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Clinical comparisons between two subsets of gastric antral vascular ectasia.

BACKGROUND: The lesions of gastric antral vascular ectasia take two endoscopic forms, diffuse red spots and red stripes. In addition, they are often associated with cirrhosis. The main aim of the present retrospective study was to determine whether differences in endoscopic appearance and presence or absence of cirrhosis have relationships to clinical features and course. METHODS: Gastric antral vascular ectasia in 30 patients was classified into 2 endoscopic subtypes, punctate type (21 patients) and striped type (8 patients); only 1 patient could not be categorized to either type. The 30 patients were divided into groups based on the presence (25) or absence (5) of cirrhosis. RESULTS: All patients with punctate-type vascular ectasias had cirrhosis, whereas only 38% of patients with the striped type had cirrhosis. All patients without cirrhosis had the striped pattern. For patients with the 2 endoscopic types as well as those with and without cirrhosis, the outcomes of endoscopic treatment were similar. CONCLUSIONS: The findings of the present study suggest that cirrhosis is strongly associated with the development of punctate-type vascular ectasias. The endoscopic appearance of vascular ectasias and the presence or absence of cirrhosis did not determine outcome of patients.

Aged↗

Estimation of growth fraction in situ in human bladder cancer with bromodeoxyuridine labelling.

A group of 8 patients with invasive bladder cancer received fractionated intra-arterial infusions of the thymidine analogue bromodeoxyuridine (BrdU), 150 mg, every 6 to 10 h for 3 days before endoscopic cold cup biopsy to label tumour cells in the proliferative pool (growth fraction). The tumour specimens were fixed and stained by an indirect immunoperoxidase method using anti-BrdU monoclonal antibody. There was an area which could not be stained with anti-BrdU monoclonal antibody surrounding the stained area where diffusion effects could be excluded. This indicates a growth fraction less than 1 and implies that a proportion of the tumour cells in bladder tumours are cycling and contributing to growth. The BrdU labelling index (growth fraction) was determined by counting the number of BrdU labelled cells in the well labelled tissue sections. The average growth fraction of invasive bladder cancer was 38.4 +/- 7.7% (range 26.9-48.1%). Grade 3 tumours averaged 42.8 +/- 5.4% labelling versus 31.0 +/- 4.4% in grade 2. The higher growth fraction may indicate greater biological malignancy. These results indicate that immunohistochemical studies of cell kinetics using BrdU monoclonal antibodies may provide information about the biological characteristics of bladder tumours in situ.

Aged↗

Murine androgen-independent neuroendocrine carcinoma promotes metastasis of human prostate cancer cell line LNCaP.

BACKGROUND: Although neuroendocrine (NE) cells in prostate cancer have been speculated to accelerate the growth and progression of surrounding cancer cells, the evidence is as yet inconclusive. We investigated the effect of an NE allograft (NE-10) and its cell line, NE-CS, which were established from the prostate of the LPB-Tag 12T-10 transgenic mouse, on human prostate cancer cell line LNCaP. METHODS: The proliferation and pulmonary metastasis of LNCaP xenografts in athymic mice with and without NE-10 allografts were evaluated. Boyden chamber assay and microarray analysis were performed to investigate changes in invasion/migration and mRNA of LNCaP cells under the influence of the NE cells, respectively. RESULTS: NE-10 did not influence the proliferation of LNCaP. The pulmonary metastasis of LNCaP with NE-10 significantly increased compared to mice without it. The NE-CS cells accelerated the in vitro invasion/migration of adenocarcinoma cells. Increased expression of mRNA of gelsolin was observed in LNCaP cells incubated with the supernatant of NE-CS cells. CONCLUSIONS: The NE-10 allograft promotes pulmonary metastasis of subcutaneously inoculated LNCaP cells by facilitating cell invasion. Secretions from NE cells upregulate the expression of gelsolin, which is an actin-binding protein, resulting in acceleration of the migration of LNCaP cells.

Adenocarcinoma↗

Dosage regimen of arbekacin for methicillin-resistant Staphylococcus aureus infection in newborns and infants.

BACKGROUND: Arbekacin (ABK) is an aminoglycoside antibiotic that has a dose-dependent bactericidal action. Because it inhibits the production of toxic shock syndrome toxin-1 (TSST-1) by methicillin-resistant Staphylococcus aureus (MRSA), it has attracted attention as a therapeutic drug for MRSA infection. In this study, the authors investigated the pharmacokinetics of ABK based on therapeutic drug monitoring (TDM), in order to establish an effective dosage regimen with minimal adverse reactions in MRSA infected newborns and infants. METHODS: Arbekacin was administered to nine MRSA infected newborns and infants between October 2000 and March 2002. Following the initial ABK administration, blood was collected and the blood concentration of ABK was measured. The blood concentrations of ABK were analyzed by the two-compartment model or by a model-independent method in order to elucidate the pharmacokinetics of ABK. Pharmacokinetic analysis was performed using WinNonlin Professional V3.1. RESULTS: The mean age at initial ABK administration was 24.0 +/- 26.0 days (postconceptional age: 39.2 +/- 3.9 weeks). The increase in the peak blood concentration of ABK was 2.40 +/- 0.20 microg/mL per mg ABK per kg bodyweight, showing great consistency among cases. The elimination half-life of ABK was 0.22-3.52 h in the alpha phase (T(1/2alpha)) and 2.42-33.44 h in the beta phase (T(1/2beta)), showing great variation among cases. The distribution volume was 0.75 +/- 0.13 L/kg, and systemic clearance was 0.054 +/- 0.012 L/h/kg. ABK alleviated clinical symptoms and inflammations in all cases. CONCLUSION: Nine newborns and infants with MRSA infection and various underlying diseases were successfully treated with TDM-based administration of ABK with no severe adverse reactions.

Aminoglycosides↗

Dynamic analysis of the resultant force acting on the hip joint during level walking.

The present study was designed to determine the resultant force acting on the hip joint during walking using a new dynamic analysis method. Our model utilized joint motion, ground reaction force, and muscle strength data from 18 women (6 normal women aged 20-24 years, 6 normal women aged 50-57 years, and 6 female patients with osteoarthritis, aged 50-66 years). We analyzed the resultant force using the multibody dynamic analysis system. To determine the factors that influence the force acting on the hip, we examined the effect of age and total hip arthroplasty. The maximum resultant force acting on the femoral head was dependent on the subject body weight and correlated with muscle strength and walking speed. The results of this study highlight the agreement between computer simulation analysis and actual measurement of the resultant force acting on the hip. Our results suggest that muscle strength and walking speed are significant determinants of the resultant force acting on the hip.

Adult↗

Chemosensitivity testing of a novel platinum analog, nedaplatin (254-S), in human gynecological carcinomas: a comparison with cisplatin.

BACKGROUND: The tetrazolium dye (MTT) assay is useful for predicting chemosensitivity. MATERIALS AND METHODS: Using the MTT assay, an in vitro chemosensitivity test was designed for nedaplatin (cis-diammine glycolato platinum; 254-S) and the results were compared with the sensitivity to cisplatin in 137 resected gynecological carcinomas. RESULTS: The mean tumor inhibition rate [I.R.; %] for nedaplatin was equal or superior to cisplatin in 15 cervical [70.7% vs. 63.9%], 65 ovarian [61.7% vs. 54.8%] and 57 endometrial carcinomas [52.1% vs. 47.7%]. In ovarian carcinomas, the I.R.s for nedaplatin were significantly higher than cisplatin in poorly-differentiated, serous and endometrioid adenocarcinomas 180.7% vs. 56.4% (p < 0.05), 77.0% vs. 64.9% (p < 0.01), and 68.2% vs. 54.6% (p < 0.05), respectively]. CONCLUSION: Our data suggest that nedaplatin has equivalent or superior antitumor activity to cisplatin in cervical, ovarian and endometrial carcinomas. In particular, nedaplatin showed a significantly better antitumor activity among the histological subtypes of ovarian carcinomas.

Antineoplastic Agents↗

In vivo 31P magnetic resonance spectroscopy for evaluation of testicular function in cryptorchid rats.

PURPOSE: To assess in vivo metabolism of rat testicles in experimental cryptorchidism, we used 31P magnetic resonance (MR) spectroscopy and compared testicular MR spectroscopic parameters with flow cytometric DNA analysis. MATERIALS AND METHODS: In vivo 31P MR spectroscopy and flow cytometric DNA analysis of rat testis were performed before and during 14 days of experimental cryptorchidism. RESULTS: The testicular phosphomonoester (PM)/ATP ratio showed a transient increase when multinuclear giant cells appeared in the seminiferous tubules. However, the ratio returned to the preoperative level when these cells disappeared. The phosphodiester (PD)/ATP ratio gradually decreased and the inorganic phosphate (Pi)/ATP ratio slowly increased. DNA flow cytometry showed a decrease in the percentage of haploid cells and an increase in the percentage of diploid cells from 7 days after cryptorchidism. The percentage of tetraploid cells did not change before and during cryptorchidism. CONCLUSION: This study indicates that in vivo 31P MR spectroscopy in combination with flow cytometric DNA analysis provides useful biochemical and histological information for evaluation of testicular function.

Animals↗

Clinical significance of p53, mdm2, and bcl-2 proteins in renal cell carcinoma.

OBJECTIVES: To improve our understanding of the clinical relevance of p53, mdm2, and bcl-2 protein overexpression in renal cell carcinoma, we retrospectively investigated the immunohistochemical expression of p53, murine double minute 2 (mdm2), and bcl-2 and the relationship of this expression to clinicopathologic characteristics. p53 regulates the transcription of downstream effectors such as the oncoprotein mdm2, and bcl-2 has been shown to inhibit apoptosis triggered by wild-type p53. METHODS: The expression of p53, mdm2, and bcl-2 protein was studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens from 112 patients whose clinicopathologic data confirmed renal cell carcinoma. RESULTS: The expression of the p53 and bcl-2 protein was recognized in 15 (13.4%) and 52 (42.0%) cases, respectively; the expression of the mdm2 protein, however, was seen in only 2 cases (1.8%). No correlation was noted between these three proteins and any clinicopathologic parameters, except p53 expression and Stage T1-2/T3-4 (P = 0.0208). However, in multivariate analysis, stage (hazard ratio 3.586; P = 0.0002), expression of p53 (hazard ratio 6.090; P = 0.0126) and of mdm2 (hazard ratio 22.016; P = 0.0156), and coexpression of p53/mdm2 (hazard ratio 6.146; P = 0.0005) demonstrated a statistically significant effect on prognosis by proportional hazards regression tests. CONCLUSIONS: Our results indicate that stage, p53 expression, mdm2 expression, and coexpression of p53/mdm2 are useful to predict the clinical outcome in patients with renal cell carcinoma.

Adult↗

Three-dimensional imaging of liver tumors using helical CT during intravenous injection of contrast medium.

PURPOSE: The goal of this work was to determine whether 3D reconstruction of images from CT during intravenous injection of contrast medium, performed in tandem with advanced rendering algorithms, could accurately depict major anatomic structures and hepatic tumors. METHOD: Thirty-one patients (22 with hepatocellular carcinoma, 8 with metastatic lesions, and 1 with intrahepatic cholangiocarcinoma) underwent CT imaging. Twenty-three of the 31 patients underwent needle biopsy or surgery, yielding a histologic diagnosis. The remaining eight patients were diagnosed from imaging findings and laboratory data. We compared the ability of maximum intensity projection (MIP) and volume-rendered technique (VRT) images to depict the hepatic veins and intrahepatic portal veins. RESULTS: Both MIP and VRT depicted the course of vessels up to the second or third branches. The techniques did not significantly differ. In this regard, in most cases, visualization of the liver surface and tumor was excellent with VRT images. CONCLUSION: Volume-rendered 3D-CT images during intravenous injection without the MIP technique produced 3D images of high quality with excellent visualization of tumors and their relationships to vital structures.

Adult↗

Comparison of bone mineral density among residents of a mountain village and a fishing village in Japan.

OBJECTIVE: To compare the bone mineral density of residents of a mountain village with that of residents of a fishing village in Mie Prefecture, Japan. METHODS: Microdensitometry was used to measure bone mineral density of the second metacarpal bone of 202 participants living in a mountain village and of 852 participants living in a fishing village to identify contributory factors for osteoporosis. The participants were interviewed using a questionnaire on alcohol consumption, fish intake, milk intake, and daily activity. RESULTS: Analysis of covariance revealed that bone mineral density was significantly higher among the participants living in a fishing village than among those living in a mountain village (2.5-2.9 versus 2.1-2.7 mmAl; p<0.001). A higher proportion of women in the fishing village than of those in the mountain village consumed alcohol (17% versus 10%; p<0.05). CONCLUSION: Nutrition may be a contributory factor to the lower incidence of osteoporosis among residents of the fishing village compared with those of the mountain village.

Absorptiometry, Photon↗

Synthesis of new N-containing maltooligosaccharides, alpha-amylase inhibitors, and their biological activities.

Fifteen new N-containing maltooligosaccharides were obtained using the chemoenzymatic method. Among these compounds, maltooligosaccharides having 6-amino-6-deoxy-D-sorbitol residue, (3R,4R,5R,6S)-hexahydro-3,4,5,6-tetrahydroxy-1H-azepine residue, and (3R,5R)-3,4,5-trihydroxypiperidine residue at the reducing end showed strong inhibitory activities for human pancreatic alpha-amylase (HPA) (EC 3.2.1.1) and human salivary alpha-amylase (HSA). The administration of (3R,4R,5R,6S)-hexahydro-3,5,6-trihydroxy-1H-azepine-4-yl O-alpha-D-glucopyranosyl-(1-->4)-alpha-D-glucopyranoside (13, IC50 = 4.3 x 10(-5) M for HPA, IC50 = 8.2 x 10(-5) M for HSA) and (3R,5R)-3,5-dihydroxypiperidine-4-yl O-alpha-D-glucopyranosyl-(1-->4)-alpha-D-glucopyranoside (18, IC50 = 3.4 x 10(-5) M for HPA, IC50 = 4.6 x 10(-5) M for HSA) to ICR mice suppressed postprandial hyperglycemia.

Animals↗

Prostaglandins from a zoanthid: paclitaxel-like neurite-degenerating and microtubule-stabilizating activities.

Two prostaglandins, PGA2 and PGB2, were isolated from the Okinawan zoanthid, Palythoa kochii, during a search for paclitaxel-like neurite-degenerating compounds from natural sources using a cell-based assay method. In the presence of PGA2 at 30 microM, the neuronal processes induced in PC12 cells by the nerve growth factor (NGF) degenerated over 24 h, whereas PGB2 had no effect on the neuronal processes of PC12 cells. This activity of PGA2 was similar to that of the microtubule-stabilizing agents, paclitaxel (Taxol) and epothilone A, unlike the microtubule-depolymerizing agent, colchicine, which brought about quick neurite degeneration within 3 h. PGA2 stimulated tubulin polymerization, although less potently than paclitaxel. An examination of structure-activity relationships across several PGs suggests that the cyclopentenone ring structure and the orientation of its dipolar moment played an important role in the paclitaxel-like neurite-degenerating activity. These results suggest that the cyclopentenone-type PGs can interact with microtubules to inhibit their function like paclitaxel.

Animals↗

Increased acid exposure in patients with gastroesophageal reflux disease influences cyclooxygenase-2 gene expression in the squamous epithelium of the lower esophagus.

HYPOTHESIS: Although genetic changes associated with the progression to Barrett esophagus and adenocarcinoma have been identified, changes in gene expression associated with gastroesophageal reflux disease have not been reported. We examined expression levels of several genes important in carcinogenesis and compared expression levels with alterations in esophageal acid exposure. PATIENTS, DESIGN, AND SETTING: Prospective analysis of 61 patients initially seen with reflux symptoms at a private academic hospital. INTERVENTIONS: Paired esophageal biopsy specimens of squamous epithelium 3 cm above the squamocolumnar junction. All patients had 24-hour pH monitoring performed. MAIN OUTCOME MEASURES: Cyclooxygenase (COX) 1, COX-2, thymidylate synthase, human telomerase reverse transcriptase (hTERT), Bcl-2 protein, survivin protein, secreted protein acidic and rich in cysteine (SPARC), tetraspan (TSPAN), and caudal-type homeobox transcription factor 2 (CDX2) messenger RNA expression analysis was performed on snap-frozen, microdissected tissue using a quantitative reverse transcriptase-polymerase chain reaction method. Linear regression and the Pearson product moment correlation were used to relate gene expression to parameters of the 24-hour pH record. RESULTS: Expression levels of COX-2 correlated positively with the 24-hour pH score (r = 0.25, P =.05). There was no correlation between the expression of other tested genes and esophageal acid exposure. There was also no significant increase in COX-2 expression in patients with esophagitis or in those who used nonsteroidal anti-inflammatory drugs. CONCLUSIONS: To our knowledge, these data provide among the first reported correlation of genetic changes and increased esophageal acid exposure in patients with gastroesophageal reflux symptoms. The changes in gene expression occur before any metaplastic changes in the tissue are apparent, and may in the future be useful in predicting which patients will progress through a metaplasia-dysplasia carcinoma sequence.

Adult↗

Calcium phosphate cement in musculoskeletal tumor surgery.

BACKGROUND AND OBJECTIVES: Calcium phosphate cement (CPC) is an injectable biocompatible bone substitute that has been used for various applications in orthopedic surgery. However, no extensive clinical studies of the use of CPC to fill bone cavities after curettage of musculoskeletal tumors have been reported. The present study reviewed the results for 56 musculoskeletal tumors treated by curettage and CPC implantation. METHODS: Assessment was based on clinical examination and radiographic findings. Variables for clinical assessment included pain, limb function, and complications. Median follow-up was 18.5 months (range 6-47 months). RESULTS: One patient experienced post-operative fractures. Three patients displayed local recurrence. One patient developed post-operative superficial wound infection, and two patients with large bony defect exhibited non-infectious serous discharge. No serious adverse effects such as deep venous thrombosis, pulmonary embolism were encountered. In all cases, CPC was radiographically well adapted to the surrounding host bone as of final follow-up. CONCLUSIONS: CPC appears to offer a useful bone substitute for the treatment of musculoskeletal tumors. As the follow-up period for this study was short, further long-term follow-up studies are needed.

Adolescent↗

Possible role of nitric oxide in 5-hydroxytryptamine-induced increase in vascular permeability in mouse skin.

In order to test the hypothesis that a 5-hydroxytryptamine (5-HT)-induced increase in vascular permeability results from a cascade triggered by activation of the synthesis of nitric oxide (NO), the vascular permeability was investigated using the Pontamine sky blue leakage method in male mice. Subcutaneous injection of 5-HT induced a dose-related increase of vascular permeability at the injection site. The vascular permeability induced by 5-HT was inhibited by pretreatment with intraperitoneal injection of ketanserin (5-HT2A antagonist) and methysergide (5-HT1/2A antagonist), less efficiently by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine (NAN-190) (5-HT1A antagonist), but not by granisetron (5-HT3 antagonist). Increase in vascular permeability induced by 5-HT was inhibited by concurrent intravenous administration of NO synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME) and methylene blue but not by the inactive enantiomer NG-nitro-D-arginine methyl ester (D-NAME). These results suggest that 5-HT increases vascular permeability by activating the 5-HT receptors and that endogenous NO is involved in this effect of 5-HT.

Amino Acid Oxidoreductases↗

Sequential laparoscopic percutaneous extraperitoneal closure for inguinal hernia during NICU/GCU hospitalization in low birth weight infants.

BACKGROUND: Inguinal hernia is common in low birth weight infants and carries a risk of incarceration. Although laparoscopic percutaneous extraperitoneal closure (LPEC) is widely used in pediatric patients, the safety of sequential LPEC during NICU/GCU hospitalization remains unclear. This study evaluated the safety and feasibility of sequential LPEC during NICU/GCU hospitalization. METHODS: We retrospectively reviewed infants who underwent LPEC between September 2018 and July 2024. Infants aged&#x2009;&#x2264;&#x2009;6 months diagnosed with inguinal hernia and treated with sequential LPEC during hospitalization were included. For comparison, infants aged&#x2009;&#x2264;&#x2009;6 months with a history of NICU/GCU hospitalization who were diagnosed with inguinal hernia after NICU/GCU discharge and underwent LPEC were identified. RESULTS: Among 302 patients, 13 met the inclusion criteria. One patient required postoperative reintubation, postoperative testicular atrophy occurred in three patients, and no hernia recurrence was observed during a median follow-up of 48 months. Compared with infants diagnosed after NICU/GCU discharge, the sequential LPEC group had significantly lower gestational age, lower birth weight, lower body weight at surgery, and more comorbidities, whereas postoperative outcomes were comparable. CONCLUSION: Sequential LPEC during continuous NICU/GCU hospitalization is feasible and can be safely performed in low birth weight infants with appropriate technical refinements.

Humans↗

Ligands for peroxisome proliferator-activated receptor gamma have potent antitumor effect against human renal cell carcinoma.

OBJECTIVES: To examine whether peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in human renal cell carcinoma (RCC) cells, and whether activation of PPARgamma by its ligands can have multiple antitumor effects on human RCC cells in vitro. METHODS: We examined the expression of PPARgamma in four human RCC cell lines by reverse transcriptase-polymerase chain reaction and immunocytochemical staining. The effects of two PPARgamma ligands, pioglitazone and 15-deoxy-Delta12,14-prostaglandin J2, on cell proliferation were investigated by 3-[4,5-dimethylthiazol-2-thiazoly]-2,5-diphenyltetrazolium bromide assay. The induction of apoptosis by the ligands was examined using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method and Annexin V assay. Furthermore, we investigated whether these ligands suppressed the production of angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor, by enzyme-linked immunosorbent assay. RESULTS: PPARgamma and retinoid X receptor, which forms a heterodimer with PPARgamma, were expressed in all RCC cell lines. In addition, immunocytochemical studies showed expression of PPARgamma protein in the RCC cells. PPARgamma ligands inhibited the cell growth in all cells in a dose-dependent manner. These ligands also induced apoptosis. Furthermore, secretion of both vascular endothelial growth factor and basic fibroblast growth factor was inhibited by these ligands in a dose-dependent and time-dependent manner. CONCLUSIONS: Ligands for PPARgamma have multiple antitumor effects in human RCC cells in vitro. Activation of the PPARgamma pathway may be a new strategy for treatment of patients with RCC.

Carcinoma, Renal Cell↗

Daily rhythm of serum melatonin levels and effect of light exposure in patients with dementia of the Alzheimer's type.

BACKGROUND: Several studies have suggested that patients with dementia experience a deterioration of biological rhythms. We investigated the daily profile of serum melatonin levels in patients with dementia of the Alzheimer's type (AD), since daily melatonin rhythm is thought to reflect the functioning of the biological clock. METHODS: Seventeen inpatients with AD, 10 psychiatric inpatients without dementia, and 11 elderly healthy volunteers participated in this study. Serum melatonin was assessed every 3 hours by radioimmunoassay. RESULTS: A daily fluctuation of melatonin levels with a significant nocturnal increase was observed in all three subject groups. However, both the AD patients and psychiatric patients without dementia showed significantly higher levels of melatonin in the daytime compared with the healthy subjects. When the effect of bright light exposure on melatonin secretion was investigated in six AD patients and five psychiatric patients without dementia, the daytime levels were markedly decreased in the patients without dementia, while no change was observed in the AD patients. CONCLUSIONS: The high levels of melatonin in the daytime associated with a lack of response to light exposure in AD patients may be due to the neurodegenerative process of this disease.

Aged↗