart tube.

Animals↗

A novel sex-determining region on Y (SRY) missense mutation identified in a 46,XY female and also in the father.

Mutations in the sex-determining gene SR Y previously identified occur in the 46, XY females. In this study, we investigated whether the SR Y mutation participates in the onset of XY sex reversal. Genomic deoxyribonucleic acids (DNA) from five XY sex-reversed females were analyzed for mutations in SR Y using polymerase-chain reaction (PCR) amplification and subsequent DNA sequencing. One of the 46, XY females suffered a novel missense mutation at position 306 of SR Y gene, wherein cytosine was replaced by adenine (CGC-->AGC), resulting in a substitution of serine for arginine at amino acid position 76 of SR Y protein. This mutation was located in Helix I of the high-mobility-group (HMG) domain. No other mutations were found in the remaining regions of the gene. Analysis of the SR Y gene in her father revealed that he carried the identical mutation version. This substitution introduces a large basic for a small polar uncharged amino acid residue in the HMG box. The fact that the father transmits the mutant SR Y copy to his offspring implies that SR Y mutations do not always occur in association with sex reversal, even when the ionic environment is altered.

Adult↗

Specialty-related disparities of readmission in patients with chronic heart failure: the importance of hospital-clinic cooperation.

OBJECT: The purpose of this study was to elucidate differences in readmission rates and late outcome in outpatients with chronic heart failure treated in different clinical settings. PATIENTS AND METHODS: This study included 65 consecutive patients who were admitted to our CCU due to acute heart failure for the first time and discharged from our institution. After their discharge, 31 were cared for by a cardiologist in the outpatient clinic of our institution (group A) and the other 34 were cared for by a general practitioner in a clinic (group B). The various findings during the acute phase and the follow-up period were retrospectively compared between the two groups. In addition, the incidence of unexpected readmission and prolonged outcomes were compared between the two groups. RESULTS: The patients in group B were older than those in group A, but no other differences were noted in patient characteristics. More patients in group A required more than one hospitalization within 6 months from discharge (group A, 35.5%; group B, 8.9%, p<0.01; follow-up period, 17.1+/-5.9 months). There was no difference in the survival rate between the groups. CONCLUSION: We concluded that stabilized outpatients should receive comprehensive care from a general practitioner to avoid the need for readmission after discharge.

Aged↗

[A patient complaining of right hypochondralgia with back pain. Aortic dissection or cholelithiasis?].

A 70-year-old woman with a past history of cholecystolithiasis was admitted to a local clinic because of right hypochondralgia with back pain. Since physical examination revealed Murphy's sign, this patient was diagnosed as acute cholecystitis. The ultrasonographic examination of the gallbladder showed a stone of the cystic duct with no definitive wall thickening. CT scan revealed dissection of the abdominal aorta. She was then referred to our hospital for further examinations. She was observed in the cardiac care unit to determine whether the aneurysm and cholecystitis were in an acute or chronic state. Blood examinations and enhanced CT scan showed that her clinical symptoms originated not from cholelithiasis but from acute closing aortic dissection, Stanford classification type B. Close cooperation with a highly developed medical facility is essential when diagnosing elderly patients with symptoms open to a variety of interpretation.

Acute Disease↗