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Biomedical subjects

K Hayashi

Publications and source records attributed to K Hayashi.

At least 73 records · Page 4Linked to original sources

[Extrapleural pneumonectomy for malignant pleural mesothelioma].

Standard treatment for malignant pleural mesothelioma (MPM) has not been proved yet. However, it has been recognized that extrapleural pneumonectomy (EPP) is a treatment of choice for epithelial MPM when combined with adjuvant therapies though EPP may frequently cause fetal complications. We report 5 cases of MPM with EPP, including 1 with good prognosis. Sixteen patients with MPM were admitted to our hospital between 1988 and 2003. Five patients underwent EPP, among which 4 were male and 1 female with ages from 46 to 61 years old. Histologically, 3 of them were epithelial and 2 were biphasic. Those with biphasic experienced acute respiratory failure and empyema, and died 81 days and 8 months after the surgery respectively. Among those with epithelial MPM, 2 are alive with no recurrence at 129 and 29 months after the surgery, and the other, followed by postoperative radiotherapy, died at 12 months. More cases with EPP or randomized controlled trials regarding EPP are necessary to evaluate efficacy of EPP for MPM.

Female↗

Multimodality treatments with endoscopic mucosal resection of esophageal squamous cell carcinoma with submucosal invasion.

BACKGROUND AND STUDY AIMS: A standard treatment for esophageal squamous cell carcinoma (SCC) with submucosal invasion is considered to be radical resection at present. In this study, we evaluated the efficacy of multimodality treatments with endoscopic mucosal resection (EMR) of esophageal SCC with submucosal invasion. METHOD: Eighteen cases of SCC with submucosal invasion were treated with EMR. Lymphatic invasion was found in 11 cases (67%), and there were no cases of blood vessel invasion. EMR was performed prior to any other treatment. Chemotherapy and/or radiotherapy were added if indicated by the histopathological features. RESULTS: There were no cases of local recurrence. Lymph-node recurrence was detected in 1 case treated with EMR alone. There were no cases of cancer death. The overall survival rate was 83% in all patients. CONCLUSIONS: Multimodality treatments with EMR were effective in treating esophageal SCC with submucosal invasion.

Adult↗

Structural and functional diversity of lysyl oxidase and the LOX-like proteins.

Lysyl oxidase (LOX) and four lysyl oxidase-like proteins, LOXL, LOXL2, LOXL3 and LOXL4, each contain a copper binding site, conserved lysyl and tyrosyl residues that may contribute to quinone co-factor formation, and a cytokine receptor-like domain. Each protein differs mainly in their N-terminal sequence, which may confer individual functions. Processing of the LOX proteins by BMP-1 and possibly other mechanisms may result in multiple functional forms. Splicing, reported for LOXL3, may also generate additional variants with unique functions. Each LOX, with its individual, developmentally regulated tissue and cell-specific expression and localization, results in a complex structural and functional variation for the LOX amine oxidases. The presence of only two LOX-like proteins in Drosophila, each with distinct spatial and temporal expression, allows for the assignment of individual function to one of these amine oxidases. Comparative expression analysis of each LOX protein is presented to help determine their functional significance.

Amino Acid Oxidoreductases↗

A novel polymorphism of the human APRIL gene is associated with systemic lupus erythematosus.

OBJECTIVE: We investigated the association of gene polymorphisms in APRIL, a new member of the TNF family, with systemic lupus erythematosus. METHODS: To detect polymorphisms of the human APRIL gene by exon-specific polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis, we first determined the structure of the human APRIL gene. We designed exon-specific oligonucleotide primers according to the genomic DNA sequence of APRIL. All of the coding regions in exons of the APRIL gene were analysed by exon-specific PCR-SSCP in 148 SLE patients and 146 unaffected controls, then the nucleotide sequences of exons that displayed aberrant bands were determined. RESULTS: The human APRIL gene comprised at least six exons with five introns, spanning approximately 2.8 kilobases of the genomic DNA. By exon-specific PCR-SSCP, we identified two novel polymorphisms at codons 67 and 96. Both had amino acid substitutions: G67R and N96S respectively. Only the 67G allele was associated with SLE in 148 Japanese SLE patients, with allele frequency 0.662 compared with 0.575 for 146 unaffected controls (P=0.0302). The frequency of the individuals who possessed at least one 67G allele in SLE patients (91.9%) was significantly higher than that in the unaffected controls (80.1%) (P=0.0036). CONCLUSION: The 67G allele of APRIL may be a contributing factor in the pathogenesis of SLE.

Adolescent↗

Oxatomide for stable asthma in adults and children.

BACKGROUND: Oxatomide is a histamine H1-receptor antagonist. As an oral agent, oxatomide may be useful in managing asthma. Some guidelines recommend oxatomide for long-term prophylaxis of asthma in children. There is no clear evidence whether children or adults with asthma benefit from oxatomide. OBJECTIVES: To determine whether oxatomide alone, or in combination with other interventions, results in better disease control in people with asthma. SEARCH STRATEGY: The Collaborative Airway Group register and Collaborations trial register CENTRAL were searched using terms: oxatomide* OR Celtect OR Pinset OR KW-4354 OR Tincet. Reference lists of all relevant trials or review articles were checked. Enquiries were made of authors of included studies and relevant pharmaceutical companies. A search of 'Igaku Chuo Zasshi' and 'J-Medicine' were made using the following terms: oxatomide (also in Japanese) or Celtect (also in Japanese) or KW-4354. SELECTION CRITERIA: Studies were randomised, placebo-controlled trials and the interventions were oxatomide or matched placebo given alone or in combination with other asthma-medication for at least 4 weeks. DATA COLLECTION AND ANALYSIS: Four independent reviewers performed assessments of methodological quality and extracted relevant data. MAIN RESULTS: Six studies are included in this review. Three studies were mainly conducted in adults, two were conducted in older children (5-16 years) and one in infants (18-25 months). Trial duration was 4 to 52 weeks. Doses of oxatomide varied between studies, ranging from 1 mg/kg/day for infants to 180 mg/day for adults. Only data on adverse events was suitable for meta-analysis. Although PEF did not change significantly in any of the studies, the FVC and FEV1 improved significantly in two. There was no uniform change in symptom scores. There was no significant difference between oxatomide and placebo treatment in use of inhaled corticosteroid or bronchodilator. Two studies showed significant improvement with oxatomide as judged subjectively by physicians. Adverse events, analysed using data from 4 parallel and one cross over study, showed oxatomide to be associated with a significantly higher risk of any adverse event (OR: 2.97, 95%CI: 1.69 to 5.22) and drowsiness (OR: 5.22,95%CI: 2.53 to 10.74). REVIEWER'S CONCLUSIONS: There is no evidence to show that oxatomide has a significant effect on the control of stable asthma. Some studies reported significant benefits in subjective parameters. There was improvement in some lung function outcomes reported, but this were not consistent across measures or studies and may represent reporting bias. Adverse events, including drowsiness, were significantly greater with oxatomide than placebo.

Adult↗

Synthesis and paralytic activities of squaryl amino acid-containing polyamine toxins.

Eight analogs 4A-7A and 4B-7B of philanthotoxin (PhTX) from wasp venom and nephilatoxin-8 (NPTX-8) from spider venom whose tyrosine or asparagine linker is replaced by squaryl (sq) amino acid or 4-amino squaryl (4-asq) amino acid have been synthesized in an efficient manner via coupling of N-acyl squaryl amino acid intermediate 19 or 26 with the corresponding polyamine part. Preliminary bioassay using crickets revealed that the analogs substituted by glutamate-type squaryl amino acid-containing NPTX 7A and 7B showed more potent paralytic activities than that of NPTX-8.

Amino Acids↗

Geometrical, functional, and histomorphometric adaptation of rat carotid artery in induced hypertension.

Acute and long-term (up to 56 days) evolution of geometry, structural properties, vascular smooth muscle (VSM) tone and histomorphometric properties of the rat common carotid arteries under induced hypertension were investigated. Hypertension was induced in 8-week old male Wistar rats by total ligation of the aorta between the two kidneys. Rats were sacrificed 2, 4, 8 and 56 days postsurgery. The arterial wall layers thicken non-uniformly during the adaptation process, the inner layers thicken more in the acute phase of hypertension, whereas the outer layers of the wall are thicker than the inner layers at the end of the adaptation phase. Collagen content in the wall media exhibits a non-linear evolution, with a rapid increase in the acute hypertension phase followed by a slower increase at long-term. The elastin content increase is slight and steady, whereas VSM shows a steady but considerable increase which outdoes the collagen increase in long-term phase. VSM tone increases rapidly in the acute phase of remodelling (0-8 days) and this increase in tone contributes to a considerable increase in arterial compliance in the operating pressure range. At long-term (56 days) VSM tone returns to near control level, but compliance is even further increased, which suggests that at long-term the compliance increase is attributed primarily to structural remodelling.

Adaptation, Physiological↗

Effect of local interaction of reactive oxygen species with prostaglandin F(2alpha) on the release of progesterone in ovine corpora lutea in vivo.

Prostaglandin (PG) F(2alpha) is implicated in the process of luteal regression in many species, and has been shown to increase the generation of reactive oxygen species. In this study, the role of reactive oxygen species in the local regulatory mechanisms of functional luteolysis in the ewe was examined. In Experiment 1, we studied local effects of hydrogen peroxide (H(2)O(2)) and its interaction with PGF(2alpha) on P secretion in ovine corpus luteum (CL) in vivo. For this purpose, a microdialysis system (MDS) was used, where only the cells surrounding the capillary membrane in the microenvironment of the CL are exposed to these factors, and the P secretory ability of the CL is maintained as if intact. The study used a multiple CL model to implant the MDS, enabling us to examine in parallel several experimental infusions into the MDS implanted in different CLs (one MDS line per CL) developed after superovulation in one ewe. On Day 8 after GnRH treatment, the MDS were implanted into multiple CL in both ovaries of six ewes. A 4-h infusion with PGF(2alpha) (10(-6)M) at 8-12 h slightly increased P release during infusion, while a 4-h infusion with H(2)O(2) (10(-3)M) at 20-24 h decreased P release at 27-38 h. A pre-infusion with PGF(2alpha) for 4h at 8-12h, followed by infusion of H(2)O(2) at 20-24 h rapidly decreased the P release at 20-40 h (P<0.05); this decrease occurred 7h earlier than in the CL treated with H(2)O(2) alone. In Experiment 2, by utilizing the MDS we also applied free radical scavengers to examine their possible weakening effect on the inhibition of P secretion in the microenvironment within the regressing CL induced by PGF(2alpha) treatment. On Day 8 after estrus, the MDS were implanted into the CL (single CL model, two MDS lines per CL). Infusion of free radical scavengers, superoxide dismutase (SOD;50mg/ml)+catalase (CAT; 10mg/ml), at 0-28 h first increased P release until 12 h (P<0.05), and consequently delayed the decrease in P release until 30 h after administration of PGF(2alpha) i.m. (P<0.05). The present results support the concept that the leading pathway from PGF(2alpha) induces an increase of reactive oxygen species in luteolysis in the ewe.

Animals↗

Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease.

Although the angiotensin receptor antagonist (ARB) shares the angiotensin-II-blocking activity with the angiotensin-converting enzyme inhibitor (ACE-I), pharmacological mechanisms of action of these agents differ. We evaluated the temporal profiles of action of ACE-I and ARB on urinary protein excretion and nitrate/nitrate (NO(x)) excretion in hypertensive (140 and/or 90 mmHg) patients with chronic renal disease (serum creatinine < 265 (range, 44-265) micromol/l or creatinine clearance > 30 (range, 30-121) ml/min). Patients with mild (<1 g/day; range, 0.4-1.0) and moderate proteinuria (>1 g/day; range, 1.1-6.9) were randomly assigned to ACE-I- and ARB-treated groups, and were treated with ACE-I (trandolapril or perindopril) or ARB(losartan or candesartan) for 48 weeks. In all groups, treatment with ACE-I or ARB decreased blood pressure to the same level, but had no effect on creatinine clearance. In patients with mild proteinuria, neither ACE-I nor ARB altered urinary protein excretion. In patients with moderate proteinuria, ACE-I caused 44 +/- 6% reduction in proteinuria (from 2.7 +/- 0.5 to 1.5 +/- 0.4 g/day, n = 14) at 12 weeks, and this beneficial effect persisted throughout the protocol (48 weeks, 1.2 +/- 0.2 g/day). In contrast, ARB did not produce a significant decrease in proteinuria at 12 weeks (23 +/- 8%, n = 13), but a 41 +/- 6% reduction in proteinuria was observed at 48 weeks. Similarly, although early (12 weeks) increases in urinary NO(x) excretion were observed with ACE-I (from 257 +/- 70 to 1111 +/- 160 micromol/day) and ARB (from 280 +/- 82 to 723 +/- 86 micromol/day), the ARB-induced increase in NO(x) excretion was smaller than that by ACE-I (P < 0.05). In conclusion, although both ACE-I and ARB reduce blood pressure similarly, the effect of these agents on proteinuria differs in chronic renal disease with moderate proteinuria. Relatively early onset of the proteinuria-reducing effect was observed with ACE-I, which paralleled the increase in urinary NO(x) excretion. Conversely, ARB decreased proteinuria and increased urinary NO(x) excretion gradually. These time course-dependent changes in proteinuria and urinary NO(x) may reflect the pharmacological property of ACE-I and ARB, with regard to the action on bradykinin.

Angiotensin Receptor Antagonists↗

Tea polyphenols reduce glucocorticoid-induced growth inhibition and oxidative stress in broiler chickens.

1. The effects of dietary polyphenols (PP) on growth and oxidative stress in the corticosterone (CTC) treated broiler chickens model were studied. 2. Chicks (Cobb strain) were divided into 3 (CTC) x 3 (PP) blocks and given diets containing CTC at concentrations of 0, 10 and 20 mg/kg. 3. The body weight gain was lower when the birds were treated with CTC. However, the high dose of PP tended to reduce the effect of CTC. 4. The abdominal fat content, plasma triglyceride concentration and liver weight were increased by CTC and reduced by PP. 5. Muscle and liver thiobarbituric acid reactive substance (TBARS) were elevated by CTC and these effects were reduced by PP. Plasma CTC concentration was increased by dietary CTC treatment and decreased by PP. 6. In conclusion, our results indicate that PP can minimise growth inhibition, hyperlipidemia and oxidative stress induced by CTC treatment in broiler chickens.

Adipose Tissue↗

Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity.

AIMS: To search for mutations in the frizzled 4 (FZD4) gene in patients with familial exudative vitreoretinopathy (FEVR) and to delineate the defective gene associated clinical features. METHODS: Direct sequencing following polymerase chain reaction of exons of FZD4 was performed for 24 probands with FEVR (18 familial and six sporadic), and some of their families. Clinical symptoms among individuals with mutations were assessed. RESULTS: Four novel mutations were identified in four patients with familial and one with sporadic FEVR. Three of these mutations were missense (M105V, R417Q, and G488D) and one was a nonsense change (W319X). M105V, R417Q, and G488D co-segregated with the disease. None of these sequence changes was found among 300 chromosomes from 150 healthy volunteers. The severity of vitreoretinopathy in the individuals involved in this study varied, but no patient with mutations in FZD4 exhibited rhegmatogenous retinal detachment although this pathology is thought to be the most common type of retinal detachment in FEVR. CONCLUSION: FZD4 gene mutations were found in some cases of autosomal dominant and sporadic FEVR. FZD4 mutations were responsible for FEVR with variable clinical manifestations.

Adolescent↗

QT dispersion and left ventricular morphology in patients with hypertrophic cardiomyopathy.

OBJECTIVE: To evaluate the relation between QT variables and disproportion of left ventricular wall hypertrophy in patients with hypertrophic cardiomyopathy. DESIGN: Retrospective analysis of the results of echocardiography and electrocardiography. SETTING: University hospital (tertiary referral centre). PATIENTS: 70 patients with hypertrophic cardiomyopathy were divided into four groups according to the distribution of left ventricular wall hypertrophy on cross sectional echocardiography: group A--hypertrophy confined to the interventricular septum; group B--hypertrophy confined to the interventricular septum and left ventricular anterior wall; group C--hypertrophy confined to the interventricular septum, left ventricular anterior wall, and lateral free wall; group D--hypertrophy involving all portions of the left ventricle. MAIN OUTCOME MEASURES: QT intervals and QT dispersion in precordial six lead ECGs. RESULTS: There were no significant differences in the maximum left ventricular wall thickness among the four groups, and maximum and minimum QTc intervals also did not differ. QTc dispersion was increased significantly in groups A and B compared with groups C and D. Dispersions of the interval from the J point to the end of the T wave (JTc dispersions) in groups A and B were also increased significantly compared with groups C and D. By linear regression analysis, QTc and JTc dispersions correlated with the ratio of the interventricular septal thickness to left ventricular posterior wall thickness (p = 0.0152 and p = 0.0075, respectively). CONCLUSIONS: QT dispersion may be affected by not only electrical inhomogeneity but also by morphological inhomogeneity of the left ventricle in patients with hypertrophic cardiomyopathy.

Adult↗

The aurora sign: an ultrasonographic sign suggesting parenchymal lung disease.

The objective of this study was to clarify the cause and clinical significance of a large number of ring-down artefact (RA) observed on the dorsal side of the right hepatic lobe on abdominal ultrasound (US). 2000 abdominal US examinations were evaluated to investigate the frequency and number of RA behind the right lobe of the liver. In this study, RA observed by subcostal or intercostal US were described as the "aurora sign" when they were numerous. US findings were correlated with high resolution CT or three-dimensional CT of the right lung base. Experimental study was also performed to investigate the mechanism of the aurora sign. The results were as follows. (1). Aurora sign was noted in 43 patients. In 37 of these 43 patients (86.0%), chest CT or plain radiography revealed diffuse interstitial changes in the right lower lung field. Three-dimensional CT of the lung and the experimental model revealed that the aurora sign derived from the irregularity of air spaces immediately below the pleura associated with interstitial pulmonary disorders. (2). One or more bands of RA were observed in 907 of the 2000 patients (45.4%). Of 177 patients with fatty liver, RA was observed in 14 (7.9%), while of the 1823 patients with no fatty liver, RA was observed in 893 (49.0%). The frequency of RA was significantly different (p<0.001) between the patients with and without fatty liver. In conclusion, parenchymal lung disease should be suspected when the aurora sign is noted on the dorsal side of the right hepatic lobe. However, RAs are rare in patients with fatty liver.

Adolescent↗

Pulmonary lesions associated with Sjögren's syndrome: radiographic and CT findings.

The aim of this study was to analyse and compare the chest radiographic and CT findings in patients with primary and secondary Sjögren's syndrome. We retrospectively evaluated the frequency of abnormality and findings of both the chest radiography (n=107) and CT (n=59) in patients with Sjögren's syndrome. Abnormal cases were classified into five patterns based on predominant CT findings. Chest radiographic and CT abnormalities were seen in 24 (22%) and in 34 (58%) patients, respectively. Most frequently observed abnormal findings were linear and reticular opacities on chest radiograph, and ground-glass opacity, interlobular septal thickening and intralobular interstitial thickening on CT in both primary and secondary Sjögren's syndrome. Centrilobular abnormalities were significantly more common in patients with primary Sjögren's syndrome (p=0.018). According to our CT classification, interstitial pneumonia (IP) pattern was the most common in patients with both primary and secondary Sjögren's syndrome. Bronchiolitis pattern was more common in patients with primary Sjögren's syndrome and lymphoproliferative disorder (LPD) pattern was only observed in primary Sjögren's syndrome. In conclusion, although the most frequently observed pattern in our CT classification was IP pattern in both primary and secondary Sjögren's syndrome, centrilobular abnormalities and LPD pattern were relatively characteristic in patients with primary Sjögren's syndrome.

Adolescent↗

Therapeutic trials for a rabbit model of EBV-associated Hemophagocytic Syndrome (HPS): effects of vidarabine or CHOP, and development of Herpesvirus papio (HVP)-negative lymphomas surrounded by HVP-infected lymphoproliferative disease.

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS), which is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD), is a distinct disease characterized by high mortality. Treatment of patients with EBV-AHS has proved challenging. To develop some therapeutic interventions for EBV-AHS, we examined the effectiveness of an antiviral agent (vidarabine) or chemotherapy (CHOP), using a rabbit model for EBV-AHS. Fourteen untreated rabbits were inoculated intravenously with cell-free virions of the EBV-like virus Herpesvirus papio (HVP). All of the rabbits died of HVP-associated (LPD) and hemophagocytic syndrome (HPS) between 21 and 31 days after inoculation. Furthermore, three HVP-infected rabbits treated with vidarabine died between days 23 and 28 after inoculation, and their clinicopathological features were no different from those of untreated rabbits, indicating that this drug is not effective at all to treat HVP-induced rabbit LPD and HPS. Three of the infected rabbits that were treated with one course, with an incomplete set of three courses, or with three full courses of CHOP treatment died of HVP-induced LPD and HPS with a bleeding tendency and/or with opportunistic infections. They died on the 26th, 62nd and 105th day after virus inoculation, respectively. CHOP treatment transiently suppressed the HVP-induced LPD and contributed to the prolonged survival time of two infected rabbits. However, it did not remove all of the HVP-infected cells from the infected rabbits, and residual HVP-infected lymphocytes caused recurrences of rabbit LPD and HPS. The most interesting finding of this experiment was observed in the infected rabbit with the longest survival time of 105 days: HVP-negative lymphomas surrounded by HVP-induced LPD developed in the larynx and ileum of this rabbit, causing an obstruction of the lumen. We concluded that these were not secondary lymphomas caused by CHOP treatment, because no suspicious lesions were detected in three uninfected rabbits that were treated with three courses of CHOP for 120 days. It is therefore necessary to clarify the mechanism by which HVP-negative lymphomas associated with HVP-induced LPD can develop. Our data from therapeutic trials using EBV-AHS animal models indicate that vidarabine is not effective as an agent to treat HVP-infected rabbits, and even the cytotoxic chemotherapy of CHOP is not sufficient to cure the HVP-infected rabbits or to prolong the survival time of infected rabbits. Further studies will therefore be required to develop better therapies to treat EBV-AHS.

Animals↗

Single-stranded conformational polymorphism analysis using automated capillary array electrophoresis apparatuses.

We describe a new environment of a single-stranded conformational polymorphism (SSCP) analysis using automated capillary array sequencers (e.g., ABI Prism 3100 and 3700). In this environment, electrophoretic conditions, settings for instrument management, and software for data analysis are adjusted for SSCP analysis. Highly reproducible results are obtained with this new system, and fragments with mutations and/or polymorphisms in different capillaries or different runs can be reliably detected. The relative peak heights between alleles are quantitative and reproducible between runs, and so allele frequencies of single nucleotide polymorphisms can be accurately estimated by a pooled DNA strategy. The method allows unattended, low-cost, and quantitative SSCP analysis using instruments that are widely accessible.

Alleles↗